BACKGROUND AND OBJECTIVES:Super movers are individuals aged ≥80 years with gait speeds ≥1.5 SDs above age- and sex-adjusted means. Super movers tend to have lower prevalence of chronic medical conditions, healthier lifestyles, and younger biological age. The aim of this study was to examine their risk of incident cognitive impairment, trajectories of cognitive decline, and brain health. METHODS:This study used a retrospective study design using data from older adults aged ≥80 without Alzheimer disease or dementia enrolled in 5 Health and Retirement Study International Network of Studies (HRS-INS), the LonGenity Study, and the RUSH Memory Aging Project (RUSH MAP). HRS-INS data were used to assess incident cognitive impairment (>1.5 SD below the age-adjusted means on any cognitive test plus impaired Instrumental Activities of Daily Living) in super movers vs nonsuper movers. Age- and sex-adjusted hazard ratios (HRs) from Cox models were pooled in a meta-analysis to obtain risk of incident cognitive impairment. LonGenity data were used to examine (1) decline in cognitive domains using linear mixed-effects models adjusted for age, sex, education, and parental longevity; (2) trajectories of global cognition before and after age 80; and (3) brain structural differences (cortical thickness, hippocampal volume) between super vs nonsuper movers. RUSH MAP data were used to assess dementia-related pathology. RESULTS:HRS-INS study (n = 3,989, baseline age 83.6-84.4 years, 47%-65% females, 358 super movers), after excluding 274 adults with cognitive impairment at baseline, super movers had lower risk of incident cognitive impairment (HR 0.49, 95% CI 0.28-0.71) over follow-ups ranged between 3.4 and 5.4 years. In LonGenity (n = 197, baseline age 84.6 [SD 3.3], 57.8% women), super movers showed slower memory and non-memory-related cognitive decline and preserved hippocampal volume in specific subfields. In RUSH MAP (n = 692, baseline age 85.6 [SD 4.0], 68.9% women), super movers had better antemortem cognition and lower Alzheimer disease and dementia prevalence, but no differences in postmortem dementia-related pathologies. DISCUSSION:Super movers show slower cognitive aging-indicated as lower risk for cognitive impairment and slower cognitive decline-and preserved hippocampal volumes. Investigating their behavioral and biological traits may reveal novel protective mechanisms against cognitive decline and dementia.

Background:Reduced heart rate variability (HRV) has been associated with cognitive decline in older adults. However, prior research relied on brief in-clinic electrocardiography (ECG) recordings to measure HRV. Using 7-day continuous ambulatory ECG monitoring, we investigated time-specific differences in HRV (i.e., differences in HRV at each time point over the course of a 24-h day) between individuals with mild cognitive impairment (MCI) and those who were cognitively normal (CN) in a cohort of community-dwelling older adults. Methods:Analyses included 81 dementia-free participants [mean age = 78, standard deviation (SD) = 5, age range = 72-95; 82% female; 38% non-Hispanic White individuals, 43% non-Hispanic Black individuals]. Among them, 20 met the Jak/Bondi criteria for MCI. Participants were instructed to wear a single-lead ECG monitor continuously for 7 days. Power spectral analyses were used to determine HRV in the high-frequency band (0.15-0.40 Hz, HF-HRV) over consecutive 5-min epochs throughout the recording. Functional additive mixed models were used to analyze participants' 24-h HF-HRV profiles to examine time-specific HRV differences between MCI and CN, after adjusting for age, sex, ethnicity, and education and further adjusting for depression, history of diabetes, and hypertension. Results:Compared to the CN group, the MCI group showed reduced HRV in the early morning (before 7 a.m.) and evening (after 7 p.m.), with the greatest difference occurring around midnight (difference: 0.6, 95% pointwise CI: 0.2, 1.1, Cohen's d: 0.75). Conclusion:Our findings highlight HRV's dynamic nature and the need to consider the time of day when investigating the relationship between HRV and cognition. Compared to daytime HRV, reduced nighttime HRV may have a stronger association with worse cognition.

BackgroundInterpreting blood-based biomarkers of Alzheimer's disease and related dementias (ADRD) in a multicultural cohort is complicated by inconsistent evidence on racial differences. Kidney function, which varies by race and influences biomarker levels, is often overlooked, potentially contributing to these inconsistencies.ObjectiveTo characterize racial differences in plasma levels of ADRD biomarkers after adjusting for comorbidities and assessed the impact of estimated glomerular filtration rate (eGFR) adjustment using either race-specific or race-neutral equations.MethodsData from the Einstein Aging Study, a multicultural cohort of older adults, included plasma biomarkers (Aβ40, Aβ42, pTau181, NfL, GFAP). Linear regression models evaluated racial differences in AD plasma biomarkers, adjusting for age, sex, body mass index, kidney function assessed via race-adjusted (eGFR-ASR) and race-neutral (eGFR-AS) equations, comorbidities (e.g., diabetes, hypertension, cardiovascular disease), and APOE ε4 carrier status.ResultsAmong 269 participants, Black participants had lower plasma levels of Aβ40 (p = 0.004), Aβ42 (p = 0.002), and NfL (p = 0.022) compared to White participants. We observed modest variation in the magnitude of racial differences depending on the method used to adjust for kidney function. However, race differences remained after adjusting for comorbidities or APOE ε4 carrier status.ConclusionsObserved racial differences in ADRD biomarkers remain unexplained by kidney function, comorbidities or APOE ε4 carrier status. Future research focusing on associations between blood-based biomarkers and gold standards of brain pathology in multicultural cohorts are essential to advance the usability of blood biomarkers.

Abstract BackgroundMigraine ranks among the leading causes of disability worldwide. Comorbid depressive symptoms are highly prevalent in patients with migraine and are associated with worsened pain severity, greater migraine-related disability, and poorer migraine prognosis. Despite this burdensome comorbidity, the treatment of these co-occurring disorders has rarely been studied. While mindfulness-based cognitive therapy (MBCT) shows promise for addressing both migraine-related disability and depressive symptoms, its traditional format—8 weekly 2-hour sessions in person—creates substantial access barriers, particularly for patients who experience frequent debilitating migraine and mood symptoms. ObjectiveThe objective of the Treatment for Migraine and Mood (TEAM-M) trial is to evaluate the feasibility of an abbreviated MBCT intervention (MBCT-Brief) delivered via telephone or videoconferencing in adults with migraine and elevated depressive symptoms. MethodsTEAM-M is a 3-site trial with a goal sample size of 145 adults with episodic migraine and elevated depressive symptoms randomized to MBCT-Brief telephone, MBCT-Brief videoconferencing, or enhanced usual care (EUC). To be eligible, participants must meet the criteria for migraine as defined by the International Classification of Headache Disorders 3rd edition, have ≥1 year of migraine history, and have mild to moderate depressive symptoms (scores 5‐19 on the Patient Health Questionnaire-9). ResultsOur primary outcomes include treatment feasibility, acceptability, and fidelity. Our secondary outcomes include headache disability, migraine-specific quality of life, and depressive symptoms. This trial was funded in May 2021. We began recruitment in November 2023 and completed enrollment in January 2026. As of May 2026, we have randomized 145 participants, of which 104 have completed the intervention and provided data for our primary outcomes. Data analysis is currently in progress, and primary outcome results are expected to be submitted for publication in spring 2027. ConclusionsThe TEAM-M trial addresses a gap in clinical care by evaluating an abbreviated version of MBCT that has scalability and accessibility advantages over full-length MBCT and the potential to address both migraine and depressive symptoms. By reducing the time commitment while maintaining the core MBCT components, MBCT-Brief can potentially address significant access barriers that often prevent patients from receiving evidence-based health care for comorbid physical and mental health symptoms. The remote delivery model offers enhanced scalability. This trial will also yield information about potential differences in telephone versus videoconferencing delivery, which will inform optimal integration into existing primary care and mental health clinic workflows, allowing for improved access to specialized care for mental health and migraine across diverse health care settings.

Recent research reveals that Alzheimer’s Disease blood-based biomarkers (BBB) are influenced by demographics as well as kidney function and comorbidities. Data on differences in BBBs by race and ethnicity are sparse. We examined whether racial/ethnic differences in BBBs persist after controlling for kidney function and comorbidities. Analyses included data from 274 EAS participants (mean age 77.57, SD 5.01, 67.5% Female, 46.4% Non-Hispanic-White, 41.2% Non-Hispanic Black, 12.4% Hispanic). BBBs included β-amyloid (Aβ40, Aβ42), Aβ42:Aβ40 ratio, pTau181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Estimated glomerular filtration rate (eGFR) was calculated using either age-sex-race-adjusted (eGFR-ASR) or age-sex-adjusted (eGFR-AS) creatinine equations (Inker et al., 2021 NEJM). History of hypertension, diabetes, stroke, myocardial infarction, angina, and congestive heart failure were ascertained by self-report. Linear regression was used to assesses race/ethnic differences in BBBs adjusted for age, sex, BMI, and MCI status. Further models adjusted for eGFR-AS, eGFR-ASR, and comorbidities. Non-Hispanic Whites were treated as the reference group. Initial models indicated significantly lower Aβ40 in non-Hispanic Black and Hispanic (global p = 0.014) individuals and lower Aβ42 in non-Hispanic Black (global p = 0.005) individuals compared to non-Hispanic Whites. Further adjustment for using eGFR-ASR attenuated racial/ethnic differences for Aβ40 (p = 0.099) and Aβ42 (p = 0.038), while adjustment using eGFR-AS did not. We observed lower levels of NfL in non-Hispanic Blacks and Hispanics (p = 0.003) adjusting for age, sex, BMI, and eGFR-AS but not when adjusting for eGFR-ASR. Both eGFR-ASR and eGFR-AS were negatively significantly associated with all BBBs. None of the comorbidities were significantly associated with any of the BBBs, and adjusting for comorbidities did not impact the observed racial/ethnic differences. Race/ethnic differences in Aβ40 and Aβ42 levels persisted after adjusting for eGFR-AS and comorbidities. Race differences in BBBs were reduced in magnitude when adjusting for eGFR-ASR, but not when adjusting for eGFR-AS. Future research should pursue adjustment using the more accurate cystatin-C eGFR equation to determine whether race differences persist. Understanding these biomarker level differences across various races/ethnicities is crucial for the future of personalized and effective diagnosis, progression monitoring, and treatment of Alzheimer's Disease.

Objectives Few studies have examined daily effects of sleep on cognition. This analysis examined both between-person and within-person associations of actigraphic sleep with daily cognitive performance ascertained via ecological momentary assessments. Methods Data are from community-residing, dementia-free older adults in the Einstein Aging Study (mean age 77.2 ± 4.7, 67.3% female, 47% non-Hispanic White, and 40% non-Hispanic Black) who were free of dementia. Over 16 days, participants wore wrist actigraphs and completed cognitive assessments six times daily using study-provided smartphones and completed overnight pulse oximetry. Brief cognitive tasks assessed four domains of cognitive function. Multilevel linear mixed-effect models assessed associations of sleep characteristics with cognitive performance. Data were aligned such that models addressed the relationship between a day’s sleep parameters and the next day’s cognitive performance, adjusted for demographics, depression, cardiovascular comorbidity, and sleep-disordered breathing. Results In adjusted models, between-person associations showed that higher average wake after sleep onset (WASO) was associated with slower average processing speed, worse working memory, and worse visual memory binding. Within-person effects showed that an individual’s processing speed was slower than usual on days following a night with greater-than-usual WASO. Sleep duration, timing, or naps were not associated with any of the cognitive tests. Conclusions Using ambulatory assessments in real-world environments, the results demonstrate short-term effects of sleep fragmentation (WASO) on processing speed the next day in dementia-free older adults. Better understanding short-term effects might identify individuals who may benefit from early interventions to prevent long-term cognitive decline.

Alzheimer's disease and related dementias (ADRD) develop over 20 years with subtle impairments in Instrumental Activities of Daily Living (IADLs). This study aimed to determine whether specific IADLs are associated with risks for cognitive impairment in pre-ADRD stages. We used Gateway to Global Aging Data (g2aging.org) from the US Health and Retirement Study. In adults ≥65 years without an ADRD diagnosis ( n  = 10, 346), IADL impairments were self-reported as difficulty in managing money, medication, reading maps, using telephone, shopping for groceries and preparing meals. Memory-related cognitive impairment was defined as ≥1.5 SD below the study-specific mean for total recall combined with poor self-reported memory. Non-memory-related cognitive impairment was ≥1.5 SD below the mean in ≥2 cognitive tests including orientation, serial 7s and backward counting. Latent class analysis was performed to identify different groups of IADLs at baseline. Cox proportional hazards models adjusted for age, sex, education, were used to determine the associations between group membership in IADLs and the risk for cognitive impairment. Models were adjusted for post-stratification sample weights. Weighted mean age of participants was 74.3 years (SD 6.8), and 58% were women. Three IADL groups were identified: A high functioning group (86%), with low probabilities of difficulty in any IADLs ; a group with moderate difficulty in specific tasks such as managing money, shopping, reading maps and making meals (10%) ; and a low functioning group (4%), with high difficulty across all IADLs. The low functioning group showed increased risk (hazard ratio [HR] 2-2.5; p  <0.001) of developing both types of cognitive impairment compared to the high functioning group (during a mean 10.3 (SD 7.2) years of follow-up). The moderate functioning group also showed an increased risk for memory- (HR 2.0, p  = 0.001) and non-memory-related impairment (HR 1.6, p  <0.001) compared to the high functioning group (Table 1). Our findings suggest that even moderate difficulty in performing specific IADLs (i.e., managing money) is associated with an increased risk for cognitive impairment in older adults. These IADLs may serve as early risk indicators and have the potential to be developed into clinical trial endpoints in pre-clinical ADRD populations.

Limited work has evaluated continuous glucose monitoring (CGM) in relation to cognitive performance, and this has been conducted largely in type 1 diabetes. We explore associations between CGM and cognition among older adults with type 2 diabetes (T2D). Data are from community-residing adults over age 60 enrolled in the Einstein Aging Study, who self-reported T2D. Participants wore blinded Abbott FreeStyle Libre 3 sensors for 14 days and completed the WAIS III Digit Span, Trails A and B, Multilingual Naming(MINT), and WAIS III Block Design. CGM metrics include mean glucose, variability(coefficient of variation), %time in range(70-180 mg/dL), %time low(<70 mg/dL), %time high(181-250 mg/dL), and %time in very high(>250 mg/dL) glucose. Linear regression models were adjusted for age, sex, education and race/ethnicity. Interim analysis of the first 30 participants(73.9±7.4yrs, 56% female) indicate that they spent 73.8% of their time in range, 16.4% in high, 8.5% in very high, and 1.3% in low glucose. Less time in low glucose was associated with better Block Design scores(β = 0.35,p=0.041). More variability showed a trend with worse MINT scores(β = 0.36,p=0.058) and more time in high showed a trend with slower Trail B performance(β = 0.37,p=0.097). Metrics were not associated with Digit Span or Trail A. A wearable CGM protocol is feasible in older adults and identified clinically relevant metrics that were associated with cognitive performance in T2D. Time in hypo- and hyperglycemia, and variability, were most predictive, with each linked to different cognitive functions including visuospatial processing, language, and executive function. Analyses will be extended to the larger sample.

Subjective cognitive concerns (SCC) have emerged as important early indicators of Alzheimer’s disease (AD) risk. Traditional measures of SCC rely on recall-based assessments, which may be limited in capturing real-time fluctuations in cognitive concerns. Ecological Momentary Assessment (EMA) offers a promising alternative by providing real-time data. This study aimed to link SCC assessed via EMA and traditional measures with blood-based AD biomarkers in a diverse, dementia-free, community-based sample based in the Bronx, NY. Einstein Aging Study (EAS) participants underwent in-person, recall-based assessments of SCC during an in-clinic visit. Additionally, EMA SCC assessments were collected once per day over two weeks. Linear regressions were conducted to examine the relationships between SCC variables and plasma biomarkers adjusted for demographics and mild cognitive impairment (MCI) status. In N = 254 participants, EMA-reported SCCs demonstrated significant associations with AD biomarkers, particularly p-tau181 (β = 0.21, p = 0.001). Further, significant associations remain across both cognitive (cognitively unimpaired vs. MCI) and racial groups. In contrast, traditional SCC measures exhibited limited associations with these biomarkers. The findings highlight the added value of EMA in capturing SCCs that could indicate early ADRD risk. EMA provides a more dynamic and potentially sensitive method for detecting early AD risk compared to traditional SCC assessments. These real-time measures could enhance early detection and clinical intervention, particularly in diverse and under-resourced populations. This study underscores the potential of EMA for broad applicability and inclusivity in monitoring AD progression and facilitating early therapeutic interventions.

BackgroundThe 5-Cog paradigm is a 5-minute brief cognitive assessment coupled with a clinical decision support tool designed to improve clinicians’ early detection of cognitive impairment, including dementia, in their diverse older primary care patients. The 5-Cog battery uses picture- and symbol-based assessments and a questionnaire. It is low cost, simple, minimizes literacy bias, and is culturally fair. The decision support component of the paradigm helps nudge appropriate care provider response to an abnormal 5-Cog battery. ObjectiveThe objective of our study is to evaluate the effectiveness, implementation, and cost of the 5-Cog paradigm. MethodsWe will enroll 6600 older patients with cognitive concerns from 22 primary care clinics in the Bronx, New York, and in multiple locations in Indiana for this hybrid type 1 effectiveness-implementation trial. We will analyze the effectiveness of the 5-Cog paradigm to increase the rate of new diagnoses of mild cognitive impairment syndrome or dementia using a pragmatic, cluster randomized clinical trial design. The secondary outcome is the ordering of new tests, treatments, and referrals for cognitive indications within 90 days after the study visit. The 5-Cog’s decision support component will be deployed as an electronic medical record feature. We will analyze the 5-Cog’s implementation process, context, and outcomes through the Consolidated Framework for Implementation Research using a mixed methods design (surveys and interviews). The study will also examine cost-effectiveness from societal and payer (Medicare) perspectives by estimating the cost per additional dementia diagnosis. ResultsThe study is funded by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (2U01NS105565). The protocol was approved by the Albert Einstein College of Medicine Institutional Review Board in September 2022. A validation study was completed to select cut scores for the 5-Cog battery. Among the 76 patients enrolled, the resulting clinical diagnoses were as follows: dementia in 32 (42%); mild cognitive impairment in 28 (37%); subjective cognitive concerns without objective cognitive impairment in 12 (16%); no cognitive diagnosis assigned in 2 (3%). The mean scores were Picture-Based Memory Impairment Screen 5.8 (SD 2.7), Symbol Match 27.2 (SD 18.2), and Subjective Motoric Cognitive Risk 2.4 (SD 1.7). The cut scores for an abnormal or positive result on the 5-Cog components were as follows: Picture-Based Memory Impairment Screen ≤6 (range 0-8), Symbol Match ≤25 (range 0-65), and Subjective Motoric Cognitive Risk >5 (range 0-7). As of December 2024, a total of 12 clinics had completed the onboarding processes, and 2369 patients had been enrolled. ConclusionsThe findings of this study will facilitate the rapid adaptation and dissemination of this effective and practical clinical tool across diverse primary care clinical settings. Trial RegistrationClinicalTrials.gov NCT05515224; https://www.clinicaltrials.gov/study/NCT05515224 International Registered Report Identifier (IRRID)DERR1-10.2196/60471

BACKGROUND:Mild traumatic brain injury (mTBI) can result in persistent neurological symptoms and signs and may contribute to late life cognitive decline. Yet, recognition of post-mTBI symptoms in older populations, especially in low-middle-income countries such as India, remains inadequate. Hence, there is a critical need to develop a screening tool to assess lifetime post-mTBI symptoms in India, which has a disproportionately high rate of TBI. OBJECTIVE:To develop the Kerala Brain Injury Questionnaire (KBIQ) to assess post-mTBI (postconcussive) symptomatology. METHODS:We examined the feasibility, reliability, and validity of the KBIQ, which assessed clinical symptoms possibly related to mTBI over the previous month in the Kerala Einstein Study (KES), based in Kerala state, India. RESULTS:682 KES participants (mean age 68.5 ± 5.7 years, 40.5% women, and 14.9% reported mTBI) without dementia completed the KBIQ. The KBIQ had high acceptability and response rates with no concerns raised during administration raised by participants or interviewers. The KBIQ demonstrated high internal consistency and good validity, as assessed by comparison to mTBI history. We used principal component analysis to determine that the KBIQ has a six-component structure. CONCLUSIONS:The KBIQ is a reliable and valid assessment of chronic postconcussive symptoms in older Indian adults. The KBIQ can be used by nonclinicians, making it suitable for widespread case detection in community settings and for prescreening individuals prior to clinic visits, helping clinicians identify potential undiagnosed health issues.

Aims:Although prior work has examined the relation of heart rate variability (HRV) to cognitive impairment, findings have been inconsistent. The association of cardiac vagal control with cognitive impairment remains unclear. Our goal was to examine the association of high frequency HRV (hf-HRV) with mild cognitive impairment and global cognition in a community-based sample of older adults. Methods:84 participants (mean age 78.1 SD 5.2 years) wore single lead ECG devices for 6-9 days. HRV in the high (0.15-0.40 Hz, [HF-HRV]) frequency band was derived using power spectral analyses. The cognitive battery included the Montreal Cognitive Assessment (MoCA) to assess global cognition, and two tests per domain for memory, executive, language, visuo-spatial and attention. Mild Cognitive Impairment (MCI) was defined using Jak-Bondi criteria. Domain specific impairment was defined as scores > 1.0 SD below age, sex, education standardized norms on at least one test in a domain. Associations of HF-HRV with cognition were examined using logistic and linear regression adjusted for demographics, diabetes, and hypertension. Results:Participants were 82% female; 39% Non-Hispanic White, 44% Non-Hispanic Black, 25% had MCI. Within domains, impairment was present in 25% (memory), 28.6% (executive function), 21.4% (attention), 17.9% (language), and 27.4% (visuospatial). HF-HRV was inversely associated with prevalent MCI (OR per 1 SD increase in ln HF-HRV: 0.47, p = 0.02) and with memory impairment (OR per 1 SD increase in ln HF-HRV: 0.52, p = 0.03). Higher HF-HRV was associated with higher MoCA score (β for 1 SD increase in ln HF-HRV = 0.65, p = 0.046). Conclusion:Higher hf-HRV, indicative of greater cardiac parasympathetic control is associated with lower odds of MCI, or memory impairment and with better global cognition after adjustment for cardiovascular risk factors. Future longitudinal studies are needed to confirm these associations.

Sleep problems are common in older adults and have been linked with risk for cognitive impairment. Data regarding associations between longitudinal changes in sleep and changes in cognitive performance among older adults are limited. Our goal was to examine whether trajectories of actigraphically defined sleep parameters differed for individuals with different patterns of change in global cognition. Analyses included 219 Einstein Aging Study participants (mean age = 77.50, SD = 5.01; 69.86% female; 47.94% Non‐Hispanic White, 42.01% Non‐Hispanic, 10.05% Hispanic; 23.74% MCI; median follow‐up = 4 years, dementia‐free). Participants wore an actigraphy watch 24 hours/day for 16 days annually (2017–2022). Standard algorithms extracted sleep duration, wake after sleep onset (WASO), sleep efficiency, sleep midpoint, and napping. Cognition was assessed via the validated 22‐item telephone Montreal Cognitive Assessment (T‐MoCA; normal cognition > 18). Latent class mixed‐effects models identified cognitive trajectories, accounting for learning effects. Generalized additive mixed‐effects models characterized sleep patterns across cognitive groups, adjusting for age, gender, and race/ethnicity. We identified three T‐MoCA cognitive trajectory groups: (1) Consistently High‐performance (N = 126) scoring across follow‐up (mean above 18), (2) Medium‐performance (N = 82) over time (mean score 15.7), and (3) Declining performance (N = 11) with an initial mean score of 15.2. These cognitive trajectory groups exhibited distinct longitudinal patterns of night‐time sleep duration (p = 0.001), WASO (p < 0.001), and sleep efficiency (p < 0.001). Night‐time sleep duration started higher and decreased more steeply in the decliner group, decreased more gradually in the medium group, and remained consistent in the high T‐MoCA group. WASO and efficiency appeared to improve over time, with the greatest improvement in Low‐performers and only gradual change in the medium and high groups. We found no significant interactions for sleep midpoint, and duration of napping. Actigraphy‐based sleep changes over five years differ by cognitive trajectories. Larger sleep changes in the declining group in the group with declining T‐MoCA scores may suggest that underying brain changes in those with more rapid cognitive decline impact sleep, although this should be confirmed in a larger sample.

BACKGROUND:Despite evidence for sex differences in cognitive performance and risk of developing Alzheimer's disease and related dementias, few studies have explored sex differences in rates of cognitive decline. Examining rates of decline using longitudinal data can critically further our understanding of healthy versus abnormal cognitive aging; however, these studies are often complicated by practice effects. Smartphone-based ecological momentary assessments (EMA) may provide a unique opportunity to address this concern by facilitating short-term intensive measures of cognitive performance, multiple times/day over multiple days in real-world settings. METHOD:The Einstein Aging Study assessed processing speed in diverse community-dwelling older adults over 6 years using the WAIS-III Digit Symbol Substitution Test (DSST) and a smartphone-based EMA Symbol Match (SM) test. DSST was assessed once annually during in-person clinic visits, and EMA SM was assessed via a burst protocol (i.e., 6 times/day over two weeks), repeated annually. Multi-level linear mixed effects models were used to evaluate sex differences in age-related cognitive decline while accounting for practice effects from exposure to repeat testing. Models were adjusted for covariates including age at baseline, years of education, and race/ethnicity. RESULT:Among 322 non-demented older adults (77.6±5.0 years; 67.1% Female; 46.3% non-Hispanic White, 40.1% non-Hispanic Black), up to 6 annual bursts of EMA (mean 3.2±1.7) were obtained during a mean of 2.8±1.9 years of follow-up. Consistent with prior literature, women performed better at baseline on both DSST number completed correctly within a set time (Table 2) and EMA SM response time (Table 3) measures. There were significant rates of decline among men in DSST and EMA SM during follow-up. For EMA SM median completion time, mean performance at baseline was not significantly different between men and women; although, women showed faster decline during follow-up (difference 216±88 milliseconds/year, p = 0.014) and slower improvement from burst assessment exposure (p = 0.002). CONCLUSION:We observed significantly faster decline in processing speed among women compared with men for EMA-based but not a conventional, paper-and-pencil test. After accounting for practice effects, smartphone-based digital EMA may be more sensitive to cognitive change and offer novel opportunities to identify possible sex differences at early disease stages.

Background and Aims:Motoric cognitive risk syndrome (MCR), a predementia condition that combines slow gait speed and subjective cognitive concerns (SCC), has broad diagnostic accessibility in resource poor settings as it is inexpensive and simple to diagnose. The ability to diagnose MCR remotely via smartphone would further increase the convenience and applicability of this syndrome. In this pilot study, we investigated the feasibility of implementing daily dairy reported SCC via smartphone in diverse individuals with MCR. Study aims included: (1) examine smartphone SCC to detect clinical status in MCR, (2) investigate the association of smartphone SCC with traditional in-clinic SCC measures; and (3) compare the relative ability of smartphone and in-clinic SCC to detect clinical status in MCR. Methods:Einstein Aging Study participants (N = 247, Mage = 77.49 ± 4.82, %female = 66, Meducation = 15.18 ± 3.65, %non-Hispanic white = 47, %non-Hispanic black = 39) completed the daily memory lapses checklist via smartphone (14-day daily dairy assessment of in vivo experiences of SCC) and a traditional in-person assessment of SCC (the cognitive change index) at annual study visits. Gait assessment and MCR diagnosis were assigned at baseline in-person assessment (MCR, n = 36). Clinical status was determined through clinical dementia rating scale sum of boxes. Linear mixed-effects models tested the association between smartphone based and in-person SCC measures with clinical status, controlling for covariates. Results:Smartphone and in-person SCC measures were highly correlated. We found significant associations between SCC and clinical status for both smartphone and in-person SCC measures in MCR. Linear mixed-effects models revealed similar associations between smartphone-based and in-person SCC with clinical status. Conclustion:Results represent a step toward viability of remote, smartphone-based assessment of SCC in MCR. Findings illustrate the merit of future research exploring a fully remote MCR diagnosis, with implications for dissemination of MCR in underserved, remote settings and more equitable access to early dementia detection in diverse populations.

Ecological momentary assessment (EMA) is increasingly used to track subjective cognitive concerns (SCC), or self-perceived memory and cognitive difficulties, in real time. This study examines how daily contextual factors—such as anxiety, stress, socialization, enjoyment, and wakefulness—influence SCC in EMA diaries. While SCCs predict future cognitive decline, their moment-to-moment relationship with daily experiences remains unclear. Using smartphone-based EMA, we explore associations between daily experiences and SCC in community-dwelling older adults. EMA captures within-person fluctuations, minimizing recall bias and facilitating assessment of transient factors that may influence SCCs. Participants from the EAS completed six surveys daily over 14 days. Cognitive lapses were assessed once per day in the evening survey, where participants also rated their difficulty staying awake (0–100). Across six surveys throughout each day, they reported if they experienced enjoyable or stressful activities since the last survey. Participants also reported their current levels of anxiety and loneliness at the time of the survey. We calculated daily counts of stressful and enjoyable events and daily averages of anxiety and loneliness. Using linear mixed-effects models, we examined the day-level cross-sectional association of contextual variables with SCCs, adjusting for age, sex, race/ethnicity, depression status, and cognitive status (cognitively unimpaired or mild cognitive decline). We also conducted a multivariable analysis incorporating these contextual variables into one model. Analyses included 310 community-dwelling participants (mean age = 77.5, SD = 4.94; 66.4% female; 47.1% non-Hispanic White, 40.7% non-Hispanic Black, 12.3% Hispanic; 70% cognitively unimpaired), contributing 11.40 diary days on average. Difficulty staying awake ( p  = 0.0159), average stress ( p  < 0.001), loneliness ( p  < 0.001), and anxiety ( p  < 0.001) were positively associated with SCCs. When examining these contextual variables simultaneously, difficulty staying awake ( p  = 0.037) and anxiety ( p  = 0.015) remained independently associated with daily total reported SCCs. Contextual variables of daily experiences on stress and emotions are associated with SCCs. Future work should incorporate these variables when using SCC as a screening tool for cognitive impairment risk. We plan to study individual vulnerabilities to contextual variables as predictors of longitudinal cognitive decline.

BACKGROUND:Alzheimer's disease and related dementias (ADRD) develop over 20 years with subtle impairments in Instrumental Activities of Daily Living (IADLs). This study aimed to determine whether specific IADLs are associated with risks for cognitive impairment in pre-ADRD stages. METHODS:We used Gateway to Global Aging Data (g2aging.org) from the US Health and Retirement Study. In adults ≥65 years without an ADRD diagnosis (n = 10, 346), IADL impairments were self-reported as difficulty in managing money, medication, reading maps, using telephone, shopping for groceries and preparing meals. Memory-related cognitive impairment was defined as ≥1.5 SD below the study-specific mean for total recall combined with poor self-reported memory. Non-memory-related cognitive impairment was ≥1.5 SD below the mean in ≥2 cognitive tests including orientation, serial 7s and backward counting. Latent class analysis was performed to identify different groups of IADLs at baseline. Cox proportional hazards models adjusted for age, sex, education, were used to determine the associations between group membership in IADLs and the risk for cognitive impairment. Models were adjusted for post-stratification sample weights. RESULTS:Weighted mean age of participants was 74.3 years (SD 6.8), and 58% were women. Three IADL groups were identified: A high functioning group (86%), with low probabilities of difficulty in any IADLs ; a group with moderate difficulty in specific tasks such as managing money, shopping, reading maps and making meals (10%) ; and a low functioning group (4%), with high difficulty across all IADLs. The low functioning group showed increased risk (hazard ratio [HR] 2-2.5; p <0.001) of developing both types of cognitive impairment compared to the high functioning group (during a mean 10.3 (SD 7.2) years of follow-up). The moderate functioning group also showed an increased risk for memory- (HR 2.0, p = 0.001) and non-memory-related impairment (HR 1.6, p <0.001) compared to the high functioning group (Table 1). CONCLUSIONS:Our findings suggest that even moderate difficulty in performing specific IADLs (i.e., managing money) is associated with an increased risk for cognitive impairment in older adults. These IADLs may serve as early risk indicators and have the potential to be developed into clinical trial endpoints in pre-clinical ADRD populations.

BACKGROUND:Ecological momentary assessment (EMA) is increasingly used to assess subjective cognitive concerns (SCCs), or self-perceived memory and cognitive difficulties, without reliance on retrospective recall. While elevated SCCs are associated with increased risk of cognitive decline, little research has examined joint longitudinal trajectories of SCCs and cognitive function. We used smartphone-based EMA to explore associations between SCC trajectories and trajectories in the telephone version of the Montreal Cognitive Assessment (T-MoCA) scores in community-dwelling older adults. METHODS:Analyses included 219 Einstein Aging Study participants (mean age = 77.50, SD = 5.01; 69.86% female; 47.94% Non-Hispanic White, 42.01% Non-Hispanic Black, 10.05% Hispanic; 23.74% MCI; median follow-up = 4 years, dementia-free). Participants reported perceived cognitive lapses once daily at night over 14 days and repeated these assessments annually (2017-2022). Cognition was assessed via the validated 22-item telephone Montreal Cognitive Assessment (T-MoCA; normal cognition > 18). Latent class linear mixed-effects models identified clusters of longitudinal changes in SCCs while adjusting for age, gender, race/ethnicity, cognitive status, and depression (GDS). Subsequently, we characterized T-MoCA trajectories across these SCC groups using linear mixed-effects models with piecewise splines to account for learning effects, adjusting for age, gender, and race/ethnicity. RESULTS:We identified two SCC trajectory groups (Figure 1): (1) a consistently low SCC group (N = 199) with a low number of SCCs and a slight non-significant longitudinal increase (SCC baseline mean = 0.74), and (2) a group with increasing SCC (N = 15) with a higher baseline mean mean (4.34) and a yearly increase of 0.81 SCCs (p < 0.001). These SCC trajectory groups exhibited distinct longitudinal patterns in the T-MoCA (Figure 2). We found no group differences in T-MoCA at baseline, nor did we observe significant differences in learning across the initial three annual assessments. The group with increasing SCCs showed declining T-MoCA scores after the initial three annual assessments (p = 0.02), whereas the group with consistently low SCCs did not demonstrate decline. CONCLUSIONS:Longitudinal SCC trajectories correlate with distinct cognitive trajectories in the T-MoCA. Our results indicate that increasing SCCs may predict declines in objective cognitive performance.

Slow gait is a robust functional marker for dementia that identifies individuals’ risk for cognitive impairment up to a decade before a clinical onset. But, what about the other end of the spectrum? This abstract presents the results on whether “super movers” (a novel phenotype of individuals aged ≥80 years without dementia and with gait speeds ≥1.5 SD of sex-adjusted cutoffs) have lower risks of cognitive impairment and/or slower cognitive decline. Data from five Health and Retirement Study International Network of Studies (HRS-INS) were used to assess the risk of cognitive impairment in super-versus non-super movers. Cognitive impairment was defined as >1.5 SD below age-adjusted cutoffs on at least one out of three tests, combined with impaired Instrumental Activities of Daily Living (Table 1). Age- and sex-adjusted hazard ratios (HR) from cox proportional hazards models were pooled in a meta-analysis to determine the overall risk for incident cognitive impairment. Data from the LonGenity study (a prospective longitudinal study in the Bronx) were used to examine the rates of decline in cognitive tests in super- versus non-super movers using linear mixed effect models adjusted for age, sex, education and parental longevity,. In individual HRS-INS, super movers showed lower risks of cognitive impairment in the ELSA (English Longitudinal Ageing Study; HR 0.31, 95% CI 0.16-0.60)) and SHARE studies (the Survey of Health, Ageing and Retirement in Europe HR 0.49, 95% CI 0.26-0.89)). In the meta-analysis, among 3,999 participants selected from 15,911=aged ≥ 65 ( n  = 358 super movers; baseline age 83.6-84.4 years) followed for 3.8-6.1 years, super movers had significantly lower risk of cognitive impairment (HR 0.49, 95% CI 0.28-0.71) (Figure 1). In the LonGenity study, ( n  = 197, baseline age 84.6 years (SD 3.3)) super movers showed a slower decline in global cognition, total recall, digit symbol substitution test and Trial Making Tests A and B (Table 2). Super movers—a novel aging phenotype—show lower risks of cognitive impairment and slower cognitive decline, in memory and non-memory related tests. Investigating the behavioral and biological factors contributing to this phenotype may reveal protective mechanisms against cognitive decline and dementia risk.