bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty and mild behavioral impairment: A longitudinal study of pre‐dementia markers
Authors: Isaza Juan C Uribe , Guan Dylan X. , Ismail Zahinoor
Published: December 2023

Background

Frailty and mild behavioral impairment (MBI) are non‐cognitive markers of dementia and have been associated with one another cross‐sectionally. Better understanding the association between frailty, MBI, and dementia is necessary to determine whether dementia prognostication could be improved by assessing for both frailty and MBI. This study investigated the longitudinal associations between frailty, MBI, and incident dementia.

Method

We analyzed data from 20,010 dementia‐free older adults from the National Alzheimer’s Coordinating Center. Frailty was operationalized using a previously published 44‐item frailty index (FI). MBI was derived from the Neuropsychiatric Inventory Questionnaire using a published algorithm; participants were classified as MBI+ if MBI symptoms were present for ≥2 consecutive visits. We used Cox proportional hazards regression to model the association between: (1) baseline FI and incident MBI; (2) baseline MBI and the incident severe frailty (FI≥0.20). We also examined whether MBI+ older adults with higher FI were more likely to develop dementia than those with lower FI. All models were adjusted for age, sex, education, and cognitive status (cognitively normal or mild cognitive impairment).

Result

Participant characteristics are described in Table 1. The hazard of developing MBI rose by 45% for every 0.1 increase in FI (adjusted hazard ratio; aHR = 1.45, 95%CI: 1.36‐1.55, p<.001) [Table 2]. Likewise, the hazard of developing severe frailty (FI≥0.20) was 97% greater in MBI+ participants compared to MBI‐ participants (aHR = 1.97, 95%CI: 1.85‐2.10, p<.001). Finally, although MBI alone was associated with incident dementia (aHR = 2.02, 95%CI:1.89‐2.17, p<.001), the hazard developing dementia further rose by 1.17 (95%CI: 1.08‐1.26, p <.001) for every 0.1 increase in FI within a sample of MBI+ participants.

Conclusion

In dementia‐free older adults, frailty is associated with the development of MBI. Further, MBI is associated with the development of severe frailty. Understanding these relationships identifies the potential to use frailty screening as an indicator of individuals who could develop MBI, and MBI screening as an indicator of individuals at risk of accumulating more health deficits. Although, MBI alone predicts incident dementia, our findings suggest that including general health measures, i.e., frailty, in modeling may improve dementia prognostication.
Blood‐brain barrier neuropathology in individuals with Down syndrome and Alzheimer’s disease
Authors: Aguilar Lisi Flores , Du Annie , Kofler Julia , Ikonomovic Milos D , Lai Florence , Brickman Adam M. , Head Elizabeth ,   Alzheimer’s Biomarker – Down Syndrome Consortium (ABC‐DS)
Published: December 2023

Background

Individuals with Down syndrome (DS) are the largest population at genetic risk of developing early‐onset Alzheimer’s disease (AD). Throughout their lifespan, individuals with DS develop the spectrum of AD neuropathology. By 40 years of age, mature amyloid beta plaques and tau neurofibrillary tangles are present in DS brains, followed by the development of AD dementia. Despite having a low frequency of vascular risk factors (i.e., hypertension, atherosclerosis), individuals with DS display significant cerebrovascular pathology, including cerebral amyloid angiopathy, increased white matter hyperintensities, microbleeds, microinfarcts, and enlarged perivascular spaces. Such pathological changes suggest that the blood‐brain barrier (BBB) undergoes neuropathological alterations and may be associated with the development of AD pathology, in DS. Nevertheless, BBB integrity has not been studied in DS. Our main objective is to investigate BBB pathology in the brains of people with DS and AD (DSAD).

Method

Post‐mortem brain tissue was obtained from the ABC‐DS study, NIH Neurobiobank, and BrightFocus Foundation. BBB components (basement membrane, endothelial cells, pericyte cell number) and BBB leakage were assessed by free‐floating immunohistochemistry in human brain tissue sections from the occipital cortex of individuals with DSAD (49‐55 years old), and their age‐matched neurotypical controls (48‐57 years old). Brain sections were digitized, and BBB components and vessel morphology were quantified using ImageJ.

Result

Our preliminary data suggest that, compared to age‐matched controls, adults with DSAD have a lower number of pericytes and lower Collagen‐IV load. A proportion of DSAD cases also had lower endothelial cell coverage and shorter blood vessels. Moreover, fibrinogen leakage was observed in the brain parenchyma of DSAD brains. Interestingly, some individuals with DSAD displayed no BBB pathological changes.

Conclusion

Individuals with DS have pathological alterations in the BBB. However, some people with DSAD may be resilient to such changes. Studies are ongoing to determine if BBB changes in DS are associated with the development and progression of AD neuropathology.
Dementia awareness, motivation and modifiable risk factors amongst older Australians in regional communities
Authors: Dodds Laura Eliza , Deckers Kay , Siette Joyce
Published: December 2023

Background

Dementia is the second leading cause of death in regional Australia. A large body of research into modifiable dementia risk factors and awareness levels has been gathered with metropolitan communities, yet this remains unexplored within regional areas. Therefore, this study aims to 1) identify awareness of modifiable dementia risk factors; 2) identify the presence/absence of modifiable dementia risk factors; and 3) explore sociodemographic and motivation characteristics associated with modifiable dementia risk in regional areas of Australia

Method

Cross‐sectional data of dementia awareness and risk levels in 180 adults >65 living in rural and remote regions within New South Wales, were collected using an online survey. Data included demographics, awareness of dementia risk factors (British Social Attitudes survey), presence/absence of modifiable dementia risk factors (LIBRA), motivation to reduce dementia risk (MCLHB‐DRR) and social connections (LSNS‐6). Descriptive analyses was used to identify awareness as well as presence/absence of risk factors and univariate associations were used to explore demographic factors and motivation characteristics, associated with dementia awareness and dementia risk.

Result

Participants had a mean age of 72.2 (SD = 5.5) years, majority were female (70%), and had less than 10 years of education (41.1%). 41.7% were from a low socio‐economic background and 97.2% were born in an English‐speaking country. A substantial proportion of participants agreed that dementia risk is modifiable (73.3%) and identified an average of 5.7 (SD = 3.1, out of 12) dementia risk factors correctly. The motivation domain of perceived susceptibility towards dementia was low (11.3 out of 20; SD = 3.4; [4‐20]), and few social connections were reported (8.2; SD = 9.3; [0‐30]).

Conclusion

Rural and remote Australian older adults having a basic understanding that dementia is not inevitable, however, they remain unaware of more than half of the risk and protective factors for dementia. Given the consistencies in dementia risk and the inconsequential association between sociodemographic variables in regional areas, future interventions should adopt a population health approach to improve awareness and create opportunities for communities to target health risk factors contributing to dementia.
3‐month melatonin supplementation to reduce brain oxidative stress and improve sleep in mild cognitive impairment: a randomised controlled feasibility trial
Authors: Schrire Zoe M , Phillips Craig L , Marshall Nathaniel , Mowszowski Loren , Naismith Sharon L , Grunstein Ron , Hoyos Camilla M
Published: December 2023

Background

Melatonin has multiple proposed therapeutic benefits including antioxidant properties, circadian rhythm synchronisation and sleep promotion. Since these areas are also recognised risk factors for dementia, melatonin has been hypothesised to slow cognitive decline in older adults.

Method

Participants with Mild Cognitive Impairment (MCI) were recruited from the community for a 12‐week randomised placebo‐controlled parallel, feasibility trial of 25mg oral melatonin daily. Primary outcomes were feasibility, acceptability, and tolerability. Secondary outcomes were brain oxidative stress, cognition, mood, and sleep at 12 weeks.

Result

Forty participants were randomised to receive melatonin or placebo. Feasibility, determined by the percentage of people who met inclusion and exclusion criteria and could potentially join the study, was 42/389, 11%. The most common reason for exclusion was age. Acceptability, the number of people who agreed to be randomised as a fraction of all potential participants, was 40/42, 95%. Adherence to the intervention and completion of the main secondary outcome (oxidative stress) was over the pre‐defined 80% threshold for all participants and reported safety outcomes were balanced between groups. The current protocol was feasible and acceptable as we reached our target of 40 participants between 60‐80 years of age with MCI. All participants were able to complete all aspects of the trial, including online visits and assessments.

Conclusion

This is promising for future trials which should conduct the study with a higher sample size and longer duration to yield necessary efficacy data.
Title: Barriers and Facilitators for American Indians and Alaska Natives to participate in Alzheimer’s Disease and Related Dementia Research
Authors: Johansson Patriki , Haakenstad Magdalena , London Sara , Mohammed Alaa , Jones Breanna , Buchwald Dedra
Published: December 2023

Background

The US National Plan for Alzheimer’s Disease prioritized the inclusion of health disparities groups in Alzheimer’s Disease and related dementia (ADRD) research in 2012, yet participation of American Indians and Alaska Natives (AI/AN) in ADRD research is significantly lower than the representation of other minorities. Among 47,165 participants in the US National Alzheimer’s Coordinating Center database, only 288 (0.6%) self‐identified as AI/AN. Without the representation of AI/AN people in ADRD research, results from studies may not benefit Tribal communities.

Method

Using community‐based participatory research methods, we conducted a qualitative study that included 6 in‐person and 1 virtual focus groups with 64 urban and rural AI/AN elders. We examined barriers to and promoters of participation in clinical ADRD research. We applied inductive thematic analysis to unpack the meanings of the qualitative data through systematic coding and identification of themes.

Result

The primary factors linked to increasing willingness to participate in ADRD research were awareness of the impact of ADRD in their community; having a family history of ADRD; having research conducted that benefits the community and future generations; and having a positive relationship to allopathic medicine and research. Challenges to research included mistrust of researchers and allopathic practitioners, concerns related to the invasiveness of the tests, cultural restrictions towards biospecimen donation, and lack of awareness and information about ADRD.

Conclusion

Future research efforts seeking to recruit AI/AN participants should consider the need for raising ADRD awareness, community‐based ADRD education, and building trust and long‐term relationships with AI/AN communities.
Machine Learning Approach to Identify Dysregulation in the Plasma Proteome of CADASIL
Authors: Keller Jonah , Fitzsimons Stephen , Park Ryan , Moury Luana , Oh Bradley C , Treiman Scott , Radabaugh Hannah , Ferguson Adam , Elahi Fanny M
Published: December 2023

Background

The plasma proteome provides information to identify dysregulated molecular pathways underlying disease. Cerebrovascular diseases often manifest a significantly different plasma proteomic signature. Cerebral‐Autosomal‐Dominant‐Arteriopathy‐Subcortical‐Infarcts‐and‐Leukoencephalopathy (CADASIL) is one such vascular brain disease. The CADASIL plasma proteome has yet to be investigated.

Method

To investigate the plasma proteome in the context of CADASIL, we used large‐scale proteomics, measuring over 7,000 proteins via aptamer‐based technology (SomaLogic) from 53 study participants (nCADASIL = 25; nControl = 28).

We employed machine learning (ML) methods as an unbiased approach to uncover disease‐associated change in proteomic networks. This approach is based on the premise that protein sets that best classify disease state could be important biological drivers of disease. We developed a novel ML method: coupling recursive feature extraction with logistic regression (LR) and XGBoost evaluators, as well maximum‐relevance‐minimum‐redundancy with Random‐Forest and F‐Statistic evaluators.

The results of all four models were selectively aggregated in order to delineate the CADASIL plasma proteome signature while minimizing overfitting to the low sample size data. We developed a 45 protein model of the CADASIL proteomic signature from these results. To evaluate the classification ability, we tested the Repeated‐Stratified‐10‐fold‐Cross‐Validation accuracy of a LR classifier. Next, we investigated whether the CADASIL proteomic signature was relevant for other neurodegenerative diseases with vascular components; the classifier was applied to an Alzheimer’s Disease (AD) dataset. Finally, the functional signature of the 45 proteins was investigated through gene ontology (GO).

Results

The LR classifier in CADASIL is 99.8% accurate. In AD, the accuracy is 71.2%. This implies the CADASIL signature shares commonalities as well as pertinent differences with other neurodegenerative diseases.

The GO of the 45 proteins resulted in GO terms corresponding to extracellular matrix and collagen, cellular membrane lipoproteins and glycolipids, and proteasome biological pathways.

Conclusion

The proposed method allows for an initial unbiased discovery of important proteomic changes associated with disease state. The identified proteins would provide starting points for mechanistic studies. In addition, a panel of proteins could be used for screening at population level for risk stratification and more in‐depth phenotyping. Next steps include investigating the biological relevance of findings in mechanistic models for therapeutic developments.
Deciphering the molecular signature of selective neuronal vulnerability in the wake‐promoting lateral hypothalamic area in Alzheimer’s disease: A digital multiplexed gene expression study across Braak stages
Authors: Satpati Abhijit , Pereira Felipe Luiz , Soloviev Alexander , Mladinov Mihovil , Leite Renata Elaine Paraizo , Suemoto Claudia Kimie , Rodriguez Roberta Diehl , Paes Vitor Ribeiro , Walsh Christine M , Spina Salvatore , Seeley William W. , Pasquallucci Carlos Augusto , Jacob‐Filho Wilson , Neylan Thomas C. , Grinberg Lea T.
Published: December 2023

Background

Sleep/wake disturbance is a common and debilitating symptom of Alzheimer’s disease (AD) that precedes cognitive loss. The lateral hypothalamic area (LHA) is critical in orchestrating the sleep/wake cycle through the neuropeptide orexin and melanin‐concentrating hormone. We previously demonstrated that LHA neurons accumulate AD‐tau from Braak stage (BB) 0 and losses ∼72% of neurons by BB6. Little is known about the molecular changes underlying LHA vulnerability during AD progression. We investigated RNA expression changes in LHA across Braak stages to close this gap.

Method

We dissected LHA from 30um‐thick sections of the brain from healthy control (HC) and subjects at progressive AD stages and extracted RNA using conventional techniques. We ran RNA transcriptomic assay using customized and neuropathology nCounter® (Nanostring) panels. The Wald statistical test was used to compare the groups, and the genes were considered differentially expressed when log2 fold‐change was > = |1| and the p‐value was <0.05.

Result

We found an upregulation of HCRTR1, LDHC, NKX6, and SLC11A1 from early stages (BB2‐3), whereas HCRTR2 RNA levels remained stable. Circadian gene PER2 was downregulated from the intermediate stages (BB4). Gene Ontology analyses detected dysregulation of neuropeptide‐ligand interaction pathways from early AD. Linoleic acid metabolism, fat digestion and absorption, and immune pathways became dysregulated at intermediate stages, while glycolysis and gluconeogenesis pathways were in late stages (BB5‐6). Of note, it is critical to consider that the massive LHA neuronal loss during AD progression may confound the interpretation of changes in late stages because of the few remaining neurons.

Conclusion

nCounter® is suitable for identifying transcriptome changes in LHA, even at early AD stages. Molecular profiling of LHA across the Braak stage revealed that the earliest changes are associated with an imbalance in neurotransmitter receptors, while the decline in metabolism and increased inflammation marked the intermediate stage. The late‐stage AD is characterized by hypoglycemia and energy deficit. Notably, discrepancies in receptor behavior can inform more effective symptomatic treatment for sleep dysfunction in AD.
Later life Body composition and Alzheimer’s disease
Authors: Canovas Rodrigo , Doecke James D , Huynh Andrew , Fowler Christopher J , Rainey‐Smith Stephanie R , Dore Vincent , Fripp Jurgen , Bourgeat Pierrick , Maruff Paul , Ames David , Rowe Christopher C , Villemagne Victor L , Ellis Kathryn A , Martins Ralph N , Masters Colin L , Yates Paul A
Published: December 2023

Background

Mid‐life obesity is linked with increased risk for late‐life dementia, however relationships between later‐life body composition and dementia are less clear.

Method

Using a combined cohort from two major observational studies (AIBL and ADNI) and categorising Body Mass Index (BMI) according to WHO criteria, we computed multivariable linear mixed‐effects models to determine association between BMI category and outcomes: brain beta‐amyloid PET quantification (centiloid); MRI (global, hippocampal and white matter hyperintensity volume); and cognition (PACC [preclinical Alzheimer cognitive composite], composite scores for attention, executive function and episodic memory). All models were adjusted by covariables age, gender, education, APOE ε4, and study (AIBL/ADNI).

Results

The cohort included 4,668 observations from 2,828 individuals (49.4% male, mean age 73.8 years, 38.2% APOE ε4 carriage, 61.8% normal cognition [NC], 25.6% Mild Cognitive Impairment [MCI], 12.6% dementia due to Alzheimer’s disease). The average BMI was 26.8 kg/m2 (0.6% underweight, 37.7% normal‐range, 41.7% overweight, 20.0% obese [BMI <18, 18‐25, 25‐30 and >30 kg/m2, respectively]).

Relative to normal‐range BMI, those with overweight‐or‐obese range BMI had a significant negative association with PET centiloid level, beta = ‐0.150 (0.037 se) and ‐0.309 (0.042), respectively (i.e. greater BMI had lower amyloid level). This remained significant for obese‐range BMI in fully‐adjusted models when restricted to only NC participants. Also, obesity was associated with greater hippocampal volume, beta = 0.192 (0.046), but this was not significant when restricted to NC only. Associations with total grey matter/cortical volume and white matter hyperintensities were not significant. Obese‐range BMI was associated with stronger performance on attention and episodic memory composites, but not for PACC and executive function. For NC‐only, there was only significant negative association between obesity and attention performance. In multivariate analyses, neither obesity category nor BMI were associated with longitudinal change in cognitive scores.

Conclusion

Presence of obesity in later life was associated with lower brain amyloid levels and less hippocampal atrophy in a mixed cohort including older adults with dementia, mild cognitive impairment and normal cognition. While mid‐life obesity is associated greater risk for AD, later life associations appear influenced by weight loss with emerging dementia.
Associations between neuropsychiatric symptoms, pathology in neuropathological cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies
Authors: Tremblay Cécilia , Shakir Neha , Zhang Nan , Adler Charles , Belden Christine , Mehta Shyamal , Shill Holly , Driver‐Dunckley Erika , Beach Thomas G , Serrano Geidy E , Atri Alireza , Choudhury Parichita
Published: December 2023

Background

Neuropsychiatric symptoms (NPS) are frequent in Alzheimer’s Disease dementia (ADD) but a higher NPS burden is found in dementia with Lewy bodies (DLB). Lewy body (LB) pathology frequently co‐occurs with AD pathology and may not meet neuropathological criteria for DLB (ADLB). Previous studies have shown that both ADLB and DLB cases have faster cognitive and/or functional decline compared to AD. However, the differences in NPS severity over disease course and survival in these pathologic subgroups is not well understood.

Method

Cases from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with a final neuropathologic diagnosis of DLB (±AD co‐pathology; n = 65), ADLB (n = 89), AD (without LB) (n = 140), and controls (no neuropathological diagnosis) (n = 82) were included. Total NPI‐Q (scores ranging from 0‐36) at time of enrollment and within 2.5 years of death were calculated for all groups. Statistical analysis utilizing ANCOVA (adjusting for age, sex, baseline MMSE and cognitive symptom duration) with pairwise comparisons, and Kaplan‐Meier curves were completed.

Result

Age at onset of cognitive symptoms was not different between pathology groups. NPI‐Q scores at enrollment were highest in ADLB (7.33 ± 4.85), and higher (p<0.001) than DLB (5.10 ± 3.37), AD (4.54 ± 3.63) and controls (1.78 ± 1.70). At final evaluation, NPI‐Q scores were highest in DLB (10.04 ± 6.28), followed by ADLB (8.0 ± 4.), and ADD (7.61 ± 5.05) when compared to controls (2.78 ± 3.97) (all p<0.001). DLB and AD demonstrated significant increases in NPI‐Q severity during follow up (p < 0.001). AD had longer survival time (5.8 years) compared to ADLB (4.0 years) and DLB (3.9 years). Subjects with NPS had a shorter median survival time (3.4 years) compared to subjects without NPS (6.5 years; p = 0.002).

Conclusion

A higher NPS burden and shorter survival is seen in both DLB and ADLB, as compared with AD. This suggests that diffuse neocortical LB pathology is not the major driver of either NPS or survival.
Evaluating the therapeutic efficacy of phytochemicals in ameliorating cytotoxic effects of amyloid beta
Authors: Chakraborty Manas , Dhiman Kunal , Gupta Veer
Published: December 2023

Background

There is lack of reliable treatment approaches to combat early cognitive impairment, as well as Alzheimer’s disease (AD). Since AD is a multifactorial disease, therapeutic approaches must be targeted on disease specific multiple‐biochemical pathways. There is a need to explore and test alternative disease modifiers which can target multiple metabolic pathways i.e., phytochemicals to combat such perturbations. This project will identify bioenergetic and viability changes that occur in response to amyloid pathology in cell models. Further, the therapeutic potential of a set of phytochemicals (safranal, berberine, taxifolin, bilobalide and vinpocetine) will be evaluated in mitigating such changes.

Method

Neuroblastoma cell lines SH‐SY5Y cells and BE (2)‐M17 have been used to model AD in vitro. They were differentiated into mature human neurons using 10 µM retinoic acid. Amyloid beta 1‐42 (Ab42) is being used to induce neurotoxicity in the cells, which will be followed by treatment with phytochemicals. MTT (3‐(4, 5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide) assay and flow cytometry will be used to evaluate cell viability, followed by sea horse assay to evaluate the oxygen consumption rate. Confocal microscopy will be used to confirm the images of amyloidosis and will be compared with the phytochemically treated group and the control group. Western blotting will be used to study the targeted pathways and proteins.

Result

Differentiation of the cells have been successfully accomplished and confirmed through morphological changes in the cells. Treatment with Ab42 is currently under progress, which will be followed by treatment with phytochemicals. The protective effect of the phytochemicals will be evaluated through MTT, and sea horse assays and pathways will be studied using western blotting.

Conclusion

This project will help to evaluate the therapeutic potential of selected phytochemicals, and thereby help to inform future pre‐clinical and clinical studies.
Human nasal beta‐amyloid 42 has a diagnostic value in discriminating Alzheimer’s disease
Authors: Jung Da Hae , Son Gowoon , Wang Shengmin , Lim Hyun Kook , Moon Cheil
Published: December 2023

Background

The key in Alzheimer’s disease (AD) therapy is a timely and accurate diagnosis for prompt drug intervention. However, due to the high cost and invasiveness of conventional biomarker analyses, including brain positron emission tomography (PET) imaging and cerebrospinal fluid (CSF)‐based assays, easy accessibility to these screening tests is often hindered. There is, therefore, a great need to develop a more accessible biomarker screening test using less invasive and cost‐effective peripheral body fluid biomarkers. Previous studies examined the non‐quantitative expression of beta‐amyloid (Aβ) in normal and AD patients' nasal discharge fluid. They identified higher expression of oligomeric Aβ in AD patients, showing a correlation with cognitive decline. However, the quantitative measurements of nasal Aβ42 levels, including the full AD continuum, remain unknown. Here, we assessed whether quantified human nasal Aβ42 levels have diagnostic performance and have the potential to be utilized as a biological risk factor in AD.

Method

161 subjects (cognitively normal (CN), n = 32; preclinical, n = 29; mild cognitive impairment (MCI), n = 73; AD, n = 27) underwent neuropsychological battery tests, including Mini‐Mental State Examination (MMSE), Clinical Dementia Rate (CDR), and Global Deterioration Scale (GDS), and amyloid‐PET scans (18F‐Flutemetamol). Their nasal discharge samples were collected, and nasal Aβ42 levels were measured via enzyme‐linked immunosorbent assay (ELISA).

Result

We found that the second‐highest quartile (Q3) group of nasal Aβ42 constituted the majority of patients with AD diagnosis (p = 0.036). The Q3 group also outnumbered the other groups in the most cognitively impaired subjects in all three neuropsychological battery tests (p = 0.008, p = 0.037, p = 0.023). Next we also found that subjects in the Q3 group exhibited most impaired cognitive function in all three neuropsychological battery tests with strong significance. When we examined the amyloid‐PET SUVR values, subjects with PET positive showed the highest SUVR.

Conclusion

Quantified nasal Aβ42 is strongly associated with cognition measurements. Nasal Aβ42 suggests the possibility for discriminating AD from non‐AD.
Assessment of racial/ethnic representation in Alzheimer’s disease genetics datasets
Authors: Xue Diane , Fohner Alison E
Published: December 2023

Background

Biased representation of populations in genetic research leads to disparities in genetics knowledge and utility. Here, we compare the racial/ethnic demographics of all participants in nationally funded Alzheimer’s disease (AD) genetics cohorts to demographics of US AD mortality.

Methods

We used death certificate data from the CDC Wide‐ranging Online Data for Epidemiologic Research (WONDER) Database to calculate age‐adjusted AD mortality of adults aged 65 years and older for 2016‐2020. We compared the racial/ethnic distributions in mortality to the racial/ethnic distribution of AD genetics participants across 16 studies in the National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) that met the following filters: Disease = `AD`; Molecular Data = `Genotype`; and Type = `GWAS` as well as five studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Demographic data was obtained directly from data or via literature review. In addition to the GWAS data, we also compared racial demographic data from sequencing studies released as part of the Alzheimer’s Disease Sequencing Project (ADSP) Umbrella (dssNIAGADS NG00067).

Results

Table 1 describes the racial/ethnic distribution of the age‐adjusted AD mortality rate of the US population from 2016‐2020. Non‐Hispanic Whites had the highest rate (per 100,000 person‐years): 254.2 (95% CI 253.5‐254.9), and Asian or Pacific Islander (AS/PI) had the lowest rate: 125.6 (123.6‐127.71). The racial/ethnic distribution of the 13,909 AD cases across 21 genotype datasets available in NIAGADS or CHARGE are presented in Table 1. Most (87.6%) of AD cases are non‐Hispanic White, with the least (0.25%) being AS/PI. Preliminary analysis of ADSP data show increased proportions of Hispanic and Black participants (Table 1).

Conclusion

The racial/ethnic distribution of AD genetics participants is representative of proportion of deaths, but after adjusting for age and population distribution, AS/PI have 50% lower mortality rate compared to non‐Hispanic Whites while comprising less than 5% of participants in genetics cohorts. While progress is being made to diversify sequencing data, AS/PI and American Indian or Alaska Natives remain underrepresented in AD genetics research, which may lead to inequitable benefits from future research and pharmaceutical treatments.
Assessment of Lifecourse Social Exposome in Brain Bank Decedents
Authors: Keller Sarah A , Powell W. Ryan , Buckingham William R. , Boone Brittney Lyons , DeWitt Amanda , Kramer Joseph A , Bendlin Barbara B , Kind Amy J.
Published: December 2023

Background

There is increasing evidence that the social exposome impacts the development of Alzheimer’s disease and related dementias (ADRD). The social exposome includes factors such as neighborhood disadvantage, and is thought to impact brain health across the lifecourse, particularly during sensitive life stages such as early childhood. Residential histories are required to assess dosage and timing of exposures, yet are rarely categorized and linked to brain bank cohorts. Our objective was to characterize the lifecourse neighborhood disadvantage across two Alzheimer’s Disease Research Center (ADRC) brain banks.

Method

After abstracting publicly available residential data, we constructed residential histories using validated metrics of neighborhood disadvantage, nationwide Area Deprivation percentile rankings (ADI), constructed for each census timeframe from 1910‐present, to measure lifecourse social exposome time‐concordantly aligned to participant life‐year. ADIs were linked for all available years between birth and death, ranging from age 0 to 103. Greater ADI values denote living in higher neighborhood disadvantage. These ADIs were linked to the residential histories for each decedent and used to calculate two sensitive life stages: ages 0‐19 and 40‐60. A repeated measures one‐way ANOVA determined variance in ADI both within and between these sensitive life stages.

Result

This sample contained 1309 decedents from two brain. To date, 1230 decedents have been linked to at least one ADI timepoint, with an average of 81% (71‐88%) of all life‐course years accounted for via ADI linkage. The mean ADI for the 0‐19 period was 23.5 (SD = 22.3, 5.0‐36.9), while the 40‐60 period was 22.0 (21.6, 5.0‐34.0). A repeated measures one‐way ANOVA found a statistically significant difference in ADI between the two windows of time.

Conclusion

Tissue banked samples are not typically characterized on social determinants of health. Here we show that determining lifecourse social exposomes are feasible using publicly available data. To our knowledge, this is the first time such characterization has been successfully performed. Efforts to link decedents to ADI timepoints are still ongoing, which will reduce missingness, enhance measurement precision, and allow for comparison between all life stages. This work provides a unique methodology for assessing the social exposome in relation to ADRD brain pathology.
Influence of education level on domain‐specific MOCA performance in the MarkVCID cohort
Authors: Thirion Marissa L. , Chatterjee Ankita , Klomhaus Alexandra , Tibbe Tristan , Vossel Keith , Kramer Joel H. , Hinman Jason
Published: December 2023

Background

Education level is a well‐recognized co‐factor for cognitive performance and a potential confounder in the application of cognitive evaluations in diverse populations. The Montreal Cognitive Assessment (MoCA) is a widely utilized screening tool for Mild Cognitive Impairment (MCI) composed of 6 domains of cognition: Executive Function (EFC), Attention and Concentration (AC), Language (LANG), Visuospatial (VIS), Memory (MEM), and Orientation (ORIEN). Education is currently accounted for globally by adding 1 point to the total MoCA score. This study considers the impact of education level on a domain‐specific scoring of the MoCA.

Method

We utilized longitudinal subject level data from one site within the MarkVCID Consortium (UCSF) composed of 578 subjects (59.5% female; 82.9% white), mean age 71.5 (+/‐ 8.7). Mean educational level was 15.3 (+/‐4.7) years. Within the cohort, 37 subjects lacked educational level and were omitted (final n = 541). Multivariate linear regression models were used to relate educational level with total and domain specific MoCA score performance at baseline while controlling for the influence of age, sex, and recognized MarkVCID biomarkers that impact cognitive performance including white matter hyperintensity (logWMH), fractional anisotropy (FA), free water (FW), and peak width of skeletonized mean diffusivity (PSMD).

Results

An age‐, sex‐adjusted model replicated a significant association of education level with MoCA total score (p<0.001, b = .336). Among the MoCA domains, EFC was most affected by education level (p<.001, b = .412), followed by AC (p<.001, b = .352). Other MoCA domains were not significantly associated with educational level. Several MoCA domains, namely MEM and ORIEN, showed an association with MarkVCID biomarkers including WMH and FW (p‐values <.001). In regression models controlled for MarkVCID imaging biomarkers, educational level remained significantly associated with total and domain‐specific MoCA performance.

Conclusion

Education does not equally contribute to all cognitive domains assessed by the MoCA, mostly affecting EFC and AC. These findings suggest that considering education level in a domain‐specific manner could provide a more accurate interpretation of the cognitive impairment.
Identifying frailty‐related clusters of Alzheimer’s and Vascular dementia: A multi‐modal data approach
Authors: Quach Jack , Nar Aditya , Maxwell Selena P , Motaghi Mahboubeh , Rockwood Kenneth , Duchesne Simon , Theou Olga
Published: December 2023

Background

The proportion of people living with dementia (PLWD) is increasing due to aging global populations. Frailty is a complex, multifactorial, and age‐related state of increased vulnerability commonly co‐occurring with Alzheimer’s disease (AD) and vascular dementia (VaD). Variability in frailty levels of PLWD motivates deeper investigation into dementia’s presenting characteristics. Machine learning techniques applied to large medical datasets can identify characterize disease phenotypes. Therefore, the aim of this study is to use unsupervised machine learning to discover frailty‐related clusters in AD and VaD.

Method

We will use data from the United Kingdom Biobank (UKBB), a large‐scale prospective cohort database which includes more than 500,000 participants aged 40‐69 years at baseline. The data include electronic health records, brain magnetic resonance imaging, polygenic risk scores, and frailty index scores. We will select features for clustering using principal component analysis. Clustering algorithms will include k‐means, affinity propagation, and latent class analysis. After cluster characterization, we will evaluate the association between clusters and prevalent AD (n = 2,634) and VaD (n = 1,664) using logistic regression models. Regression models will be stratified by sex and adjusted for age. Receiver‐operating curve will be plotted, and area‐under the curve will be compared using C‐statistics. This study is supported by the Canadian Consortium on Neurodegeneration in Aging Trainee Synapse Project Funds. Our data application has been approved by UKBB.

Result

We expect that the clustering algorithms will reveal several clusters of similar PLWD and allow evaluations based on shared patterns of regional brain atrophy, the degree of frailty, and polygenic risk. In addition, we also expect that clusters characterized by high frailty levels will be associated with prevalent AD and VaD.

Conclusion

Frailty is an important factor in the clinical evaluation of PLWD. The use of unsupervised machine learning techniques may reveal distinct high‐risk clusters that are related to prevalent AD and VaD. This work may improve early identification of PLWD and aid in the development of personalized care and therapy for people at risk of AD and VaD.
A Comparison of the Prevalence of Diabetes between Aging Rural and Urban Indians.
Authors: PANDEY SHRUTI , Lingegodwa Abhishek Mensegere , Malo Palash Kumar , Hameed Shafeeq K Shahul , Issac Thomas Gregor , Sundarakumar Jonas S.
Published: December 2023

Background

Diabetes is one of the important modifiable risk factors for dementia. Its prevalence has been increasing rapidly in the past few decades across the world, particularly in India. However, among Indians, there are prominent lifestyle differences between rural and urban residents. Hence, understanding diabetes prevalence in these two distinct populations is essential to understand the differential risk for dementia in rural and urban Indians.

Method

Cross‐sectional (baseline) clinical data from two ongoing prospective cohort studies, namely Srinivaspura Aging, Neuro Senescence and Cognition (SANSCOG) study in rural India and Tata Longitudinal Study of Aging (TLSA) in urban India was utilized for the present study. A total of 6002 participants – 4913 rural (SANSCOG) and 1089 urban (TLSA) were included. Diagnosis of diabetes was made using self‐reported history and / or fasting blood glucose level of > 126 mg/dl. Chi‐square test of independence was used to assess the group differences between the rural and urban participants – both overall and gender‐wise and age group‐wise.

Result

The mean age of participants was 63.93 ± 9.56 years and 58.74 ± 9.88 years for the urban and rural cohorts, respectively. Prevalence of diabetes was significantly higher in urban than rural subjects – overall (33.6% vs. 19.3%, p<0.001) as well as among males (38.4% vs. 24.1%, p<0.001) and females (28.7% vs. 14.8%, p<0.001). Similarly, on age stratification, urban subjects had significantly higher prevalence than rural subjects in the age groups <65 years (28.1% vs. 18.3%, p<0.001) and ≥65 years (39.5%vs. 21.3%, p<0.001).

Conclusion

Urban subjects had significantly higher diabetes prevalence than rural subjects across both genders and age groups. In view of the association of diabetes with dementia risk, these findings could imply that urban Indians may be at higher risk for pathological cognitive impairment and dementia as compared to their rural counterparts. However, longitudinal follow of these participants with cognitive monitoring is required to establish a causal association.
Memory Concerns and Cognitive Change in a Diverse Cohort of Oldest Old Individuals: LifeAfter90 Study
Authors: Chen Nancy X , Corrada María M. M. , Kawas Claudia H. , George Kristen M , Lor Yi , Glymour M. Maria , Gilsanz Paola , Farias Sarah Tomaszewski , Mayeda Elizabeth Rose , Gradwohl Natalie M , Peterson Rachel , Whitmer Rachel A.
Published: December 2023

Background

Whether subjective evaluations of cognition can accurately predict cognitive decline is not well understood in ethnically diverse populations nor oldest‐old. In a multi‐ethnic cohort of adults aged 90+, we aim to investigate the association between self‐perceived memory concerns and objectively measured cognitive change.

Method

LifeAfter90 is an active longitudinal cohort study of Kaiser Permanente Northern California members ages 90+ with no prior dementia diagnosis. Verbal episodic memory (VEM) and executive function (EF) were assessed every 6 months between July 2018 and March 2022 using the Spanish and English Neuropsychological Assessment Scales (SENAS). At baseline, participants answered the question “Are you concerned that you have a memory or other thinking problem?” We evaluated associations between memory concerns and domain‐specific cognition at baseline and over time using linear mixed models with random intercepts and slopes, adjusted for baseline age, sex, race/ethnicity, education, interview mode (in‐person or phone), and practice effects. Sensitivity analyses stratified by 1) gender and 2) age (+/‐ 95 years).

Result

At baseline, participants (n = 975) had a mean age of 92.4 (SD = 2.3) years, 61% were women, 73% were racial/ethnic minorities, and 36% reported memory concerns (Table 1). Memory concerns were associated with worse baseline VEM (b = ‐0.17, 95% CI ‐0.27,‐0.07; Table 2) and EF (b = ‐0.08, 95% CI ‐0.15,‐0.01; Table 3), but not associated with rate of change for either domain. When stratified by gender, both men and women with memory concerns had worse baseline VEM (b = ‐0.21, 95% CI ‐0.36,‐0.06 and b = ‐0.15, 95% CI ‐0.27,‐0.02, respectively; Table 2). Additionally, men with memory concerns had worse baseline EF (b = ‐0.19; 95% CI ‐0.30,‐0.08; Table 3). Among participants younger than 95 years, memory concerns were associated with worse baseline VEM (b = ‐0.15, 95% CI ‐0.25,‐0.04; Table 2) and EF (b = ‐0.10, 95% CI ‐0.17,‐0.02; Table 3).

Conclusion

In this diverse cohort of oldest‐old, those with subjective memory concerns had worse baseline VEM and EF. Although memory concern may suggest objective cognitive impairment, it is not associated with decline over the short term; (an average follow up time of 1.05 years). Additional follow up will identify how changes in memory concerns may be associated with cognitive change.
Correlation between cognitive status of patients and score of Story Memory test
Authors: Lee Yunji , Kim Hyunsook
Published: December 2023

Background

Dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) are referred to a continuum of cognitive impairment. But it is difficult to distinguished in clinical practice. Recently, the Korean version of Story Memory (SM) in the Korean‐Mini Mental State Examination, 2nd Edition: Expanded Version (K‐MMSE‐2: EV) was released to use. Thus, we aimed to find the correlation between cognitive status and score of SM test.

Method

Twenty‐three patients with SCD, MCI, or mild dementia between ages of 60 and 80 were participated. They underwent K‐MMSE‐2, and Seoul Neuropsychological Screening Battery‐Second Edition (SNSB‐II). The correlation between score of standard version K‐MMSE‐2(T‐score) and SM score were analyzed. To identify the related functional brain area, analysis was performed with each domain in SNSB‐2 and SM scores.

Result

SM score was associated with scores of standard version of K‐MMSE‐2(p = 0.013, Pearson correlation = 0.511). Also, the SM score have significant correlation with memory domain score of SNSB‐2(p = 0.048, Pearson correlation = 0.447).

Conclusion

We found that patients' cognitive function and SM score have a positive relationship. It might be used to identify patients who might have progressed to Dementia or are about to progress. Also, MCI patients can be identified in early.
Exploring acceptance of monitoring technology in home‐based dementia care: A survey study among informal carers
Authors: Wrede Christian , Braakman‐Jansen Annemarie , van Gemert‐Pijnen Lisette
Published: December 2023

Background

There is growing interest to support home‐based dementia care via contactless monitoring technologies which do not require any body contact and allow informal carers to remotely monitor health and safety of people with dementia (PwD). However, sustainable implementation of such technologies requires a better understanding of informal carers’ acceptance. This study therefore aimed to explore 1) acceptance towards different use scenarios, 2) acceptance towards different contactless sensor types, and 3) differences between accepters and refusers of contactless monitoring technology for home‐based dementia care.

Method

A cross‐sectional online survey was conducted among n = 304 informal carers of community‐dwelling PwD (Mage = 58.5±10.7; 71% female) in the Netherlands and Germany. Questions targeted informal carers’ general acceptance towards contactless monitoring technology, their acceptance towards 5 different use scenarios, their acceptance towards 7 different contactless sensor types, as well as their own and their care recipient’s personal characteristics. Data were examined using descriptive and bivariate analyses.

Result

Acceptance towards different use scenarios for contactless monitoring technology varied significantly (p<.001). The intention to use contactless monitoring technology was highest for detecting emergency situations (e.g., falls, wandering), and lowest for predicting acute situations (e.g., fall prediction). Acceptance towards different contactless sensor types varied significantly as well (p<.001). RF‐based sensors (e.g radar) and light sensors were considered most acceptable, whereas camera‐based sensors and audio sensors were seen as least acceptable for home‐based dementia care. Lastly, accepters and refusers of contactless monitoring technology significantly differed regarding gender (p = .010), their relation with the PwD (p = .003), eHealth literacy (p = .025), personal innovativeness (p<.001), experience with safety technology (GPS trackers, alarm buttons) (p = .002), and the PwD’s type of cognitive impairment (p = .035) and housing situation (p = .023).

Conclusion

Our findings can help to make better‐informed decisions during development and implementation of contactless monitoring technology to support home‐based dementia care, thereby increasing the chance of achieving a fit between technology, user, and use context.