bluuebunny/crossref_metadata_2025 huggingface dataset:
The brain health champion study: A health coaching intervention with mobile technology in older adults with mild cognitive impairment or risk factors for dementia – An update
Authors: McFeeley Brittany M , Krivanek Taylor , Nicastri Casey M , Ramirez‐Salazar Sergio , Babazadeh Demsina , Altman Abby , Daffner Kirk R , Gale Seth A
Published: June 2023

Background

Extensive evidence suggests that adherence to brain‐healthy behaviors can slow the rate of cognitive decline and decrease risk of dementia. We previously demonstrated that a health coaching intervention, including weekly phone calls, facilitated adherence to recommendations for brain‐healthy behaviors in older adults with mild cognitive impairment (MCI) or mild dementia. The current study extends this research to include cognitively normal, older adults at risk for dementia and adds a mobile health platform, two‐way texting, and wearable fitness trackers, to the health coaching intervention. Although subjects are still enrolling, the number of participants has increased substantially from our earlier report and data show promising trends.

Method

Participants, age 60‐79, with MCI or dementia risk factors are being randomized to the Brain Health Champion (BHC) intervention or a counseling and education (CE) control. In BHC, with guidance from a health coach, participants set personalized goals, reinforced by weekly video calls, mobile messaging, one dietitian consult, and 30‐minute in‐person or virtual visits every six weeks. In CE, educational materials sent every six weeks supplement usual care. Changes in physical activity, diet, social/cognitive engagement, neuropsychological test scores, and metrics of behavioral health are being measured over six months using questionnaires, wearable fitness trackers, and photographed food logs. Maintenance of behavior changes is also being assessed six months post‐intervention.

Result

Thirty‐four participants have enrolled in the study, with 27 (15 BHC, 12 CE) completers to date. All participants successfully operated the mobile technology by themselves or with caregivers’ assistance. Current trends show BHC participants increased participation in cognitive activities and adherence to a Mediterranean diet based on photographed food logs compared to CE. Participants in both arms show significantly increased scores on the composite neuropsychological assessment (pre‐ and post‐study), quality of life measures, and an increase in active minutes from pre‐ to post‐assessments.

Conclusion

Trends in the data indicate that the BHC program may be effective for promoting brain‐healthy behaviors, particularly increasing cognitive activities and Mediterranean diet adherence. Additionally, participating in a brain health study, regardless of intervention, may promote meaningful changes in quality of life and improved cognition.
Physiological biomarkers of silent brain damage leading to cognitive impairment and Dementia – direct and accessible clinical evidence
Authors: Tanne David
Published: June 2023

Background

Cognitive assessment is the best clinical tool to detect cognitive impairments, yet it is evident only at late stages of disease progression. In contrast, silent brain network changes occur at early stages of the disease and it is estimated that a large proportion of dementias may be prevented or at‐least delayed if detected during early pathophysiology stages. Neuroimaging studies have shown that silent brain network findings, including white matter hyperintensities, lacunar infarctions and temporal atrophy are evident before objective cognitive impairment is detected and even more in ‘at risk’ population with risk factors for dementia. We aimed to evaluate direct physiological biomarkers that provide accessible clinical evidence of silent brain network damage that precede clinical cognitive findings and provide early clinical biomarkers that can facilitate early interventions.

Method

Brain network performance was evaluated in 168 subjects ‘at risk’ for developing dementia (Table 1). Direct electrophysiological imaging (“Delphi”) was used to measure magnetically induced brain network electrophysiological response. MRI scans included T1, T2, FLAIR, Diffusion Weighted Imaging (DWI) and (SWI). They were analysed according to Fazekas scale for white matter Hyperintensities (WMH), lacunar Infarctions and medial temporal lobe atrophy (MTA). Objective cognitive evaluations were performed by a neuropsychologist interview and a computerized cognitive battery (NeurotraxTM).

Result

Direct electrophysiological imaging (“Delphi”) was able to distinguish between severities of different MRI detected silent brain network damage findings. Magnetically induced direct electrophysiological response wave form adherence (WFA) significantly decreased with increase in WMH (Fig.1A; p<0.0001) and increase in MTA levels (Fig.1B; p<0.0001). Furthermore, WFA significantly decreased in subjects with lacunar infarctions (Fig.1C; p<0.0001).

Conclusion

Silent brain network deficits preceding dementia and cognitive decline are widely under detected due to lack of accessible tools. Data presented in this study demonstrates “Delphi” technology’s ability to detect silent brain network damage findings and severity levels that are identified in MRI scans. “Delphi” is a clinically accessible, direct, and objective technology that can facilitate early detection, prevention, delayed progression and management of mild cognitive impairment and dementia.
The effect of the lockdown during the COVID‐19 pandemic on the risk of developing dementia; A cohort study
Authors: Baron Daniel Hendrik , Sinclair Lindsey I , Carslake David J , Coulthard Elizabeth
Published: June 2023

Background

Increased social activity, relationships and being cognitively active have been associated with decreased risk of dementia. The COVID‐19 pandemic has significantly influenced these and increased the feeling of loneliness throughout society. Protective measures against the virus, such as social distancing and isolation, were enforced to reduce contact between people. We hypothesised that this would lead to an increased risk of transition to dementia.

Method

We obtained data from the Brains for Dementia (BDR) cohort, which has been collecting roughly annual data on 3,726 older adults with and without dementia since 2008. Data continued to be collected during the lockdowns, although by telephone and /or video call instead of in person. Individuals diagnosed with dementia at study entry were excluded from this study as were individuals with only one visit. Cognitive status was classified using the CDR global score.

Poisson regression with cubic splines to account for differences in age was used to compare the rate ratio of developing dementia before/after March 1st 2020.

Result

Out of 2,242 individuals, 205 individuals developed dementia before and 40 developed dementia after 1/3/20. The rate ratio of developing dementia after 1/3/20 was 0.770 (95% CI 0.438 – 1.356, p = 0.366) but there was evidence that this differed with age.

Conclusion

The chance of individuals developing dementia did not change significantly after the first lockdown, although power was low. We will now perform sensitivity analyses to assess whether the type of assessment or using the CDR sum of boxes/MMSE to define cognitive status alters this relationship.
Copper ions and the R peptides of tau: structural and functional study
Authors: Seneviratne Dev , Martic Sanela
Published: June 2023

Background

One of the common neurodegenerative disorders is the aggregation of Tau protein plays a major role in Alzheimer’s disease. Transmission metals ions such as Cu, Zn, and Fe are vital ingredients that must maintain homeostasis in the biological system. Tau Protein has four repeat peptide units (R1 R2 R3 R4) which may coordinate divalent copper ions to form neurofibrillary tangles (NFTs) and generate reactive oxygen species (ROS).The abnormal amount of Cu2+ accumulation in the intracellular environment, regulating the biological systems is not clearly understood.

Method

The main objective of this study was to evaluate the coordination of four R peptides to Cu2+ by MALDI‐MS‐TOF and determine the interaction of Cu2+ ions with peptides (R1 R2 R3 R4) of Tau protein in vitro. Also, their role in the formation of ROS with a natural reducing agent‐ ascorbate was probed.

Result

As the principal findings of this experiment, metal ion coordinated all 4 R peptides, via His and Cys residue including N terminal and amide groups. All the metallo‐peptide complexes were singly charged peaks, and observed even in the presence of ascorbate. R2 and R3 peptides formed the homodimers by disulfide bond formation. The metallo‐peptides were antioxidants and prooxidants depending on the conditions, indicating that a complex behavior may exist in the biological setting.

Conclusion

This work indicates that metal ions interact with R peptides, which may mitigate ROS levels. The finding of this study is greatly beneficial for understanding the Tau protein behavior to develop a potential medication.
Alzheimer’s Disease (AD): High cholesterol is associated with lower Mini‐Mental State Exam (MMSE) scores
Authors: Komatsu Caroline , Komatsu Ricardo S.
Published: June 2023

Background

Alzheimer’s Disease (AD) is the leading cause of dementia in the elderly. The epsilon 4 allele of the apolipoprotein E gene that encodes the major brain lipid carrier and metabolic disorders, such as obesity and type 2 diabetes, were identified as AD risk factors, suggesting that abnormal lipid metabolism could influence the progression of the disease. Additionally, lowering cholesterol is associated with reduced central nervous system (CNS) amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies.

Method

154 outpatients with the diagnosis of AD conforming to criteria proposed by NINCDS‐ADRDA (2011), followed‐up at a public university hospital, had their cholesterol levels assessed and MMSE scores evaluated.

Results

90 patients (58,44%) presented high cholesterol (total cholesterol level ≥ 190 mg/dL and/or LDL level ≥ 130 mg/dL) and 64 patients (41,56%) presented cholesterol normal range (total cholesterol level < 190 mg/d L and/or LDL level < 130 mg/dL). From the high cholesterol group, 10 patients (11,11%) presented severe cognitive impairment (MMSE < 10), 50 patients (55,55%) presented moderate cognitive impairment (MMSE = 10 – 20) and 30 patients (33,34%) presented mild cognitive impairment (MMSE > 20). From the cholesterol normal range group, 5 patients (7,81%) presented severe cognitive impairment, 19 patients (29,69%) presented moderate cognitive impairment and 40 patients (62,5%) presented mild cognitive impairment. Both groups, high cholesterol and cholesterol normal range, had on average the same educational level: 2,91 and 3,42 years, respectively.

Conclusion

In this sample of patients with AD, high cholesterol is associated with lower MMSE scores when compared to cholesterol normal range.
Does aerobic exercise affect physical function and quality of life in those diagnosed with dementia? A systematic review
Authors: Marocco Samantha L , O'Connor James J , York Ashley , Haab Ricki , Drake Austin
Published: June 2023

Background

It has been proposed that aerobic exercise can have positive effects on people who have cognitive impairments. While systematic reviews have been completed on the effects of aerobic exercise on the cognitive function in those with Alzheimer’s Disease, there has yet to be a systematic review that focuses on the effects of aerobic exercise on physical function and quality of life in patients diagnosed with dementia. The purpose of this systematic review is to analyze the existing literature concerning how aerobic exercise should be prescribed to those with dementia.

Method

Multiple databases were searched for randomized controlled trials published from: Medline Complete, CINAHL Complete, Cochrane Central Register, SportsDiscus, PEDro, Health Source, PubMed, Ageline, Health Reference Center Academic, OT Seeker, and Science Direct. Our search included articles published from January 2011 through February 2021. A screening of relevant articles was then performed to identify literature to be included in the systematic review. Data was extracted for the following information: specific details about the study populations, interventions, and outcomes of significance related to the review analysis.

Result

Ten studies, all of which were found to be fair to excellent quality according to the PEDro scale, met the inclusion criteria for this systematic review. Overall results indicated positive effects of aerobic exercise on the physical functioning of patients diagnosed with dementia. Many of the studies indicated a change with small effect sizes for the outcome of physical function. Other outcomes such as cognition, activities of daily living, and quality of life had inconsistent effect sizes between studies.

Conclusion

The results of this systematic review indicate that there is currently mild to moderate evidence in support of implementing an aerobic exercise program for patients diagnosed with dementia. Additional higher quality studies are needed to establish specific exercise parameters that promote physical function in people with dementia.
Hippocampal place cells exhibit impairments in spatial information coding in an APP‐knock in model of Alzheimer’s Disease
Authors: Wood Ruth A , Burton Stephen , Katsouri Loukia , Greenaway Borgel , Chan Dennis , O'Keefe John
Published: June 2023

Background

The hippocampus is one of the first cortical regions to exhibit Alzheimer’s Disease (AD) pathology. The spatially‐related firing of hippocampal place cells provides the cellular basis for spatial memory and this is impaired relatively early in AD, yet few studies examine place cell activity in AD mouse models. We undertook an in‐depth characterisation of hippocampal pyramidal cell activity in an APP knock‐in model of AD.

Method

Microdrives carrying 8 tetrodes were implanted into the left CA1 hippocampal subfield of 14‐month female mice (four APPNL‐G‐F, four wild‐type littermates). Mice undertook daily foraging sessions in an open field and ran on a linear track as CA1 activity was recorded. On completion of experiments, 40µm coronal sections of fixed brain tissue were stained using Cresyl Violet to verify tetrode placement and Thioflavin‐S to quantify amyloid β plaque burden.

Result

270 cells were recorded (119 wild‐type, 151 APPNL‐G‐F). CA1 pyramidal cells were classified as “place cells” or “non‐place cells” based on their spatial information content (bits/spike). Pyramidal cells recorded in wild‐type mice had significantly greater spatial information content than APPNL‐G‐F pyramidal cells (Figure 1), and a higher proportion were classified as place cells. Wild‐type place cells had significantly greater spatial information content than APPNL‐G‐F place cells. Corresponding differences were identified in place field size (Figures 2, 3). A positive correlation was identified between Aβ plaque burden and pyramidal cell spatial information content in the four APPNL‐G‐F mice (Figure 4).

Coordination of place cell firing by the hippocampal theta rhythm was disrupted in APPNL‐G‐F mice; phase‐locking of pyramidal cells and place cells was significantly reduced (Figure 5), there was less coherence in the preferred theta phase across the pyramidal cell population, and a reduction in theta phase precession was observed.

Conclusion

APPNL‐G‐F CA1 place cells exhibited deficits in both rate coding and temporal coding of spatial information indicating that amyloid β pathology, in the absence tau tangles, was associated with a disruption of hippocampal place cell function. These results provide preliminary support for the hypothesis that disruption of hippocampal function by AD pathology manifests as altered place cell activity and spatial behaviour.
Challenges and approaches when addressing dementia in the context of chronic comorbid conditions in primary care settings
Authors: Sideman Alissa Bernstein , Alagappan Cecilia , de Jesus Alma Hernandez , Ma Melissa , Dohan Daniel , Rosen Howard J. , Chodos Anna H , Possin Katherine L , Borson Soo , Rankin Katherine P
Published: June 2023

Background

A diagnosis of dementia impacts all other comorbid conditions and areas of patient care. Yet, in primary care settings, dementia is often underdiagnosed and misdiagnosed due to competing clinical concerns. Delayed diagnosis and care of dementia can lead to more rapid cognitive decline, and increased hospitalizations, health care costs, and mortality. The objective of this work was to understand the challenges and successful approaches among primary care providers working in safety net settings when caring for patients with dementia and co‐existing chronic conditions.

Methods

Qualitative interviews focused on practices and challenges diagnosing and caring for patients with dementia, challenges related to comorbidities, needs for practice improvement, and successful approaches. Data was analyzed using thematic analysis.

Results

We interviewed primary care physicians (n = 29) and primary care nurse practitioners (n = 6) based in California safety net settings in the SF Bay Area, Central Valley, and Southern California. PCPs identified the following comorbidities as most challenging to co‐manage with dementia: mental illness (depression/anxiety), hypertension, diabetes, heart disease, stroke, pain, substance use, and trauma. Most PCPs made a distinction between poorly controlled and well‐controlled chronic conditions. Challenges identified included: difficulty differentiating symptoms of dementia from other conditions, medication management and adherence; time constraints when making decisions about prioritizing acute comorbidities or dementia; need for family/caregiver involvement; and challenges controlling comorbid conditions when dementia is present. Successful approaches included: using team‐based care and targeted referrals (e.g. social work, community health workers, geriatrics); the importance of familiarity and long‐term relationships with patients; finding ways to involve family members; and simplifying visits, care plans, and communication.

Conclusion

PCPs face difficulties when providing care to patients with dementia and comorbid conditions, but they also identified opportunities for improvement by sharing successful approaches used in challenging healthcare settings. Findings can help shape intervention development to better support PCPs.
Application of neurovascular uncoupling and whole brain network connectomics to assess the role of genetic and dietary risk factors in the LOAD2 mouse model
Authors: Silvola Rebecca , Persohn Scott C , Oblak Adrian L , Lamb Bruce T , Bedwell Amanda A , Eldridge Kierra , Speedy Rachael , Howell Gareth R , Sasner Michael , Territo Paul R ,   MODEL‐AD Center
Published: June 2023

Background

As research efforts to discover and develop promising future therapeutics continues, the necessity to develop clinically significant Alzheimer’s disease (AD) mouse models and analysis is more important than ever.

Method

The study utilizes a novel MODEL‐AD (Model Organism Development and Evaluation for Late‐onset AD) mouse model that incorporates APOE4, Trem2*R47H, and humanized amyloid‐beta (Aβ) allele into C57BL/6J (B6) mice to produce LOAD2. Two cohorts of male and female LOAD2 mice received either control or high fat diet (HFD) followed by brain metabolism imaging using 18F‐FDG PET/CT. Brain regions were segmented using the Paxinos‐Franklin atlas and analyzed using a whole brain neurovascular uncoupling and connectivity approach. To do this, we computed z‐score statistics for all mice relative their control diet group, and conducted hierarchical modularization of all 28 brain regions and statically compared results across sex and high‐risk diet in 12‐month‐old mice.

Result

An initial network analysis detected metabolic hypo‐perfusion and metabolism for female mice, while males showed neurovascular uncoupling. Hierarchical analysis revealed primary modules within the whole brain network. These primary modules were then further modularized to yield a final breakdown of six secondary sub‐modules consisting of 3‐7 brain regions. Predominate functional associations of the sub‐modules’ brain regions were sensory (S) and learning (L), while sub‐module 2.1 had the strongest visual (V) representation. Statistical analysis of the six sub‐modules exhibited significant, module‐, sex‐, and dietary‐dependent effect for LOAD2 mice on high fat diet (HFD) by 12mo.

Conclusion

The incorporation of APOE4, Trem2*R47H, and humanized Ab sequence in combination with HFD induced age‐dependent LOAD‐relevant changes in neurovascular coupling and whole brain network connectivity consistent with known brain circuit variations observed clinically. These findings support application of this newer LOAD2 mouse model to improve knowledge regarding disease mechanism. Additionally, our connectivity analysis approach shows promise for implementation in future therapeutic development and testing.
Measurement invariance of the Cognitive Function Index across race in the A4 study
Authors: Ruthirakuhan Myuri , Cogo‐Moreira Hugo , Amariglio Rebecca E. , Buckley Rachel F. , Sperling Reisa A. , Swardfager Walter , Black Sandra E. , Rabin Jennifer S.
Published: June 2023

Background

Accumulating evidence suggests that subjective concerns expressed by cognitively normal older individuals may be a sensitive indicator of early Alzheimer’s disease (AD). The Cognitive Function Index (CFI) is a 14‐item questionnaire developed to assess subjective decline in cognitively unimpaired individuals. Previous studies have reported that greater CFI scores are associated with greater amyloid burden and faster cognitive decline in cognitively unimpaired individuals. These findings, however, have been found in predominantly White samples, and the equivalence of the CFI across different races has not been investigated. The goal of this study was to evaluate measurement invariance (i.e., equivalence) of the CFI across race using data from the Anti‐Amyloid in Asymptomatic AD (A4) Study.

Method

This study analyzed screening data from the A4 Study. Participants (N = 5735) were classified as Black, Asian, or White using self‐reported race. Latino/Hispanic individuals were excluded due to low numbers (N = 232). A multi‐group confirmatory factor analysis using a single‐factor model was conducted in Mplus to evaluate invariance of the CFI across race. Acceptable model fit was confirmed using the following: χ2/df <3, comparative fit index>.95, and the root‐mean‐square error of approximation (RMSEA)<.1. Measurement invariance was established with a ∆comparative fit index≤.01, and ∆RMSEA≤ .015 between invariance tests.

Result

Of the individuals included N = 267 were Black, N = 277 were Asian, and N = 5241 were White (mean±SD age: 71.7±4.9, education (years): 16.4±3.0, and male: 2466 (43%)). Configural, metric, scalar, and strict measurement invariance was supported by race (Table 1).

Conclusion

The results demonstrate equivalent performance of the CFI across cognitively unimpaired participants who self‐identify as Black, Asian, or White. Differences between these groups measured by the CFI can be considered to reflect true inter‐group differences in subjective cognitive concerns rather than differences in the measurement properties of the scale. Future work should examine measurement invariance of the CFI in additional racial/ethnic groups.
Genetic association of apolipoprotein E genotype with EEG alpha rhythm and resting‐state functional MRI connectivity in non‐demented adults during aging
Authors: Ponomareva Natalya V , Andreeva Tatiana , Protasova Maria , Kolesnikova Ekaterina P , Malina Daria , Kanavets Elena V. , Konovalov Rodion , Krotenkova Marina V. , Fokin Vitaly , Illarioshkin Sergey , Rogaev Evgeny I
Published: June 2023

Background

The ε4 allele of the apolipoprotein E (APOE) genotype is a major genetic risk factor for Alzheimer’s disease (AD), but the mechanisms underlying its influence are not completely understood. The study was aimed at determining the possible effect of APOE genotype on spontaneous EEG alpha rhythm characteristics and on the resting‐state functional MRI (fMRI) connectivity (rsFC) in large brain networks in non‐demented adults during aging.

Method

We examined individual alpha peak frequency (IAPF), the EEG alpha sub‐bands power and the fMRI rsFC in 137 non‐demented volunteers, age range 26‐79 years, stratified by APOE genotype. APOE ε3/ε3 subgroup (APOE4‐) included 91 subjects, APOE ε4/ε3+ (APOE4+) subgroup – 46 subjects. The individuals underwent resting‐state fMRI of the brain, the CONN Matlab/SPM‐based toolbox was used to study connectivity in brain networks (Whitfield‐Gabrieli and Nieto‐Castanon, 2012). Informed written consent was obtained from all participants. All subjects underwent a neurological examination and cognitive screening.

Result

The presence of the APOE4+ genotype was associated with lower IAPF and lower relative power of the 11‐13Hz alpha sub‐bands. The age‐related alpha rhythm slowing was more pronounced in the APOE4+ than in the APOE4+ non‐carriers. The negative rsFC between the left hippocampus and the right posterior parietal cortex was reduced for the APOE4+ carriers compared to the APOE4‐ carriers. EEG IAFT showed a significant inverse correlation between rsFC of the left hippocampus and the right posterior parietal cortex.

Conclusion

APOE4+ genotype is associated with marked age‐related alpha rhythm slowing and the dysfunction of the inhibitory large‐scale hippocampal networks. Inhibitory deficit of these networks function, interconnected with alpha rhythm slowing, may be related to learning and memory impairments and contribute to the subsequent AD development.

This study was supported by Russian Science Foundation (Project No. 19‐75‐30039, genotyping)
Feasibility of remote assessment of language and cognition in healthy subjects with heterogeneous educational levels
Authors: Silagi Marcela , D´Ávila Maria Isabel Freitas , Almeida Isabel Junqueira de , Pisetta Paola May , Carthery‐Goulart Maria Teresa , Senaha Mirna L H , Beber Bárbara Costa , Oliveira Maira O , Nitrini Ricardo , Brucki Sonia
Published: June 2023

Background

The COVID‐19 pandemic is accelerating the use of telemedicine in the management of chronic neurological diseases. However, studies on the feasibility of assessing language and cognition are still scarce, especially in developing countries in which education is very heterogeneous. This pilot study evaluated the feasibility of using telemedicine for linguistic‐cognitive assessment, by comparing the performance of healthy adults in face‐to‐face and online assessments in a Brazilian sample. We also verified the influence of age and education on the two assessment forms.

Method

The sample consisted of 15 cognitively healthy subjects, aged between 57‐70 years (M = 63.2; SD = 4.6) and between 8‐22 years of education (M = 14.7; SD = 4.3). The Western Aphasia Battery‐Revised (WAB‐R) (Kertesz, 2007; Neves et al., 2014) was used for language assessment, with subtests for spontaneous speech, auditory verbal comprehension, repetition, naming, reading, and writing. The Addenbrooke’s Cognitive Examination‐revised version (ACE‐R) (Mioshi et al., 2006; Carvalho e Caramelli, 2007) was used for a brief cognitive screening and is composed of five subscales assessing attention and orientation, memory, fluency, language, and visuospatial skills. Subjects were randomly evaluated both face‐to face and online, with an interval of 1‐6 months.

Result

No differences were found in both WAB‐R and ACE‐R scores obtained in a face‐to‐face versus online environment. However, performance was associated with different sociodemographic variables in the two different evaluation contexts. In face‐to‐face assessment, there was a positive correlation between education and writing subtests (Spearman r = 0.878; p = 0.004). In the remote form of evaluation, there was a negative correlation between age and auditory verbal comprehension (Spearman r = ‐0.722; p = 0.043), and a positive correlation between education and spontaneous speech (Spearman r = 0.871; p = 0.004), auditory verbal comprehension (Spearman r = 0,768; p = 0,025), writing (Spearman r = 0.727; p = 0.040) and Aphasia Coefficient score (Spearman r = 0.736; p = 0.037).

Conclusion

The absence of statistical difference between the two forms of evaluation demonstrated the viability of remote assessment of language and cognition in healthy subjects, despite the more significant influence of education in this evaluation form. Further studies will be conduct to verify the feasibility of remote assessment in individuals with mild cognitive impairment and dementia.
Analysis of glucocorticoid responsive and circadian clock molecules in Alzheimer’s disease brain tissues.
Authors: Srinivasan Mythily
Published: June 2023

Background

Under basal non‐stressed brain conditions, a control system that includes an inherent molecular clock activation, immunomodulatory role of glucocorticoids and nuclear factor‐kappa B (NF‐κB) signaling is essential to prevent excessive inflammation and to effectively return to homeostasis. This results in a continuous competition between feedback and feedforward control. Chronic stress and dysregulated molecular clock are implicated as significant risk factors for neurodegeneration. In unstimulated mice, the core clock gene BMAL1 and the glucocorticoid induced leucine zipper (GILZ, a glucocorticoid responsive gene) are highly expressed in hippocampal microglia. The expressions of these two genes are positively correlated with circulating corticosterone. Mechanistically, GILZ inhibits nuclear translocation of NF‐κB p65 and functions as an anti‐inflammatory molecule. BMAL1 on the other hand, independent of its circadian partner CLOCK, inhibits the glucocorticoid receptor mediated transactivation of GILZ. Elevated plasma corticosterone and age‐related decrease in BMAL1 are associated with increased activation of NF‐κB p65 and susceptibility to neuropathology. We have observed that the GILZ expression in the hippocampus is inversely related to that of NF‐κB p65 and IBA1 in mouse models of Alzheimer’s disease (AD). Taken together, we hypothesize that the GILZ expression will correlate positively with core clock genes and negatively with markers of gliosis and inflammation in neurodegenerative diseases.

Method

We evaluated the expressions of circadian markers BMAL1 and Period genes (Per1, Per2 and Per3); that of glial cell surface markers Iba1 and GFAP and that of GILZ and NF‐kB as markers of inflammatory system in AD brain tissues by immunohistochemistry and real‐time polymerase chain reaction (RT‐PCR).

Result

GILZ expression was reduced in the hippocampus and pre‐frontal cortex of AD tissues, was inversely related to p65, Iba1 and GFAP expressions and directly related to BMAL1 and Per2.

Conclusion

GILZ could potentially function as a molecular modulator at the intersection of the three systems.
Sustained Effect 1 Month After CSF Tap Test in Normal Pressure Hydrocephalus
Authors: Ryoo Nayoung , Park Young Ho , Han Sang‐Won , Kim SangYun
Published: June 2023

Background

The response to CSF tap test (TT) has been considered an indicator of normal pressure hydrocephalus (NPH) and a predictor of shunt effectiveness. Although the effects of the CSF TT are thought to be transient, the duration of those effects has not been studied in detail.

Method

We performed a retrospective analysis of 32 consecutive patients with NPH who underwent quantitative gait analysis before, immediately after, and 1 month after the CSF TT. Responses to the TT were defined as a 15% or greater improvements in step length or walking speed.

Result

Immediately after the CSF TT, 24 of 32 patients showed a response on step length or walking speed. Among the 24 patients with a response immediately after the TT, a sustained response 1 month after the TT was maintained in 16 patients. Furthermore, among the 8 patients without an immediate response, 5 patients showed a delayed response 1 month after TT.

Conclusion

The effects of the CSF TT on gait parameters were sustained for 1 month in approximately half of the patients with NPH. Decreased tensile strength of the ventricular wall after the TT might explain the sustained effects.
The impact of mental health outcomes on cognition during the COVID‐19 pandemic in older adults with remitted depression, mild cognitive impairment, or normal cognition
Authors: Jassal Simi , Rahmadian Amanda Putri , Kathirkamathamby Sankeetha , Yu Jeffrey , Verhoeff Nicolaas Paul L.G. , Mulsant Benoit H. , Herrmann Nathan , Mah Linda
Published: June 2023

Background

Older adults may be vulnerable to worsening cognition during pandemics because of public health restrictions that increase social isolation and negatively impact mental health. In the current study, we assessed mental health outcomes during the COVID‐19 pandemic and their relationship with cognitive status at 6 months in older adults with remitted major depressive disorder (rMDD), mild cognitive impairment (MCI), or normal cognition (NC).

Method

The sample consisted of 108 older adults enrolled from ongoing studies [37M, mean age = 70.6 (SD = ±5.75)], including 71 NC, 21 rMDD, and 16 MCI]. Participants completed self‐report measures including the Patient Health Questionnaire‐9 to assess depression, Patient Reported Outcomes Measurement Information System to assess anxiety, Perceived Stress Scale to assess general stress, Impact of Events Scale‐Revised to assess post‐traumatic stress, and the Clinical Dementia Rating Scale (CDR) at baseline, 3 and 6 months. Repeated measures ANCOVA of mood and cognitive measures with time as a within‐subject factor and covariates of parent study and mood/memory diagnosis assessed change over time in mental health and cognition. Regression modelling of CDR Sum of Boxes (CDR‐SB) score at 6 months with baseline mood and anxiety scores as predictors and age, gender, parent study, and mood/memory diagnosis as covariates were used to assess the association between mental health and future cognition.

Result

Mood and cognition did not significantly vary over the three time‐points. Depression and general stress at baseline were predictive of CDR‐SB at 6‐month follow‐up, accounting for 14% of its variance (F(6,55) = 2.69, p = .023, B = .28, p = .038; F(6,72) = 3.16, p = .008, B = .21, p = .088, respectively). Neither anxiety nor post‐traumatic stress symptom severity predicted CDR‐SB.

Conclusion

These findings are consistent with epidemiological studies supporting associations between depression or stress and risk of dementia (Byers & Yaffe, 2011; Stuart & Padgett, 2020). Limitations of the study include non‐random sampling and small rMDD and MCI samples. Nevertheless, these preliminary findings suggest the need to address adverse mental health outcomes in seniors during the COVID‐19 pandemic to potentially reduce risk of future cognitive decline.
Traveling waves induced by gamma entrainment can explain its therapeutic effects for Alzheimer’s disease
Authors: Alamalhoda Mohammad Amin , Lahijanian Mojtaba , Aghajan Hamid , Vahabi Zahra
Published: June 2023

Background

Non‐invasive 40Hz sensory‐induced brain entrainment has shown promising results in Alzheimer’s disease (AD) therapy (Chan et al., medRxiv, 2021; Chan et al., Alzheimer’s & Dementia, 2021). We previously reported on the network‐level mechanisms underlying the spatial and temporal coherence of the induced brain rhythms during gamma entrainment in dementia patients (Lahijanian et al., bioRxiv, 2021). Here, we posit that the induced gamma oscillations propagate as traveling waves circling each hemisphere of the cortex, and that the induction of such waves can explain the spatiotemporal coherence between the frontal and parietal/occipital regions reported to be involved in cognitive processes.

Method

EEG data were recorded from two healthy young adults during multi‐trial visual entrainment sessions with 22Hz flickering light. Due to the harmonic property of the brain’s entrained response (Jones et al., Journal of Alzheimer’s Disease, 2019), gamma entrainment was achieved at 44Hz. Separately, EEG data were recorded from 11 dementia patients in multi‐trial auditory entrainment sessions with 40Hz chirp input. The phase of the spatiotemporal pattern at the target gamma frequency was calculated across the entire scalp as an indicator of traveling waves.

Result

Shortly after the stimulation onset in the young healthy adults, a circling traveling wave is observed in each hemisphere (Fig. 1). The onset and the homogeneity of the induced wave pattern is modulated by the power of the 44Hz entrained oscillations (Fig. 2). The dementia patients can be divided into two groups of entrained and non‐entrained according to the induced gamma power (see Lahijanian et al., bioRxiv, 2021), and the travelling wave effect can be occasionally observed during the stimulation in the entrained group and not in the non‐entrained group.

Conclusion

Cortical traveling waves modulate the brain dynamics and play a critical role in functions ranging from sensory processing to memory consolidation (Muller et al., Nature Reviews Neuroscience, 2018). Gamma entrainment induces traveling waves that connect the occipital/parietal regions of the cortex to the frontal region through the temporal region. The traveling wave promotes spatiotemporal coherence across the brain and hence can serve as a network‐level mechanism for explaining the therapeutic effects of gamma entrainment.
MR image harmonization based on cross‐center style transfer using deep generative adversarial network
Authors: Jeong Hyun Jae , Song Young‐Hun , Seong Joon‐Kyung , Noh Young , Seo Sang Won
Published: June 2023

Background

Due to heterogeneities in protocols such as magnetic field strength, coil channels, and scanner manufacturers, data shift problems occur. This causes a serious performance drop in predictions tested to other hospitals. We proposed a multi center‐cross transfer network aimed to adapt institutions with minimal loss of predictions for Alzheimer disease.

Method

Three datasets collected from hospitals with different manufacturers and protocols were included in this study (Table1). We used a deep generative adversarial network (GAN) consisting of 4 models: The generator learns to generate images by inputting a source image and a style code. The style encoder and mapping network extracts the style code of images and transforms into style spaces of multiple domains. The discriminator distinguishes between real and fake images from multiple domains. The integrated model was adjusted while training based on four losses: adversarial loss, cycle‐consistency loss, style‐reconstruction loss, and style‐diversification loss. To resolve the data imbalance problem, 1200 slices were randomly extracted per institution. For validation, we evaluated how well the proposed deep learning model transforms images while maintaining image quality and variation. Next, classification was performed using a convolutional neural network model (Resnet 50) to check how successfully transfers styles of an institution to another one.

Result

We quantitatively evaluated transfering styles between the desired source and reference institution (Figures 1 and 2). Through interpolation and consistency loss coefficient differences, the source to reference transformation process can be checked continuously (Figure3). The proposed model performed well with SSIM of 0.897, LPIPS of 0.862, which are metrics for assessing quality and variation of image transfering model. To predict harmonization ability, we compared classification performance between each pair of datasets before and after style transfering, respectively. The accuracies for each pair shows dramatic decrese in performance of discriminating different centers: ADNI‐SMC (91.20 to 64.35), ADNI‐GMC (96.52 to 66.66) and GMC‐SMC (87.84 to 57.89).

Conclusion

We proposed a multi center‐cross transfer network that freely converts protocol at any desired institution. This work will be able to predict Alzheimer’s biomarkers robustly by harmonizing all data from multiple hospitals, while preserving disease properties encoded in the dataset.
Associations of self‐rated mental and physical work demands with cognition are dependent in a cross‐sectional sample of the Health and Retirement Study
Authors: Hickman Ruby , Bakulski Kelly M , Brandt Daniel , Faul Jessica D , Ware Erin B
Published: June 2023

Background

The number of older adults remaining in the workforce is growing, but little is known about how physical and mental work demands jointly affect cognitive health. This study assessed whether self‐rated physical and mental work demands were associated with cognition among older working adults and whether their associations were dependent.

Methods

Our cross‐sectional sample consisted of 6,376 working older adults in the 2004 wave of the Health and Retirement Study. Self‐rated work demands were summarized from four questions about frequency of mental or physical demands in the respondent’s current job. Cognition was assessed using a subset of the Telephone Interview for Cognitive Status. We used multivariable linear regression to test for associations and additive interaction between physical and mental work demands and cognition, adjusted for age, sex, race, education, and practice effect.

Result

Independently, higher physical work demands were associated (P<0.001) with poorer cognition and higher mental work demands were associated (P<0.001) with better cognition. In an interaction analysis, the effect of one work demand measure became more negative as level of the other increased (B for interaction = ‐0.22, 95% CI: ‐0.42, ‐0.02). A one‐point increase in mental work demands was associated with 0.69 (95% CI: 0.40, 0.99) points higher cognition score when physical work demands were lowest. At the highest level of physical work demands, mental work demands were not associated with cognition (0.11, 95% CI: ‐0.28, 0.49). A one‐point increase in physical work demands was not associated with cognition (0.09, 95% CI: ‐0.30, 0.48) when mental work demands were lowest. At the highest level of mental work demands, physical work demands were associated with ‐0.53 (95% CI: ‐0.78, ‐0.29) points lower cognition score. The highest predicted cognition score was for the highest mental and lowest physical work demands. Results were robust to additional adjustment for health and behavior covariates.

Conclusion

The associations of self‐rated mental and physical work demand with cognition were dependent. Beneficial cognitive effects of mental work demands may not apply to workers with physically demanding jobs. Future studies should strongly consider examining interactions to capture the range of work demand effects.
Head‐to‐Head comparison between Philips Gemini TF64 and Siemens Biograph Vision 600 for brain amyloid Centiloid quantitation
Authors: Li Shenpeng , Bourgeat Pierrick , Bozinovski Svetlana , Huang Kun , Guzman Rodney , Williams Robert , Fripp Jurgen , Villemagne Victor L , Rowe Christopher C. , Dore Vincent
Published: June 2023

Background

The Centiloid (CL) scale calibrates the beta‐amyloid (Aβ) deposition from different PET tracers to a standardised 0‐100 CL unit scale. As imaging sites update their PET cameras, most are switching to digital detector systems with superior resolution and sensitivity that may affect quantitation. This has significant implications for dementia clinical trials. In this study, we examine the impact on CL quantification between Philips Gemini TF64 and Siemens Biograph Vision 600.

Method

Seven subjects (76.4±2.2 yo) were imaged with 18F‐NAV4694 on both Gemini TF64 and Biograph Vision consecutively with an average scan interval of 25.1±11.2 weeks. The injected doses were 200MBq and 100MBq, respectively. On the Gemini TF64, the PET images were reconstructed by LOR‐RAMLA algorithm with smoothing parameter setup as ‘SHARP’. On Biograph Vision, the PET images were reconstructed by OSEM‐3D (8 iterations and 5 subsets, TOF enabled) with 3mm post Gaussian smoothing. A T1 MRI image was acquired for each subject. As per the standard Centiloid method the whole cerebellum was used as the reference in SUVR images, and all images were processed using CapAIBL to calculate the CL using both MR‐based and MR‐Less spatial normalisation.

Result

Figure 1 shows the CL images of a subject scanned on Gemini TF64 and Biograph Vision within sixteen weeks. The Biograph Vision images have higher contrast and higher spatial resolution despite using half of the dose. Figure 2 shows the linear regression plot of the scanner comparison. Biograph Vision CL are progressively higher than those obtained from the Gemini TF64 as the CL value rises (Table 1). There were no significant differences between the MR‐based and MR‐less results.

Conclusion

Biograph Vision yields higher SUVR and therefore CL values compared to Gemini TF64 in a head‐to‐head comparison. These results show that the selection of PET camera has a significant impact on CL quantification, which needs to be considered when merging cohorts from different studies or changing cameras during longitudinal studies or trials. These initial results indicate that the CL difference could be corrected by a linear transform.
Can a family caregiver provide an evidence‐based falls prevention intervention to the person with cognitive impairment or dementia they care for?
Authors: Panzer Victoria , Smith Veronica , Wakefield Dorothy , Maher Joanne , Ham Carolyn Rose , Fortinsky Richard H
Published: June 2023

Background

Falls are a common reason that persons with cognitive impairment or dementia (PwCID) cannot remain at home. FallsTalk is a one‐month evidence‐based falls prevention program that focuses attention on the individual causes of losses of balance or falls. FallsTalk encourages new falls prevention behaviors, which have been shown to decrease falls. We adapted FallsTalk for family Caregiver (FCG) administration to a PwCID with a recent history of falls to determine if FallsTalk‐Caregiver could influence the number of new falls prevention behaviors reported by the FCG or the number of falls.

Method

Thirty‐four Dyads (FCG+PwCID) were trained to conduct brief daily falls prevention discussions together. Dyads were randomly assigned to receive either standardized paper (FallsTalk,n = 14) or computer‐tailored (FallsTalk‐Caregiver,n = 20) discussion suggestions based on prior concerns expressed by the FCG. All Dyads had FallsTalk training, had daily discussions together and received weekly check‐in calls. The FCGs reported weekly on the number of falls and new falls prevention behaviors (#newFPBs); as well as any changes in the PwCID’s health, care or living arrangements during the intervention period. FCGs continued to enter the number of falls and status changes weekly into a secure web‐site using a subject ID, until medical (significant health status change) or residential (no longer living at home permanently) endpoint was reached, or 52 weeks were completed. Poisson regression models compared the number of new falls prevention behaviors and weekly fall rate between groups. Fall rates were annualized for comparison with published residential care fall rates.

Result

Dyads receiving FallsTalk‐Caregiver reported significantly more #newFPBs (MeanPaper = 5.34 (SEM = 0.68, CI = 3.48‐5.93), MeanComputer = 8.46 (SEM = 0.76, CI = 7.48‐10.40); p = .004) during the intervention month. FallsTalk‐Caregiver PwCIDs experienced a significantly lower fall rate (MeanPaper = 0.073/week (SEM = .015, CI = 0.049‐0.109), MeanComputer = 0.040/week (SEM = .008, CI = 0.027‐0.060); p = .047). Annualized fall rates (Falls/year for Dyads with > = 12 weeks) were (MeanPaper = 3.64/year, n = 13; MeanComputer = 2.08/year, n = 19.

Conclusion

FallsTalk‐Caregiver provides an effective means to encourage new falls prevention behaviors to prevent losses of balance and falls. Despite the diversity of the Dyad’s home environment and varied PwCID diagnoses, FCGs matched or bettered the annual fall rates achieved by professional caregivers in skilled nursing facilities (Resident Falls/year = 2.33 (Residents without a PwCID diagnosis); 4.05 (Residents with a PwCID diagnosis).