bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the relationship between mild traumatic brain injury, later‐life brain health and cardiorespiratory fitness in a community‐dwelling sample of older adults
Authors: Markovic Shaun J , Fitzgerald Melinda , Peiffer Jeremiah J , Scott Brendan R , Brown Belinda M
Published: December 2021

Background

Traumatic brain injury (TBI) has been recognised as an important global health priority. Mild traumatic brain injury (mTBI), also known as concussion, accounts for up to 90% of all TBI diagnoses. Accumulating evidence also suggests that mTBI may be a risk factor for later‐life cognitive decline and neurodegeneration, including Alzheimer’s disease and other forms of dementia. Physical activity and exercise have received increasing attention as a potentially cost‐effective mechanism to attenuate age‐related declines to cognitive functioning and brain volume. However, little is known about the interaction between maintaining a higher level of physical fitness later in life and its impact on markers of brain health in individuals with a history of mTBI in the general population.

Method

79 community‐dwelling older adults (mean age 68.72 ± 4.28 years, 54.4% female) underwent a comprehensive cardiorespiratory fitness assessment and magnetic resonance imaging. Participants also completed a retrospective mTBI history questionnaire.

Result

25 (32%) of the study participants reported sustaining at least one lifetime mTBI. No differences in total hippocampal or white matter volumes were found between participants who had a history of mTBI and those who did not. However, participants with a history of mTBI had, on average, a significantly higher total grey matter volume (581.16 ± 19.44) in comparison to controls with no mTBI history (570.05 ± 17.22), p = 0.005. Subsequent analyses found that cardiorespiratory fitness did not moderate the relationship between mTBI history and any of the MRI metrics examined.

Conclusion

The results of this study suggest that later‐life cardiorespiratory fitness, in isolation, does not protect the brain from mTBI‐induced global or regional volumetric changes. Tracking longitudinal post‐mTBI physical activity habits will be critical to elucidating whether longer‐term cardiorespiratory fitness patterns are more influential in determining later‐life neurocognitive outcomes.
The impact of the COVID‐19 pandemic on nutritional status in Alzheimer's disease
Authors: Castagna Alberto , martis Ilaria , Ruberto Carmen , Fabbo Andrea
Published: December 2021

Background

In March 2020, the WHO declared a global pandemic due to the novel coronavirus SARS‐CoV‐2 and several governments planned a national quarantine in order to control the virus spread. Acute psychological effects of quarantine in frail elderly subjects with special needs, such as patients with dementia, have been poorly investigated. The aim of this study was to assess modifications of nutritional status during quarantine in patients with Alzheimer’s Disease (AD).

Methods

Participants were recruited from patients referring to Center for Cognitive Disorders and Dementia in Italy. A total of 205 patients were included. A structured telephone interview was delivered to family caregivers of patients with diagnosis of Alzheimer disease (AD). At baseline (T0) and month 6 (T1) since quarantine declaration, nutritional risk assessment were assessed by Self.Mini Nutrition Assessment (Self MNA).

Results

A total of 205 subjects (79,6 ± 6,4 years old, M=42%) were enrolled. A baseline according with the Self‐MNA test score, 32,7% were classified as malnourished, whereas 42% of were at risk of malnutrition. A T1 according with the Self‐MNA test score, 37,1% were classified as malnourished, whereas 46,3% of were at risk of malnutrition.

Conclusion

Quarantine induces a rapid increase malnourished and risk of malnutrition an AD. Health services need to plan a post‐pandemic strategy in order to address these emerging needs.
Early detection of dementia and mild cognitive impairment with BrainCheck
Authors: Sun Kevin H , Huang Bin , Ghomi Reza Hosseini
Published: December 2021

Background

Nearly 14 million people in the United States and upwards of 152 million people globally in the coming decades are suffering from dementia. Early detection of dementia provides access to timely interventions and knowledge to improve patient health and quality of life before symptoms become severe. However, current rates of undetected dementia are reported as high as 61.7%. Mild cognitive impairment (MCI) is an early symptomatic clinical stage of dementia, thus, identification of this level of cognitive impairment is important for early detection. Current clinical practices, cognitive screening assessments (MoCA, etc.), and neuropsychological testing needed for the diagnosis of MCI shows itself to be time‐consuming and resource‐limited. An accurate and reliable computerized cognitive tool that could be more rapid and maximize accessibility to both patients and providers is needed to address the expected uptick in dementia, especially in the current era of practicing amidst the COVID‐19 pandemic.

BrainCheck is a computerized cognitive testing tool and has been validated previously for its diagnostic accuracy for dementia‐related cognitive decline. In this study, our objective was to evaluate BrainCheck’s ability to distinguish between Dementia, Mild Cognitive Impairment (MCI), and Normal Cognitive (NC) for the potential use of early dementia detection.

Method

Ninety‐nine participants associated with the University of Washington’s Memory and Brain Wellness Center were clinically evaluated with a form of Dementia (n=42), Mild Cognitive Impairment (MCI)(n=22), or had Normal Cognition (NC)(n=35). Individual BrainCheck assessments and the Braincheck Overall Scores were compared statistically among their diagnostic groups. Also, Pearson correlation coefficients were calculated between participant BrainCheck Overall Scores and their MoCA scores.

Result

We found significant differences between the NC, MCI and Dementia groups based on the participants’ BrainCheck battery performances, where participants with more severe cognitive impairment performed worse across the individual assessments and on BrainCheck Overall Scores. Braincheck Overall Scores also achieved >88% sensitivity/specificity for separating NC from Dementia, and >77% sensitivity/specificity in separating the MCI group from NC/Dementia groups. Furthermore, Braincheck Overall Scores highly correlated with MoCA scores (ρ=0.69, p<0.001).

Conclusion

BrainCheck distinguished between diagnoses of Dementia, MCI, and NC, providing a potentially reliable tool for early detection of cognitive impairment.
Optical coherence tomography in the diagnosis of primary neurodegenerative diseases
Authors: Makhnovich Ekaterina Vladimirovna , Bogolepova Anna Nicolaevna
Published: December 2021

Background

Currently, the priority is the early diagnosis of dementia, which is due to an increase in the life expectancy of the population. In connection with the improvement of criteria of Alzheimer's disease on the basis of which a diagnosis is made only when severe cognitive deficit, prevented the diagnosis of documentah stages, although a neurodegenerative process is started before the onset of clinical symptoms, which should be treated with medications. Recently, the world community has been focused on identifying new predictors of cognitive deficits, as such, scientists ' hopes are focused on optical coherence tomography.

Method

90 patients were examined and divided into 3 groups: the first group included patients with Alzheimer's disease (NINCDS ADRDA), the second group included patients with vascular dementia(NINDS‐AIREN), and the third group ‐ patients with open‐angle glaucoma. The groups were comparable by gender, age, and baseline socioeconomic status. All patients underwent a comprehensive neurological and neuropsychological examination, as well as optical coherence tomography.

Result

According to the results of OCT in the area of the optic disc, no statistically significant differences in the width of the neuroretinal margin were found in the groups. The results of OCT in the macular region revealed a decrease in the retinal thickness and inner plexiform layer in the upper and lower quadrants and bilateral region, as well as reducing the thickness of the nerve fibers of the ganglion layer in a lower quadrant and bilateral region in groups of AD and glaucoma, compared with SoD group (p <0.05). In the foveal region, there was a decrease in the thickness of the retina, the ganglion cell layer, and the inner plexiform layer of the retina in patients with SoD compared to patients with AD and glaucoma (p <0.05).Based on the data obtained, it can be concluded that in AD, degenerative retinal changes are observed in the perifoveal region, and in SoD, the process is more pronounced in the foveal (central) region of the retina.

Conclusion

a comprehensive ophthalmological examination can become one of the key and affordable methods of early diagnosis of AD.
Agreement of amyloid PET and CSF biomarkers in a clinical cohort
Authors: Guillén Núria , Contador José , Tort‐Merino Adrià , Balasa Mircea , Martínez Neus Falgàs , Olives Jaume , Castellví Magdalena , Juncà‐Parella Jordi , Borrego‐Écija Sergi , Bosch Beatriz , Fernández‐Villullas Guadalupe , Ramos‐Campoy Oscar , Antonell Anna , Perissinotti Andrés , Augé Josep Maria , Sanchez‐Valle Raquel , Lladó Albert
Published: December 2021

Background

The amyloid deposition (A) in the 2018 ATN classification of Alzheimer disease can be assessed by CSF Aβ 1‐42 or amyloid PET. Although the agreement between them is high, it is not exact.

Method

We selected patients from the Alzheimer’s disease and other cognitive disorders Unit at Hospital Clínic of Barcelona with available amyloid PET and lumbar puncture, with a maximum difference of time of one and a half year between them. We used F18 Florbetapir (n=27), F18 Florbetaben (n=7), F18 Flutemetamol (n=16) or 11C‐PIB (n=2) as tracers for amyloid PET. CSF Aβ 1‐42, total tau (tTau) and phosphorylated tau (pTau) were measured using INNOTEST® Fujirebio until June 2019 and using LUMIPULSE® Fujirebio after June 2019. We analyzed the agreement between amyloid PET and CSF biomarkers.

Result

We included 52 patients. They had been diagnosed of Alzheimer disease (n=32), frontotemporal dementia (n=11), Lewy body disease (n=2) and psychiatric disorders (n=7) (Table 1).

There was a perfect agreement between CSF biomarkers and amyloid PET when CSF biomarkers were all normal or all altered (Figure 1): All patients with CSF A+T+N+ (n=19) had a positive amyloid PET and all patients with CSF A‐T‐N‐ (n=7) had a negative amyloid PET. Agreement decreased with other CSF results. Only 11/19 patients with CSF A+T‐N‐ had a positive amyloid PET. 31/32 (97%) patients with positive amyloid PET had low Aβ 1‐42 levels (A+) but only 11/20 (55%) patients with negative amyloid PET had normal Aβ 1‐42 levels (A‐).

Conclusion

CSF biomarkers and amyloid PET showed a perfect agreement when CSF biomarkers were all normal or all altered. For other CSF ATN results, agreement with amyloid PET was much lower.
Longitudinal differences in instrumental activities of daily living (AIDLs) in participants with subjective cognitive complaints (SCCs) according to neuropsychiatric symptoms (NPS) severity
Authors: Mallo Sabela C. , Lojo‐Seoane Cristina , Campos‐Magdaleno Maria , Vieites Ana Nieto , Facal David , Ismail Zahinoor , Juncos‐Rabadán Onésimo , Pereiro Arturo X
Published: December 2021

Background

Severity of the neuropsychiatric symptoms (NPS) is expected to have a negative impact on IADL, adding to the effect that cognitive decline can have and could lead to further impairment of functionality. Our objective was to analyze differences in IADL between two longitudinal evaluations in SCC participants with null, intermediate, or high levels of NPS at baseline considering the influence of the cognitive status.

Method

The sample consisted of 242 older adults with SCCs from the CompAS (Compostela Aging Study) and followed up 18‐24 months. Participants were classified according to absence (score ≤ 33th; MBI‐C total score=0), intermediate (score between 33th and 66th; MBI‐C total score ≥0 and ≤5; M=2.18, SD=1.10), and high level of NPS (score ≥ 66th; MBI‐C total score >5; M=10.83, SD=5.32) measured at the baseline by the Mild Behavioral Impairment‐Checklist (MBI‐C). Functionality was assessed by the short version of the Amsterdam‐IADL (A‐IADL‐Q‐SV). A repeated measures mixed‐ANOVA was performed to test intergroup (two groups: null‐NPS=92; Intermediate‐NPS=70; High‐NPS=80) and intra‐subject (two measurements: A‐IADL‐Q‐SV scores at baseline and at follow‐up) differences. In order to test the between‐group differences subtracting the effect of the cognitive objective decline, CAMCOG‐R total score was subsequently introduced as covariate.

Results

Mixed‐ANOVA of repeated measures showed significant differences between groups in all the pairwise comparisons (Null‐NPS<Intermediate‐NPS<High‐NPS), indicating lower A‐IADL‐Q‐SV scores associated to the groups with higher MBI‐C scores, F(2,239)=22.41, p<.001, ηp2
=.158, observed power=1.0 (Figure 1). Measurement main effect and Group*Measurement interaction were not significant. Inclusion of CAMCOG‐R total score as covariate did not alter the results but size effect for the Group differences slightly decreased, F(2,238)=18.28, p<.001, ηp2
=.133, observed power=1.0.

Conclusions

Functionality decline was significantly associated to the severity level of NPS. The consideration of cognitive status as covariate only slightly reduced the size effect observed in between‐group differences, which suggests a certain independence of the NPS in the deterioration of functionality. Longitudinal differences in IADL were not observed in the 18‐24 months follow‐up interval.
CSF p‐Tau/Aβ40 ratio predicts longitudinal hypometabolism and cognitive decline in amyloid‐negative elderly adults
Authors: Guo Tengfei , Landau Susan M. , Jagust William J. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2021

Background

Tauopathy can be measured with PET imaging and CSF phosphorylated tau (p‐Tau), and recent studies have suggested that CSF p‐Tau may be superior to tau PET for detecting early tau increase. We recently found the use of a CSF p‐Tau/Aβ40 ratio improved the associations with Alzheimer’s disease (AD) biomarkers over CSF p‐Tau. However, the significance of elevated CSF p‐Tau in the absence of abnormal Aβ is unclear, as is how it relates to neurodegeneration, cognitive decline, and other factors.

Method

We analyzed 201 non‐demented ADNI participants who were Aβ‐ on both CSF Aβ42/Aβ40 and PET, and who had concurrent Aβ PET, CSF (Aβ40, Aβ42 and p‐Tau181), white matter hyperintensities (WMH), and vascular risk factors measured within one year. Of these, 81 individuals had 18F‐fluorodeoxyglucose (FDG) PET and adjusted hippocampal volume (aHCV). We also examined available longitudinal CSF, aHCV, FDG PET and Preclinical Alzheimer’s Cognitive Composite (PACC) measurements in 20‐40% of participants.

Result

In Aβ‐ individuals, older age, male sex, greater WMH burden and hypertension (Fig. 1) were related to elevated CSF p‐Tau/Aβ40, which was associated with temporoparietal (metaROI) hypometabolism and hippocampal atrophy (Fig. 2). Longitudinally, lower CSF Aβ42/Aβ40, higher WMH, and hypertension predicted faster CSF p‐Tau/Aβ40 increase over around 5 years (Fig. 1), and higher CSF p‐Tau/Aβ40 predicted faster FDG SUVR decrease (Fig. 2) over around 3 years. Furthermore, baseline CSF p‐Tau/Aβ40 was associated with subsequent PACC decline over around 5 years, and this was partially mediated by glucose metabolism and fully mediated by hippocampal atrophy (Fig. 3).

Conclusion

Our results suggest that both cerebrovascular disease and subthreshold levels of Aβ, as well as age, are related to CSF p‐Tau/Aβ40 accumulation. Crucially, evidence of this CSF tau pathology shares features with AD including an AD‐like pattern of hypometabolism and hippocampal atrophy. Thus, this phenotype of Aβ‐ CSF tau elevation is similar to AD, which implies that it may represent an Aβ‐independent pathway to AD, a clinical syndrome that mimics AD, or very early interaction between Aβ and vascular disease that underlies neurodegeneration and cognitive decline.
Physical activity interventions and their effects on cognitive function in people with dementia: A systematic review
Authors: Cardona Maria Isabel
Published: December 2021

Background

As Western societies are rapidly ageing; cases of dementia have also significantly increased. Dementia has a remarkable impact not just on individuals but also on their families, communities, and society [1]. Thus, physical activity (PA) appears in the literature as an alternative non‐pharmacological approach to effectively address dementia effects [2].

Methods

in order to identify and summarize PA interventions and their effects on cognitive function in persons with dementia (PwD), a systematic review was conducted in different electronic databases including PubMed, Embase, APA PsycNET, and Web of Science. Selected studies were randomized controlled trials written in English, published between 2000 and 2020, implemented among PwD, who received a PA intervention, and their cognitive functioning was measured at baseline and follow‐up.

Results

Twenty‐three Randomized Controlled Trials (RCTs) met the eligibility criteria and were included in this review. Moreover, it complements evidence from other reviews by including eight studies that were not considered before. Overall, studies continue to present methodological limitations. However, six studies implemented in the last five years, have shown more solid methodological designs, including larger sample sizes and more comprehensive measurement tools. These studies did not report improvement in the cognitive function of PwD.

Conclusion

Retrieved data acquired through this review showed that it remains unclear whether PA improves cognitive function on PwD, our findings suggest an increase in studies methodological aspects. Moreover, new evidence reported that probably multimodal PA interventions, light to moderate intensities, and long‐term programs are more likely to benefit cognition of PwD. However, future studies should continue addressing methodological barriers and exploring optimal dose‐responses to assure conclusive results regarding PA effectiveness on PwD cognitive functioning. 1. Nations, U., World Population Ageing. United Nations, P.D. Department of Economic and Social Affairs, Editor. 2019: New York. 2. Livingston, G., et al., Dementia prevention, intervention, and care. Lancet, 2017. 390(10113): p. 2673‐2734.
Contribution of cerebrospinal fluid Alzheimer biomarkers to the diagnosis of Creutzfeldt‐Jakob disease
Authors: Faraut Elise , Formaglio Maïté , Gabelle Audrey , Grangeon Lou , Magnin Eloi , Martinaud Olivier , Boutoleau‐Bretonnière Claire , Cognat Emmanuel , Quillard‐Muraine Muriel , Maltête David , Wallon David
Published: December 2021

Background

The definite diagnosis of Creutzfeldt‐Jakob disease (CJD) requires a neuropathological examination revealing the presence of the pathogenic prion protein. As a reliable in vivo diagnosis is required for clinical care, without pathological confirmation, diagnostic criteria for CJD have been proposed including neuroimaging, electrophysiology and 14.3.3 protein positivity in cerebrospinal fluid (CSF) but their accuracy remains suboptimal. Tau protein in cerebrospinal fluid was found to be extremely elevated in CJD and the phosphorylated‐Tau to Tau ratio (P‐Tau/Tau) was reported to be decreased for some CJD patients.

Method

We first aimed to evaluate the efficiency of the P‐Tau/Tau ratio to distinguish CJD from other neurodegenerative disorders in a cohort of patients with a rapidly progressive cognitive disorder and high CSF Tau level above 1000 pg/ml. Then, retrospectively gathering 49 CJD patients from 7 French University Hospital, the Alzheimer CSF biomarkers and the P‐Tau/Tau ratio sensitivity were compared to current CJD diagnosis criteria. A P‐Tau/Tau ratio value below 0.075 was considered as indicative of CJD.

Result

The diagnoses in the first cohort of 24 patients were: CJD (n = 11), Alzheimer disease (n = 11), Frontotemporal dementia (n = 1) and a Gayet‐Wernicke’s encephalopathy (GWE) (n = 1). Using the threshold of 0.075, the ratio P‐Tau/Tau correctly categorized all CJD patients and only one patient, with GWE, was wrongly classified (fig. 1). The area under the curve of the P‐Tau/Tau ratio was 95% (IC 95% 0.85‐1.0). In the 49 CJD series, the ratio was abnormal in 100% of the patients, while the clinical criteria were met in 81.6% and 91.7% for neuroimaging, 50% for helectroencephalogram and 55.1% for protein 14‐3‐3.

Conclusion

Alzheimer CSF biomarkers with Tau level and P‐Tau/Tau ratio may increase diagnosis accuracy for positive and differential diagnosis of CJD with a complementary value to current validated diagnosis criteria. They could be particularly helpful in clinical practice for patients with rapid cognitive decline and Tau > 1000 pg/ml or in atypical cases with unmet diagnosis criteria.
Multidomain interventions for the prevention of dementia and cognitive decline: A Cochrane systematic review and meta‐analysis
Authors: Hafdi Melanie , Hoevenaar‐Blom Marieke P , Richard Edo
Published: December 2021

Background

With no effective pharmacological therapies, risk factor modification may be a suitable intervention for dementia prevention. To date, no single‐domain intervention has convincingly shown to reduce the risk of developing dementia. Targeting more than one risk factor might have additive or even synergistic effects. In this Cochrane systematic review, we investigated the effect of multidomain intervention studies on the prevention of dementia and cognitive decline

Method

We searched ALOIS (the Cochrane Dementia and Cognitive Improvement Group's register), MEDLINE, Embase, PsycINFO, CINAHL, Web of Science Core Collection, LILACS, and ClinicalTrials.gov from origin to April 2020. We included randomized controlled trials (RCTs) targeting at least two dementia risk factors simultaneously, with >400 participants and >12 months of follow‐up. Data were pooled using random‐effect models. This abstract is based on a pre‐peer review version of a Cochrane Review (protocol DOI: 10.1002/14651858.CD013572).

Result

The search identified 13.039 studies. Nine RCTs fulfilled the inclusion criteria and could be included in the review and meta‐analysis; two studies reported incident dementia as outcome, all nine studies reported a measure for cognitive decline. Overall pooled risk ratio (RR) for dementia was 0.94 (95% confidence interval (CI) 0.76‐1.18, I2<10%) and standardised mean difference (SMD) for cognitive decline measured with a neurological test battery (NTB) 0.03 (95% CI 0.01‐0.06, I2<10%). SMD in mini‐mental state examination (MMSE) score was 0.00 (95% CI ‐0.03‐0.04). Subgroup analyses suggested modest favourable outcomes on cognitive decline (NTB) for participants with worse baseline cognitive status (SMD 0.06 (0.01‐ 0.11) for low baseline MMSE vs. SMD 0.01 (‐0.01‐0.04) for high baseline MMSE), though this difference was not significant (p=0.12). There was no difference between groups with respect to adverse events (mortality, cardiovascular disease and stroke). The overall quality of evidence was moderate to high.

Conclusion

Multidomain interventions did not improve the overall risk of dementia. There was a modest effect on cognitive decline measured with a NTB, though this effect was not convincingly supported by other cognitive assessment scores. Future research in populations at increased risk could have important implications for dementia prevention strategies.
The association of serum immunoglobulins with cognition and dementia: The Rotterdam Study
Authors: Khan Samer R. , Yaqub Amber , Wolters Frank J. , Ikram M. Kamran , Dalm Virgil A.S.H. , Chaker Layal , Ikram M. Arfan
Published: December 2021

Background

Chronic neuro‐inflammation has emerged in recent years as important pathological process underlying dementia, including Alzheimer’s disease. Most studies so far have investigated the innate immune system, but the role of the adaptive immune system remains largely unknown. We investigated the association of serum immunoglobulins (IgA, IgG, IgM) as markers of the adaptive immune system with cognitive function and risk of dementia.

Method

This study was embedded in the Rotterdam Study, an ongoing prospective population based cohort study, and included participants with baseline measurements (between 1997 and 2009) of serum immunoglobulins and informed consent for follow‐up. We performed Cox proportional hazard regression analyses to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum immunoglobulins and risk of dementia until 2016 (longitudinal). We performed linear regression analyses to quantify the cross‐sectional association between serum immunoglobulins and cognition summarized into global cognition as well as separate cognitive test scores. Effect estimates are adjusted for age, sex, lifestyle and cardiovascular factors.

Result

We have included 8,768 participants with a mean age of 64 years and of whom 57% are female. Due to non‐proportional hazards, the follow‐up time was divided into two strata (≤10 and >10 years). We found that IgM was associated with a lower risk of dementia after ten years in women (HR: 0.71; 95% CI: 0.58‐0.86). When restricting analyses to participants with immunoglobulin levels within the reference range and excluding users of immunomodulating medication, we found that IgM was associated with a lower risk of dementia after 10 years in the entire population (HR: 0.78; 95% CI: 0.62‐0.97). We furthermore found that higher IgG levels were associated with lower scores of global cognition, Stroop I, and Stroop II (betas ranging from ‐0.01 to ‐0.02; p‐value <0.002 for all).

Conclusion

Higher IgM levels are associated with a decreased risk of dementia in women and in all participants with reference range immunoglobulin levels. Higher IgG levels are associated with worse cognitive test outcomes. Our results suggest a protective effect of the adaptive immune system on dementia onset, but possibly a reversed effect on cognitive function.
Effects of the lifestyle of the elderly before and after COVID‐19 on subjective health, depression and quality of life: The application of multiple group analysis
Authors: Yang Min Ah , Park Ji‐Hyuk
Published: December 2021

Background

The purpose of this study is to identify differences in effectiveness between the two periods before and after COVID‐19 by using a multiple group analysis to determine the effect of the lifestyle(physical activity, activity participation, and nutrition) of the middle and older people on subjective health, depression and quality of life.

Method

Among those aged 55 and older, the study measured lifestyle, subjective health, depression, and quality of life for a total of 327 people. We used SPSS 25 for general characteristics of subjects, descriptive statistical analysis of variables, and AMOS 20 for validation of variables, affirmative factor analysis, and effectiveness analysis on paths.

Result

Multiple group analysis shows that the path of health→depression was significant at 99% confidence before COVID‐19 and between activity participation→quality of life at 90% confidence.

Conclusion

Comparison of final research models from two periods before and after COVID‐19 shows that social isolation resulting from COVID‐19 negatively affects depression and quality of life. These results suggest that health care is essential for middle‐aged and elderly people, and that measures should be taken to address the restrictions on participation in activities caused by social isolation.
A novel specific Aβ42 oligomer antibody ameliorates the neurotoxicity of patient‐derived brain extracts
Authors: Sandberg Anders , Rodriguez Rosa Crespo , Correa Ernesto Berenjeno , Morrema Tjado , Hoozemans Jeroen J. , Scheper Wiep
Published: December 2021

Background

In Alzheimer’s disease (AD), the neurotoxicity of amyloid‐β 1‐42 (Aβ42) stems mostly from soluble oligomeric aggregates of this peptide. However, the study of these aggregates has been hampered by their unstable and elusive nature, thus questioning the very definition of them as distinct targets for drug development. Here, we assess the toxicity of physiologically‐derived Aβ using extracts from deceased patients and controls in primary neuron cultures. By using a monoclonal antibody with a unique binding profile, ALZ‐201, we demonstrate that all of the Aβ toxicity observed in human‐derived brain extracts stem from soluble Aβ42 aggregates.

Method

Brain tissue samples from 10 individuals were confirmed as AD (n=7) and non‐AD (n=3) cases using IHC staining for Aβ and p‐Tau aggregates. Extracts were prepared as described in Hong et al. 2018 (doi:10.1007/s00401‐018‐1846‐7) and immunodepleted with either the antibody 4G8 (removes all Aβ), ALZ‐201 (100% specific for non‐fibrillar soluble Aβ42 aggregates) or an isotype control to ALZ‐201 (does not bind any Aβ). Fractions were biochemically characterized, and toxicity assays were performed in primary mouse neuronal cultures using an automated cell imaging platform.

Result

The total Aβ content was higher in AD cases, as expected. The toxicity of the patient extracts exceeded those obtained from non‐AD cases with respect to neuronal loss and morphological determinants such as synapse density and measures of neurite complexity. Immunodepletion using 4G8 dramatically reduced Aβ in the AD patient samples and the control samples. This is in contrast to immunodepletion using ALZ‐201 or the isotype control, for which there was no detectable difference. Despite this remarkable difference in Aβ content, the therapeutic effect of depletion with 4G8 and ALZ‐201 was comparable, whereas there was no effect after depletion using the isotype control.

Conclusion

The results demonstrate that very small amounts of soluble aggregated Aβ42 likely account for a large part of the toxicity in AD patients. The unique antibody, ALZ‐201, is capable of depleting these without targeting other forms of Aβ. Since this natural toxic form of Aβ is extremely low in abundance, this feature may be a critical attribute for achieving a true therapeutic effect in actual patients.
Centiloid harmonisation strategies across longitudinal studies: Evaluation on AIBL, ADNI and OASIS3
Authors: Bourgeat Pierrick , Li Shenpeng , Tosun Duygu , Benzinger Tammie L.S. , Burnham Samantha C , Weiner Mike W. , Morris John C. , Masters Colin L , Rowe Christopher C , Fripp Jurgen , Dore Vincent , Villemagne Victor L
Published: December 2021

Background

The Centiloid (CL) was proposed to harmonise the quantification of Amyloid PET images across tracers, scanners, and processing pipelines. However, several groups have reported differences across tracers and scanners. In this study, we aim to evaluate the impact of different pre/post‐processing harmonisation steps on the consistency of longitudinal data across multiple large studies.

Method

All Amyloid PET data in AIBL (N=3830), ADNI (N=3453) and OASIS3 (N=1398) were quantified using the Centiloid SPM pipeline. SUVR were converted into Centiloids using each tracer’s respective transform. All images were smoothed to a uniform 8mm FWHM PSF. Both Raw and 8mm FWHM smoothed images were quantified. For Florbetapir, we evaluated using both the standard Whole Cerebellum (WC) and a Composite WM+WC reference region, which has been previously shown to improve longitudinal consistency. Additionally, our recently proposed Non‐negative Matrix Factorisation quantification (NMF: Neuroimage 2021) was applied to all spatially and SUVR normalised images. Longitudinal consistency was evaluated using: fitting error when fitting a regression line to each subject; percentage of longitudinal changes exceeding 95th percentile of changes seen with PiB when using a single scanner (6.56CL/y in the negative and 17.06CL/y in the positive); Spearman rank correlation ρ between the baseline Centiloid and the rate of change.

Result

Figure 1 illustrates the longitudinal consistency, while the fitting error and percentage of outliers are presented in Table 1. These results indicate that the 8mm FWHM smoothing reduced some of the variability, but its impact was limited. Using the Composite reference region on Florbetapir had a bigger impact in reducing the variability. The best results were however obtained when using the NMF method, compared to SPM. Figure 2 shows the baseline vs rate of CL changes. These plots also show a moderate influence of the FWHM smoothing, and a stronger influence of the Composite reference region. They also show that the NMF method produced the highest Spearman and peak CL/y regardless of the pre‐processing or normalisation method used.

Conclusion

FWHM smoothing has moderate impact on longitudinal consistency or outliers. A Composite reference region including subcortical WM should be used for Florbetapir longitudinal Centiloids. NMF improves consistency over SPM.
Adherence to the MIND diet and cognitive performance in the ELSA‐Brasil study
Authors: Ferreira Naomi V , Lotufo Paulo A , Bensenor Isabela M , Barreto Sandhi Maria , Viana Maria Carmen , Caramelli Paulo , Marchioni Dirce Lobo , Suemoto Claudia K
Published: December 2021

Background

Adherence to healthy dietary patterns such as the MIND diet has been associated with better cognition, but little is known about this relationship in studies from low‐ to middle‐income countries. This study aims to investigate the association between adherence to the MIND diet and cognitive performance in the ELSA‐Brasil study baseline.

Method

Adherence to the MIND diet score was assessed using a food frequency questionnaire and cognitive performance was evaluated using three cognitive domains: memory domain (immediate word list recall, late word list recall, word list recognition), fluency domain (semantic and phonemic verbal fluency) and executive domain (Trail Making test version B). We used z scores for the three domains and created a standardized global composite score. We used linear regression to investigate the association between MIND diet adherence and cognitive performance adjusted for sociodemographics and clinical variables. We also investigated interactions between adherence to the MIND diet and age, race, and education.

Result

MIND diet adherence was associated with better cognitive performance in all three domains and with global cognition in unadjusted analysis. However, adherence to the MIND diet was related to a worse performance in the executive domain in a full adjusted model (Table 1). Adherence showed significant interaction with age, race and education, suggesting better cognitive performance with higher adherence in older people (Figure 1), white participants (Figure 2) and those in higher levels of education (Figure 3), but a lower cognitive performance with higher adherence in those in lower levels of education (Figure 3).

Conclusion

MIND diet adherence was associated with worse performance in an executive function test. Older, white and high‐educated participants had better performance with higher adherence scores.
An investigation of HCV as a predictor of cognitive decline: The Bio‐Hermes protocol
Authors: Wolz Robin , Bork Jason , Cordell Cyndy , Hughes Lynne , Bullock Roger Alan , Cerroni Giulio , Dwyer John , Mohs Richard
Published: December 2021

Background

A 2018 NIA‐AA Research Framework extended the biological definition of Alzheimer’s disease (AD) from biomarkers of amyloid (A) and tau (T) to include measures of neurodegeneration (N) thus enabling more detailed staging and identification of participants potentially closest to clinical decline (N+) (AlzheimersDement.2018;14(4):535‐562). This framework is only partially implemented in clinical trials as N is rarely considered a selection criterion. Hippocampal volume (HCV) measured from magnetic resonance imaging (MRI) has been proposed as a widely available, robust tool to define N+ (AlzheimersDement.2014;10(4):421‐429.e3).

Method

Participant selection through N+ will be validated in a sub‐study of the Bio‐Hermes trial planned by the Global Alzheimer’s Platform Foundation®. The Bio‐Hermes trial will assess biomarkers of Aβ, phospho‐tau, and neurofilament light in approximately 1,000 participants in three cohorts: cognitively normal, mild cognitive impairment, probable AD. A baseline MRI will be performed in approximately 200 additional participants randomized in a substudy. A pre‐defined HCV cut‐off from the Learning Embeddings for Atlas Propagation (LEAP) algorithm was identified to define N+ status (NeuroImage.2010;49(2):1316‐1325). The sub‐study will enrol participants willing to forgo treatment studies for 12 months to allow standardized measures of progression. Correlation with clinical measures and clinical decline will be compared in N+ and N‐ populations in the three cohorts to validate the benefit of full ATN staging in trial design.

Result

While most publications using the LEAP algorithm for N+ AD patient stratification define N+ cut‐offs based on HCV percentiles in the analysed dataset (Neurobiology of Aging. 2012;33:2272–2281, Neurology. 2013;80(12):1124‐1132, , Neurology. 2016; 87(12):1235–124, Alzheimers Dement. 2018;14(7):1076, Alzheimers Dement. 2020; 10.1002/alz.037912), one study deployed percentiles from a healthy reference cohort (Neurobiology of Aging. 2014;35:808‐818). Based on prior work and simulations of the Bio‐Hermes trial cohorts, the N+ cut‐off was set at HCV=5.4cm3.

Conclusion

The presented study design validates the use of MRI as inclusion criterion in AD clinical trials to fully implement ATN staging. As MRI is a standard tool during screening for AD clinical trials, additional participant characterisation can be achieved at minimal extra cost and burden, significantly improving trial power.
The association between long term blood pressure variability with incident dementia and cognitive impairment: A systematic review and meta‐analysis
Authors: Jia Pingping , Lee Helen WY , Chan Joyce YC , Tsoi Kelvin KF , Yiu Karen KL
Published: December 2021

Background

Dementia cases continues to grow in the era of ageing population, with its number approaching 50 million. Accumulating evidence has shown that high blood pressure increases the risk of dementia and cognitive decline. In recent decades, some studies demonstrate that blood pressure variability (BPV) may contribute to cognitive decline and incident dementia independent of the blood pressure level. However, due to the inconsistence of statistical results and clinical methodology, the magnitude of this relationship remains ambiguous. A clear understanding of the role of BPV in dementia may shed light to etiology and early prevention of dementia. This study aims to assess the association between BPV with incident dementia and cognitive impairment.

Method

We searched MEDLINE, Embase, PsycINFO, CINAHL and Web of Science from December 2020 for articles describing trials, retrospective and prospective cohort studies in adults that assessed the association of long‐term BPV (measured through clinic blood pressure monitoring) with incident dementia and cognitive impairment. 5681 papers were identified and eventually 12 articles with full text and 3 abstracts with enough information were included in the quantitative analysis. Of these 15 studies, 2 articles report both dementia and cognitive decline or dysfunction as outcomes, while 5 studies report dementia as an outcome and 8 studies report cognitive decline or dysfunction.

Result

Hazard Ratio and linear regression coefficient were converted to a standardized one. We found that increased long‐term variability in systolic blood pressure was associated with higher risk of all‐cause dementia [pooled standardized HR of 1.1 (95%CI, 1.01, 1.19)]. Compared to people in lower BPV group, people in higher BPV group was 1.17 times more likely to develop dementia [pooled HR 1.17 (95%CI,1.12, 1.22)]. Cognitive decline was associated with higher SBPV [pooled linear coefficient for MMSE score is ‐0.11(95%CI, ‐0.17, ‐0.05)],which means MMSE score decreases by 0.11 per SD increase in SBPV.

Conclusion

Our findings suggested that higher long‐term blood pressure variability increases both the risk for incident dementia and cognitive decline.
Capturing functional change in early Alzheimer’s disease: Comparing instruments and scoring techniques to detect subtle decline
Authors: Dubbelman Mark A. , Jutten Roos J. , Harrison John E , Ritchie Craig W. , Aleman André , de Jong Frank Jan , Scheltens Philip , Sikkes Sietske A.M.
Published: December 2021

Background

Functional decline is a gradual process occurring along the Alzheimer’s disease (AD) continuum, starting years before dementia onset. Different instruments, such as the ADCS‐ADL and the Amsterdam Instrumental Activities of Daily Living Questionnaire (A‐IADL‐Q) aim to capture early functional changes. In the current study, we compared measurement instruments and scoring techniques to find the optimal measurement technique for detecting functional impairment in early AD.

Method

Study partners of participants from the international ‘Capturing Changes in Cognition’ study cohort completed both the A‐IADL‐Q and ADCS‐ADL over the course of one year (mean follow‐up 10.8±2.3 months). For both measures, we computed the following scores: (1) sum score, (2) weighted average, and (3) number of items with maximum score. For the A‐IADL‐Q, we also computed item response theory (IRT) scores, using predetermined parameters that take into account varying difficulty of included items (see Jutten et al., 2017). To compare the ability to detect changes over time for each scoring method, we performed linear mixed modeling, adjusted for sex and baseline age.

Result

We included 159 individuals (72.2±8.4 years old, 45% female) with subjective cognitive decline (SCD, N=12), mild cognitive impairment (MCI, N=66) or mild dementia (N=81). Overall, a significant decline in functioning was detected with all scoring techniques (all p<.01), except the technique of the number of items with most impairment for the ADCS‐ADL (see Table 1). When comparing decline in the diagnostic groups (see Figure 1 and Table 1), linear mixed models showed functional decline in all scoring techniques of both instruments in mild dementia. In MCI, all A‐IADL‐Q scoring methods showed a significant decline over time (p<.05), whereas the ADCS‐ADL scores did not. No decline was detected in SCD.

Conclusion

The A‐IADL‐Q showed greater sensitivity to functional decline over one year than the ADCS‐ADL in those with MCI. Our findings suggest that the ability to detect subtle functional changes appears to be mostly dependent on instrument, and to a lesser extent on the scoring technique used. These findings imply that the selection of appropriate instruments is pivotal for optimal longitudinal study design, and clinical trial design in patients with MCI.
Healthcare expenditure attributable to dementia with Lewy bodies in Japan: LIFE Study
Authors: Ono Rei , Nakatsuka Kiyomasa , Uchida Kazuaki , Fukuda Haruhisa
Published: December 2021

Background

Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia, yet scarce evidence is available about healthcare expenditure after diagnosis. This study aimed to quantify the healthcare expenditure attributable to DLB using claims data.

Method

This study design was the prospective cohort study. The analysis was conducted using the LIFE Study database, which comprises municipality‐level information centred on claims data. Claims data from April 2014 to March 2019 were obtained from ten rural cities (n=170,919, mean age: 73.4 years, woman: 99,210). The study subjects were individuals who had received new diagnoses of DLB (ICD‐10 code G31.8 and F02.8) in October 2014 or later. The healthcare expenditures for three years were estimated for subjects with adequate follow‐up data for the respective periods. Using the expenditures incurred during the six‐month period before DLB diagnosis as a comparator, the expenditures trend incurred after DLB diagnosis were estimated through fixed‐effects models.

Result

Of them, 277 individuals with new diagnoses of DLB were identified. Their mean age was 82.0 years, 188 (67.9%) were women. The fixed‐effects model estimated that the first, second months after DLB diagnosis were associated with higher expenditures of US$1,766.7 (US$1 = ∖103.8, P < 0.001) and US$1,366.3 (P < 0.001), respectively, when compared with the pre‐DLB period (US$663.6). The expenditures stabilized in the first, second, third years (US$524.9, US$440.5, US$609.0).

Conclusion

Healthcare expenditure in first and second months after DLB onset were much higher than those of the pre‐DLB period.
Impaired recognition of disgust is related to subcortical volume loss in amyotrophic lateral sclerosis
Authors: Canu Elisa , Leocadi Michela , Castelnovo Veronica , Magno Maria Antonietta , Riva Nilo , Poletti Barbara , Silani Vincenzo , Filippi Massimo , Agosta Federica
Published: December 2021

Background

The impairment in detecting disgust in Amyotrophic Lateral Sclerosis (ALS) has been hypothesized to be related with the integrity of subcortical structures. However, this has not been demonstrated yet and was the aim of the study.

Method

Twenty ALS patients without cognitive/behavioural symptoms and 52 matched healthy controls (HC) underwent a brain MRI scan and a neuropsychological assessment including the Comprehensive Affect Testing System (CATS) investigating emotion recognition. Composite scores were calculated by summing up the correct answers for each emotion. Gray matter (GM) volumes of the subcortical structures were obtained using FIRST in FSL. Sociodemographic, cognitive and MRI data were compared between groups. In ALS patients, CATS significant findings were correlated with the subcortical volumes, ECAS performances, patients’ mood and behaviour.

Result

ALS patients performed significantly worse than HC at the CATS, and they were significantly less able to recognize disgust. No GM volume differences were observed between groups. In ALS patients, a low performance in disgust recognition was related with a reduced volume of the left pallidum and with low performances at the ECAS.

Conclusion

In a sample of cognitively/behaviourally unimpaired ALS, we demonstrated an altered ability to correctly recognize disgust and a potential role of basal ganglia in the altered processing of this emotion. These findings, together with the relationship between the altered disgust recognition with lower ECAS performances in patients, suggest that disgust could be the first emotion to be hit in ALS cognitive decline. These findings offer new potential markers for monitoring extra‐motor progression in ALS. Supported by: Italian Ministry of Health (GR‐2013‐02357415); European Research Council (StG‐2016_714388_NeuroTRACK).