 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Vas-Cog Journal
No.7 July 01. 2021

Official Journal of Vas-Cog Japan Society
Review article

Kunihiro Miki, et al.

“Blood-brain barrier disruption: A key interface between
coronavirus disease 2019-related systemic inflammationand cognitive impairment”

Masaki Kondo, et al.

“The application of positron emission
tomography to vascular dementia”

Case report

Yoshio Omote, et al.

“A Unique Case of Takayasu arteritis with
Leukoencephalopathy”
1

ISSN : 24239372

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Table of Contents

Editorial policy of this journal ��������������������

4＜ Review article ＞
Blood-brain barrier disruption: A key interface between coronavirus
disease 2019-related systemic inflammation and cognitive impairment ��5

T he application of positron emission tomography to vasculardementia  ���������������������������� 15＜ Case report ＞
A Unique Case of Takayasu arteritis with Leukoencephalopathy  ��� 25
Greetings from Vas-Cog Japan, the Japanese Society for Vascular Cognitive
Impairment ���������������������������� 30
Welcome to Vas-Cog Japan 2021  ������������������ 31
Welcome to Vas-Cog 2022
Theme: Cerebral small vessel disease and cognitive impairment,
frailty, sarcopenia �������������������������� 33
Meeting report of Vas-Cog Asia 9 from Busan � ������������ 35
Board members / councilors��������������������� 36
Articles of Association of the Japanese Society for Vascular Cognitive
Impairment ���������������������������� 38
Vas-Cog Journal Submission Instructions for authors ��������� 40
Vas-Cog Journal Authorship Agreement  ��������������� 43
Sponsors  ����������������������������� 45
Editor’s Note/
The past and future annual meeting of Vas-Cog Japan �� Inside Back Cover

3

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Editorial policy of this journal
Toshiki Mizuno, MD & PhD

Professor of Neurology,
Kyoto Prefectural University of Medicine
It’s my great honor to work as a chief editor of the1)		Da Mesquita S, Papadopoulos Z, Dykstra T, et al.

Vas-Cog Journal. The aim of the Journal is to clarify

Meningeal lymphatics affect microglia responses

vascular factors influencing cognitive impairment andand anti-Abeta immunotherapy. Nature 2021.

behavior. At first, vascular factors affecting the central2)		Rasmussen MK, Mestre H, Nedergaard M. The

nervous system (CNS) mainly involve atherosclerotic

glymphatic pathway in neurological disorders.

changes in arteries. However, not only arteries but

Lancet Neurol 2018;17:1016-1024.

also an excretory clearance system involving veins and3)		Preston SD, Steart PV, Wilkinson A, Nicoll JA,

diseases . Recent research about an excretory system

amyloid angiopathy in Alzheimer’s disease:cerebrospinal fluid is related to neurodegenerative

Weller RO. Capillary and arterial cerebral

1)

in the CNS proposed two important pathways, called

defining the perivascular route for thethe glymphatic pathway and the perivascularelimination of amyloid beta from the humanpathway. The glymphatic pathway directs flows

brain.

towards the venous perivascular and perineuronal

Neuropathol

2003;29:106-117.

spaces, clearing solutes from the neuropil intomeningeal and cervical lymphatic drainage vessels2).

The perivascular drainage system, an intramural peri-

arterial drainage (IPAD) system, is along the basement
membrane of capillary and arterial walls.

Intraparenchymal material moves towards theleptomeningeal arteries at the surface of the brain
through this pathway and, finally, to cervical lymph
nodes3). However, it has been unclear whether theperivascular drainage and the glymphatic systems are

distinct pathways, and whether they coexist or arecompetitive. New research is needed to clarify theroles of these pathways, and should be performed

with cellular experiments, animal models, and humanimaging studies. Molecular and physiologicalbiomarkers are also important to clarify the role ofvascular factors in cognitive impairment and behavior.
This research presents a new approach forinvestigation of cognitive impairment. The Vas-Cog
Journal welcomes all kinds of research concerning

cognitive impairment and behavior from Japan andAsian countries.

4

Appl

Neurobiol

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Kunihiro Miki；Shuko Takeda；Tsuneo Nakajima；Ryuichi Morishita
Review article

Blood-brain barrier disruption: A key interface
between coronavirus disease 2019-related systemic
inflammation and cognitive impairment

Kunihiro Miki, BSc1); Shuko Takeda, MD, PhD1,2);
Tsuneo Nakajima, MD3); Ryuichi Morishita, MD, PhD1)

1) Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University
2) Osaka Psychiatric Medical Center, Osaka Psychiatric Research Center3) Department of Geriatric and General Medicine, Graduate School of Medicine,
Osaka University
Short Title: Inflammation in COVID-19, BBB disruption, and CI
Disclosures: Authors have no potential conflicts of interest to declare.
Abstract:

The prevalence of dementia has increased with the rising aging population worldwide, and aging anddementia are known risk factors for delirium, a condition that is closely related to inflammation, such as

coronavirus disease 2019 (COVID-19). COVID-19 is caused by severe acute respiratory syndrome coronavirus
2. It originated in Wuhan city, China in early December 2019 and has spread rapidly worldwide ever since.

The elderly population are at a higher risk of contracting the virus than other age groups. Evidence has
shown that many patients with COVID-19 exhibit symptoms of delirium, disproportionally affecting theelderly, and this is concerning due to the close association between dementia and delirium. Impairment of
cerebrovascular functions, especially the blood-brain barrier, plays a key role in delirium and subsequent
dementia caused by inflammation from infectious diseases, such as COVID-19.

Key Words: Blood-brain barrier, systemic inflammation, COVID-19, cognitive impairment, infectious diseases,delirium

Correspondence to:
Shuko Takeda

Department of Clinical Gene Therapy, School of Medicine, Osaka University
2-2 Yamada-oka, Suita 565-0871, Japan

Tel: 81-6-6210-8351, Fax: 81-6-6210-8354
Email: takeda@cgt.med.osaka-u.ac.jp

Dementia and delirium

million worldwide and predicted to double within the

cognitive impairment has become an unavoidable

similar symptoms of dementia, has shown to affectnext 20 years1). Delirium, an acute condition with

With the increasing aging population worldwide,

50% of elderly people (aged 65 years and older)2).

problem affecting both the medical and the

Risk factors for delirium can be divided into threehealthcare system. The number of people suffering

categories: predisposing factors, facilitating factors,

from dementia, a chronic neurodegenerative disease,and precipitating factors. Predisposing factors

increases every year with an estimate of up to 43

5

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Blood-brain barrier disruption: A key interface between coronavirus disease 2019-related systemic inflammation and cognitive impairment
include old age (60 years and older), heavy alcohol

to 50% of patients with VaD experience delirium, thestroke and brain damage, such as dementia.

early-onset Alzheimer’s disease (AD) or

consumption, depression, and history of ischemia or

prevalence of which exceeds that of patients withfrontotemporal dementia7,10).

Predisposing factors are important in screening

While the relationship between dementia andhigh-risk patients. Facilitating factors do not directly
contribute to causing delirium, and these include

delirium remains unclear, several mechanisms haveenvironment or physical restraint. Precipitating

brain such as metabolic derangements, certain drugs

been proposed. For example, certain insults to thestress, sleep impairment, and changes in the physical(e.g., anticholinergics), ischemia, and immunologicalfactors can directly cause delirium, and these include

stressors could alter neurotransmitter concentrations

the use of anesthetics, hypoxia, infection, andcausing acetylcholine deficiency or dopamine excess,invasive surgery. However, with sufficient support

thus resulting in neuronal dysfunctions 11,12). In

from the medical staff, facilitating and precipitating

addition, hypoxia and cerebral ischemia may directly

factors can be improved to a certain degree,cause cerebral dysfunction through impaired

ultimately decreasing the risk of developing delirium.

cerebral blood flow and metabolism13). Evidence also

Dementia and delirium are distinct healthshowed that certain anesthetics can directlyconditions that are closely related. Study has shown

contribute to the accumulation of beta-amyloids,that a single episode of delirium could increase thechance of developing dementia later in life2) andwhich is also a fundamental part of AD14). Anotheraccelerates the rate of neurodegeneration. A study

theory known as the threshold hypothesis has alsodementia found that those who were affected withdementia have fewer neuronal connections, it

including 560 people aged 70 years or more without

been proposed. As the brains of patients withdelirium had significantly greater cognitive decline

becomes more difficult to deal with inflammation andthan those who were not . Another cohort study

infection, not only resulting in delirium but also

3)

including 309 acutely ill patients showed that 32%

advancing the disease. Inflammation in response toof patients experiencing delirium progressed towards

an infection or other stress (i.e., surgery or acutedementia, while only 16% of those who were notillness) could also cause neuronal dysfunction. Cases

delirious progressed to dementia . A meta-analysis

such as this can occur in various mechanisms, such4)of 23 studies showed that patients who developed

as apoptosis, activation of microglia and astrocytes,
and altered neurotransmission15). All these studies

delirium during a hospital stay had a 2.3 times

provide valuable insights into the close relationshipgreater risk of developing dementia than those who

did not . Moreover, a study has shown that the

between dementia and delirium. In this review, we

5)

duration of delirium could also be an importantfocus on the blood-brain barrier (BBB) changes

factor in developing dementia later in life, wherein

associated with systemic inflammation, and how

patients with a longer duration of delirium

these changes link dementia and delirium.

experiencing worse global cognition and executivefunction at 3 and 12 months6). The reverse is also

Systemic inflammation and BBB

with dementia. A study showed that 37% of patientsof delirium remains unknown, which could betheir hospital stay.7) Furthermore, vascular dementia

evidence has shown that interaction between several

true, with delirium being more prevalent in patients

The exact molecular mechanism of the pathology

with dementia experienced delirious attacks during

attributed to its multifactorial causation. However,(VaD) is often associated with delirium , and thebiological factors might be the cause of the8)pathological changes in patients with VaD are

disruption of the large-scale neuronal network in theassociated with cholinergic deficits , which is also abrain, leading to acute cognitive dysfunction2). These9)risk factor of delirium. Studies have shown that 40%

contributing factors of delirium include the6 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Kunihiro Miki；Shuko Takeda；Tsuneo Nakajima；Ryuichi Morishita
dysregulation of neurotransmitters, inflammation,

it can result in impairment of alpha-synuclein

electrolyte disorders, and genetic factors. Other

the brain. Furthermore, it is well known thatphysiological stressors, metabolic derangements,

clearance and the accumulation of alpha-synclein inacetylcholine deficiency occurs in DLB26), a risk

factors can also directly interact withneurotransmission or cellular metabolism, including

factor for delirium.

hypoxia, and impaired glucose oxidation. This review

endothelial cells between blood and the brain andbetter understand the relationship between

entering the CNS. In contrast to the leaky capillary

The BBB is composed of cerebrovascular

drugs, hypercortisolism, electrolyte disturbances,

selectively prevents substances in the blood fromwill focus on the role of inflammation in delirium toendothelium in peripheral organs, the BBB is sealed

coronavirus disease 2019 (COVID-19) and delirium.

by tight junctions and possesses various channels,

The dysregulation of cytokines is believed to be

receptors, and enzymes to allow substance transport.

the main factor in the involvement of inflammation inThis allows transport across the BBB to be highly

delirium. Studies have shown that the use of

selective, which benefits the CNS in various ways. Forinterleukins in rat models alters the acetylcholine
levels and activity

16)

and mediate exotoxic

example, pathogens, blood cells, and certain

neurodegeneration17). A studyshowed that aging cancytokines do not enter the CNS through the BBB.

alter the CNS and peripheral levels of certain

Antibodies and certain antibiotics are also prohibited

cytokines (IL-1 beta and TNF alpha) 18). On thefrom crossing the BBB, making drug and vaccine

contrary, other studyshowed that aging is notdevelopment difficult in some cases. Examples ofassociated with cytokine level chages19). A study

molecules that are allowed to cross the BBB include

conducted on mice showed that changes in glial

insulin, leptin, TNF alpha, and epidermal growth

reactivity in the aging brain can exacerbate

factor, among others. The BBB is also important inneuroinflammatory cytokine responses . Symptoms

supplying the brain with energy, as the brain lacks

20)

associated with illness and delirium such as astorage for carbohydrates. Disruption of the BBB candecrease in cognition, depression of mood, anddramatically change the environment of the CNS.

lethargy known as “sickness behavior” are now

During systemic inflammation, the BBB can bechanged both histologically and molecularly 27),

believed to have been caused by peripheral
inflammatory cytokines .

resulting in cytokine entry into the CNS. As stated,

21)

A study showed that out of 261 patients withcytokine dysregulation can lead to sickness behavior

dementia, 19.4% experienced delirium, in whichand delirium. This phenomenon likely occurs

34.4% were diagnosed with VaD, dementia with thethrough the dysregulation of neurotransmitters andhighest precentile22). VaD is well associated withthe activation of glial cells in the presence of certain

cerebrovascular pathologies, such as disruption of

inflammatory cytokines.

the BBB. Interestingly, 31.8 % of patients were

Various conditions have also been associated withdiagnosed with dementia with Lewy bodies (DLB).

the disruption of BBB. Neuroinflammation following

patients, which was initially believed to be intact,

Following a stroke, the tight junction integrity in the

Recent evidence showed that BBB of synucleinopathy

ischemic stroke is shown to disrupt the BBB.

may be disrupted through a proinflammatory

BBB decreases, which can lead to vasogenic edema,

response . Studies have also shown that alpha-hemorrhagic transformation, ultimately increasing

23)

synuclein can cross the BBB bidirectionally, withmortality. The levels of inflammatory cytokines, such

LRP1 being a potential efflux transporter for alpha-as IL-1 beta and TNF-1 alpha, are upregulated in the

synuclein24). LRP1 is also involved in the efflux ofbrain following cerebral ischemia, with evidencebeta-amyloids and is downregulated in AD . If thispointing that inflammatory cytokines can increase25)

the permeability of the BBB28). Neurotransmittersdownregulation is also present in synucleinopathies,

7

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Blood-brain barrier disruption: A key interface between coronavirus disease 2019-related systemic inflammation and cognitive impairment
released from hypoxic neurons during an ischemic

However, if this mechanism is obstructed, the flow ofto neural tissues, of which the BBB regulates .

walls of blood vessels. During severe systemic

stroke can also cause permanent neurotoxic damage

beta-amyloids can stagnate and accumulate on the29)

Another condition associated with changes to the

inflammation where vascular endothelial cells are

BBB is multiple sclerosis (MS). MS is an autoimmune

potentially damaged by inflammatory cytokines, thedisease characterized by the infiltration of

BBB disruption caused by CAA can be possibly

lymphocytes and macrophages through the BBB andamplified. In addition, the accumulation ofsubsequent breakdown of the myelin sheath inbeta-amyloids can induce inflammation, i.e., CAA inneurons. A feature of MS involves the early

itself can cause vascular inflammation. Albumin

breakdown of the BBB, allowing lymphocyte entry30).

quotient, a common biofluid marker of BBB
breakdown, is shown to elevate in AD38). This

Changes to the BBB may also play an importantphenomenon is believed to be induced by vascularrole in AD via the accumulation of beta-amyloid

inflammation caused by CAA and BBB disruption. As

through intake at the BBB and the decrease of thebeta-amyloids in CAA disrupt the BBB, peripheral

clearance of beta-amyloids. Evidence suggests that

inflammation can have a stronger influence on the

85% of beta-amyloid clearance is through the BBB,
via LRP-1, LRP-2, and APOJ31). Some studies have

CNS. This event can be the mechanism causing

shown that vascular factors such as hypertension ,delirium accompanied by systemic inflammation and32)

diabetes33), hyperlipidemia 34), and cardiovasculardisease35)

eventually resulting in the onset of dementia.

can be risk factors of AD. Several AD

animal models, which include models derived fromCOVID-19, dementia, and delirium

develop an early BBB breakdown36). Cerebral amyloid

identified in Wuhan city, China in early December

breakdown. CAA is the pathology that involves the

100 million confirmed cases and over 2.5 million

mutations in APOE4, APP, and PSEN1 have shown toCoronavirus disease 2019 (COVID-19) was firstangiopathy (CAA) is also related to the BBB

2019 and has spread rapidly worldwide, with overdeaths to date39). It is caused by severe acuteaccumulation of beta-amyloid on the walls of
cerebral vessels. While CAA can be observed in

respiratory syndrome coronavirus 2 (SARS-CoV-2).

be more prevalent in AD. In CAA, beta-amyloids are

disproportionally affect the elderly. Age is the major

COVID-19,

physiological changes related to aging, it is known todelirium,anddementiaallrisk factor for neurodegenerative diseases, and overknown to accumulate in the outer and middle layers

50% of elderly people in hospitals are affected byof vascular smooth muscle cells. The maindelirium 2), while older patients with COVID-19

component of the accumulated beta-amyloid is

experience the most severe and prolonged course of

amyloid-beta 40, which is in contrast to the main

the disease40). Data have shown that up to 67% ofcomponent of amyloid plaques or amyloid-beta 42.

The accumulation of beta-amyloid on the walls ofpatients with COVID-19 exhibit signs of delirium

tunica media and endothelium, resulting in theas reported in various studies could be attributed to(Table 1). Differences in the prevalence of delirium

cerebral vessels can lead to the degeneration of

the differences in the average age of the cohorts anddisruption of the BBB. Studies with animal models

the difficulty of diagnosing delirium. As shown,and postmortem brain of patients with AD suggest

delirium can be listed as a feature of COVID-19. Signs

that CAA is not accompanied by the increase inof delirium could sometimes be present without the

production of APP, the precursor to beta-amyloid,usual febrile responses such as cough or fever. Withbut is caused by the dysfunction of beta-amyloid
clearance from the brain37). Beta-amyloids in brain

data suggesting that 40% of all cases have noradiographic abnormalities on presentation 41) ,interstitial fluid are known to be excreted to thecurrently, there are proposals listing delirium as one of

cerebral spinal fluid through the perivascular space.

8 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Kunihiro Miki；Shuko Takeda；Tsuneo Nakajima；Ryuichi Morishita
Table 1.
Prevalence of delirium in patients with COVID-19

Reference

Study size

Age

Prevalence of delirium in
COVID-19 patients

Pun, Brenda T. et al., 202157

2088

64 (median)55%

Helms, J. et al., 202058

58

－

67%

Kennedy, M. et al., 202056

817

77 (mean)

28%

Ticinesi, A. et al., 202059

852

73 (mean)

11%

Mao, L. et al., 202060

214

52 (mean)8%

Khan, Sikandar H. et al., 202061

268

58 (mean)29%

the diagnostic criteria for COVID-19, because thedirectly contribute to the development of somepossibility of overlooking a potential COVID-19 caseneurodegenerative diseases.

without considering delirium exists. While the exact

There is evidence showing that the SARS-Cov-2

cause of this phenomenon remains unknown, it could

can directly infect the brain, via various proposed

Many aforementioned risk factors of delirium can be

the receptor-binding domain of the spike protein to

be attributed to the multifactorial nature of delirium.

pathways. The virus infects the cell by the binding of

associated with COVID-19, such as inflammation,

the receptor angiotensin-converting enzyme 2(ACE2), after cleavage by furin46). Many neurons andischemia, and anesthetics. A mass cohort study has

neuroglia with high vascularization and permeable

shown that patients with COVID-19 have a higher

BBB express both ACE2 and furin, therefore prone torisk of developing complications including dementia,

SARS-CoV-2 infections. Another pathway suggests

mood disorder, insomnia, and ischemic stroke thaninfluenza patients 6 months after the diagnosis42).

that SARS-CoV-2 enters the brain through the nasal

One of the main features of severe COVID-19 isepithelium, which brings the virus into the olfactory
bulb47). Studies also showed that neuropilin-1 may

systemic inflammation known as the “cytokine

storm.” As previously stated, systemic inflammation

also be involved in the viral infection of SARS-CoV-2

presents as sickness behavior or delirium. Duringanti-neuropilin-1 antibody can significantly reduce

into the brain48), and tests showed that monoclonal

can lead to undesirable changes to the BBB, which

viral infection49). However, in all cases, the SARS-

some cases of systemic inflammation caused bysepsis, sepsis-associated encephalopathy 43) andCoV-2 infection to the brain is yet to be fully

sepsis-associated delirium44) were observed. The

understood.

sepsis-associated encephalopathy can often trigger

Another clinical symptom of COVID-19 is thesevere cognitive impairments and exacerbates

decrease in blood oxygenation caused by pneumonia.

suggested that the systemic inflammation triggered

is associated with respiratory failure and severe

neurodegenerative pathology 44) . It has been

In severe cases, widespread inflammation of the lungby some severe COVID-19 cases is similar in scale tohypoxia. This omnipresent hypoxia is likely to affectthat of sepsis45), thus similar cognitive deterioration

the brain and may have negative effects including

can occur and will boost existing neurodegenerative

respiratory alkalosis and energy deprivation. A

pathologies. Since some neurodegenerative diseases

decrease in arterial oxygen saturation below 75% cancause impairment of neuronal activity50). Hypoxia canare associated with BBB changes, it is likely that thealso cause damage to neural cells due to the rapid

BBB change caused by the systemic inflammation can

9JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Blood-brain barrier disruption: A key interface between coronavirus disease 2019-related systemic inflammation and cognitive impairment
increase in reactive oxygen species, against which

experienced a delirious attack are more likely toto defend.

making the understanding of the mechanism linking

the weak brain antioxidative defenses have few ways

develop dementia than those who have not, thus

Systemic inflammation associated with COVID-19

dementia and delirium an important task for both theis known to increase blood levels of fibronectin,

medical and scientific communities. Studies have also

likely through the stimulation of its liver synthesis51).

shown that cerebrovascular pathologies are likely

This phenomenon can facilitate blood clot formation,

key interfaces in linking dementia and delirium. CAA

and it has been shown that approximately 20% topathologies seen in dementia, such as AD, can

50% of COVID-19 cases were complicated bydisrupt BBB, and this BBB disruption can cause

thrombotic and thromboembolic manifestations52),

delirium through the entry of various cytokines andwith stroke reported in approximately 5% ofdysregulation of neurotransmitters. Changes to thehospitalized patients53). Stroke is associated with

BBB independent of dementia may also cause

secondary neurodegeneration and increased risk ofdelirium, weakening the brain and increasing the riskboth VaD and AD. Therefore, the relationship can beof developing dementia.

drawn linking COVID-19 associated thrombosis and

COVID-19 exhibits diverse clinical symptoms, theneurodegenerative diseases.

understating of which will be key for overcoming the

be seen when considering the nature of thepresents as a clinical feature of COVID-1956). We

Furthermore, the indirect effects of COVID-19 canpandemic. Recent evidence has shown that delirium

pandemic. The risk of developing delirium can beproposed the following mechanism linking

family member assisting the patient with self-

dementia later in life. Infection caused by various

COVID-19, delirium, and the risk of developing

reduced up to 40% with steps such as having aorientation54), which is a difficult task when dealing
with COVID-19

55)

pathogens, including SARS-CoV-2, can cause systemic. The psychological stresses

inflammation, resulting in BBB disruption. As ainvolved in coping with COVID-19 infection, the lack

result, the disruption allows inflammatory cytokinesof physical contact, and the isolation from family are

to enter the CNS, dysregulating neurotransmitterslikely to trigger depression, which in itself is a well-and activating glial cells, causing delirium.

known risk factor of dementia.

Furthermore, SARS-CoV-2 can directly infect thebrain, and although not proven, it possible may beConclusion

the cause of delirium observed in COVID-19.

BBB is key in understanding CNS conditions, such

Through various neuropathologies, delirium canas dementia and delirium. As BBB is highly important

ultimately cause dementia, and pathologies present

in maintaining the environment of the CNS, changes

in dementia can cause additional BBB disruption,

to the BBB may lead to drastic results. For example,

resulting in a vicious cycle (Figure 1).

the pathology of CAA involves the accumulation of

Delirium and dementia are and may continue to bebeta-amyloid protein in cerebrovascular wallsa challenge for the world that requires urgent

amyloids, most of which occurs across the BBB.

both dementia and delirium will more likely become

through the impairment of the clearance of beta-

intervention. With the global COVID-19 pandemic,

Other conditions such as DLB, MS, and stroke also

more prevalent in the future due to the direct andinvolve BBB changes, the mechanism which is likely

indirect interaction between COVID-19, delirium, andto be necessary for understanding the saiddementia. We believe this review will provide

conditions.

valuable insights to the existing literature to better

Dementia and delirium are two closely linked

understand the cerebrovascular mechanism involved

conditions that are prevalent worldwide with thein linking the three conditions.

increasing aging population. Patients who have10 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Kunihiro Miki；Shuko Takeda；Tsuneo Nakajima；Ryuichi Morishita

Direct viral infection

Pathogen

Delirium

SARS-CoV-2
Systemic
inflammation• Neurotransmitterdysregulation• Glial cell activation

Bacteria

FungusDementia

Inflammatory
cytokines

Neuropathologies

Aβ TauBBB
breakdown
CAA

Figure 1.
Proposed mechanism of pathogen-induced delirium through BBB breakdown resulting in the development of dementia.

Acknowledgements

Long-term Cognitive Decline: A Meta-analysis.

This work was supported by JSPS KAKENHI Grant

JAMA neurology 77, 1-9, doi:10.1001/

Scientists (A)) and the research grant from Cell6)		Pandharipande, P. P. et al. Long-term cognitive

jamaneurol.2020.2273 (2020).

Number 17H05080 (grant-in-Aid for Young

impairment after critical illness. The New

Science Research Foundation.

England journal of medicine 369, 1306-1316,

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14

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Masaki Kondo；Toshiki Mizuno
Review article

The application of positron emission tomography tovascular dementia

Masaki Kondo, MD, PhD; Toshiki Mizuno, MD, PhD
Department of Neurology, Kyoto Prefectural University of Medicine

Short title : PET for vascular dementia
Disclosures : The authors declare no conflict of interest.
Abstract :Positron emission tomography (PET), one of the functional imaging modalities, visualizes the brain function
based on the retention of radioisotope-labeled ligands. PET facilitates imaging of localized or diffuse
metabolic disturbances responsible for cognitive impairment, and it is effective for differentiating vasculardementia (VaD) from degenerative dementia such as Alzheimer disease (AD). However, the confounding
pathology and interaction between VaD and AD have become a focus of interest. Cerebrovascular disease and
AD not only occur together but they also interact.
This review overviews the role of structural and functional imaging to diagnose vascular dementia, andsummarizes the usefulness of PET to analyze the pathophysiology and differentially diagnose vasculardementia, using data on oxygen metabolism and amyloid accumulation in the brain.
In our study, cerebral cortical retention of Pittsburgh compound-B (11C-PIB) was noted in more than half of
VaD patients. Various types of low perfusion of cerebral blood flow were observed in patients, but low
perfusion areas were not associated with cortical PIB retention, and the oxygen extraction fraction (OEF) was
increased in 3/5 of those with retention.
Key Words : positron emission tomography, vascular dementia, Pittsburgh compound-B (PIB), oxygen
extraction fraction (OEF)

Corresponding Author:
Masaki Kondo
Department of Neurology, Kyoto Prefectural University of Medicine
465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan
Tel.: +81-75-251-5794, Fax: +81-75-211-8645
E-mail: maskondo@koto.kpu-m.ac.jp

I. Introduction

detect inflammatory changes and their interaction

functional imaging modalities, visualizes the brainof mixed dementias after stroke1).

Positron emission tomography (PET), one of thewith amyloid deposition, leading to the development

In this review, firstly, we overview the role offunction based on the retention of radioisotopelabeled ligands. PET facilitates imaging of localized

structural and functional imaging to diagnose

cognitive impairment, and this tool is effective forapplication of PET to analyze the pathophysiology

vascular dementia. Next, we summarize the usefulor diffuse metabolic disturbances responsible forand differentially diagnose vascular dementia (VaD).

differentiating vascular dementia from degenerative

Lastly, we introduce our data on oxygen metabolism

dementia such as Alzheimer disease (AD). It can also

15

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

The application of positron emission tomography to vascular dementia
and amyloid accumulation in the brains of patients

PET can support the clinical diagnosis by visualizing

with VaD.

cerebral functions in typically affected brain
regions3) (Fig. 1).

II. Vascular dementia and neuroimaging

III. Vascular dementia and positron emission

VaD is defined based on the clinical diagnosis of

tomographydementia and cerebrovascular disease derived fromPET can be applied to measure regional cerebral

the clinical course and imaging, and their causal
association2). Typical VaD leads to dementia after ab l o o d f l o w, o x y g e n c o n s u m p t i o n , g l u c o s e

progression of dementia with repeated stroke

molecular changes. The data improve the assessment

stroke episode (post-stroke dementia) or step-wisemetabolism, which reflects synaptic alteration, andepisodes.

of the causal pathology and differential diagnosis.

Although cerebral infarcts are important toAfter the 1980s, PET scanners and radioisotope

identify patients with dementia, their presence does

ligands could be used to measure regional brain

not necessarily mean that they are the cause of theperfusion and metabolism and were clinicallyapplied4). In Japan, PET study using 15O-tracer wasdementia or that they have contributed to it. It

approved for clinical use in 1996, and that using

remains controversial whether a specific set of
lesions, based on their size and anatomic

18

F-fluorodeoxyglucose (FDG) to screen for cancer in

2002. Whole-body PET using FDG has spread rapidly

distribution, are the cause of or contribute to thedevelopment of dementia3).

for the purpose of evaluating patients with malignant

To investigate the association between vasculartumors.

● Oxygen metabolism and cerebral blood flow

lesions and cognitive decline, structural imaging

such as computed tomography (CT) or magnetic

Quantitative assessment of brain perfusion andresonance imaging (MRI) and functional imaging

metabolism using an 15O-tracer has been applied toclinical practice. Whereas CT and MRI are able topatients with cerebral artery stenosis or occlusion. The

evaluate the perfusion grade or indication of surgery inincluding PET have been used in research andobservation of hypoperfusion or hypometabolism

detect morphological lesions, these modalities cannot

patterns withdetermine the functional consequences of the

15

O-labeled compounds provides

important information on cerebral blood flow and theunderlying pathological changes. On the other hand,

Structural images

Functional images

CT
MRI

PET
(MRI)

Vascular lesions
Tumor
Atrophy
ventricular dilatation

CBF
Metabolism
Neurotransmitter/receptor
Molecular deposition

Fig.1

Structural and functional images

PET is a functional imaging modality and can measure cerebral blood flow, metabolism, neurotransmitters andreceptors, and molecular deposition in the brain.

16 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Masaki Kondo；Toshiki Mizuno
metabolic reserve that are considered to be key factors

cerebral regions is always displayed as a

● Glucose metabolism

anatomical navigation function to PET due to theirin the diagnosis and treatment of brain ischemia5).

hypometabolic area in PET. MRI and CT add an

PET scanners have rapidly become used widely inspatial resolution, so hybrid PET/CT and PET/MRI

research centers, and many clinical studies offacilitate improved anatomical detail. They have been

dementia patients using FDG-PET have clarified

installed in research centers and become useful tools

features of brain metabolism in various types ofto obtain data on brain activity with good spatial
resolution as well as morphological information10).

dementia, such as AD, frontotemporal lobar● Amyloid and tau

degeneration (FTLD), and dementia with Lewy bodies(DLB)6). Degenerative dementias show characteristic

PET tracers have enabled the detection ofpatterns of regional hypometabolism. AD patientspathogenetic depositions such as amyloid and tau inshow hypometabolism in temporoparietal and frontal

AD. Amyloid accumulation can be imaged by
Pittsburgh compound-B (11C-PIB)11) or several newer

association areas but relative recessing of primary

F-labeled tracers12,13). Tau imaging is the newest tool

cortical areas, basal ganglia, and the cerebellum.

18

FTLD patients exhibit distinct frontal orfor noninvasive assessment of neurodegenerative

asymmetrically centered in the frontolateral cortex

Postmortem and tau-imaging studies generate data

showed reduced glucose metabolism in the primary

topographical distribution in a brain, and so tau

conditions such as AD and non-AD tauopathies14).

frontotemporal metabolic impairments, typicallyon not only the amount of tau deposition but also its

and anterior pole of the temporal lobe. DLB patients

imaging might be more relevant and more closely

visual cortex in addition to that in the posterior
association areas .

associated with neurodegeneration and cognitive3)

decline than Aβ15,16).

Comparing VaD with other forms of dementia,

Since Alzheimer pathology and cerebral vascular

lower-level metabolism in the deep gray nuclei,
cerebellum, primary cortices, middle temporal gyrus,

lesions commonly coexist, the interaction between

differentiate VaD from AD, whereas lower-level

Jang et al. reported that the association between Aβ/

the two pathologies has been of marked interest.

and anterior cingulate cortex could be used totau brain accumulation detected by PET andmetabolism in the hippocampal region, andcognitive decline was stronger in a subcorticalorbitofrontal, posterior cingulate, and posteriorparietal cortices differentiated AD from VaD .

vascular cognitive impairment group compared with

7)

an AD-related cognitive impairment group17).

Decreases in perfusion and glucose metabolism● Active microglia and inflammation

distributed in vascular territories were notedbilaterally and involved the frontal lobes in VaD8).

The common neuropathological events in both

FDG-PET can clearly differentiate scattered areas ofvascular and degenerative disorders induce

from the typical metabolic pattern in AD . Other

astrocytes as well as activation and upregulation of

focal cortical and subcortical hypometabolism in VaD

inflammation and proliferation of microglia and3)studies reported that vascular groups including

several inflammatory compounds. This reactive

patients without dementia exhibited decreased

inflammation can be imaged by radiolabeled ligands

metabolism in frontal and parietal lobes but not infor the peripheral benzodiazepine receptor, called thetemporal lobes nor the precuneus. In addition, a VaD

translocator protein (TSPO), not only in the area ofgroup showed decreased metabolism bilaterally in

the infarct but also in degenerating projection areas
remote from the primary ischemic lesion18). The

deep nuclei, specifically the caudate nucleus, globus
pallidus, and thalamus .

interaction of an inflammatory reaction and amyloid

9)● PET/CT and PET/MRI

deposition may be associated with the development

The vascular pattern of specifically injuredof post-stroke dementia and can be studied by PET

17

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

The application of positron emission tomography to vascular dementia
with a TSPO ligand, PK 11195, and PIB19). PET

structural imaging as a first step and three main

regarding the association between active microglia

sequences, in which amyloid PET, 18F-FDG-PET, andstudies were reported involving small vessel diseaseand vascular lesions

20)

diagnostic pathways with distinct biomarker

in addition to amyloid

dopamine transporter SPECT are assigned different

imaging . In a PET study using a TPSO ligand withorders on diagnostic evaluation depending on clinical21)

presentation27). In another algorithm, the initial part

neuropathological comparison, elevated TPSO
binding provided evidence of inflammatory

in tertiary memory clinics involves routine tests forspaces in cerebral small vessel disease . Sample

vascular dementia) including structural imaging.

typical dementing disorder (e.g., amnestic AD,

activation localized to vessel walls and perivascular20)

data in human stroke patients are reported,

When the diagnosis is unclear, they suggest

suggesting the possibility of being able toperforming FDG-PET, and then using amyloid
biomarkers28). Since vascular dementia is diagnosed

differentiate two separate pathological mechanisms:

based on clinical symptoms and vascular lesions,an Aβ-dependent cortical mechanism and a non-Aβ

pure vascular dementia is not a PET-applicable-dependent, neuroinflammation-related subcorticalmechanism .

dementia. However, vascular dementia is sometimes

21)● Benzodiazepine ligands
11

associated with AD or other neurodegenerative

C-flumazenil, (FMZ), a ligand binding to central

pathologies. Amyloid PET and tau PET can be used tobenzodiazepine receptors, is useful for evaluatingclearly resolve the comorbidity of amyloid and tau
pathology when PET shows negative findings29).

neuronal viability. In a report of patients withextensive leukoaraiosis, the presence of dementia

IV. Amyloid accumulation and oxygen metabolism

was associated with a reduced distribution volume ofin vascular dementia

FMZ in widespread areas of the cerebral cortex22).

Differences in neuronal integrity in the cerebral

The confounding pathology and interaction

cortex might determine whether patients with

between VaD and AD have attracted interest, such as

benzodiazepine receptor ligand of single photon

vascular factors to AD. Cerebrovascular disease andleukoaraiosis become symptomatic. 123I-iomazenil, aamyloid accumulation in VaD and the contribution ofemission computed tomography (SPECT), may also

AD not only occur together but they also interact, asshown in the Nun study30). The high manifestation rate

reveal underlying pathophysiological differences in
the frontal lobe among VaD, mixed AD/VaD

of clinically relevant cognitive impairment after stroke

the cerebral cortex .

and metabolic changes leading to AD. A hypothesis

might be related to the interaction of vascular risks

dementia, and AD, reflecting the neuronal integrity in
23)● Neurotransmitters and receptors

based on recent reports supports the view that

PET tracers facilitate the study of selectively

vascular lesions may modify the pathophysiology ofaffected neurotransmitter and receptor systems, theAD (AD with vascular lesions), while they may be adirect cause of cognitive decline31). Cognitive decline

cholinergic system in AD or the dopaminergic system. In the evaluation of parkinsonism using

in VaD may be associated with the amyloid pathology:

be measured separately, and latent neurodegenerative

angiopathy directly affecting the cognition, or thein DLB

24,25)

PET, dopamine pre- and post-synaptic functions canlatent amyloid pathology or cerebral amyloid

pathological findings or dopaminergic neuronalamyloid pathology may reciprocally contribute todamage caused by vascular lesions can bevascular lesions.

detected .

We introduce our data on oxygen metabolism and26)● A diagnostic algorithm for PET

amyloid accumulation in the brains of ten VaD

with optimal time-points for PET biomarkers:

consistent with probable VaD based on the

Chételat et al. proposed a diagnostic algorithm

patients (Table 1). Eight of them had diagnoses

18 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Masaki Kondo；Toshiki Mizuno
Table 1

Characteristics of vascular dementia patients

M: male, F: female, PIB: Pittsburgh compound-B, PIB+: apparent cerebral cortical retention,
PIB ± : cortical retention in focal small areas, PIB-: no cortical retention. OEF: oxygen extraction fraction,
MMSE: mini-mental state examination, FAB: frontal assessment battery, MoCA: Montreal cognitive assessment.

Case

age
(years)gendereducation(years)

PIB subtype of VaD increased OEF MMSE

FAB

MoCA

1

84

M

16

+

strategic

+

17

8

14

2

77

F

9

+

subcortical

-

24

14

11

3

86

M

9

+

cortical

+

15

9

6

4

82

M

16

+

subcortical

+

26

13

13

5

83

M

12

+

subcortical

-

25

5

13

mean

82.4

21.4

9.8

11.4

6

79

M

20

±

subcortical

-

25

14

19

7

87

M

9

±

subcortical

+

20

10

14

M

9

±

subcortical

-

8

72

mean

79.3

12.4

12.7

23

14

16

22.7

12.7

16.3

9

85

M

11

-

subcortical

-

23

17

15

10

77

M

9

-

subcortical

-

29

11

22

mean

81.0

26.0

14.0

18.5

10.0

Association Internationale pour la Recherché etpatients exhibiting AD-like hypoperfusion werecriteria2), and the remaining two (cases 2 and 10)

one of them showed hippocampal atrophy (Case 1),l’Enseignement en Neurosciences (NINDS-AIREN)

revealed to be PIB-positive (Cases 1, 2, and 5) andwere diagnosed according to diagnostic criteria ofwhile decreased perfusion areas also included frontal

subcortical ischemic vascular dementia32). Subtypesof vascular dementia

33)

lobes, basal ganglia, and the thalamus. The additional

were strategic single infarct

hypoperfusion areas were consistent with a previous
report on VaD9). Three of five PIB-positive patientsdementia (one patient: case 1), cortical vascularshowed lobar microbleeds on *T2-MRI (Cases 2, 3,

dementia (one patient: case 3), and subcorticaland 5), and these patients may have suffered fromvascular dementia (eight other patients).

cerebral amyloid angiopathy.

In our study, 50% (5/10) of VaD patients exhibited

We provide further information on four patients

apparent cerebral cortical retention of PIB (Fig.2)

and PIB retention of focal small areas in threewith increased oxygen extraction fraction (OEF).

Frontal assessment battery (FAB) scores were notthalamic infarction, MMSE score of 17, and aCase 1: An 84-year-old male, with dementia after left

patients. Mini-mental state examination (MMSE) andvascular risk of hypertension. MRI showedsignificantly different between PIB-retention andleukoaraiosis and lacunas in white matter and the left

non-retention groups. However, the Montreal cognitive

thalamus. PET showed PIB retention in the bilateral

assessment (MoCA) score of the PIB-retention group

frontal inferior portion and right parietal medial

was significantly lower than that of the partial-

portion, low perfusion in bilateral frontal, temporal,

retention and non-retention groups (Fig. 3). Age andand parietal areas without sensory-motor areas, andeducation showed not significant difference between

mildly increased OEF in bilateral frontal and parietalgroups. PIB retention areas were not associated withareas (Fig. 4).

low perfusion areas, and the patient with dementia

Case 3: An 86-year-old male, with dementia after

after cortical infarcts (Case 3) showed diffuse corticalmultiple infarcts (cerebellum, occipital lobes, left

PIB retention in the remaining hemisphere. Three

19

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

The application of positron emission tomography to vascular dementia

Case 1Case 2
1.0

Case 4

Case 3

Case 50Fig. 2

11

C-PIB-PET of vascular dementia patients with apparent cortical retention

N-Methyl-[ C]2-(4-methylaminophenyl)- 6-hydroxybenzothiazole (PIB) was prepared at Nishijin Hospital, Kyoto.
PIB radiosynthesis was performed using a simplified method.
The PIB retention outcomes that were evaluated were based on Distribution Volume Ratio (DVR) measures.
DVRs were generated using the cerebellum as a reference.
11

MMSE

30

25

20

20

15

15

10

10

5

5

0

PIB +

±

MoCA

30

25

0

－

PIB +

±

－

FAB
20
15
10
5
0

Fig. 3

PIB +

±

－

Comparison of cognitive tests between PIB-positive and -negative groups

PIB: Pittsburgh compound-B, PIB+: apparent cerebral cortical retention,
PIB ± : cortical retention in focal small areas, PIB-: no cortical retention.
Although MMSE and FAB scores showed no significant difference between groups,
the MoCA score in the PIB+ group was significantly lower (Kruskal-Wallis test p=0.039).

20

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Masaki Kondo；Toshiki Mizuno

Case 1

1.0

0
40

0
0.7

R

0

Fig. 4

MRI and PET of Case 1

The first row is brain MRI, the second row is 11C-PIB-PET, the third row is cerebral blood flow (CBF),
and the fourth row is the oxygen extraction fraction (OEF) using PET and 18O-compounds.
MRI showed leukoaraiosis and lacunas in the white matter and left thalamus. PET showed PIB retention in the bilateralfrontal inferior portion, right parietal medial portion, low perfusion in bilateral frontal, temporal, and parietal areas
without sensory-motor areas, and mildly increased OEF in bilateral frontal and parietal areas.

thalamus, and left frontal lobe), MMSE score of 15,

left frontal area, low perfusion in the right frontal

multiple brain infarctions in vertebro-basilar and left

and parietal areas (Fig. 7).

and a vascular risk of hypertension. MRI showed

area, and mildly increased OEF in bilateral frontal

middle cerebral artery areas. PET showed PIB

Increased OEF patients did not show significantly

retention right-dominantly in frontal, temporal, andlower scores in MMSE, FAB, or MoCA than patients

low perfusion in left frontal, temporal, and parietal

in OEF included three PIB-positive patients and one

parietal areas and the right parietal medial portion,with non-increased OEF. Those showing an increase

areas, bilateral occipital areas, and prominently

patient with PIB focal retention, but no PIB-negative

increased OEF in bilaterally diffuse cerebral areas

patient. They showed no apparent arterial stenosis(Fig. 5).

detected by MRA or cervical ultrasonography,

Case 4: An 82-year-old male, with dementia after left

suggesting misery perfusion in vessels smaller thanhemiparesis and gait disturbance, MMSE score of 26,

those detected by the devices. Our data suggest thatand vascular risks of hypertension, diabetes mellitus,

an increase of OEF might be caused by lowerand hyperlipidemia. MRI showed leukoaraiosis andperfusion at a smaller artery or capillary level. A PIB-

lacunas in white matter. PET showed PIB retention inpositive patient with prominently increased OEF inright temporo-occipital and parietal areas, lowdiffuse areas (case 3) showed lower scores of MMSE,

perfusion right-dominantly in bilateral frontal areas,

FAB, and MoCA. Such a patient may have suffered

and mildly increased OEF in bilateral frontal andfrom a complicated pathophysiology involving

parietal areas (Fig. 6).

smaller artery dysfunction and an amyloid

Case 7: An 87-year-old male, with dementia withpathology.

parkinsonism, mild left hemiparesis, MMSE score of

20, and a vascular risk of hypertension. MRI showed

Acknowledgements

right thalamus. PET showed PIB focal retention in the

Number JP20dm0107567.

leukoaraiosis and lacunas in white matter and theThis research was supported by AMED under Grant

21

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

The application of positron emission tomography to vascular dementia

Case 3

1.0

0
30

0
0.7

0

R

Fig. 5

MRI and PET of Case 3

MRI showed multiple brain infarctions in vertebro-basilar and left middle cerebral artery areas.
PET showed right-dominant PIB retention in frontal, temporal, and parietal areas and the right parietal medial portion,
low perfusion in left frontal, temporal, and parietal areas, and bilateral occipital areas, and prominently
increased OEF in bilaterally diffuse cerebral areas.

Case 4

1.0

0
40

0
0.7

R

0

Fig. 6

MRI and PET of Case 4

MRI showed leukoaraiosis and lacunas in white matter. PET showed PIB retention in the right temporo-occipital andparietal areas, right-dominant low perfusion in bilateral frontal areas, and mildly increased OEF in
bilateral frontal and parietal areas.

22 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Masaki Kondo；Toshiki Mizuno

Case 7

1.0

0
40

0
0.7

R

0

Fig. 7

MRI and PET of Case 7

MRI showed leukoaraiosis and lacunas in white matter and the right thalamus. PET showed PIB focal retention in theleft frontal area, low perfusion in the right frontal area, and mildly increased OEF in bilateral frontal and parietal areas.

PET study was performed in cooperation with6)		Bohnen NI, Djang DS, Herholz K, et al.

Nishijin Hospital.

Effectiveness and safety of 18F-FDG PET in theevaluation of dementia: a review of the recent

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24

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Yoshio Omote, et al.
Case report

A Unique Case of Takayasu arteritis with
Leukoencephalopathy
Yoshio Omote, MD, PhD; Yuko Kawahara, MD, PhD;
Nozomi Hishikawa, MD, PhD; Emi Nomura, MD, PhD; Ryo Sasaki, MD;
Namiko Matsumoto, MD; Yuki Taira, MD; Chika Matsuoka, MD;
Mami Takemoto, MD, PhD; Ryuta Morihara, MD, PhD;
Toru Yamashita, MD, PhD; and Koji Abe, MD, PhD
Department of Neurology, Graduate School of Medicine,
Dentistry and Pharmaceutical Sciences, Okayama University

Abstract

Takayasu arteritis is primarily a granulomatous large vessel vasculitis mainly involving the aorta and its

main branches. Here we report a 45-year-old woman developing gait disturbance and visual loss withabnormal lesions in bilateral pons, left cerebellum and bilateral occipital to parietal areas on brain magnetic

resonance imaging (MRI). Her symptoms and brain MRI findings were refractory to initial steroid therapy, butmuscle weakness in left upper limb later occurred with new abnormal lesion in right frontal area withGadolinium-enhancement. The brain biopsy finally demonstrated a marked gliosis and demyelination withcytotoxic helper T cell and microglia accumulation predominantly around the small vessel, and the new brain
lesion plus new neurological symptoms improved after the second steroid therapy except for visual loss. The
present case reported a unique intracranial small vessel involvement in the course of Takayasu arteritis.
Key words: Takayasu arteritis, leukoencephalopathy, brain biopsy, small vessel, IL-6
Abbreviations: CD, cluster of differentiation; CSF, cerebrospinal fluid; CT, computed tomography; ESR,
erythrocyte sedimentation rate; 18F-FDG PET, Fluorine-18 fluorodeoxyglucose positron emission tomography;

FLAIR, fluid attenuated inversion recovery; Gd, Gadolinium; IgG, immunoglobulin G; IL-6, interleukin-6; MRA,
magnetic resonance angiography; MRI, magnetic resonance imaging.
Corresponding author: Prof. Koji Abe

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama
University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.

Tel: +81-86-235-7365; Fax: +81-86-235-7368; E-mail: pvil123y@okayama-u.ac.jp
Introduction

resonance imaging (MRI) with hyperintense white

primarily a granulomatous large vessel vasculitis

report a first case of cerebral lesions with Takayasu

well as coronary and pulmonary arteries . Cerebral

demyelination with cytotoxic T cell and microglia

matter lesions on T2-weighted image2). Here weTakayasu arteritis known as “pulseless disease” isarteritis, who demonstrated a marked gliosis andmainly involving the aorta and its main branches, as
1)lesions associated with Takayasu arteritis areaccumulation around the small vessel confirmed by

supposed to be mainly caused by ischemia due tobrain biopsy.

large vessel stenosis. However, small vessel ischemic

lesions are also reported on brain magnetic

25

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

A Unique Case of Takayasu arteritis with Leukoencephalopathy
Case report

revealed no obvious stenosis (Fig. 1C). Brain MRI

disturbance (left >> right) in two months. She had anof pons, left cerebellar hemisphere and bilateral

A 45-year-old woman developed a progressive gaitshowed high intensity lesions in bilateral tegmentum

immediate history of Takayasu arteritis treated withoccipital to right dominant bilateral parietal areas on

aspirin for previous 6 months. Although she

fluid-attenuated in version recovery (FLAIR) images

admitted to a nearby hospital found hyperintensities(Fig. 1D) without enhancement on Gadolinium (Gd)in bilateral occipital to parietal areas on T2-weighted-enhanced T1-weighted images (Fig. 1E). Fluorine-18

image of brain MRI on day -46, she was not treatedfluorodeoxyglucose positron emission tomography(18F-FDG PET) revealed decreased uptake of thethere because autoantibodies and cerebrospinal ﬂuid

tracer in the above lesions (Fig. 1F, arrowheads) on(CSF) analysis were normal. However, the symptoms

day 8. Because an autoimmune encephalopathy waswere getting worse, and thus she admitted to oursuspected at this moment, three cycles of

hospital for further examination.

intravenous high-dose methylprednisolone (1000 mg

On admission (day 1), bilateral bruits were audible

per day, 3days) were started on day11. Althoughat supraclavicular fossa, and neurolog ical

visual loss was sustained, truncal ataxia was

examinations showed diminished visual acuity andgradually improved. She discharged from ourtruncal ataxia. Neither papilledema nor inflammatory

hospital on day 46 and transferred to a differentchange in fundi was found. There were no otherhospital for rehabilitation.

abnormal neurological findings in motor, sensory or

However, she later noticed muscle weakness in left

autonomic systems. Serum analyses showed normal
white blood cells count (6,740 /μL, normal 3,300-

upper limb around day 60 and gradually worsen.

rate (ESR, 64 mm/h, 103 mm/2h), and mild elevation

Serum analyses showed a normal ESR (8 mm/h, 21Thus, she came to our hospital on day 99 again.

8,600/μL) with increased erythrocyte sedimentation

mm/2h) and C-reactive protein (0.09 mg/dL), and aof C-reactive protein (0.4 mg/dL, normal 0.00-0.14

mild elevation of IL-6 (4.3 pg/mL). A CSF study

mg/dL), immunoglobulin G (IgG, 1,917 mg/dL,

showed normal cell counts (1 /µL, monocyte 100%),

normal 861-1,747 mg/dL), and elevation of

mildly elevated protein (100 mg/dL, normal 10-40

immunoglobulin A (721.8 mg/dL, normal 93-393

mg/dL) and IL-6 (4.5 pg/mL). Brain MRI showed a

mg/dL) and immunoglobulin E (1,494 IU/mL, normal

new high intensity lesion on FLAIR image (Fig. 1G,< 170 IU/mL). Serum autoantibody test showed

arrowhead) with Gd-enhancement appeared in rightelevation of anti-thyroglobulin antibody (11.1 IU/

frontal area (Fig. 1H, arrowhead).

mL, normal < 5.0 IU/mL) and anti-cardiolipin IgG

18

F-FDG PET

revealed a further decreased uptake in the rightantibody (34 U/mL, normal < 9 U/mL), and serum

frontal to parietal lesions (Fig. 1I, arrowheads) oninterleukin-6 (IL-6) was greatly elevated (2,680 pg/

day 105. In order to confirm the diagnosis, brain

mL, normal < 4.0 pg/mL).

biopsy was performed from white matter lesions of

A CSF study showed normal pressure (initial 130

and terminal 50 mmH2O), mildly elevated cell counts

right frontal and parietal lobe by stereotaxic(11 /µL, monocyte 100%) and protein (100 mg/dL,

technique on day 115. Pathological study found a

normal 10-40 mg/dL) with normal glucose level (47marked gliosis with demyelination and a diffuse

mg/dL) and IL-6 (3.5 pg/mL, normal < 4.3 pg/mL).

accumulation of lymphocytes predominantly aroundCSF oligoclonal bands were detected.

small vessel (Fig. 2). Elastica van Gieson (EVG) stain

Whole body computed tomography (CT) revealed

revealed that there was perivascular space without

aortic stenosis with calcification in descending aortainternal elastic lamina or smooth muscle in the small(Fig. 1A, arrowhead) and CT angiography revealed

vessel. Immunohistological examination showed thatright subclavian artery stenosis (Fig. 1B, arrowhead).

monocytes were mainly positive for cluster ofBrain magnetic resonance angiography (MRA)

differentiation 3 (CD3), CD8 and CD68, weakly26 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Yoshio Omote, et al.

Figure 1(A) Whole body CT shows aortic stenosis with calcification in descending aorta (arrow), and (B) CT angiography showsright subclavian artery stenosis (arrow). (C) Brain MRA shows no obvious stenosis. Brain MRI shows (D) high intensity
lesions in pons, left cerebellar hemisphere and bilateral occipital to parietal areas on FLAIR images (E) without
enhancement on Gd-enhanced T1-weighted images. (F) 18F-FDG PET on day 8 shows a decreased uptake of the tracer in
the above lesions (arrows). (G) Brain MRI showed a new high intensity lesion on FLAIR image (arrow) on day 99 (H)with Gd-enhancement appeared in right frontal area (arrow). (I) 18F-FDG PET on day 105 shows a further decreased
uptake in the right frontal to parietal lesions (arrows).

positive for CD4, and negative for CD20 (Fig. 2),

and a hypometabolism on 18F-FDG PET (Fig. 1F).

accumulation in the lesions. After the brain biopsy,

the high intensity lesions in bilateral occipital lobe

suggesting that cytotoxic T cell and microglia
threecyclesofintravenous

Clinically, her visual acuity gradually worsened as

high-dose

extended to parietal lobe. Neither papilledema nor

methylprednisolone (1000 mg per day, 3days) were

inflammatory change in fundi was found. Therefore,

started again on day 117, and administration of oral

the indicated visual loss was might be due toprednisolone (20 mg/day) was started in day 134.

inflammation-related damage in the tract to theWith those therapies, weakness in the left limb was

visual cortex. Her symptoms and brain MRI findings

gradually improved. On day 127, brain MRI showed

were refractory to initial steroid therapy, but muscle

high intensity lesions were slightly expanded on

weakness in left upper limb later occurred with new

FLAIR image (Fig. 1J), whereas frontal enhanced

high intensity lesion in right frontal area with Gd-

lesion disappeared on Gd-enhanced T1-weighted

enhancement. The brain biopsy finally demonstrated

image (Fig. 1K). Finally, she discharged on day 144.

a marked gliosis and demyelination with cytotoxic
helper T cell and microglia accumulation (Fig. 2), andDiscussion

the new brain lesion plus new neurological

We described a patient who suffered fromsymptoms improved after the second steroid therapy

Takayasu arteritis, eventually developing gait

except for visual loss (Fig. 3).

disturbance and visual loss with high intensity

Takayasu arteritis is primarily a granulomatous

lesions in bilateral pons, left cerebellum and bilaterallarge vessel vasculitis, which is characterized by

occipital to parietal areas on FLAIR images (Fig. 1D)

stenosis, occlusion and sometimes aneurysm of the27

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

A Unique Case of Takayasu arteritis with Leukoencephalopathy

Figure 2
Pathological study on brain biopsy samples shows a marked gliosis with demyelination and a diffuse accumulation oflymphocytes predominantly around small vessel. EVG stain revealed that there was perivascular space without internal
elastic lamina or smooth muscle in the small vessel. Immunohistological examination showed that monocytes weremainly positive for CD3, CD8 and CD68, weakly positive for CD4, and negative for CD20. Bar: 100μm.

Figure 3
Clinical course of the present case.

aorta and its main branches1,2). The pathogenesis ofvessel. On the other hand, there was no eosinophilic

positive, CD8 positive, but not CD4 positive cytotoxic

lesion5). These findings suggested that inflammation

Takayasu arteritis is cellular infiltration of CD3

red neurons which indicated acute ischemia in the

T cell , macrophages, CD4 positive T cell, CD8of small vessels might reflect T2 high intensity of3)positive T cell, natural killer T cell and γδ T cell inbrain MRI. EVG stain revealed that there was

4)

aortic tissue. In the present case, the brain biopsy

perivascular space without internal elastic lamina or

showed the accumulation of mainly CD68 positivesmooth muscle in the small vessel, and the diameter

microglia, and CD3 and CD8 positive cytotoxic T cell,of this artery was about 30 to 100μm, therefore, thisweakly CD3 and CD4 positive helper T cell (Fig. 2),

small vessel with inflammation was supposed to be apost-capillary venule6), but is pathologically similar

which happened predominantly around the small

28

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Yoshio Omote, et al.
References

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Conflicts of interest

Neuropathol

Dec;67(12):1113-21.

The authors declared no potential conflicts ofExp

Neurol.

20087)		Noris M, Daina E, Gamba S, Bonazzola S, Remuzzi

interest.

G. Interleukin-6 and RANTES in Takayasu
arteritis: a guide for therapeutic decisions?

Acknowledgement

Circulation 1999; 100: 55–60.

We appreciate the patient’s cooperation. This work

was partly supported by a Grant-in-Aid for Scientific
Research (B) 17H0419611, (C) 15K0931607,

17H0975609, and 17K1082709, and by Grants-in-

Aid from the Research Committees (Kaji R, Toba K,
and Tsuji S) from the Japan Agency for Medical

Research and Development 7211800049,
7211800130, and 7211700121.

29

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Greetings from Vas-Cog Japan, the JapaneseSociety for Vascular Cognitive Impairment
Ryuichi Morishita, MD, PhD
President: The Japanese Society for
Vascular Cognitive Impairment

Since Vas-Cog Japan was first established at 11 years
ago, it has developed considerably. The society
progressed under the strong leadership of former
Presidents Prof. Ken Nagata and Prof. Koji Abe,aiming to promote both basic and clinical research on
vascular cognitive impairment and dementia. I took
over as president of the society. I would like toexpress my sincere gratitude to all members of VasCog Japan for their kind cooperation, assistance, andfriendship.
The Vas-Cog Japan society has been steadily growing,
thanks to the efforts of the Chairman for Increasing
Membership and Public Relations, Prof. Haruo Hanyu.
As of March 2021, we have 183 active members, up
from 143 last year, including 25 directors and 64
councilors, and the membership is expected tocontinue to increase in the future. Furthermore, thefinancial structure has been going very well, year by
year. Under the guidance of Prof. Yoshio Ikeda, theChairman of Financial Affairs, we can expect thesociety’s finances to continue to grow in the future. I
sincerely thank the members, councilors, anddirectors who have supported the society since its
establishment for these achievements. Our society
has now met the requirements in terms of member
numbers, membership management, and publicationof journals to apply to be registered as an academicorganization with the Science Council of Japan. At
present, the Chairman for the Promotion of Becominga Society, Prof. Katsuya Urakami, is overseeing ourapplication for registration. Regarding conflicts ofinterest (COI), we have set up a COI committee andprepare provisions under the direction of thechairman of this committee, Prof. Masahiko Suzuki
We have published an annual newsletter since 2014.
The newsletter has been widely distributed to related
academic societies in various countries and has been
well accepted, thanks to the hard work of former
President Prof. Koji Abe. Due to the efforts of thechief editor of the academic magazine, Prof. Mikio
Shoji, it has developed into the Vas-Cog Journal, ajoint publication with Vas-Cog Asia. Last year, Prof.

Toshiki Mizuno took over the role of chief editor of
the journal. We continue to focus on improving thecontent of the journal in terms of the quality of
published articles, as well as the look of the journal interms of style and presentation.
The COVID-19 outbreak resulted in the cancelation ofacademic conferences worldwide, including the 11th
annual meeting of Vas-Cog Japan 2020, which wasintended to be held 12 and 13 September 2020 at
Awa Kanko Hotel, Tokushima, with Prof. MasatakaSata, Department of Cardiovascular Medicine,
Institute of Biomedical Sciences, Tokushima
University Graduate School and Prof. Shunya
Takizawa, Department of Neurology, Tokai University
School of Medicine as the chairpersons. The
conference is now scheduled to take place in thesame venue on 28 August 2021. Hopefully, we will
have a safe and exciting meeting this year. Up-to-date
information on the conference will be available on the
Vas-Cog Japan website closer to the scheduled date.
Our affiliate Vas-Cog Asia plays an increasingly
significant role in the field of vascular dementia
research. Vas-Cog Asia 9 was held on the web-based
platform on 4 December, jointly with the Asia-Pacific
Stroke conference. The 10th anniversary meeting of
Vas-Cog Asia will be held in India this year.
The effects of the COVID-19 pandemic continue to befelt in many countries. It remains difficult to know
how long the COVID-19 outbreak will last and when
we will be able to get our lives back to normal. Recent
studies have pointed to a relationship between
COVID-19 and dementia. Vas-Cog Japan, a uniqueacademic society covering a wide variety ofinterdisciplinary fields, such as cardiology, neurology,
and brain surgery, will continue to work on basic andclinical research to elucidate the pathogenesis ofvascular dementia and develop effective therapeutics,
fighting against the COVID-19 pandemic as well. The
society has an exciting future, and we look forward to
your participation in the society going forward.
30

10 March 2021

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Welcome to Vas-Cog Japan 2021

Department of Cardiovascular Medicine
Institute of Biomedical Sciences
Tokushima University Graduate School

Department of Neurology
Tokai University School of Medicine

Masataka Sata

Shunya Takizawa

It is our great honor to welcome you to the 11th

to vascular dementia,” “Dementia and cardiovascularannual meeting of the Japanese Society for Vasculardiseases” and “Protective and exacerbating factors in

Cognitive Impairment (Vas-Cog Japan 2021). This

vascular dementia.”

year’s meeting will be held on August 28th, 2021 on

We are planning two special

symposia organized by young investigators fromWEB. The meeting, which was scheduled in

vascular and neurological medicine.

September last year originally, has been postponed

We are expecting many doctors and researchersfor one year due to COVID-19 pandemic. We areon neurology, geriatric medicine, cardiology,

participate it on remote. Accumulating evidence

meeting. We are looking forward to seeing you atplanning complete WEB meeting, where you canmetabolic diseases and pharmacology to attend thesuggests that life-style related diseases, such as

Vas-Cog Japan 2021 on web!

hypertension, diabetes, and dyslipidemia, are risk
factors not only for cardiovascular diseases but also

for dementia. Thus, it would be fascinating
opportunity for the expert researchers inatherosclerosis and dementia to communicate eachother to understand recent advances in both areas.

The main theme of the meeting is “Dementia practicefrom vascular and neurological medicine”. We arefocusing on the close relationship between thevascular diseases and the pathogenesis of neuronaldegeneration causing dementia. The special lectures
will be given by Prof. Takayoshi Shimohata from Gifu

University and Prof. Tomoya Yamashita from Kobe

University. Educational lectures will be given by Prof.
Koji Abe from National Center Hospital, National

Center of Neurology and Psychiatry and Prof.
Yuishin Izumi from Tokushima University. We areorganizing three symposia “Frontiers in researches incerebrovascular blood flow and metabolism related

31

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

32

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Welcome to Vas-Cog 2022
Theme: Cerebral small vessel disease and cognitive
impairment, frailty, sarcopenia

Department of Neurology. Tokyo Women’s
Medical University

Department of Geriatric Medicine Kyorin
University School of Medicine

Kazuo Kitagawa

Koichi Kozaki

It is our honor to host the 11th annual meeting ofamyloid angiopathy are also included in cerebral

the Japanese Society for Vascular Cognitive
Impairment (Vas-Cog Japan 2022). 11thsmall-vessel disease.

annualFrailty and sarcopenia are the process of being

meeting is scheduled to be held August 6th, 2022 indisabled in the old age. Frailty is defined by

Kozaki. Although we are under the threat ofslowness, and exhaustion, and physical inactivity.

Tokyo with co-chairs of Professor Kitagawa and5-domains; body weight loss, physical weakness,

detestable COVID-19 infection at this time June

Sarcopenia is defined by muscle weakness, physical2021, we are hoping that the conference will be held

weakness and muscle loss. Recent findings are

face-to-face in August 2022. This time we areshowing that both frailty and sarcopenia are in partplanning to have a meeting with the theme ofrelated to cerebral small and large vessel disease.

“Cerebral small vessel disease and cognitive

Together, cerebral small vessel disease is a morbid

impairment”. Recent progress in the field of cerebral

condition causing cognitive impairment, dementia,

things, especially a close relation of cerebral small

important issue, and have a great time exchanging

small vessel disease has been showing us a lot offrailty, and sarcopenia. We would like to revisit thisvessel disease with cognitive impairment or possibly

opinion with participants face-to-face. We hopewith frailty and sarcopenia, both are major cause of2022 Vas-Cog conference will shed the light on thisdisability in the older adults.

important issue. We would like all the members to

Cerebral small vessel disease is closely related tosubmit an abstract, attend the meeting and makelifestyle-related diseases such as hypertension,

active discussion next year. Please join us!

diabetes, dyslipidemia, and others. Cerebral small
vessel disease is in part a cause of lacunar infarction
and ischemic white matter lesion, so-called“leukoaraiosis”. Lacunar infarction and ischemic
white matter lesion can be the cause of vasculardementia in the form of “small-vessel type” in the

NINDS-AIREN criteria. Recent evidence shows
cerebral microbleeds, cortical microinfarction and

33

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

34

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Meeting report of Vas-Cog Asia 9
from Busan
Koji Abe, MD, PhD

The first Vas-Cog Asia President

I would like to celebrate the great success of Vas-dementia (VD), behavioral and psychiatric symptoms

Cog Asia 9, which was held on the completely web-of dementia (BPSD), and their important vascular

based style in Busan (Korea) on December 4

involvement.

afternoon (2020) always jointing with Asia-Pacific

Vas-Cog Asia society is an independent society

Stroke Conference (APSC) based on the greatwith 24 directors from most Asian countries andMalaysia) and Joung-Ho Rha (APSC2020 Chair,elucidate the mechanism of vascular factors insupports by Professors Tan Kay Sin (APSO president,

many active members, which is dedicated to

Korea) and Professors Hee-Joon Bae, Byung-Chul

Alzheimer’s disease and related dementia, and to

Lee, and Hye Won Yoon (Hosts of Vas-Cog Asia 9,

contribute potential therapy for dementia people inSeoul). This Vas-Cog Asia 9 was originally planned toAsia. Many vascular risk factors (VRFs) are related tobe held in Seoul on September 11 (2020). However,cognitive decline and affective-emotional changes inan unexpected pandemic of CORONA (Covid-19)

dementia patients especially in elder or eldering

beginning 2020 January in Wuhan (China) forced

countries in Asia.

the postpone and the meeting place/style moving.

Next Vas-Cog Asia 10 anniversary is going to be

Even under such difficult situations, we welcomed

held in India (2021) under direction of our President

Indonesia, and China. There were variety of

Yamashita (Okayama). All of you are welcome toabout 40 participants from Korea, Japan, Taiwan,

Tsong-Hai Lee (Taipei) and Secretary General Toru

important presentations in the present conference.

actively join these forthcoming Vas-Cog meetings to

Many basic science, translational research, clinicalpresent and discuss on vascular factors of all type

trials and evidence were discussed especially on thedementia.

aspects of Alzheimer’s disease (AD), vascular

35

January 10, 2021

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）



Board members / councilors* indicates new board member or councilor.

● Executive Advisor

Ken Nagata (Yokohama General Hospital)

Hiroshi Mori (Nagaoka Sutoku University)● President

Ryuichi Morishita (Osaka University)● Executive Directors (General Affairs)
Yoshio Ikeda (Gunma University)● Executive Directors

Masahiro Akishita (The University of Tokyo)

Takayoshi Shimohata (Gifu University)

Koji Abe (Okayama University)

Ken Shinmura (Hyogo College of Medicine)

Masafumi Ihara(National Cerebral and Cardiovascular Center)

Kazuma Sugie (Nara Medical University)

Atsushi Iwata(Tokyo Metropolitan Geriatric Medical Center
Hospital)

Hidekazu Tomimoto (Mie University)

Masahiko Suzuki (The Jikei University)
Yukihito Higashi (Hiroshima University)
Etsuro Matsubara (Oita University)

Katsuya Urakami (Tottori University)

Miyuki Matsumura(Tokyo Women’s Medical University)

Yasuyuki Ohta *(Yamagata University)
Kenjiro Ono (Showa University)

Toshiki Mizuno(Kyoto Prefectural University of Medicine)

Kazuo Kitagawa(Tokyo Women’s Medical University)

Shokei Mitsuyama (Kumamoto University)

Koichi Kozaki (Kyorin University)

Masaru Mimura (Keio University)

Issei Komuro (The University of Tokyo)

Masaki Mogi (Ehime University)

Masataka Sata (Tokushima University)
Munehisa Shimamura (Osaka University)● Auditors

Yumi Kameyama (The University of Tokyo)

Shuko Takeda (Osaka University)36 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）● Councilors

Ayumi Takamura (Tottori University)

Hitoshi Aizawa (Tokyo Medical University)
Satoshi Abe (Shimane University Hospital)

Shunya Takizawa (Tokai University Oiso
Hospital)

Nobuyoshi Ishii (Oita University)

Kentaro Deguchi (Okayama City Hospital)

Jun Iwanami (Ehime University)

Takashi Tokashiki (Okinawa National Hospital)

Takahiko Umahara(Mizuno Memorial Rehabilitation Hospital )Eiichiro Nagata* (Tokai University)

Yasuhiro Aso (Oita Prefectural Hospital)

Yasushi Takeya (Osaka University)

Masaki Ikeda (Saitama Medical University)

Hiroo Ichikawa (Fujigaoka Rehabilitation Hospital) Hiroo Terashi (Tokyo Medical University)
Yasuo Terayama (Shonan Keiiku Hospital)
Ryoko Imazeki (Tokai University)
Takahiko Tokuda
Shinichiro Uchiyama(National Institutes for Quantum and(International University of Health and Welfare/Radiological Science and Technology)
Sanno Hospital and Sanno Medical Center)
Kazuaki Nagashima (Gunma University)
Yumiko Uchiyama (Kudanzaka Hospital)

Yu Hasegawa(International University of Health and Welfare)

Takao Urabe(Juntendo University Urayasu Hospital)

Haruo Hanyu (Tokyo General Hospital)

Yasuto Higashi (Himeji Central Hospital)

Sumito Ogawa (The University of Tokyo)

Nozomi Hishikawa (Okayama University)

Hiroshi Kataoka*(Nara Medical University)

Haruhisa Kato (Tokyo Medical University Hospital) Toshiya Fukui (Kawasaki Memorial Hospital)
Yukio Fujita (Gunma University)

Tatsushi Kamiya(Kamiya Clinic/Nippon Medical School)
Noriyuki Kimura (Oita University)

Masatsugu Horiuchi(Hanwa Daini Senboku Hospital/
Ehime University)

Takeshi Kuroda*( Showa University)

Yasuhiro Manabe (Okayama Medical Center)

Taro Kojima (The University of Tokyo)

Takafumi Miyachi (Yanai Medical Center)

Masaki Kondo(Kyoto Prefectural University of Medicine)

Kazuhiro Muramatsu(Saiseikai Yokohamashi Tobu Hospital)

Hirofumi Sakurai (Tokyo Medical University)

Hideki Mochizuki (Osaka University)

Nobuya Kawabata (Yachiyo Hospital)

Hitomi Kurinami (Nippon Life Hospital)

Koki Makioka (Gunma University Hospital)

Minoru Kouzuki (Tottori University)

Tohru Minamino (Juntendo University)

Hisatomo Kowa (Kobe University)

Li-Juan Min (Ehime University)

Kenji Sakai (Kanazawa University Hospital)

Kenichi Meguro (Tohoku University)

Naoyuki Sato(Center for Development of Advanced Medicine
for Dementia)

Satoshi Yano*(Showa University)

Masayuki Satoh (Tokyo Metropolitan Public
University Corporation)

Shuhei Yamaguchi(Shimane Prefecture Hospital Bureau)

Takashi Yamazaki (Yokohama General Hospital)
Toru Yamashita (Okayama University)

Soichiro Shimizu (Tokyo Medical University)

Masahito Yamada (Kudanzaka Hospital)
Mikio Shoji (Geriatrics Research Institute Hospital/ Hiroshi Yoshizawa
Gunma University/Hirosaki(Tokyo Women’s Medical University)
University)
Koji Wakayama (The University of Tokyo)
Yoshiki Takao (Kurashiki Heisei Hospital)
Yosuke Wakutani (Kurashiki Heisei Hospital)
Daiki Takano (Yokohama General Hospital)

37

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Articles of Association of the Japanese Society for Vascular Cognitive Impairment
Chapter 1.Name(Name)
Article1
The society shall be named Nihon Nokekkan Ninchisho
Gakkai Sokai and shall be written as “the Japanese Society
for Vascular Cognitive Impairment” (abbreviated as
Vas-Cog J) in English.

society shall fill in the designated application form,
with the annual membership fee, and shall apply to thesecretariat’s office.
Article8
Supporting members are individuals or organizations
who agree with the purpose of the society and pay the
supporting membership fees to support activities of thesociety.

(Offices)
Article2
The Society’s head office shall be in 2-2 Yamadagaoka,
Suita-city, Osaka 565-0871

Article9
Advisers have an achievements in development related
to vascular lesions and cognitive impairment especiallyand shall be determined by the Board of Directors with
Board Member’s recommendation. Advisers shall be
exempt from the annual membership fee.

Chapter 2.Purpose and Business Activities(Purpose)
Article3
The society is established for development of a new
field of study of cognitive impairment. To this end, thesociety shall study clinical basic research with a wide
field of vision about related matters of vascular lesion
and cognitive impairment in Japan; also shall exchange
informat ion w ith internat ional researchers; shalluncover causes of cognitive impairment andparticipation of vascular lesions, then shall research
the possibilities for drug development.

Article10
Members shall disqualify his/her membership if he /shefalls under any of the following cases:
1.	C a s e s i n w h i c h h e / s h e s u b m i t s a w i t h d r a w a lapplication to the society.
2.	Cases in which he/she has not paid the annual
membership fee for three years, and refuses
demands of payment.
3.	Any other case in which he/she violates the articles
of incorporat ion and other regulat ions or has
damaged the reputation of the society, and Board of
Councilors shall determine his/her dismissal fromthe society.

(Business Activities)
Article4
The society shall engage in the following businessactivities to achieve the purpose provided in thepreceding article:(1)	B usiness activities such as publication of academic
journals(2)	B usiness activities such as holding annual meetings(Annual meetings shall be financed by theparticipants’ entry fees but other organizations may
co-host the meetings. )(3)	B usiness activities such as supporting and awarding
study relating to the medical treatment of vascularcognitive impairment.
(4)	A ny other business activities for achieving the
purpose provided in the preceding article.

Article11
Regular members and st udent members shall be
accepted an adjournment with notification by the
Representative Director, if they separately establish
fixed conditions.
Chapter4.Officers and Councilors
Article12
The society shall have the following officers.
Board Members :twenty six members
Auditors :two members
Article13
The society shall have Councilors.

Chapter3.Members

Article5
The society shall be comprised of the following types ofmembers:
1. Regular members
2. Student members
3. Supporting members
4. Advisers

Article14
Auditors and additional Board Members outside theBoard Members specified above, shall be determinedaccording to a separate process. Councilors shall also
be determined according to a separate process. The
Chairman shall be selected by a recommendation of theBoard of Directors. Each committee leader shall bechosen by the Representative Director, then approvedby the Board of Directors. The Representative Director,
the Chairman, the Leader of Society Promotion, theLeader of Finance, and the Chief Editor shall bemembers of the Board of Directors.

Article6
Any member shall be distributed academic journals andmay present his/her study in annual meetings,
symposiums and lectures.
Article7
Regular members and student members who agree withthe purpose of the society, are individuals, who shall
pay the annual membership fees separately designatedby the General Assembly. Any applicant who joins the

Article15
The Representative Director shall represent the society,control the performance of the society work and38 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Article23
The Representative Director shall hold a Board of
Councilor’s Meeting temporarily if requested by morethan one-third of the councilors.

convene the Board of Councilors.
The Representative Director and Board Members shallorganize the Board of Directors, and manage the workof the society.
T h e Re p r ese n ta t ive Direc tor shall report bu dgetstatements, account settlement, human resources ofBoard Members and any of the other main work of thesociety to the Board of Councilors and the General
Assembly.

Articles24
Meetings of the Board of Directors shall be called by
the Representative Director if necessary. Meetings ofthe Board of Directors require attendance of over twothirds of members, and shall be decided by over half of
the Board Members in attendance. In case a vote is atie, the Representative Director shall determine how toproceed. Individuals nominated by the Representative
Director may attend a Board of Directors Meeting.

Article16
The society shall have a Board for Society Promotion, aBoard of Finance and an Editorial Board.
The Representative Director may establish other boards
with the approval of the Board of Directors. Except incases discussed in Article14, each leader of eachcommittee shall be nominated by the Representative
Director from among the Board Members, then be
approved by the Board of Directors. Members ofcommittees shall be approved by the Board of
Directors, and then the Representative Director shallcommission him/her. Terms for committee members
last four years and maybe renewed indefinitely.

Chapter6.Accounts
Articles25st
The fiscal year of the society shall commence on Apr 1
stof every year and shall end on Mar 31 of the following
year.
Articles26
The society shall be financed by annual dues,s u p p o r t i n g m e m b e r s’ f e e s , v a r i o u s s u b s i d e s a n d
donations.

Article17
Auditors shall audit accounting, and shall give advice tothe Board of Directors about managing the society.
Auditors shall not hold any other offices and committee
assignments.

Articles27
Expenses of the society shall be processed by thegeneral fund account and special fund account.

Article18
Officers and Councilors shall serve a term of one fiscal
year. The Representative Director, Executive Director,
Board Members, Auditors and Councilors’ terms are twoyears, and they may serve a maximum of two terms in arow.
Officers shall reach the mandatory retirement age on
March 31st of the year in which they become 65 years
old.

Articles28
The general fund account shall record all income andexpenditures excluding the special fund account.
Articles29
The special fund account shall record income andexpenditures to assure a stable financial basis for thesociety. There shall also be provision to record income
and expenditure of funds established for special
purposes.

Article19
If a vacancy o ccurs, the Board of Directors shallappoint new Board Members if necessary, but those
newly appointed members’ terms are bound by theremaining period of their predecessors.

Article30
Establishment of each kind of fund, transfer of funds, anduse of funds shall be approved by the Representative
Director.

Article20
Councilors shall organize the Board of Councilors, anddiscuss issues necessary to the management of thesociety.

【Additional rules】
1.	Any revision of the so ciety’s art icles shall beapproved by the Board of Directors.
2.	The Board Members shall not be paid for theirduties.
3.	The articles of the society shall take effect from the
day following approval by the Board of Directors.
4. The annual member fee shall be ￥5,000.
5. The date of foundation shall be October 01,2014.

Article21
The Chairman shall represent the society in the fiscal
year, and shall carry out their mission as arepresentative of the society.
1.	The Chairman shall be nominated and then confirmedby the Board of Directors.
2.	The Chairman’s term is one year, from the day
following the end of the previous Annual Meeting to
the day the current Annual Meeting finishes.

Established on October 01, 2014
Revised on September 18, 2015
Revised on August 06, 2016
Revised on May 01, 2017
Revised on April 01, 2018
Revised on August 03, 2019

Chapter5.Council
Article22
Annual Meeting, Board of Councilors and General
Assembly shall be held once a year.

39

JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Vas-Cog Journal Submission Instructions for authors
Vas-Cog Journal is an official journal of the JapaneseSociety of Vascular cognitive impairment. Original
Art icles deal with either clinical or experimental
investigation of the vascular cognitive impairment. The
journal will also consider the publication of review
articles. Manuscripts must conform to Recommendations
for the Conduct, Reporting, Editing and Publication of
Scholarly Work in Medical Journals (ICMJE
Recommendations) (http:// www.icmje.org/
recommendations/).
Submission of a manuscript to Vas-Cog Journal
implies that the article is original and that no portion(including figures or tables) is under considerationelsewhere or has been previously published in any form
other than as an abstract. Previous publication includes
publishing as a component of symposia, proceedings,
transactions, books (or chapters), articles published by
i nv i t a t i o n s o r r e p o r t s o f a ny k i n d , a s w e l l a s i nelectronic databases of a public nature.
Submission of a manuscript implies that, when
accepted for publication, the authors agree toautomatic transfer of the copyright to the Japanese
So ciety of Vascular Cognit ive Impairment. Every
reproduced figure or table must have permission fromthe copyright holder. Authors should obtain permissionin advance of manuscript submission, and clearly statethat in the figure/table legend. Examples:(1) Adaptedfrom reference no. xx with permission. (2) Reproducedwith permission from xxxx, et al. Neurology 2018; 91:
xx – xx.
When reporting experiments on human subjects,
indicate whether the procedures followed were inaccordance with the ethical standards of the
responsible committee on human experimentation(institutional or regional). The participants’ informed
consent should be obtained and should be indicated in
the text. When reporting experiments on animals,
indicate whether institutional or national guidelines forthe care and use of laboratory animals were followed.
In accordance with the Clinical Trial Registration
Statement from the International Committee of Medical
Journal Editors (http://www.icmje.org/), all clinical
trials published in Vas-Cog Journal should be
registered in a public trials registry at or before theparticipant recruitment. Refer to CONSORT 2010
guidelines (http://www.consort-statement.org/) for
randomized clinical trials, and the STROBE statement(http://www.strobe-statement.org/) for observational
studies (cohort, case-control, or cross-sectional
designs).
Submission of Manuscripts:
At least the first author and corresponding author
should be members of Japanese Society of Vascular
Cognitive Impairment. All manuscripts must be
submitted electronically through online submission
system in the official web site of Japanese Society of
Vascular Cognitive Impairment (http://www.plus-s-ac.
com/vas-cogj/). The submitting author should upload
the manuscript files in appropriate word and PDF fileformats according to the instructions provided. Before
complet ing submission, the submitt ing author isrequired to thoroughly check the PDF file.
Authorship Agreement:
After submission through the online submission
system, the contact/submitting author should complete
the “Authorship Agreement” form (http://www.plus-sac.com/vas-cogj/kaishi.html) with all co-authors’signatures, and email it to the Editorial Office (vascogj@plus-s-ac.com). Because any addit ional coauthors cannot be approved after the manuscript has
been accepted, ensure that all co-authors have been
properly listed during the submission process. If
additional authors are included in a revised manuscript,
the contact author of the manuscript is required toprovide another “Authorship Agreement” form signedby the added authors as well as detailed reasons fortheir addition.
Manuscript Format:
All manuscripts should be written in English (USspelling) and prepared according to the following
specifications.
1.	The main document should be typewritten by wordwith double spacing and include the following in
general: (1) Title page, (2) Abstract, (3) Key words,(4) Text, (5) Acknowledgements, (6) References and(7) Legends for Tables and/or Figures. This word
file should be sent to the office with attachedconverted PDF file of final published style.
2.	Pages should be numbered consecutively in thissequence, beginning with the title page.
3.	The title page must have the following content:(1)	C omplete title of the paper; Abbreviations are
not acceptable in the title.
(2)	N ame(s) of author(s) with highest academicd e g r e e ( s ) ; O n l y M D, P h D, o r B S c c o u l d b e
included.
(3)	Affiliations of all authors at the time of the study;i.e., department and institution(4)	Short title; Up to 50 characters including spaces
can be used.
(5)	D isclosures; Information of all COI, grants,
sources of funding related to the manuscript
should be declared.
(6)	Name and address of the author responsible forcorrespondence(7)	Total word count of the manuscript(8)	Total numbers of Tables, Figures and Supplementaryfiles
4.	Abstracts in manuscript types “Original Article of
C l i ni c a l or E x pe ri me nt a l R e s e a rc h” s houl d b e
structured, and consist of the following 3 headings:
	1: Background: Rationale for study; 2. Method andResults: Brief presentation of methods andpresentation of significant results; Note that bothcategories should be included under the one
heading. 3. Conclusions: Succinct statement of datainterpretation
5.	Units of measurement should be SI units, except forblood pressure, which should be expressed in
mmHg. Do not spell out numbers and standard unitsof measurement except at the beginning ofsentences. Use Arabic numerals and standard40 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

abbreviations to indicate numbers and units.
6.	References must be numbered consecutively as they
appear in the text and be listed in the same
numerical order at the end of the article. They
should accord with the system used in the Uniform
Requirements for Manuscripts Submitted to
Biomedical Journals. Only published manuscripts
are accepted as references. If a reference is from a
yet-to-be-published book, include ‘In Press’ as wellas the anticipated year of publication. If a referenceis published online only, the “D.O.I” or “URL as wellas the last available date accessed” should be
provided. The titles of referenced journals should be
abbreviated to the style used in Index Medicus(http://www.nlm.nih.gov/tsd/serials/lji.html). All
author names should be listed when referenced
material has 3 or less authors; when it has 4 ormore, only the first 3 authors’ names should belisted, with “et al.” at the end.
Examples:(1)	Y a m a s h i t a T, K a m i y a T, D e g u c h i K , e t a l .
Dissociation and protection of the neurovascular
unit after thrombolysis and reperfusion inischemic rat brain.J Cereb Blood Flow Metab.
2009 (4):715-25.
(2)	T a k e d a S a n d M o r i s h i t a R . D i a b e t e s a n dAlzheimer’s Disease. In: Yamagishi S, editor.
Diabetes and Ag ing-related Complicat ions.
Springer, 2018; 101-111(3)	T akeda S, Wegmann S, Cho H, et al. Neuronal
uptake and propagation of a rare phosphorylated
high-molecular-weight tau derived from
Alzheimer’s disease brain.Nat Commun. 2015 Oct
13;6:8490. doi: 10.1038/ncomms9490.
7.	All figures in a manuscript are recommended to be
in full color; publication in color requires page
charge of JPY65,000 for one color page (see also“VI. Publication Charges”). For invited articles,
publication in color is cost-free for one page andrequires JPY65,000/one exceeding color page.
Letters and symbols in figures should be clear andof sufficient size to be legible after reduction to thewidth of one column. Specify the size to be printed,
if necessary.
8.	C o n t e n t o f s u p p l e m e n t a r y f i l e s w i l l o n l y b e
published in the online journal. Therefore, if a
supplementary file contains References, they should
be separate from those in the Main Document, andonly refer to the content in the supplementary
file(s). There is a size limit of 5 MB for uploaded
supplementary file(s) per manuscript.

supplementary files, normally occupies 1 journal page.
3. Review Article (Invited)“Review Article” is usually invited one upon requestfrom the Editor-in-Chief, but we will also consider
limited number of non-invited submissions. Total word
count is less than 6,000 words and less than 220 words
for Unstructured Abstract. Number of Table and Figures
are less than 8 and less than 3 supplementary figures.
No limitation of numbers of references.
4. Editorial (Invited)“Editorial” normally occupies no more than 2 journal
pages about subject manuscript should be cited Upon
request from the Editor-in-Chief. Total word count isless than 1,500 words and no abstract, less than 2
Table or figures and less than 15 references.
5. Case Report
Total word count is less than 3,000 words and lessthan 100 words for Unstructured Abstract. Number ofTable and Figures are less than 4 and 20 references.
Vas-Cog Journal encourage submission by young
researches in this section.
6. Letter to the Editor and Author’s Reply
This is an opinion-letter to a manuscript which has
been published in Vas-Cog Journal. The manuscripts
must not exceed 1,000 words in length and have no
more than 5 co-authors.
Authors who submit or resubmit manuscripts to thejournal are required to have all of their manuscript files
strictly reflect the requirements outlined here. Whenany part does not, we cannot start either the initial orrevision review process. “Total word count” is the total
number of all words appearing in the manuscript files,
except for the text in Table(s) and Figure(s). Note thatlegends for these are included in the “ Total word
count”.
III. Conflict of Interest Disclosure Policy:
The submitting author should complete the online
form in the submission system and have the same
information included in “Disclosures” in the main
document in order to disclose all authors’ relationshipsthat could be perceived as real or apparent conflict(s)of interest. When submitting a manuscript for
publication, all authors are required to disclose any
financial relationship (within the past 12 months) witha biotechnolog y manufacturer, a pharmaceut ical
company, or other commercial entity that has been
involved in the subject matter or materials discussed in
the manuscript. When a manuscript has been acceptedfor publication, all disclosed COI will appear in thearticle.
Example:Disclosures：A (author name) serves as a consultant toZ (entity name); B’s spouse is chairman of Y; C received
a research grant from X; Deceived lecture fees from V;
E holds a patent on U; F has been reimbursed by T for
attending several conferences; G received honoraria for
writing promotional material for S; H has no conflict ofinterest.

II. Manuscript Types:
1. Original article
Total word count is less than 6,000 words and lessthan 220 words for Abstract. Number of Table andFigures are less than 8 and less than 3 supplementary
figures. No limitation of numbers of references. Three
to 5 Keywords and structured abstract with 3 headings
are other requirements.
2. Images in Vascular Cognitive Impairment
Images in “Vascular Cognitive Impairment” should
contain a novel color image with scientific impact. Notethat we do not accept any case reports. The manuscript
consisted of less than 400 words, 1 figure and 2

IV. Review of Manuscripts:
All original manuscripts are usually evaluated by 2
reviewers assigned by the Editors.
V. Proofs:

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JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

EDITORIAL ADVISORY BOARD
Ryuichi Morishita (Department of Clinical Gene
Therapy, Osaka University)
Yo s h i o I k e d a ( D e p a r t m e n t o f N e u r o l o g y, G u n m a
University Graduate School of Medicine)Ken Nagata (Yokohama General Hospital)
Hiroshi Mori (Nagaoka Sutoku University)
Masahiro Akishita (Department of Geriatric Medicine,
Graduate School of Medicine, The University of Tokyo)
Koji Abe (Department of Neurology Okayama University
Medical School)
Masafumi Ihara (Department of Neurology, National
Cerebral and Cardiovascular Center)A t s u s h i I w a t a ( D e p a r t m e n t o f N e u r o l o g y, To k y oMetropolitan Geriatric Medical Center Hospital)
Katsuya Urakami (Section of Environment and Health
Science, Department of Biological Regulation, Faculty of
Medicine, Tottori University)
Yasuyuki Ohta (Division of Neurology and Clinical
Neuroscience, Department of Internal Medicine III,
Yamagata University School of Medicine)K e n j i r o O n o ( D e p a r t m e n t o f N e u r o l o g y, S h o w a
University School of Medicine)
Kazuo Kitagawa (Department of Neurology. Tokyo
Women’s Medical University)
Koichi Kozaki (Department of Geriatric Medicine Kyorin
University School of Medicine)
Issei Komuro (Department of Cardiovascular Medicine,
The University of Tokyo Graduate School of Medicine)
Masataka Sata (Department of Cardiovascular Medicine,
Tokushima University Graduate School)
Munehisa Shimamura (Department of Neurology /Department of Health Development and Medicine,
Graduate School of Medicine, Osaka University)
Takayoshi Shimohata (Department of Neurology andGeriatrics, Gifu University Graduate School of Medicine)Ken Shinmura (Department of General Medicine, Hyogo
College of Medicine)
Kazuma Sugie (Department of Neurology, Nara Medical
University School of Medicine)
Masahiko Suzuki (Department of Neurology Katsushika
Medical Center The Jikei University School of Medicine)
Hidekazu Tomimoto (Department of Neurology, Mie
University)
Yukihito Higashi (Department of Regeneration and
Me d i c i ne , R e s e a rc h C e nt e r f or R a d i a t i on G e nome
Medicine,Research Institute for Radiation Biology andMedicine, Hiroshima University)
Etsuro Matsubara (Oita University Faculty of Medicine
Department of Neurology)
Miyuki Matsumura (Department of Neurology, Instituteof Geriatrics,Tokyo Women’s Medical University)
Toshiki Mizuno (Department of Neurology, Kyoto
Prefectural University of Medicine)
Shokei Mitsuyama (Department of Pharmacology andMolecular Therapeutics, Kumamoto University
Graduate School of Medical Sciences)
Masaru Mimura (Department of Neuropsychiatry, Keio
University School of Medicine)
Masaki Mogi (Department of of Pharmacology, Ehime
University Graduate School of Medicine)

Galley proofs of accepted manuscripts will be sent tothe authors for their correction. Changes should be
limited to typographical errors or errors in thepresentation of data. Excessive corrections may berejected by editors and/or be charged to the authors.
VI. Publication Charges:
Free for publication charge in manuscript submission
rules within total word count, Tables, Figures andReferences. JPY8,000/one exceeding page charge(JPY65,000 for one color page).
VII. Reprints:
Reprints are available in a multiple of 100 copies
when ordered w ith the return of the proofs. The
approximate cost per 100 copies is JPY10,000,
including color pages. Free PDF publication.

EDITORIAL BOARD
Editor-in-Chief
Toshiki Mizuno
Department of Neurology
Graduate School of Medicine, Kyoto Prefectural University of Medicine
Senior Associate Editor
Shuko Takeda
Department of Clinical Gene Therapy,
Graduate School of Medicine, Osaka University
Associate Editors
Masayuki Satoh	Department of Dementia and Neuropsychology,
Advanced Institute of Industrial Technology,Tokyo Metropolitan Public University Corporation
Hirofumi Sakurai	Department of Geriatric Medicine, Tokyo Medical University
Masafumi Ihara
Department of NeurologyNational Cerebral and Cardiovascular Center
Toru Yamashita
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,

42 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Vas-Cog Journal
Authorship Agreement
Each author must read and sign the statements on
1. Authorship Responsibility, 2. Copyright, and 3. Disclosure Declaration.
1. Authorship Responsibility.
	Author(s) certify that the manuscript is original and that neither the manuscript nor one with substantiallysimilar content has been previously published or being considered for publication elsewhere in any form otherthan an abstract. Author(s) have read the manuscript and approved its submission to Vas-Cog Journal.
2. Copyright.
	In consideration of the acceptance of the work for publication, the authors agree to transfer all copyrightownership to the Japanese Society for Vascular Cognitive Impairment (Vas-Cog Japan).
3. Disclosure Declaration.
	All relevant financial, personal or professional relationships with other people or organizations must be
disclosed in the online form and main document. Otherwise, the signature indicates author(s) have no
relationships or conflicts to disclose. Authors’ disclosures will appear after the “Acknowledgments” section in
the accepted article.
*Multiple pages may also be accepted. Please copy and use this form if it is necessary.
	<CAUTION> We do not accept any additional co-authors after the manuscript has been accepted. Please makesure that you add all co-authors in the revision process.

Manuscript title:1)

Author’s Print Name:
Signature:2)

Author’s Print Name:
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3)

Date:

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Signature:

6)

Date:

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5)

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4)

Date:

Date:

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Date:

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JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

7)

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9)

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44

 JAPANESE SOCIETY OF VASCULAR COGNITIVE IMPAIRMENT（2021 NO.7）

Editor’s Note
Shuko Takeda, MD, PhD.

Associate Professor
Department of Clinical Gene Therapy, School of Medicine, Osaka University, Japan
Osaka Psychiatric Medical Center, Osaka Psychiatric Research Center, Osaka, JapanThe brand-new Vas-Cog Journal is now in its
second year of using a submissions and peer-review
procedure, which was introduced with the aim ofestablishing the publication as a fully-fledged
academic journal of international repute. To further
this aim, the intention is to collaborate with Vas-Cog
Asia and Vas-Cog World to publish articles submitted
by researchers from a wider geographical area. Thisis also the second year of the new editorial board
under the chief editorship of Prof. Toshiki Mizuno,
who took over from Prof. Mikio Shoji.

I would like to express my gratitude andadmiration to the editorial board and all themembers of Vas-Cog Japan for the successful
publication of Vas-Cog Journal No.7 under the
arduous conditions of the COVID-19 pandemic. Its
impact on the medical world has been enormous,with the activities of many medical organizations andacademic societies yet to return to the new normal.
Under the present conditions, the successful
publication of Vas-Cog Journal No. 7 after a delay ofseveral months is no mean feat. I would also like to
add that, without a shadow of a doubt that and in
spite of COVID-19, we at Vas-Cog Japan will continue
to carry out our academic and scientific activities.

The current issue contains two review articles anda case report on vascular dementia. There are also
reports on the Vas-Cog Japan Annual Meeting, which
was postponed from last year, and the Vas-Cog Asia
Meeting, which was held online.

There are indications that strongly suggest
COVID-19 causes severe inflammation and theformation of thrombi. It has also emerged thatstrokes and cognitive dysfunction are serious
sequelae of COVID-19. This all means the role VasCog Japan will play in this pandemic and beyond willalmost certainly be extremely significant.

The COVID-19 pandemic will continue into thisyear, and I very much hope that our members andreaders will remain safe and in good health.

The past and future annual meeting of Vas-Cog JapanThe 1 st Meeting : August, 2010 (Tokyo) Chairman : Ken Nagata and Toshiya Fukui

The 2nd Meeting : August, 2011 (Tokyo) Chairman : Koji Abe and Shokei Mitsuyama

The 3rd Meeting : August, 2012 (Tokyo) Chairman : Ryuichi Morishita, Yasuo Terayama, and Koji Abe
The 4th Meeting : August, 2013 (Tokyo) Chairman : Mikio Shoji and Haruo Hanyu

The 5th Meeting : August, 2014 (Kyoto) Chairman : Toshiki Mizuno and Hidekazu Tomimoto

The 6th Meeting : August, 2015 (Tokyo) Chairman : Nobuya Kawabata and Shuhei Yamaguchi

The 7th Meeting : August, 2016 (Kanazawa) Chairman : Masatsugu Horiuchi and Masahito Yamada
The 8th Meeting : August, 2017 (Tokyo) Chairman :Shinichiro Uchiyama and Issei Komuro

The 9th Meeting : August, 2018 (Beppu) Chairman : Katsuya Urakami and Etsuro Matsubara
The 10th Meeting : August, 2019 (Tokyo) Chairman : Masahiro Akishita and Yoshio Ikeda

The 11th Meeting : August, 2021 (Tokushima) Chairman : Shunya Takizawa and Masataka Sata

The 12th Meeting : August, 2022 (Tokyo) Chairman : Kazuo Kitagawa and Koichi Kozaki
The 13th Meeting : August, 2023 (planned) Chairman : Masahiko Suzuki

The 14th Meeting : August, 2024 (planned) Chairman : Takayoshi Shimohata
The 15th Meeting : August, 2025 (planned) Chairman : Kazuma Sugie- to be continued -49