bluuebunny/crossref_metadata_2025 huggingface dataset:
Alzheimer’s Disease and related dementias prevalence higher in Appalachian counties within Central Appalachia
Authors: Wing Jeffrey , Rajczyk Jenna , Burke James
Published: January 2025

Background

Alzheimer’s disease and related dementias (ADRD) prevalence varies geographically in the US. The Appalachian region has lower educational attainment and health care access barriers compared to non‐Appalachian regions. The objective of this proposal is to assess whether the geographic variation of ADRD in Central Appalachia is explained by county‐level sociodemographic factors or access to care.

Methods

Centers for Medicare and Medicaid Services Public Use Files from 2015‐2018 were used to estimate county‐level ADRD prevalence among all fee‐for‐service beneficiaries in Central Appalachia (Kentucky, North Carolina, Ohio, Tennessee, Virginia, and West Virginia). Negative binomial regression was used to estimate prevalence overall, by Appalachian Regional Commission’s Appalachian/non‐Appalachian designation, and by rural/urban (Rural‐Urban Continuum Codes) classification. Models were then adjusted for: (1) county‐level demographics including age, gender, Medicaid eligibility, and comorbidities (atrial fibrillation, chronic kidney disease, depression, diabetes, heart failure, hyperlipidemia, hypertension, ischemic heart disease, schizophrenia/other psychotic disorders, and stroke); (2) sociodemographics (race/ethnic distribution, education, aging population distribution, and renter‐occupied housing); and (3) diagnostic access (PCP visits, neurology visits, and imaging scans).

Results

A total of 592 counties comprise the Central Appalachian region where 43% (n = 255) are Appalachian and 45% (n = 267) are rural counties. The prevalence of ADRD did not vary over the time period but was higher for Appalachian counties both overall (PR: 1.03; 95% CI: 1.02, 1.04) and after adjustment (PR: 1.02; 95% CI: 1.00, 1.03) compared to non‐Appalachian counties. This difference was similar among rural and urban counties (p = 0.326). These differences did vary across the states in the region (p = 0.0040). In North Carolina and Tennessee, Appalachian counties had higher ADRD prevalence, while in Ohio and Tennessee, rural counties have lower ADRD prevalence.

Conclusion

There is a consistent difference between Appalachian and non‐Appalachian counties, with Appalachian counties having relatively higher ADRD prevalence (in the range of 2.0‐3.0% times higher) than non‐Appalachian counties. These differences persisted even after considering age, education, other sociodemographic factors and access to care measures.
Characterizing Disease Modifying Effects Using Overall Treatment Effect Across all Post‐Baseline Visits
Authors: O'Gorman John , Chen Tianle , Wang Guoqiao
Published: January 2025

Background

The well‐accepted statistical efficacy inference approach for Alzheimer’s disease (AD) clinical trials compares the absolute difference in change from baseline at the last study visit using MMRM (henceforth referred to as MMRM‐Last‐Visit). Recent AD clinical trials have shown that treatment effects may be manifested prior to 18 months. The objective is to evaluate models estimating an overall treatment effect across all post‐baseline visits that may characterize disease modifying effects in contemporary early AD clinical trials.

Method

We will evaluate the performance of: (1) MMRM‐Last‐Visit, (2) MMRM‐All‐Visits, estimating an overall treatment effect across all post‐baseline visits, (3) Linear mixed effects (LME) model with time being continuous, comparing the slopes across treatment groups, (4) Constrained LME, comparing the slopes which constraining the treatment groups to have the same mean baseline, (5) Longitudinal data analysis model with natural cubic spline in time (LDA‐NCS), modeling the raw data and comparing the absolute difference in change from baseline at the last visit (LDA‐NCS ‐Last‐Visit), (6) Constrained LDA‐NCS, similar to LDA‐NCS while constraining treatment groups to have the same mean baseline, and (7) proportional/percentage MMRM (pMMRM), which models the percentage reduction across all post‐baseline visits. Simulated data mimicking disease modifying effect in contemporary early AD trials were used for the evaluation. Subsequently, we evaluate the performance using bootstrapping techniques.

Result

We will present simulation results that mimic a range of assumptions from contemporary early AD trials, including sample size, power, and type I error results.

Conclusion

Models estimating an overall treatment effect across all post‐baseline visits have shown promise in characterizing disease modifying effects seen in contemporary early AD clinical trials and may help accelerating drug development.

This study was funded by Biogen, JO and TC are employees and shareholders of BIogen.
Priorities to Support Care Partners of People Living with Dementia: Results of a Modified Delphi Process
Authors: Dawson Walter D , Gelmon Sherril B , Reed Jenn Hollandsworth
Published: January 2025

Background

Alzheimer’s disease and related dementias (ADRD) place substantial burdens on care partners. The need to better support ADRD care partners through policy actions is high, specifically to enhance existing services and reduce inequities experienced by historically underserved communities.

Method

Between July and September 2023, a modified Delphi process was employed to determine policy and program priorities for supporting Oregon‐based care partners. Representatives of organizations serving people living with ADRD and their care partners, as well as organizations serving selected historically and currently underrepresented communities, were invited to participate (N = 40). Prospective participants created and categorized a preliminary list of ideas during an initial meeting. The eight thematic categories (Care Partner Supports, Programs/Services, Information Resources, Care Coordination, Data Systems/Technology, Policy, Funding/Financing, and Professional Education/Workforce Development) framed the three surveys for the Delphi process. In survey 1, respondents received the list of ideas and were invited to generate up to five additional priority ideas per category. In survey 2, participants reviewed the revised list and rated each idea on a five‐point scale of importance. In survey 3, participants were presented with the mean importance score for each idea and then indicated five top priorities for each thematic category.

Result

The 15 ideas with the highest weighted scores were each endorsed by at least 60% of survey 3 respondents, and were arrayed across six of the thematic areas: Care Partner Supports = 4, Programs/Services = 3, Funding/Financing = 3, Information Resources = 2, Care Coordination = 2, and Professional Education/Workforce Development = 1.

Conclusion

The use of the Delphi process facilitated input from individuals with different perspectives, and gave all participants’ contributions equal weight, achieving a balance of power and minimization of bias that might not have occurred through methods such as in‐person discussion and debate. This process identified specific and actionable priorities to better support Oregon care partners through program development and policy action, and may have applicability elsewhere.
Food insecurity and dementia risk in US older adults: results from the Panel Study of Income Dynamics
Authors: Leung Cindy W , Insolera Noura E , Wolfson Julia A , McEvoy Claire T , Ryan Lindsay H , Friedman Esther M , Langa Kenneth M , Heeringa Steven G , Hao Wei
Published: January 2025

Background

Growing research suggests that food insecurity is associated with worse cognitive functioning; however, longitudinal studies are needed to examine food insecurity and dementia risk.

Methods

Using data from the 2013‐2021 Panel Study of Income Dynamics, the longest running nationally representative household panel survey, we examined the effects of food insecurity on dementia risk among 3,232 adults (≥65 years). Food insecurity was assessed biennially using the US Household Food Security Survey Module since 2015. Dementia risk was assessed bienially using the Eight Item Interview to Differentiate Aging and Dementia (AD8) since 2017. We used inverse probability weighting and marginal structural models to account for the time‐varying nature of food insecurity and sociodemographic and health confounders.

Results

In the sample of US households with older adults (mean age (SE), 69.7 (0.2) years, 57% female), the weighted prevalence of food insecurity ranged from 5.3‐7.0% and the weighted prevalence of dementia risk ranged from 20.7‐21.8%. After accounting for baseline and time‐varying confounders, there was a two‐fold association between food insecurity and dementia risk (OR 2.11, 95% CI 1.12, 3.98). In sensitivity analyses, results were similar when expanding the exposure definition to include milder forms of food insecurity, and the outcome definition to include informant‐reported memory loss. Associations were not further modified by sex, race and ethnicity, or household participation in the Supplemental Nutrition Assistance Program.

Conclusions

Food insecurity is a modifiable social determinant of health. Interventions and policies are needed to reduce food insecurity and promote healthy aging for older adults
Loneliness During COVID‐19: An Overlooked Risk Factor for Post‐Pandemic Cognitive Decline in Older Adults
Authors: Harb Alaa , da Silva Fernanda Carini , de Jesus Maria Clara Ferreira , Willey Grace , Souza‐Talarico Juliana Nery
Published: January 2025

Background

The COVID‐19 pandemic led to widespread social isolation and loneliness, especially among older adults aged 60 years and above. Loneliness is increasingly recognized as a significant public health concern given its association with adverse physical and mental health outcomes. However, less is known about the potential impact of loneliness on cognitive health and decline in older adults during the COVID‐19 pandemic specifically.

Methods

A systematic review was conducted to examine the evidence on the relationship between loneliness and cognitive decline in older adults during the COVID‐19 pandemic. A comprehensive search was performed in MEDLINE (PubMed), CINAHL (EBSCO), PsycINFO (EBSCO), EMBASE, Scopus, AgeLine, and ProQuest for relevant studies published after January 2020 using PRISMA guidelines. Additional manual searches supplemented the database search. Inclusion criteria were studies with validated measurements of both cognitive function and COVID‐19 pandemic exposure in adults aged 60 years and older. Four paired reviewers independently assessed the identified studies for eligibility based on the predetermined criteria.

Results

The search identified 9 eligible longitudinal studies with a total combined sample of 4,810 older adults. Three studies specifically measured loneliness using validated scales such as the UCLA Loneliness Scale. The most common assessment of cognition was the Mini‐Mental State Examination (MMSE), which was used in 8 of the 9 studies. Of the 4 studies examining the association between loneliness and cognitive decline, 3 reported a significant relationship even after adjusting for potential confounding factors including age, sex, and education level. However, the specific cognitive domains affected and magnitude of the association varied across studies.

Conclusion

The available evidence from this systematic review suggests higher loneliness is significantly associated with cognitive decline in older adults during the COVID‐19 pandemic. This relationship remained even after accounting for demographic and socioeconomic characteristics. These findings highlight the need for post‐pandemic public health strategies that foster social engagement and interaction while maintaining appropriate physical distancing measures. Such approaches may help mitigate the secondary effects of the pandemic on mental and cognitive health among older adults. Further research is warranted to elucidate the complex interrelationships between social isolation, loneliness, and cognitive decline.
Social media responses to the approval of lecanemab in Japan: sentiment analysis
Authors: Sato Kenichiro , Niimi Yoshiki , Ihara Ryoko , Iwata Atsushi , Arai Tetsuaki , Iwatsubo Takeshi
Published: January 2025

Background

Lecanemab, an anti‐amyloid therapy for early Alzheimer’s disease (AD), received full FDA approval in July 2023 and subsequent approval in Japan in September 2023. Public reaction on social media was mixed, reflecting opinions on its efficacy, safety, and cost. We aimed to evaluate public perception of lecanemab’s approval on social media, aiming to inform future communications and development strategies for anti‐amyloid treatments.

Method

We analyzed Japanese‐language social media posts from X (formerly Twitter) and Facebook, collected within two weeks of lecanemab’s approval. Using GPT‐4, we assessed sentiments towards the drug, focusing on efficacy, adverse effects, societal impact, and overall impression.

Result

Out of 478 posts, with 93.3% from X, sentiment analysis showed 43.7% negative, 26.6% neutral, and 29.7% positive overall impressions, with a significant difference by platform (p = 0.021). The predominant concern in negative posts was societal impact. There was moderate to good agreement between GPT‐4 and human ratings (kappa > 0.4) for all categories. Specific patterns of attitudes were observed depending on the overall impression to lecanemab’s approval. Medical professionals significantly expressed negative impressions (odds ratio = 1.679).

Conclusion

Responses to lecanemab’s approval displayed specific patterns, emphasizing the need for targeted communication and research direction on anti‐amyloid therapies.
Impact of Metabolic Syndrome Longitudinal Changes on Cognitive Health: A 10‐Year Follow‐up Study in Middle‐Aged Adults
Authors: Lin Hsiu‐Fen , Chen Cheng‐Sheng
Published: January 2025

Background

Metabolic syndrome (MS) has been linked to cognitive functions, yet limited research has explored the longitudinal effects of changes in MS on cognitive performance. This study aims to investigate the predictive impact of longitudinal MS status on cognitive performance and dissect its sex‐specific influence over a 10‐year follow‐up.

Method

In this community‐based prospective cohort study, 766 healthy subjects underwent baseline MS status assessment between 2006 and 2011. Changes in MS status and cognitive performance were evaluated from 2016 to 2021 using the Montreal Cognitive Assessment (MoCA). MS change status was categorized into four groups: never MS, ever MS with improvement, newly onset MS, and persistent MS. Linear regression analysis was used to assess the impact of longitudinal MS changes on endpoint cognition status while controlling for covariates. Categorical variables were dummy‐coded, and sex‐specific effects were examined by reanalyzing the data divided by sex.

Result

Subjects had a mean age of 54.50 ± 8.03 years at baseline, with a mean follow‐up duration of 10.40 ± 0.79 years; 39.2% were men. The MoCA score in the persistent MS group was significantly lower than that in the never MS group (adjusted p = 0.020). However, no significant differences in MoCA scores were observed between the never MS group and the ever MS with improvement group (adjusted p = 0.759) or the newly onset MS group (adjusted p = 0.469). Further analysis of cognitive domains revealed that memory and language were the most significantly affected. In assessing sex‐specific effects, a significant association was found only in women, with no significant associations observed in men.

Conclusion

Persistent MS status contributes to cognitive decline over a 10‐year period, contrasting with the lack of impact in those with improving or newly onset MS status. This effect is particularly pronounced in middle‐aged women. The findings suggest that modifying MS status among middle‐aged individuals, especially women, may be beneficial in preventing future cognitive decline.
Masupirdine (SUVN‐502): Phase‐3 Study for the Potential Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type, an Update
Authors: Nirogi Ramakrishna , Abraham Renny , Ravula Jyothsna , Jetta Satish , Benade Vijay , Shinde Anil , Rasheed Mohammed Abdul , Badange Rajesh Kumar , Goyal Vinod Kumar , Palacharla Veera Raghava Chowdary , Subramanian Ramkumar , Jayarajan Pradeep
Published: January 2025

Background

Alzheimer’s disease (AD) agitation is a distressing neuropsychiatric symptom characterized by excessive motor activity, verbal aggression, or physical aggression. Agitation is one of the causes of caregiver distress, increased morbidity and mortality, and early institutionalization in patients with AD. Current medications used for the management of agitation have modest efficacy and have substantial side effects. Therefore, there remains an urgent clinical priority for effective and safe treatments for agitation in AD.

Serotonin‐6 (5‐HT6) receptors are widely expressed in the brain regions including the cortex, dorsal hippocampus, and striatum; brain areas centrally involved in mood and behavior. Blockade of 5‐HT6 receptors may have a potential therapeutic utility in managing agitation. Masupirdine is a potent and selective 5‐HT6 receptor antagonist and is being developed as a potential treatment for agitation associated with AD.

Method

Masupirdine was evaluated in animal models of aggressive behaviors like resident‐intruder task and dominant‐submissive assay. The cognitive and motor performances were assessed using the alternating lever cyclic ration schedule.

Subgroup analyses of a Phase‐2, 26‐week proof‐of‐concept clinical study (NCT02580305) based on the neuropsychiatric inventory scale were carried out.

A Phase‐3, double‐blind, randomized, placebo‐controlled, global study is in progress to explore the efficacy, safety, tolerability, and pharmacokinetics of masupirdine in patients with agitation in dementia of the Alzheimer’s type (NCT05397639 and EudraCT 2021‐003405‐22).

Result

Oral administration of masupirdine significantly (p<0.05) attenuated aggressive behaviors in the resident‐intruder task and dominant‐submissive assay. In the alternating lever cyclic ration schedule, no changes were observed in the cognitive and motor performances after treatment with Masupirdine (p>0.05).

Potential beneficial effects in reducing agitation/aggression symptoms were observed in the post hoc analyses of the Phase‐2 study of masupirdine in AD patients.

Updates from the ongoing Phase‐3 study (NCT05397639 and EudraCT 2021‐003405‐22) will be presented in the poster.

Conclusion

Outcomes from animal models of aggression and subgroup analysis of the Phase‐2 study suggest that masupirdine may alleviate agitation. The Phase‐3 study results may inform the therapeutic utility of masupirdine for the treatment of Alzheimer’s agitation. Phase‐3 study data readout is anticipated in Q1/Q2 2025.
Enhancing Dementia Care in Rural Communities: A Tele‐rehabilitative Approach through Community‐Centered Technology Integration
Authors: Corvini Marguerite , Wang Jing , Arthanat Sajay
Published: January 2025

Background

Resource‐constrained rural areas face significant challenges in providing access to healthcare resources, especially for older adults, including those living with Alzheimer’s disease and related dementia (ADRD). We seek to address these gaps by equipping six rural community sites in New Hampshire and Maine with tele‐rehabilitative equipment. Libraries and community centers that serves youth and older adults, vital in rural communities, are identified as key partners to advance digital health literacy, equity, and telemedicine services for older adults including those living with ADRD, with the University of [blind for review] Center for Digital Health Innovation (CDHI).

Method

The project includes one hub site, one hub/end‐user site, and four end‐user sites spread across rural communities in New Hampshire and Maine. Each location will receive advanced tele‐rehabilitative tools, such as video conferencing and virtual reality (VR) technologies. The [blind for review] CDHI is responsible for equipment deployment, local staff training, and the formulation of telehealth programs tailored to meet the needs of older adults, particularly those with ADRD. We will obtain feedback from users and staff through focus groups regarding the barriers and facilitators to accessing and integrating the telehealth resources leveraging the strategic role of libraries and community centers in these communities.

Result

The implementation of the project is set to bolster tele‐rehabilitative service capacity across the consortium, potentially impacting around 70,000 rural residents. Expected outcomes include insights into the barriers and facilitators impacting access to specialized healthcare services for older adults with dementia and specific community engagement strategies in rural settings.

Conclusion

This initiative represents a focused strategy to address healthcare and educational disparities experienced by older adults, including those with ADRD, in rural settings. By integrating advanced technology with community engagement, it not only aims to improve the quality of life for these individuals but also sets a precedent for similar rural development programs, striving to close the gap in healthcare and education in resource‐limited areas.
The effects of six months of the adapted Otago Exercise Program on cognition and falls relative to usual care alone among people living with dementia in residential care facilities: A pilot feasibility randomized controlled trial
Authors: Jehu Deborah A
Published: January 2025

Background

There are no evidence‐based exercise guidelines to reduce falls in people living with dementia (PWD). The purpose of this pilot randomized controlled trial (RCT) was to determine the 1) feasibility and acceptability, and 2) effect of exercise on cognition and falls (exploratory) relative to usual care alone among PWD.

Methods

We randomized PWD to the exercise (n = 21) or usual care group (n = 21) at two residential care facilities in our pilot parallel, assessor‐blinded RCT (1:1) [NCT05488951]. We examined feasibility (recruitment, data collection, dropout rates, adverse events, adherence) and acceptability (satisfaction). Our adapted physical therapist‐led Otago Exercise Program consisted of 1 hour of strength, balance, and walking 3x/week for 6 months in groups of 5‐7 PWD. At baseline and 6 months, participants completed the Color‐Word Stroop 3‐2 (primary), Montreal Cognitive Assessment (MOCA); Trail‐Making test, Digit Span Forward/Backward; Benton Judgment of Line Orientation; Boston Naming Test; Rey Auditory Verbal Learning Test; Digit Symbol Substitution Test, and the Health Utilities Index‐3 (HUI‐3). We pulled falls monthly from medical charts. We performed intent‐to‐treat (ITT; n = 42) and per protocol analyses (n = 9 with ≥2x/week exercise adherence, n = 21 usual care), controlling for age, race, sex, and the MOCA.

Results

Recruitment and enrolment were completed in 7 months (36% female; 17% African Americans; Age:82.1±8.1years; MOCA:10.2±5.9points). The attrition rate was 19.0%, exercise adherence was moderate (60.2±34.5%; 47/78 exercise sessions), and satisfaction was good (4.2/5 points). The trial established protocol safety, with no adverse events related to the intervention. The ITT analysis revealed no differences in the Color‐Word Stroop (primary), but better executive function (Digit Span Backwards) following exercise relative to usual care (p<0.05). The per‐protocol analysis revealed better executive function (Digit Span Backwards) and HUI‐3 following exercise relative to usual care (p<0.05). There were no effects on falls (exercise:13 falls, n = 8 recurrent, n = 1 injurious; usual care:13 falls, n = 10 recurrent, n = 4 injurious).

Conclusion

This pilot RCT was feasible and acceptable. Any amount of exercise appears to improve executive function, with at least 2x/week exercise also benefiting quality of life among PWD. These findings may have implications for targeted treatment strategies and inform a larger trial powered for falls in PWD.
Clinician Attitudes and Confidence on the Detection and Management of Cognitive Impairment: Results from the Davos Alzheimer’s Collaborative Early Detection Program
Authors: Ferrell Phyllis Barkman , Murray James F. , Ball Daniel E , dos Santos Filho Otelo Corrêa , Lima Marcilea Dias de Sá Paiva , Govia Ishtar , Robinson Janelle , Kowa Hisatomo , López‐Ortega Mariana , McKean Alison , Chambers Wendy , Baksh Magda R. , Baldivieso Valeria , Willis Deanna R , Fowler Nicole R , Selzler Katherine J.
Published: January 2025

Background

Early symptoms of cognitive impairment are frequently undetected. The Davos Alzheimer’s Collaborative System Preparedness (DAC‐SP) Early Detection program implemented a digital cognitive assessment (DCA) in primary care and other non‐specialty settings to increase the rate of detection of cognitive impairment.

Methods

The DAC‐SP Early Detection program was initiated in 2021 in seven healthcare systems across six countries. Clinicians were trained on a DCA, including positive tests for cognitive impairment and diagnostic assessment. Prior to training or naïve to implementing a DCA in clinical practice, clinicians’ attitudes and confidence in diagnosis and managing dementia were assessed using the validated General Practitioners Attitude and Confidence Scale for Dementia (GPACS‐D), which is comprised of 15 items in three subscales: Confidence in Clinical Abilities, Attitude towards Care, and Engagement. Each item is measured on a 5‐point Likert scale (1 = strongly disagree; 5 = strongly agree), and subscale scores are standardized. A total of 265 pre‐training surveys were completed across the 7 sites. The GPACS‐D results were calculated by averaging individual physician results per the validated scoring algorithm. The cross‐site results were calculated by taking an equally weighted average across the seven sites.

Results

The GPACS‐D results across the seven sites are presented in Table 1. Across all sites, baseline attitude towards care was the highest of the three subscales. For most sites, confidence in clinical abilities received the lowest scores, with engagement scores only modestly higher. The total and subscale scores were consistent across sites, supported by the relatively low standard deviation.

Conclusion

The findings from the GPACS‐D total and subscale scores suggest that prior to receiving training on using a digital cognitive assessment for their patient populations, clinicians’ attitudes towards the diagnosis and management of cognitive impairment were similar across the seven sites, and independent of the country in which they practice. Despite positive attitudes toward care, the results suggest that education or training focused more on engagement and confidence may improve early detection and care of patients with cognitive impairment, particularly as new diagnostic and therapeutic options emerge.
Remote sleep and memory assessments in older adults with mild cognitive impairment and dementia: Recruitment, retention, and completion of home‐based study tasks
Authors: Gabb Victoria Grace , Blackman Jonathan , Morrison Hamish , Biswas Bijetri , Li Haoxuan , Turner Nicholas , Whone Alan , Coulthard Elizabeth
Published: January 2025

Background

Poor sleep is associated with neurodegenerative diseases underlying dementia and mild cognitive impairment (MCI), including Alzheimer’s disease (AD) and Lewy body disease (LBD). Performing assessments within clinical or laboratory settings may influence validity, however feasibility of home sleep and memory assessments in this population is currently undetermined. This study aimed to identify whether remote home‐based sleep and memory research including wearable technology was feasible in older adults with MCI and dementia.

Method

Adults aged over 50 with MCI or dementia due to AD or LBD and matched controls (HC) were asked to complete 8 weeks (55 nights) of continuous wrist actigraphy and daily sleep diaries via a mobile application. During one of these weeks, participants were also asked to collect 10 serial saliva samples for cortisol and melatonin assays, wear a wireless electroencephalography (EEG) headband during sleep for 7 nights, and complete 6 short verbal memory tests via videoconferencing. Feasibility metrics on recruitment, retention, data completion, and study support were collated.

Result

Recruitment: 129 individuals were potentially eligible during pre‐screening. 44 (34.1%) participants consented to take part. 41 participants (AD = 10, LBD = 11, HC = 20; mean age 71.1, range 57‐81; 22.0% female) met screening criteria and were enrolled. Barriers to recruitment included concerns about ability to complete study tasks, impact on sleep from study assessments, and unfamiliarity with digital technology. Retention: 40/41 (97.6%) participants completed the study. 1 participant withdrew post‐baseline due to personal circumstances. Data completion: Across tasks, data completion rates were high and similar across subgroups. 97.3% (389/400) of saliva samples, 90.0% (144/160) of verbal memory tasks, 93.5% (2,056/2,200) of sleep diaries, 97.0% (2,133/2,200) nights of actigraphy, and 91.4% (256/280) of EEG recordings were completed. Reasons for missing data included technical issues, scheduling difficulties (work/caring commitments), illness, and forgetting to complete or difficulty understanding tasks. Study support: 10 participants (AD = 3, LBD = 7) reported receiving external support (partner or relative) during the study. Regular researcher support was provided via email, video calls, and scheduled SMS/email/in‐app reminders.

Conclusion

Remote, technology‐supported sleep and memory research is feasible in older adults with MCI/dementia and could contribute towards longitudinal, naturalistic, and convenient sleep and memory profiling.
Subjective Social Status, Brain Health, and Cognitive Reserve Across Race/Ethnicity and Sex/Gender
Authors: Scambray Kiana A. , Nelson Monica E , Morris Emily P. , Palms Jordan D , Taylor Lauren , Sol Ketlyne , Schupf Nicole , Brickman Adam M. , Manly Jennifer J. , Zahodne Laura B.
Published: January 2025

Background

Subjective social status in the US (SSS) is related to physical, mental, and cognitive health independent of socioeconomic status, yet few studies have assessed SSS in one’s community or examined how SSS may function differentially across the intersection of race and gender. This study aimed to assess the relationships between SSS‐US, SSS‐community, brain health, and cognitive reserve utilizing an intersectional lens to extend the literature on social determinants of Alzheimer’s disease and related dementia (ADRD) risk.

Methods

Participants were 867 older adults from the Washington Heights‐Inwood Columbia Aging Project (WHICAP). SSS relative to the US and one’s community were based on the MacArthur Scale of SSS. Brain health was operationalized as total volume of white matter hyperintensities (WMH), total gray matter volume, total hippocampal volume, and mean cortical thickness across nine AD signature regions. Cognitive reserve was operationalized as residual variance in an episodic memory composite after accounting for all brain health measures. Separate multiple linear regressions assessed unique relationships between the two SSS predictors and the brain health and cognitive reserve outcomes while adjusting for sociodemographics. Multiplicative interaction terms examined whether associations involving SSS were moderated by sex/gender, race/ethnicity, and their intersection.

Results

There were no relationships between SSS‐community or SSS‐US and brain health across the full sample. Among White women, higher SSS‐community was associated with lower WMH (B = ‐0.33, p = 0.047). Among Black men, higher SSS‐community was associated with lower hippocampal volume (B = ‐0.31, p = 0.04). In sensitivity analyses, higher SSS‐community was associated with lower hippocampal volume among older (B = ‐0.30, p = 0.048), but not younger (B = ‐0.21, p = 0.37) Black men. Neither SSS‐US nor SSS‐community was associated with cognitive reserve.

Conclusions

This study highlights the value of assessing community standing in addition to US standing to understand social determinants of ADRD risk, as community standing may be more predictive of brain health. From an intersectional lens, community standing may be most strongly related to cerebrovascular health among White women, who appeared more sensitive to both low and high community standing. Counterintuitive findings among Black men likely reflect selective survival. Further research should explore longitudinal relationships between community standing and brain health.
Cardiac Biomarkers, Subclinical Brain Vascular Changes, and Cognitive Decline: Post Hoc Analysis of the SPRINT Trial
Authors: Zhang Wenxin , Ascher Simon B. , Dolui Sudipto , Nasrallah Ilya M. , Lu Yuan , Neitzel Julia , Toledo Estefanía , Glodzik Lidia , Hughes Timothy M. , Berry Jarett D , Ma Yuan
Published: January 2025

Background

Subclinical cardiovascular disease (CVD), assessed by high‐sensitivity cardiac troponin T (hs‐cTnT) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), is linked to cognitive decline, but the associations in hypertensive adults and the underlying brain pathologies remain unclear. It is also undetermined whether an intensive blood pressure treatment compared to a standard treatment may slow down cognitive decline associated with subclinical CVD.

Method

We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial, where older adults with hypertension were randomized to an intensive treatment (systolic blood pressure (SBP) target of < 120 mm Hg) or standard treatment (< 140 mm Hg). Serum hs‐cTnT and NT‐proBNP concentrations were measured at baseline, with elevated levels defined as ≥ 14 ng/L for hs‐cTnT and ≥ 125 pg/mL for NT‐proBNP. Global and domain‐specific (memory, processing speed, language, and executive function) cognitive function was assessed using a battery of neuropsychological tests at baseline and during the follow‐up (year 2, year 4, and year 6) in 2733 participants with biomarker measurements. White matter lesions, cerebral blood flow, and brain tissue volume were assessed by brain MRI at baseline and 4 years of follow‐up in a subset of 639 participants.

Result

Elevated levels of both hs‐cTnT and NT‐proBNP were associated with accelerated decline in cognitive function across all four domains after adjusting for potential confounding factors. The group with elevated levels of both cardiac biomarkers showed the fastest decline, with a greater annual decline rate of 0.033 (95% CI, 0.024 to 0.041) in standardized z‐score of global cognitive function compared to the group with normal hs‐cTnT and NT‐proBNP. Elevated levels of both cardiac biomarkers were also associated with a faster progression in white matter lesions, but not with changes in total brain tissue volume and cerebral blood flow. Intensive SBP treatment did not attenuate these associations compared to standard treatment (all P for interaction > 0.05).

Conclusion

Elevated hs‐cTnT and NT‐proBNP levels were associated with accelerated cognitive decline and progression of white matter lesions regardless of SBP treatment assignment. Subclinical CVD may contribute to the progression of white matter lesions and thus leads to accelerated cognitive decline.
High Pesticide Exposure Events and Subjective Cognitive Decline among U.S. Farmers
Authors: Yuan Yaqun , Plassman Brenda L , Song Shengfang , Luo Zhehui , Parks Christine G , Fleenor Julie , Madsen Corrine , MacDonald Heather , Davis Scott , Li Chenxi , Hofmann Jonathan N , Freeman Laura E. Beane , Sandler Dale P. , Chen Honglei
Published: January 2025

Background

Pesticide exposure may contribute to cognitive decline, but empirical evidence is limited. We examined high pesticide exposure events (HPEE) in relation to subjective cognitive decline among farmers in the Pesticide and Sense of Smell Study (PASS), a sub‐cohort of the Agricultural Health Study (AHS).

Method

This analysis included 2365 predominantly white male farmers from Iowa and North Carolina (aged 70±10 years) who enrolled in AHS from 1993‐1997 and participated in PASS in 2020‐2021. Subjective cognitive decline was assessed in the PASS sub‐cohort using the 14‐item Cognitive Function Instrument (CFI), and significant decline was defined as a CFI score ≥ 4. HPEEs were assessed in 1993‐1997, 1999‐2003, and 2005‐2010 in the AHS cohort and in 2020‐2021 in PASS. We estimated the association of HPEE on SCD using a doubly robust, weighted least‐square method, accounting for study design, sampling, non‐response, and multiple covariates, including demographics, lifestyle factors, and major chronic diseases.

Result

A history of HPEE was associated with significant subjective cognitive decline across all HPEE assessments in the AHS and PASS. Using the HPEE reported in PASS as an example, compared with those who never had any event, the risk ratio (RR) for those who reported HPEE was 1.57 (95% confidence interval: 1.35, 1.89). The association appeared stronger for more HPEE events (RR: 1.89 vs. 1.45 for ≥3 vs. 1‐2 events), longer delay in washing with soap and water (RR: 1.74 vs. 1.51 for waiting >1 vs. ≤ 1 hour), HPEE exposure via the respiratory/digestive tract (RR: 1.84 vs. 1.33 for dermal contact only), HPEE with subsequent symptoms (2.04 vs. 1.36 for ≥2 vs. no symptoms). Data on HPEE exposure to specific pesticides are limited, but we found significant associations of HPEE with SCD for alachlor, atrazine, 2,4‐D, and glyphosate.

Conclusion

This study provides preliminary evidence that high pesticide exposure may contribute to subjective cognitive decline among older farmers.
Behavioral Reaction to Amyloid β Status Disclosure Among Research Participants with High‐AD Risk in Israel
Authors: Golan Sapir , Beeri Michal S , Zadok Maya , Ben‐Meir Mery , Rozen Yael , Shutsberg Revital , Bem‐Moshe Ariela , Heymann Anthony , Azuri Yossi , Ganmore Ithamar , Ravona‐Springer Ramit , Hoffmann Chen , Domachevsky Liran , Lesman‐Segev Orit H.
Published: January 2025

Background

Amyloid beta (Aβ) deposition marks an early stage in the progression of Alzheimer's disease (AD), detectable in‐vivo years before symptoms emerge and targeted by recently FDA‐approved drugs. This has propelled advancements in understanding, measuring, and treating AD, paving the way for disease prevention in those at risk. However, the psychological impact of disclosing Aβ status to cognitively unimpaired individuals remains underexplored. Our study aimed to evaluate the behavioral responses to Aβ status disclosure in this population.

Method

Two observational studies and two clinical trials incorporating Aβ‐PET were conducted, involving research participants who received information on Aβ‐PET scans, results, and interpretation. Questionnaires were administered before the scan and four‐to‐six months post‐disclosure to assess anxiety, depression, subjective memory complaints, and motivation for risk‐reduction behaviors. Bivariate analysis and mixed models were employed to analyze responses, with logistic regression used to identify predictors of unfavorable responses to negative scan disclosure.

Result

Among 178 participants with amyloid‐negative scans (mean age 64, 57% females) and 21 with amyloid‐positive scans (mean age 77, 38% females), no significant pre‐scan differences were observed. Negative amyloid disclosure correlated with reductions in all domains tested, including memory complaints, depression, anxiety, and motivation to change lifestyle (p≤0.001). Positive amyloid disclosure also resulted in decreases, particularly in anxiety and depression, albeit to a lesser extent and with greater variability (0.007<p<0.07 for pre to post PET change in amyloid positives vs. negatives). Higher education was linked to fewer memory complaints post‐negative Aβ PET disclosure (Odds ratio=0.79, CI=0.65‐0.97, p=0.02).

Conclusion

In conclusion, as AD enters an era of disease‐modifying and preventive treatments, understanding how cognitively normal adults respond to AD biomarker status disclosure becomes crucial. Negative amyloid results offer a comforting effect, reflected in reduced subjective memory concerns and lower anxiety, depression, and motivation for lifestyle changes. However, caution is needed to prevent false reassurance. Positive amyloid results also provide comfort, albeit to a lesser extent and with more variability. Lower education levels may predict unfavorable responses to negative amyloid disclosures.
How does different types of exercise promote cognitive function? What do we know?
Authors: Liu‐Ambrose Teresa
Published: January 2025

Our current understanding of how exercise promotes cognitive function largely stems from animal studies and is restricted to aerobic exercise training (AT). It is widely hypothesized that AT induces neurotrophic factor cascades (i.e., BDNF, IGF‐1, and VEGF), a central mechanism mediating exercise‐dependent benefits in cognitive performance. However, evidence regarding the effect of AT on neurotrophic factors in humans is equivocal. Notably, whether AT‐induced changes in neurotrophic factors are associated with AT‐induced changes in cognitive function is largely unknown. The dearth of mechanistic evidence is even more pronounced for resistance training (RT).

Both AT and RT may also promote cognitive function by reducing peripheral cardiometabolic risk factors for neurodegeneration (e.g., hypertension, type 2 diabetes, hypercholesterolemia), as well as systemic inflammation associated with these risk factors. Specifically, cardiovascular disease and type 2 diabetes are associated with chronic low‐grade systemic inflammation reflected by elevated levels of C reactive protein and cytokines. Systemic inflammation can impair neurotrophic factor signaling, exacerbate the metabolic syndrome, and accelerate cognitive decline. Similar to neurotrophic factors, the roles of cardiometabolic risk and systemic inflammation in exercise‐induced improvements in human cognitive performance are not well established.

A better understanding of the underlying biological mechanisms of different types of exercise training will greatly advance our ability to refine and develop novel exercise (and other) strategies for dementia prevention. In this session, we will discuss/debate the selection and measurement of biomarkers in randomized controlled trials of exercise in individuals with or without cognitive impairment.
Novel Alzheimer’s disease blood‐based biomarkers in exercise trials
Authors: Karikari Thomas K , Erickson Kirk I. , Esteban‐Cornejo Irene
Published: January 2025

Regular exercise has been shown to have beneficial effects including reducing risk of developing Alzheimer’s disease (AD). However, it is unclear if exercise has direct effects on AD pathophysiology. To this end, several emerging initiatives have been established to investigate plasma biomarker changes in relation to exercise among older adults. The aim of this talk is to described plasma biomarker results in two exercise‐based randomized controlled trials. The Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) is a completed multi‐site randomised dose‐response exercise trial of 12‐month duration that targeted over 600 cognitively normal 65–80‐year‐old adults in the United States. Participants were randomized into three different groups of exercise intensity. The second study is the Active Gains in brain Using Exercise During Aging (AGUEDA) is a 24‐week, single‐site two‐arm, single‐blinded trial that recrtuited n = 90 cognitively normal adults aged 65‐80 and living in Spain. In both studies, blood samples were collected at baseline as well as the end of the intervention. A mid‐study blood collection was further performed in IGNITE. Additionally, neuroimaging measures of amyloid and neurodegeneration were obtained, so were cognitive assessments using established tools. We performed measurements of plasma p‐tau217, p‐tau181, NfL, GFAP and amyloid beta 42/40 by immunoprecipiation‐mass spectrometry in all participants and at all timepoints. We will evaluate the time‐dependent profiles of these blood biomarkers, their associations with exercise intensity and neuroimaging markers, as well as potential moderating effects by demographic (e.g, sex, age, education, family history), and genetic factors (APOE e4 genotype). The results will be crucial to understanding associations between exercise and brain health.
Blood pressure variability and global cognition in Black and White older adults over 18 years: a population‐based cohort study
Authors: Dhana Anisa , Decarli Charles , Dhana Klodian , Desai Pankaja , Evans Denis A , Rajan Kumar B
Published: January 2025

Background

Variability in blood pressure has been associated with cerebrovascular disease independently of the adverse effects of hypertension or average blood pressure. We investigated whether visit‐to‐visit blood pressure variability is associated with global cognition in older adults.

Method

This study included 4,783 individuals aged 65 and older participating in the Chicago Health and Aging Project, a biracial population‐based study. Blood pressure was measured by a trained research assistant at each study visit, 3 years apart. Blood pressure variability was calculated as the sum of the absolute differences of blood pressure between successive measurements, divided by the number (n‐1) of assessments. Global cognition was assessed by a battery of 4 standardized cognitive tests. Linear regression model was used to evaluate the association of blood pressure variability during the study period with global cognition at the last study visit. The regression model was adjusted for age, sex, race, education, physical activity, cognitive activity, smoking, depression, co‐morbidities (hypertension, heart disease, stroke, and diabetes), baseline cognition, and the time being in the study.

Result

Of 4,783 individuals, 3009 (62.9%) were women, 3146 (65.8%) were Black or African American adults, and the average age of the study population was 71.3 years. Higher systolic and diastolic blood pressure variability was associated with lower cognitive scores. A 1‐SD increase in systolic blood pressure variability was associated with a 0.030 SD lower global cognition (𝛽‐0.030, 95%CI ‐0.055 to ‐0.006). For African American individuals, the 𝛽 estimate was ‐0.040 (95%CI ‐0.069 to ‐0.011), and for White adults, it was ‐0.008 (‐0.052 to 0.036). Similar associations were observed for diastolic blood pressure. In the analysis stratified by antihypertensive medication use, the variability in blood pressure was associated with a lower cognitive score among people who were not on medication, respectively 𝛽 for comparing the 3rd vs. the 1st tertile was ‐0.102 (95%CI ‐0.195 to ‐0.010). There was no association among people who were receiving medication for hypertension.

Conclusion

Elevated blood pressure variability, particularly in older African American adults, is associated with a lower global cognitive score.