bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of recruitment incentives in early Alzheimer’s disease clinical trials
Authors: Ritchie Marina , Witbracht Megan G. , Russ Eunji , Sajjadi S. Ahmad , Thai Gaby , Tam Steven , Gillen Daniel L , Grill Joshua D
Published: January 2025

Background

Amid recent approvals, early Alzheimer’s disease (AD) remains an active area of treatment development, but research on the utility of recruitment incentives in early AD trials remains limited. We examined how trial design features impact enrollment decisions among Mild Cognitive Impairment (MCI) patients and their family members.

Method

We performed a conjoint analysis experiment to compare early AD patients’ preferences for trial features. Individuals with MCI were asked to rate their willingness to participate in a series of trial scenarios (using a 7‐point ordered scale) that varied in four pre‐selected factors, each with two levels. Three trial incentives were included: 1) active‐control design with participants randomized to an investigational anti‐amyloid therapy or aducanumab (vs. placebo control), 2) tau PET disclosure (vs. no return of tau PET results), and 3) remote study partner participation (vs. required in‐person study partner participation). We included one negative control (5% vs. 25% risk of brain swelling). We used a generalized estimating equations (GEE) model to account for within‐subject correlation and to assess the utility of the differing factor levels. An exchangeable working correlation structure was used for parameter estimation, and robust variance estimates for model coefficient estimates were used for final inference.

Result

Among 26 patients with MCI (mean [SD] age 78.3 [8.2], 31% female, 85% non‐Hispanic White), returning tau PET results had the highest utility (est: 0.47; CI: 0.13, 0.81; p = 0.007). Trials with the option for remote study partner participation showed a similar trend in utility (est: 0.29; CI: ‐0.05, 0.63; p = 0.097). Trials with active‐controlled design (est: 0.01; CI: ‐0.33, 0.35; p = 0.956 did not demonstrate significant utility and trials with higher risk of brain swelling had a negative utility (est: ‐0.64; CI: ‐0.99, ‐0.30; p<0.001) (Figure 1).

Conclusion

These findings suggest that returning biomarker results may have a greater impact on participant enrollment decisions than would use of active‐controlled designs or providing the option for study partners to participate remotely.
Association of Prenatal Pesticide Exposure with Plasma Aβ 42/40 Ratio in Midlife: Evidence from the Child Health and Development Studies
Authors: Richardson Jason R , Mhatre‐Winters Isha , Cirillo Piera , Krigbaum Nickilou , Factor‐Litvak Pam , Go Young‐Mi , Jones Dean P , Cohn Barbara
Published: January 2025

Background

Environmental factors are increasingly being recognized as significant contributors to Alzheimer’s and Related Dementias (ADRD). Previously, we reported that higher serum concentrations of DDE, the highly persistent metabolite of the pesticide DDT was associated with increased risk of Alzheimer’s disease. We further demonstrated in cell and animal models that DDT and DDE increase amyloid pathology in the brain (Fig. 1). However, little is known about the effects of prenatal exposure on amyloid in humans.

Method

Offspring born into the Child Health and Development Studies (CHDS) pregnancy cohort from 1960 ‐1963 in Oakland, CA were recruited for a diverse follow‐up study of health disparities in 2010. Participants completed cognitive function assessments, and provided interview data and blood samples, in their late 40’s to early 50’s. Aβ 42/40 was measured from the stored plasma taken in midlife using the Quanterix Neurology 3‐Plex A kit. Prenatal p, p’‐DDE, measured in archived maternal pregnancy serum, was available for this pilot sample, n = 160. Associations were estimated in linear, and binomial and multinomial logistic regression models, adjusted for race and sex.

Result

Higher prenatal p, p‐DDE was associated with lower Aβ 42/40 in mid‐life (Fig. 2). In logistic models (Table 1), the Odds Ratio [OR] estimating lower Aβ 42/40 (tertiles 1 or 2 vs. tertile 3) = 2.6; 95% Confidence Limits [CL] = 1.0‐6.9 and OR = 3.2; 95% CL = 1.1‐9.8 for p, p‐DDE tertiles 2 and 3, respectively. Test of trend across p, p’‐DDE tertiles was significant (P‐value = 0.04). Associations were robust to multiple alternative modeling approaches (Table 1). Adjustment for achieved education in mid‐life did not alter results.

Conclusion

Higher prenatal exposure to DDE is associated with lower plasma Aβ 42/40 in midlife, a putative prodromal marker for ADRD. Identification of individuals or populations more highly exposed to DDT/DDE may determine those at increased risk for ADRD later in life and allow for early intervention and prevention from progression to ADRD.
Marital Status and living arrangements, Brain Reserve, and Cognitive Reserve Among Diverse Older Adults
Authors: Lee Ji Hyun , Scambray Kiana A. , Morris Emily P. , Sol Ketlyne , Palms Jordan D , Zaheed Afsara B , Manly Jennifer J. , Brickman Adam M. , Zahodne Laura B.
Published: January 2025

Background

Marital status is an important but often overlooked sociodemographic factor that could shape cognitive health in late adulthood. Being married is shown to be linked to lower risk of dementia, but less is understood about underlying mechanisms contributing to this relationship, such as brain reserve (BR) and cognitive reserve (CR). Further, less is known about how living arrangement, independent of marital status, is associated with late‐life cognition. The current study examines (1) associations between marital status, BR, and CR among diverse older adults and (2) whether living arrangement is linked to BR and CR among unmarried adults.

Method

Cross‐sectional data come from the Washington Heights‐Inwood Columbia Aging Project (WHICAP; N = 778, 41% Hispanic, 33% non‐Hispanic Black, 25% non‐Hispanic White; 64% women). Self‐reported marital status was categorized as currently married, previously married (i.e., divorced, separated, widowed), and never married. Magnetic resonance imaging (MRI) markers of BR included regional cortical thickness (in Alzheimer’s disease signature regions), hippocampal volume, gray matter volume, and white matter hyperintensities. CR was defined as residual variance of an episodic memory composite after residualizing MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender. Age and education was controlled and physical health and income were explored as mediators.

Result

Marital status was associated with CR, but not BR, among White and Hispanic subgroups, and among women, such that those who were previously married had lower CR than their married counterparts. Never married women also had lower CR than married women. Among men only, marital status was associated with BR, but not CR, such that previously married men had lower gray matter volume than married men; however, this finding was not independent of income. Among currently unmarried individuals, living with others was not associated with greater BR nor CR. All findings were independent of age, education, and physical health.

Conclusion

Our findings show differential links between marital status and reserve mechanisms across race and ethnicity and sex/gender, underscoring the importance of examining marital status in older adult’s brain health. Future studies should examine other mechanisms that link marital dissolution and lower CR and nuanced contexts of marital history.
The association between mid‐life personality traits and late‐life dementia risk in the Wisconsin Longitudinal Study
Authors: Strait Brittani J. , Trane Ralph , Lange Kate , Asthana Sanjay , Williams Victoria J.
Published: January 2025

Background

Personality traits, namely higher neuroticism and lower conscientiousness, are predictive of dementia, although the complex relationship has yet to be fully explained. With >60 years of prospectively collected data, the Wisconsin Longitudinal Study (WLS) provides a unique opportunity to thoroughly evaluate this association in a population‐based randomly selected cohort. Using a gold‐standard diagnostic approach to characterize dementia prevalence, we leverage life course WLS data to examine the association between mid‐life personality traits and late‐life dementia risk.

Method

Big Five personality traits (neuroticism, conscientiousness, openness, extraversion, and agreeableness) were prospectively measured in 1993‐94 at mid‐life (ages 54‐55). Cognitive status was determined in late‐life starting in 2020 (age 81) using a two‐phased approach. Participants were first screened via the Telephone Interview for Cognitive Status (TICS‐m), with those scoring below cutoff (≤28) selected for additional comprehensive medical and cognitive assessment reviewed by a multi‐disciplinary clinician consensus panel to determine dementia diagnosis. To evaluate the association between midlife personality traits and late‐life all‐cause dementia risk, we performed a binary logistic regression controlling for age, sex, ApolipoproteinE‐4 (ApoE‐4) status, adolescent IQ, education, comprehensive smoking history, and lifetime burden of systemic health factors (hypertension, diabetes, stroke, heart disease).

Result

3765 WLS participants were included in analyses. The overall logistic regression model was statistically significant (Chi2(14) = 207.52, p<0.001), explaining 12.3% of the variance in dementia outcome. Each unit increase in mid‐life conscientiousness corresponded to a 4.5% decrease in the odds of late‐life dementia (OR = 0.955 [95% CI: 0.926‐0.985], p = 0.003), while the remaining four personality factors were not predictive of dementia risk.

Conclusion

Using a longitudinal population‐based cohort, we find that lower mid‐life conscientiousness increases risk for dementia in late‐life, and conversely, higher mid‐life conscientiousness is protective for late‐life dementia. Although prior research suggests higher neuroticism is also associated with dementia outcomes, our data did not support this finding. Future work should explore potential pathways and mechanisms by which personality traits affect cognition and neurodegenerative disease risk, including the possible mediating role of personality‐associated health behaviors.
Glycoproteome‐wide analyses in the dorsolateral prefrontal cortex identified glycopeptiforms associated with cognitive decline in specific cognitive domains
Authors: Beeri Michal S , Levin Yishai , Morgenstern David , Tikotzki Nili , Levy Hila , Cooper Itzik , Klein Hans‐Ulrich , Bennett David A. , Yu Lei , Buchman Aron S
Published: January 2025

Background

Molecular omics studies of aging brains have identified genes and proteins related to cognitive decline. Identifying proteins that are linked to specific cognitive abilities has potential to catalyze the development of targeted therapies for specific cognitive deficits. Posttranslational modifications of proteins with glycans modify protein function. Here, we identified glycopeptiforms associated with decline in specific cognitive domains.

Method

We studied brains of 366 older decedents from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) with annual cognitive testing, postmortem indices of ten AD/ADRD pathologies and proteome‐wide data, from dorsal lateral prefrontal cortex (DLPFC). We quantified 11,012 glycopeptiforms from DLPFC using liquid chromatography with tandem mass spectrometry, which is able to identify both glycated and glycosylated glycopeptiforms, two distinct molecular processes. We employed linear mixed‐effects models controlling for age, sex and education to identify glycopeptiforms associated with decline in five cognitive domains (episodic memory, semantic memory, working memory, perceptual speed and visuospatial abilities) correcting for multiple comparisons (p<5×10‐6). In further analyses, we adjusted for 10 neuropathologies and for the constituent proteins of the glycopeptiforms.

Result

We found eight glycated (Table 1) and eight glycosylated glycopeptiforms (Table 2) that were significantly associated with cognitive decline. Glycated glycopeptiformswere associated primarily with decline in working memory. In contrast, glycosylated glycopeptiforms were associated with all cognitive domains except for visuospatial abilities. Higher levels of glycated glycopeptiforms were always related to faster cognitive decline while higher levels of glycosylated glycopeptiforms were primarily associated with slower cognitive decline. Three glycopeptiforms identified weresituated on the protein neuronal pentraxin 2, linked to AD. The HexNAc(5)Hex(4)Fuc(2) glycan composition appeared in half of the significant glycosylated glycopeptiforms while only in <0.05% of the 11,000 glycopeptiforms, suggesting its specific involvement in cognition. Adjustment for 10 neuropathologies attenuated 3 of the 25 significant associations. Adjustment for the constituent proteins did not alter any of the results suggesting that the post‐translational modification itself may have a role in cognitive decline.

Conclusion

Glycopeptiforms in aging brains may contribute to decline in distinct cognitive abilities. Further drug discovery targeting these glycopeptiforms may lead to therapies that prevent specific cognitive deficits.
Examination of sleep metrics from spectral analysis, self‐report, and the Sleep Profiler to establish test‐retest reliability in an Alzheimer’s disease cohort
Authors: Pedersen Taylor J , McCullough Austin A. , Toedebusch Cristina D , Hess Ashley , Richardson Rachel , Morris John C. , Holtzman David M. , Gordon Brian A. , Lucey Brendan P
Published: January 2025

Background

It is thought that sleep plays a role in the development and course of Alzheimer’s disease (AD). There are numerous metrics and methods to gather sleep data including measures from self‐reports, actigraphy, or EEG. There has been limited research examining the reliability of these variables over time in healthy individuals as well as the optimal method to gathering such data. We sought out to determine which sleep metrics are the most reliable over a long timescale in a cohort of amyloid negative individuals.

Method

Sleep was assessed over six nights at home using three instruments simultaneously: single‐channel EEG (scEEG) (Sleep Profiler, Advanced Brain Monitoring, Carlsbad, CA), actigraphy (Actiwatch2, Philips Respironics, Andover, MA), and sleep diaries. Participants returned three years later for their second visit using the same sleep assessments. Longitudinal data was analyzed for 19 cognitively normal individuals (CDR = 0) who were amyloid negative by PET. To determine the most reliable method of gathering sleep data, we grouped the metrics into three categories: spectral analysis, self‐reports, and Sleep Profiler data. We then examined the intraclass correlation coefficient (ICC) between visits as a measure of reliability.

Result

Spectral analysis demonstrated the highest test‐retest reliability (mean ICC = 0.798, min. ICC = 0.578, max. ICC = 0.877) followed by the sleep profiler data (mean ICC = 0.558, min. ICC = 0.405, max. = 0.932). Self‐report data exhibited the lowest test‐retest reliability (mean ICC = 0.485, min. ICC = 0.150, max. ICC = 0.729) (Fig. 1). In examining metrics with high ICC values from each category, individual slow wave activity (SWA) data remained highly consistent between visits (ICC = 0.874) (Fig. 2A). REM Latency was the strongest sleep profiler metric and had an ICC value of 0.862 (Fig. 2C). Within self‐report data, the daytime napping questionnaire had the highest test‐retest reliability (ICC = 0.729) (Fig. 2B).

Conclusion

Spectral analysis proved to be the most reliable metric in assessing sleep in amyloid‐negative individuals. Given their lower reliability the Sleep Profiler and self‐report questionnaires are likely not sufficient to evaluate sleep quality alone. Further analysis in amyloid‐positive individuals is being conducted.
The Long‐Term Effects of the Care Ecosystem Dementia Care Management Program on Quality of Life and Caregiver Well‐being
Authors: Possin Katherine L , Dulaney Sarah , Wood Andrew J , Bonasera Stephen , Allen Isabel Elaine , Sideman Alissa Bernstein , Kanzawa Mia , Merrilees Jennifer , Lee Kirby P , Chiong Winston , Braley Tamara , Hooper Sarah M , Gearhart Rosalie , Medsger Helen Bundy , Harrison Krista L , Hunt Lauren , Kiekhofer Rachel , Chow Chris , Miller Bruce L. , Guterman Elan L
Published: January 2025

Background

Dementia care management programs, including the Care Ecosystem, have been shown to improve patient and caregiver outcomes, reduce unnecessary healthcare expenditures, and are the focus of Medicare’s new GUIDE payment model. Until now, prior research has focused on evaluating the effectiveness of participating for a short (eg, 12‐month) time frame. The purpose of this study was to evaluate the effects of the Care Ecosystem when delivered for up to 5 years or end of life.

Methods

Of the 804 PLWD‐caregiver dyads enrolled in the previously reported single‐blind 12‐month RCT of the Care Ecosystem (NCT02213458), 456 reported high baseline caregiver burden and were included in this extension trial (NCT04287738). Telephone‐based dementia care management was delivered by a trained care team navigator, with a team of dementia specialists. Primary outcome: PLWD quality of life (QoL‐AD); Secondary: caregiver depression (PHQ‐9), self‐efficacy (Care Ecosystem Self‐Efficacy scale), and burden (Zarit‐12), and PLWD ED and hospital use. The cumulative treatment effect was the sum of the average treatment effect on each outcome at each timepoint, weighted by the number of active participants over time. Linear mixed effects models were used to estimate the treatment effect at the annual timepoints. Caregivers’ perspectives on the value of longer care were derived via semi‐structured interviews after 5 years of participation.

Results

In this prespecified analysis including 297 dyads randomized to Care Ecosystem participation and 159 dyads to usual care, the cumulative 5‐year treatment effect on quality of life, caregiver depression and self‐efficacy were significant; there was a trend for caregiver burden. These treatment effects were most robust during the first 2‐3 years of the study (Figure). The cumulative treatment effects on ED and hospital use were not significant. Most caregivers who participated for the 5 full years indicated that the emotional and practical support was helpful for the duration, but many derived the greatest benefit during the first few years when they were newer to being a caregiver.

Conclusion

The benefits of dementia care management on PLWD quality of life and caregiver well‐being are sustained for five years, with the greatest effects in the first 2‐3 years.
Investigation of correlation between negative communication and characteristics of caregivers of people with dedmentia
Authors: da Silva Amanda Gorziza , Gheno Lucimara Lehmen , Fernandez Liana Lisboa , Rieder Carlos Roberto Mello , Beber Bárbara Costa
Published: January 2025

Background

Caregivers of people with dementia (PwD), assuming the responsibility for another life, can become physically and emotionally overwhelmed, leading to increased psychiatric symptoms such as anxiety and depression. Similarly, the level of neuropsychiatric symptoms in PwD is associated with caregiver burden. Faced with this burden and the challenges of managing dementia, caregivers may potentially channel their feelings of frustration and exhaustion from caregiving into the way they communicate with the person with dementia. It is important to identify the determinants of negative communication by caregivers to develop educational programs to improve communication. The objective of this study was to verify the correlation between negative communication and characteristics of caregivers of PwD.

Method

This is an excerpt from a descriptive cross‐sectional observational study involving a sample of 11 caregivers. We collected sociodemographic data and information regarding the characteristics of care. The following tools were administered to caregivers of PwD: Negative Communication Scale (NCS), which assesses the caregiver’s negative communication through questions related to daily communication with the patient; Zarit Burden Scale, which assesses caregiver burden; Mini‐Mental State Examination (MMSE), a screening test for a quick evaluation of cognitive function. Statistical analyses were conducted using Chi‐Square and Spearman tests with a significance level of 5%.

Result

The study included 11 caregivers of PwD. Their characteristics are presented in Table 1. Table 2 shows the correlations between the NCS and characteristics of the sample. There was a positive correlation between the NCS and education, suggesting that the higher the education, the worse the perception of the caregivers regarding their use of negative communication. Despite the absence of statistical significance, there was a trend for positive correlations with MMSE and Zarit scores. Additionally, there was no significant difference in the NCS when compared between sexes (p = 0.57) and types of relationships of the caregivers with the PwD (p = 0.48) (Chi‐Square test).

Conclusion

Education may be correlated with the occurrence or perception of negative communication acts used by caregivers. Despite the presented correlations, it is necessary to increase the sample size to demonstrate/confirm these correlations, as well as trends in correlations.
The relationship between APOE genotype and dementia varies by genetic ancestry and race/ethnicity
Authors: Gilmore Marian J , Varga Alexandra M , Schaefer Catherine , Banda Yambazi , Hoffmann Thomas J. , Glymour M. Maria , Weinmann Sheila A , Choquet Hélène , Smith Ning , Gilsanz Paola , Massimino Stefan , Brenowitz Willa D
Published: January 2025

Background

Some evidence suggests the effect of APOE genotype on dementia risk may vary by race/ethnicity and genetic ancestral background. We evaluated APOE genotype and associated dementia risk by genetic ancestry, with a focus on expanding research among participants with non‐European ancestry.

Method

The Kaiser Permanente Research Bank (KPRB), one of the largest biobanks in the US, enrolled members of an integrated health system, collected genotyping and health surveys and link to electronic health records (EHR). Genetic ancestry proportions (range 0‐1) were estimated using the program ADMIXTURE. First diagnosis of all‐cause dementia was collected from EHR over a mean follow‐up time of 14.6 years. Logistic regressions evaluated associations of APOE e4 and e2 allele status with dementia adjusted for sex and age. We tested interactions between APOE and race/ethnicity (from self‐report and/or EHR) and separately APOE and genetic ancestry.

Result

Preliminary analyses included 180,345 participants (mean age at consent 56.17 years), including 17,356 Asian, 11,595 Black, 926 Hawaiian/Pacific Islander, 22,663 Hispanic, 3,714 multiracial, and 498 Native American/Alaska Native participants. APOE e4 allele prevalence was highest among Black participants (34%) and lowest among Asian participants (17%). APOE e2 allele prevalence was highest among Black participants (17%) and lowest among Hispanic (8%) and Native American/Alaskan Native (9%) participants. APOE e4 allele (but not APOE e2) significantly interacted with both race/ethnicity and genetic ancestry, although associations were elevated among all groups. The association of APOE e4 with dementia diagnosis (n = 8,288) was strongest among White participants (OR: 1.67; 95%CI:1.59,1.75) and was significantly lower among Black (OR interaction: 0.83; 95%CI:0.69,0.99) and Hispanic participants (OR interaction:0.79; 95%CI:0.65,0.95). Similarly, the association of APOE e4 with dementia increased with higher proportion of European ancestry (OR interaction:1.30, 95%CI:1.13,1.49). The association of APOE e4 allele with dementia was reduced with higher proportion African ancestry (OR interaction:0.71, 95%CI: 0.57,0.90), and Native American ancestry (OR interaction: 0.52, 95%CI: 0.30,0.91).

Conclusion

In preliminary analyses, we found APOE e4 allele association with dementia differed by European, African, and American genetic ancestries, which correlated with differences by race/ethnicity. Our findings suggest genetic ancestral background is important when utilizing APOE genotype in determining risk for dementia.
Perceptions and experiences of living with dementia in sub‐Saharan Africa: a systematic review of qualitative studies
Authors: Guerchet Maëlenn , Boyer Alexandre , Preux Pierre‐Marie
Published: January 2025

Background

In sub‐Saharan Africa (SSA), the number of people living with dementia is expected to double every 20 years, from 2.7 to 7.6 million. Understanding beliefs, perceptions and experiences relating to dementia, care, and help‐seeking are critical to understanding the nature of the problem and designing research programmes, interventions and services which meet locally defined needs. We carried out a systematic review of the scientific qualitative evidence on the perceptions and experience of living with dementia in SSA.

Method

We conducted a systematic review of qualitative studies (open‐ended in‐depth interviews, focus‐group discussions and ethnographic methods) including people living with dementia (PLWD), family caregivers of PLWD, paid caregivers, healthcare workers, traditional and faith healers with experience of treating PLWD, and community members. The search strategy to identify relevant articles used the search terms “(dementia OR Alzheimers)” AND “(qualitative OR anthrop* OR ethnog* OR cultural OR understand* OR belie* OR experien* OR phenomenol*) AND “(Africa OR sub‐Saharan Africa OR [list of countries included in SSA according to World Bank definition]), in eight databases (PubMed, BiblioInserm, PsycINFO, PsycARTICLE, Web of science, Google Scholar, IENT et DATAD – Database of African Theses and Dissertation). A thematic synthesis approach was then used.

Result

The search retrieved 4967 abstracts. Following abstract screening and full‐text assessment, 16 studies were eligible from 10 different countries (South Africa, Tanzania, Nigeria, Ghana, Republic of Congo, Central African Republic, Kenya, Ethiopia, Uganda, and Burkina Faso). Overall, there was a lack of awareness of dementia among the community and no equivalent term for dementia was identified in any local languages. Often it was believed that although not experienced by everyone, dementia‐like symptoms were part of “normal ageing”. Participants frequently reported problems with memory and communication as well as problems typically associated with co‐morbidities of old age (pain, sight/hearing problems).

Conclusion

Qualitative evidence regarding dementia perceptions and experiences in African populations remains limited compared to quantitative evidence. Findings suggest that there is a desire to gain a better understanding of the lived experience of dementia, which is essential to design culturally sensitive education, to counteract stigma and to enhance management of the condition.
Self‐awareness of acute post‐stroke cognitive decline
Authors: Caf Kim , Rakusa Martin
Published: January 2025

Background

Post‐stroke cognitive impairment is a serious complication which could be easily overlooked. Our study aimed to evaluate patients' awareness of post‐stroke cognitive impairment.

Methods

We included 74 patients (40 women) after acute stroke. Cognitive decline was assessed using the self‐reported questionnaire, the Montreal Cognitive Assessment (MoCA) and the Hachinski Ischaemic Score (HIS). A previously validated cut‐off score of 24/25 [1] was used to determine cognitive impairment. Patients were divided into four groups. Demographic data and MoCA score were compared among four groups using ANOVA.

Results

The mean age of patients was 68.4 years (SD 14.32), the mean MoCA was 21.8 (SD 5.75), and the mean HIS was 8.1 (SD 2.8). Both self‐reported post‐stroke cognitive impairment incidence and MoCA‐evaluated incidence were 63%. MoCA score significantly correlated with education (r = 0.36; p<0.001) and age (r = ‐0.38; p<0.001), but not with HIS.

Thirty‐one patients were aware of their cognitive decline (MoCA 18.2; SD 1), 16 denied cognitive decline despite mean MoCA 20 (SD 1), 16 falsely reported cognitive decline (MoCA 27; SD 0.4), and 11 correctly denied cognitive impairment (MoCA 27, SD 0.4). There were no significant differences between groups in HIS.

For self‐reported post‐stroke cognitive impairment, sensitivity was 66%, specificity was 59%, positive predictive value was 66%, and negative predictive value was 59%. The accuracy rate was 57%, and precision 63%.

Conclusions

our results demonstrate that cognitive impairment is common in patients after acute stroke. However, self‐awareness is low. Therefore, it is necessary to search for post‐stroke cognitive impairment actively, especially in older, lower‐educated patients.

Reference

[1] Potocnik J, Ovcar Stante K, Rakusa M (2020) The validity of the Montreal cognitive assessment (MoCA) for the screening of vascular cognitive impairment after ischemic stroke. Acta Neurol Belg 120:681‐685. https://doi.org/10.1007/s13760‐020‐01330‐5
Should the perspective of subjective memory decline differ between cognitively unimpaired individuals and their informants? Baseline results of the BRASCODE Cohort
Authors: Santos Rhaná Carolina , Carnevalli Sarah Vitoria Bristot , De Souza Haniel Bispo , Souza Victória Tizeli , Giordani Manuella Edler Zandoná , da Mota Simone Sieben , De Marchi Bruno De Olive , Formoso Carolina Rodrigues , Rivas Gabriela Raquel Paz , Carvalho Guilherme Da Silva , Beltrami Lucas Bastos , Suwa Samuel Masao , Slaviero Wesley , de Albuquerque Ana Letícia Amorim , Strelow Matheus Zschornack , Borelli Wyllians Vendramini , Carello‐Collar Giovanna , Chaves Marcia L Fagundes , Zimmer Eduardo R. , Castilhos Raphael Machado
Published: January 2025

Background

Subjective Cognitive Decline (SCD) is characterized by cognitive complaints in cognitively unimpaired (CU) individuals. Its condition displays considerable heterogeneity etiologies, including neurodegenerative diseases. Our aim is to compare the memory complaints between patients with SCD and their informants in the BRASCODE cohort.

Method

The BRASCODE cohort includes CU individuals aged >65 presenting memory complaints and at least one SCD‐plus criteria. The MCS was held separately with both participants and informants. Additionally, baseline sociodemographic and Mini Mental State Examination (MMSE) data were held. Participants and informant’s concordance regarding patients' memory complaints was assessed using the MCS scale. If both answers were ≥ 7, there was concordance. The continuous variables were described as median (interquartile range, IQR) and categorical variables as frequencies. Scores of the MCS scale ranges from 0 to 14, with scores ≥ 7 indicating complaint; and were compared using Spearman’s rho and Mann‐Whitney test.

Result

Data were collected between March‐2022 and December‐2023. 143 SCD patients were included (mean age = 69; 72.2% female). The median MCS‐patient and MCS‐informant was 8 and 5, respectively. The patients have a median of 3 SCD‐plus criteria, most with complaints at age ≥ 60 and with concerns regarding memory. The SCD‐patient scale correlated negatively with patient age (rho = ‐0.244; p = 0.003) and positively with informant’s SCD scale (rho = 0.305; p = 0.0002), but not with patient education nor with MMSE results. Most participants (86, 60.1%) and their informants' perceptions disagree about patients' memory decline. The participants in the group with concordant MCS scores had lower education (11 vs 16) and were more balanced in relation to sex (32 [56.1], 71 [82.6]) than the group with discordante responses. The patients' age and MCS were not different between the groups.

Conclusion

The baseline results show that most dyads disagreed regarding participants' memory decline. In addition, the presence of informant perception of decline may be a risk factor for a future cognitive decline. The AD biomarkers analysis as well as one and two‐year follow‐ups may yield valuable insights into the correlation between patients' and informants' reported complaints.
Neurocognitive Predictors of Financial Capacity: Exploring Commonalities in Brain Structure and Predictive Value of MRI in Pre‐Dementia Stages of Alzheimer’s Disease
Authors: Le Kayla , Bieger Andrei , Schlickmann Thomas Hugentobler , De Bastiani Marco , Gehres Sarah Wehle , Borelli Wyllians Vendramini , Zimmer Eduardo R. ,   ADNI
Published: January 2025

Background

Several studies have shown that financial capacity constitutes a vital component of instrumental activities of daily living. However, there is insufficient research investigating the relationship between financial impairment, brain volume changes and cognitive decline in Alzheimer’s disease (AD). Here, we examine the association between brain volume changes and financial capacity in cognitively unimpaired (CU) and mild cognitively impaired (MCI) individuals.

Method

A total of 344 individuals who had completed the Financial Capacity Instrument‐ Short Form (FCI‐ SF) assessment and underwent magnetic resonance imaging (MRI) imaging from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were selected. Volume and cortical thickness average were extracted from the MRI images. Table 1 reports demographic information. Linear regression analysis explored associations between the structural brain features and the total FCI‐Score. The model was adjusted for age, gender, education and race. Lastly, stepwise regression analysis was performed to determine the predictors of financial capacity.

Result

MCI individuals performed significantly worse on the FCI‐SF compared to CU individuals (p < 0.01, Cohen’s d = ‐ 0.55). Our model indicates that the temporal lobe and parahippocampus are bilaterally associated with the FCI‐Score (Figure 1). Stepwise regression analysis revealed that left parahippocampus thickness (p < 0.05) is a significant predictor for the FCI Score (Figure 1).

Conclusion

Our results are consistent with earlier research showing changes in financial capacity in pre‐dementia stages, emphasizing important brain structures with potential predictive character. These findings enhance our comprehension of how brain structural changes are linked to deficits in financial skills before dementia and further evidence to consider these as early warning signs for cognitive decline.
Socioeconomic and health‐related disparities associated with healthy brain aging in Latin American countries
Authors: Da Ros Lucas Uglione , Borelli Wyllians Vendramini , de Bastiani Marco Antônio , Aguzzoli Cristiano Schaffer , Schilling Lucas Porcello , Santamaría‐García Hernando A , Pascoal Tharick A. , Rosa‐Neto Pedro , da Costa Jaderson Costa , Ibáñez Agustín , Suemoto Claudia Kimie , Zimmer Eduardo R.
Published: January 2025

Background

Latin American Countries (LACs) have major health‐related inequities due to historical, cultural, and social aspects. These factors have been suggested as important determinants of healthy aging in LACs. Here, we evaluated classic and socioeconomic risk factors for healthy brain aging across five large cohorts of LACs.

Method

Risk factors for healthy aging were evaluated using machine‐learning models in 41,092 individuals across five LACs ([Brazil, n = 9,412], Colombia [n = 23,694], Chile [n = 1,301], Ecuador [n = 5,235], and Uruguay [n = 1,450] (Fig. 1A). Healthy brain aging was evaluated using z‐scored cognitive and functional ability data with selected risk factors (Age, Sex, Diabetes, Education, Isolation, House Condition, Hypertension, Heart Disease, Alcohol Consumption, Physical Activity, Smoking, Falls, and Mental Health Problems). The fitness of models was evaluated with Mean Standard Error (MSE) and Raw Mean Standard Error (RMSE) extracted from Ridge Regressions Models (adjusted p<0.05).

Result

Regarding cognition, our machine‐learning model with LACs was significant. The most important risk factors were mental health symptoms, education, country, physical activity, alcohol consumption, falls, socioeconomic status, isolation, age, and smoking status. No significant effects of heart disease, hypertension, sex, and diabetes were found (Fig. 1B). The model assessing functionality in LACs was also significant and presented the following order of risk factors: physical activity, mental health symptoms, falls, heart disease, alcohol consumption, diabetes, sex, hypertension, age, SES, education, education, and smoking status. Country and isolation did not reach statistical significance (Fig. 1C).

Conclusion

Our findings demonstrated that social and health disparities outweigh classic risk factors, such as age and sex, for cognitive and functional decline in LACs, highlighting the need to identify risk factors for healthy brain aging in underrepresented populations.
The Strengthening, engaging, and empowering dyads through nutrition & wellness study: a dyadic community‐based nutrition intervention for older adults with diabetes and cognitive impairment
Authors: Ceide Mirnova E , Johnson Samantha , Darapaneni Ruchika , Zwerling Jessica L
Published: January 2025

Background

A meta‐analysis of over 2.3 million individuals in 14 studies showed that individuals with type II diabetes (T2DM) are at a 60% increased risk for development of any dementia compared to those without T2DM. A Whole Food, Plant Based dietary (WFPB) pattern has been associated with lower blood glucose levels and decreased insulin requirements. As older adults at risk for Alzheimer’s disease (AD) may be dependent on care partners for nourishment, it is imperative to involve the caregiving dyad in a lifestyle intervention. We propose a collaboration between our center of excellence for AD and a community‐based organization (CBO) that empowers people through WFPB nutrition. We will pilot a dyad‐focused nutritional educational series for older adults with T2DM and CI and their care partners in a local senior center.

Method

In this single arm study, we will recruit 2 cohorts (English N = 15 and Spanish N = 15) of older adults (≥65) with T2DM and CI and their care partners to participate in 4 WFPB nutrition classes. Each class consists of: 1 hour of education and 1 hour of a culinary demonstration. We will also include 2 care partner support sessions co‐led by the nutrition facilitator and geriatric social worker at weeks 3 and 6.

Result

In order to establish feasibility, we will assess important baseline characteristics of our participants including: food insecurity, cognition (Telephone MoCA), and multisensory integration (CatchU® mobility application). Acceptability, appropriateness, and feasibility of the intervention will be assessed quantitatively and qualitatively in debrief interviews. We will evaluate the preliminary efficacy on the intervention dietary pattern (including the MIND diet screen), diabetes self‐efficacy, and diabetes management: mean weekly glucose (logs and continuous glucose monitors).

Conclusion

We will engage a high‐risk cohort of older adults with T2DM and CI through an inclusive and pragmatic study design. Rather than developing a novel nutrition intervention, we will leverage two local CBOs to provide the intervention and the location. This project will yield pilot data for a pragmatic randomized controlled trial of a dyadic nutrition intervention to improve metabolic health and cognition in older adults at‐risk for AD, especially those with diabetes.
Delphi Method Exploration of Dementia Program Metrics: Preliminary Insights from Expert Panel
Authors: Gholizadeh Shadi , Neal Matthew , Hayes Kirk , Geiss John Mark
Published: January 2025

Background

Measuring the effectiveness of dementia care programs is essential for ensuring quality care and aligning with value‐based care principles, especially in practical, real‐world clinical settings. A Delphi method, a consensus‐building approach among experts, was used to identify practical metrics for evaluating dementia programs. The expert panel comprised a clinical psychologist, two healthcare executives, and a physician experienced in person‐centered care for older adults in residential and facility settings.

Method

The Delphi method involved a series of structured questionnaires sent to the panelists. The process began with open‐ended queries regarding crucial outcomes and indicators for dementia care effectiveness. Through iterative rounds, the panel’s collective input was used to hone in on the most relevant and practical metrics for real‐world clinical assessment of dementia programs.

Result

The expert panel reached a consensus on several key metrics, including patient and caregiver satisfaction, efficacy in managing behavioral symptoms, reduction in emergency room visits and hospital admissions, and medication adherence. Additional metrics included health behaviors among patients and caregivers, caregiver perceptions of burden and resilience, and the actual engagement with and utilization of recommended caregiver support and education. A notable discussion point was the mode and frequency of assessing these metrics, with a recognition of the need for parsimony to minimize patient and caregiver burden and practicality and ease of assessment and scoring for non‐clinical medical staff.

Conclusion

This Delphi study provided critical insights into relevant metrics for dementia program evaluation. The identified preliminary metrics serve as a foundation for further refinement with a broader expert panel, including considerations for assessment methods and frequency. The ultimate aim is to develop a comprehensive, practical set of metrics that accurately reflects dementia care program quality and impact, catering to the needs of smaller clinical practices. These measures will support continuous improvement and adherence to value‐based care goals, enhancing dementia care quality across diverse clinical settings.
Clinical and epidemiological baseline characterization of dementia cases in a specialized center in Recife
Authors: de Luna Mariana Albuquerque , Negri Camila Oliveira , Lima Bruna Cristina de Oliveira , de Albuquerque João Augusto de Macedo Cavalcanti , Moutinho Bárbara Nascimento , Júnior Ilo de Vasconcelos Ximenes , Silva Mariana Leandro , da Silva Tatiana Caldas Neves , Queiroz Barbara Matos Almeida , Barbosa Breno José Alencar Pires
Published: January 2025

Introduction

Dementia numbers are increasing rapidly with a substantial contribution from low and middle‐income countries. There’s a limited number of reports in Brazil, mostly modest initiatives from south‐eastern, more developed regions. With a population of approximately 1.6 million individuals, Recife is among the largest cities of Northeast Brazil, a region of steep social disparities and high prevalence of low‐literacy. The aim of this study was to describe the sample of patients followed at a dementia outpatient clinic in a tertiary center in Recife

Methods

this is a single‐center, descriptive and health records‐based analysis of patients evaluated in the dementia outpatient clinic of the Neurology and Neurosurgery Unit at the Federal University of Pernambuco between 2018 – 2023.

Results

168 medical records were analyzed, of which 137 met the inclusion criteria. 44.59% were male, with a mean age of 66 years. 29.3% of the sample had 8 to 11 years of formal education. On the other hand, 21.7% were illiterate. The mean baseline score on the Mini‐Mental score was 17. Alzheimer’s disease was the most frequent diagnosis (25%), followed by frontotemporal dementia (9.46%), Lewy body disease (4.05%) and Pure Vascular dementia (4.05%). The woman’s main caregiver was her offspring (79%). The man´s main caregiver was his partner (84%). 44% of the sample had hypertension and diabetes (25%). 20% were alcoholic and 19% were smokers. The average follow‐up time for severe dementia was 30.4 months. 66.4% of our sample underwent magnetic resonance imaging and 16% had access to molecular imaging methods.

Conclusion

patients referred for evaluation were mostly in moderate to advanced stages of dementia, with a significant prevalence of mixed‐type and non‐Alzheimer’s pathologies. This data could suggest a referral bias and poor access to specialized clinics. Despite a modest sample size and heterogeneous data, the present study may contribute towards a better characterization of dementia numbers in the Northeast of Brazil.
Alzheimer disease incidence increases with country‐level intake of Omega‐6 Polyunsaturated Fatty Acids
Authors: Ciesielski Timothy H , Durodoye Razaq O , Tosto Giuseppe , Pericak‐Vance Margaret A , Haines Jonathan L. ,   Alzheimer’s Disease Genetics Consortium (ADGC), Williams Scott M
Published: January 2025

Background

Evidence from diverse fields implicates lipid dysfunction in Alzheimer Disease (AD) pathogenesis. However, lipid consumption at the individual level does not vary greatly within most study cohorts, and multiple lipids are rarely well‐measured concurrently. In contrast, mean lipid intakes at the country‐level can be precisely estimated and can vary substantially across countries. These can be compared to annual age‐standardized Alzheimer Disease incidence (ASAIR) to assess the role of lipid consumption in population risk.

Methods

Mean country‐level lipid intake estimates were compared to ASAIR in 183 countries across all 6 inhabited continents. Penalized spline regression analysis including a lag between intake and incidence was used to assess nonlinearities in the relationships between 5 lipids and ASAIR. We then used multivariable‐adjusted linear regression models to quantify the linear portions of these relationships. Validation was conducted using longitudinal within‐country changes between 1990 and 2019.

Results

Bivariate penalized spline regression analyses revealed non‐linearity in the relationships between saturated‐fat, trans‐fat, dietary cholesterol and ASAIR. For each lipid, ASAIR increased with increasing intake up to a threshold, however in the lower‐powered longitudinal validation attempts these associations in the low‐intake range were not significant. Omega3 and Omega6 Polyunsaturated‐Fatty‐Acids (PUFA) exhibited linear relationships between intake and ASAIR in the spline analyses. The multivariable‐adjusted linear regression model revealed a positive association between Omega6‐PUFA (as a % of total energy intake) and ASAIR (β = 2.44; 95%CI: 1.70, 3.19; p = 1.38×10−9). Longitudinal analyses comparing the percent change in the country‐level intake from 1990 to 2010 to the percent change in ASAIR from 1990 to 2019 further supported the direction and significance of this relationship (β = 0.036; 95%CI: 0.015, 0.057; p = 8.21×10−4).

Conclusions

Our results indicate that higher levels of Omega6 PUFA consumption associate with increased incidence of AD globally. From a public health point of view, national recommendations or policy to decrease Omega6 PUFA consumption could have substantial benefits in reducing the burden of AD. The scale of benefits will vary by country, but in the US alone our results predict that a 2 SD decrease in mean Omega‐6 PUFA intake would reduce ASAIR by 8% (∼28,000 incident cases).