BACKGROUND:The energetic cost of walking increases with age and is linked to physical function impairment, but its relation to cognitive impairment is unknown. METHODS:A total of 687 initially cognitively normal older adults (mean age 74.0 ± 7.2 years, 52% women) underwent repeated walking energy expenditure assessments (V̇O2) and adjudicated cognitive diagnoses over 7.6 ± 3.8 years. We examined (1) trajectories in the energetic cost of walking prior to any clinical diagnosis of cognitive impairment, comparing adults who later developed cognitive impairment versus those who did not, and (2) the baseline energetic cost and future risk of cognitive impairment using linear mixed-effects and Cox regression models. RESULTS:Ninety-one participants (13%) progressed to cognitive impairment. Progressors exhibited a steeper increase in energetic cost than non-progressors (B = 0.13; p = 0.003). Higher baseline cost predicted impairment among adults ≥75 years (hazard ratio [HR] = 1.1, 95% confidence interval [CI] = 1.00 to 1.20, p = 0.039), but not those aged 65 to 74 (HR = 0.91, 95% CI = 0.81 to 1.01, p = 0.089). CONCLUSION:Walking efficiency provides a physiological link between mobility and cognitive health; preserving efficiency may reduce risk of Alzheimer's disease and related dementias.

Background and ObjectivesAging is associated with changes in circadian rhythms. Rest-activity rhythms (RARs) measured using accelerometers are markers of circadian rhythms. Altered circadian rhythms may be risk factors of neurocognitive outcomes; however, results are mixed, and previous studies were often conducted in homogeneous populations. We aimed to assess the association between circadian RARs and incident dementia in a racially diverse sample of older adults.MethodsThis was a retrospective examination of data from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort study conducted at 4 US centers. ARIC participants who wore the Zio XT (R) long-term continuous monitoring patch in 2016-17 for >= 3 days and were free of prevalent dementia were included. RARs were derived from investigational accelerometer data from the patch. Nonparametric RARs included relative amplitude (rhythm strength), intradaily variability (rhythm fragmentation), and interdaily stability (rhythm consistency). Cosinor RARs included measures of rhythm strength (amplitude, mesor) and circadian timing (acrophase). Dementia cases were adjudicated through 2020 using in-person and phone assessments, hospitalization codes, and death certifications. Cox proportional hazards models were used.ResultsOf the 2,183 participants (mean +/- SD age 79 +/- 4.5 years, 58% female, 24% Black), 176 (8%) developed dementia. The median follow-up time was 3 years, and the mean Zio XT Patch wear time was 12 days. After multivariable adjustment, each 1-SD decrement in relative amplitude and 1-SD increment in intradaily variability were associated with 54% (95% CI 32%-78%) and 19% (95% CI 2%-38%) greater risk of dementia, respectively. Amplitude and mesor were associated with elevated dementia risk after multivariable adjustment (hazard ratios per 1-SD decrement: 1.43 [95% CI 1.15-1.78] and 1.33 [95% CI 1.08-1.63], respectively). A later acrophase was associated with 1.45 times (95% CI 1.01-2.07) greater risk of dementia compared with a normal acrophase.DiscussionUsing accelerometer data from a commonly used ambulatory ECG monitor, weaker and more fragmented circadian RARs and later peak activity time were prospectively associated with elevated dementia risk in older Black and White adults. Limitations of our study include the lack of dementia subtype data and objective sleep disorder measurements. Further research to determine whether circadian rhythm interventions can reduce dementia risk is warranted.

BACKGROUND:Sensorimotor impairments, including sensory (vision and hearing) and motor (standing balance, gait, chair stands, grip strength) deficits, are prevalent in older adults and are associated with an increased risk of dementia. Understanding the individual and combined effects of these impairments on dementia risk may enhance early detection and preventive strategies. We examined the association between baseline sensory difficulties and motor impairments, individually and collectively, with dementia over up to 11 years. METHODS:We used data from the National Health and Aging Trends Study (NHATS), a nationally representative study of US community-dwelling Medicare beneficiaries aged ≥ 65 years. Participants cognitively unimpaired at baseline in 2011 were followed annually through 2022. Baseline exposures included self-reported sensory difficulties (vision, hearing) and objectively measured motor impairments (standing balance, gait speed, chair stand, grip strength). The primary outcome was incident dementia, assessed annually based on NHATS consensus procedures. Survey-weighted Cox proportional hazards models assessed the association between each impairment and number of impairments and incident dementia, adjusting for demographics and clinical conditions. RESULTS:The analytic sample included 3847 participants (weighted average age 73.9 (95% CI, 73.7-74.1) years, 56% women). Over an average follow-up of 5.2 years, vision difficulty (HR = 1.34; 95% CI, 1.13-1.60), standing balance impairment (HR = 1.23; 95% CI, 1.10-1.39), slow gait speed (HR = 1.49; 95% CI, 1.34-1.67), impaired chair stand performance (HR = 1.31; 95% CI, 1.18-1.47), and weak grip strength (HR = 1.31; 95% CI, 1.13-1.51) were each independently associated with higher dementia risk. Compared to no impairments, dementia risk increased significantly with three or more sensorimotor impairments (HR = 1.44 to 1.96). CONCLUSIONS:In this nationally representative cohort, vision difficulty and motor impairments were independently associated with increased dementia risk over up to 11 years. The presence of multiple sensory difficulties and motor impairments substantially increased the risk of dementia, emphasizing the importance of their early detection and management to reduce dementia risk.

INTRODUCTION:Day-to-day variability of rest-activity patterns may have a multifaceted relationship with dementia risk, but empirical evidence is sparse. METHODS:We included 2332 dementia-free participants (79 ± 4.6 years, 58% female, 24% Black) who had ≥ 3 days of ZioXT accelerometer data from the Atherosclerosis Risk in Communities Neurocognitive Study in 2016 and 2017. Variability of physical activity (PA) volume was operationalized as median absolute deviation (MAD) of (1) daily average PA, (2) average PA during the most active 10 hours (M10), and (3) average PA during the least active 5 hours (L5). Variability of PA timing was defined as MAD of (1) the start time of the M10 interval and (2) the start time of the L5 interval. Participants were followed until incident dementia, death, last contact, or December 31, 2022. We used cause-specific Cox regression to estimate variability measures with incident dementia. RESULTS:After a median 5.2-year follow-up, 319 (13.7%) of individuals developed dementia. Higher MAD of daily average PA and M10 were associated with lower hazard of dementia (dose-response trend: P < 0.001), whereas higher MAD of L5 was associated with higher hazard of dementia (P = 0.046). Higher MAD of the start time of M10 was associated with higher hazard of dementia (P < 0.001), and a similar association was observed for MAD of the start time of L5 (P = 0.037). After further adjusting for daily PA volume, all associations persisted except for MAD of the start time of L5 interval. The findings were in general consistent across subgroup and sensitivity analyses. DISCUSSION:In this large older adult population, greater variability of daily PA volume, particularly during wake periods, and lower variability of PA timing, a marker of circadian phase, are associated with lower dementia risk. Research on the stability of interdaily rest-activity rhythms should consider potentially opposing relationships of types of PA variability with dementia risk.

INTRODUCTION:Identifying precursors to mild cognitive impairment (MCI)-the transitional stage between unimpaired cognition and dementia-is a public health priority. While sensory and motor impairments are each linked to MCI, their integrated contribution as a sensorimotor construct remains underexplored. METHODS:We analyzed cross-sectional data from two US cohorts: Atherosclerosis Risk in Communities (ARIC; n = 880) and Baltimore Longitudinal Study of Aging (BLSA; n = 681), excluding individuals with stroke, Parkinson's disease, or dementia. A composite sensorimotor score-based on hearing, vision, olfaction, balance, gait speed, and grip strength-was created using factor analysis. Structural equation modeling assessed associations with MCI, adjusting for key covariates. RESULTS:Higher sensorimotor function was associated with lower odds of MCI: ARIC odds ratio (OR) = 0.53 (95% confidence interval [CI]: 0.40-0.71); BLSA OR = 0.59 (95% CI: 0.43-0.81). DISCUSSION:Sensorimotor function appears robustly related with MCI in a large sample of older adults. These findings highlight the potential value of incorporating sensorimotor assessments in early detection for cognitive decline. Longitudinal research is needed to understand temporality.

The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a landmark 2-year randomized clinical trial evaluating multidomain lifestyle interventions for dementia prevention in older adults at elevated risk. Its effectiveness and national reach represent an important step towards scaling prevention science in diverse, real-world settings. However, the trial also underscores a persistent challenge in lifestyle medicine: the prioritization of feasibility over optimization. In this commentary, we review U.S. POINTER through a precision medicine lens and outline strategies to integrate standardized core elements with flexible, individualized components that can amplify both potency and applicability. We emphasize three priorities: (1) tailoring interventions to drive physiological adaptations; (2) leveraging the synergistic potential of related behavioral domains; and (3) targeting sleep and circadian health as central intervention components. While U.S. POINTER advances feasibility and community participation, a more tailored, mechanistically informed approach could increase effect sizes and extend benefits to populations historically excluded in prevention research. Personalized strategies should not be confined to pharmacology-they must also guide behavioral interventions. Designing lifestyle programs that stimulate measurable adaptations, leverage behavioral synergy, and align with circadian biology offers the potential to produce greater and more durable cognitive benefits.

Introduction:Chronic widespread musculoskeletal pain (CMP) is a primary condition of Veterans who were deployed to the Persian Gulf War. The mechanisms that underlie CMP in these Veterans are unknown and few efficacious treatment options exist. This study tested the effects of 16 weeks of resistance exercise training (RET) on gray matter (GM) volume and white matter (WM) microstructure in Gulf War Veterans (GWVs) with CMP compared to GWV waitlist controls (WLC). Methods:Fifty-four GWVs were randomly assigned to 16 weeks of RET (n = 28) or WLC (n = 26). Training involved 10 resistance exercises to involve the whole body, was supervised and individually tailored, and progressed slowly to avoid symptom exacerbation. Outcomes assessed at baseline, 6, 11 and 17 weeks and 6- and 12-months post-intervention included GM volume (voxel-based morphometry), WM microstructure (diffusion tensor imaging), pain [short form McGill Pain Questionnaire (SF-MPQ) and 0-100 visual analog scale (VAS)], fatigue (0-100 VAS), and mood (Profile of Mood States). Muscular strength was assessed at baseline, 8 and 16 weeks, and training volume was tracked throughout the 16-week intervention. Primary analyses used linear mixed effects models with Group, Time, and the Group*Time interaction as fixed factors and subject and slope as random factors to test the differential effects of RET and WLC on brain structure and symptoms. All neuroimaging analyses used the False Discovery Rate to correct for multiple comparisons at an alpha of 0.05. Results:Strength increased significantly across the trial for the RET group (p < 0.001). There were significant Group*Time interaction effects for pain ratings (SF-MPQ total; p < 0.01) and the Profile of Mood States total mood disturbance score (p < 0.01). There were no Group or Group*Time effects for GM volume or WM microstructure. There were no significant associations between strength, symptoms, and brain structure (p > 0.05). Conclusion:Sixteen weeks of low-to-moderate intensity RET (i) improved musculoskeletal strength and (ii) did not exacerbate symptoms, but (iii) was insufficient to alter brain structure in GWVs with CMP.

Impairments in sensory and motor function are common in older adults and have been linked with higher prevalence of dementia. However, their independent associations with dementia have not been examined in a nationally representative population. Cross-sectional analysis of the National Health and Aging Trends Study (NHATS; Round 11/2021) of U.S. Medicare beneficiaries. Dementia was classified per NHATS protocol as none, possible, or probable dementia. Vision measures included presenting binocular distance visual acuity, near visual acuity, and contrast sensitivity. Hearing measures included the pure tone average of the better ear. Motor function measures included gait speed, chair stands time, balance score, and grip strength. Dichotomized or categorized presence of impairment in each sensory and motor function was defined and used as the main exposures. Multivariable survey-weighted logistic regression was used to assess the independent associations of sensory and motor function impairments with dementia status. Our final analytic sample included 2,379 participants with 36.6 ≥ 80 years, 56.2

Higher levels of physical activity, measured through accelerometry, have shown associations with several indices of brain and cognitive health in middle-to-late aged individuals. The association of physical activity and AD-specific biomarkers measured through positron emission tomography (PET), however, remains unclear. Previous studies show no direct association of physical activity with amyloid-PET levels, but associations with the onset of amyloid positivity remain unexplored. This study used estimated amyloid onset age (EAOA), defined as the age at which a participant is expected to attain the amyloid positivity threshold based on longitudinal PET, to investigate if higher levels of physical activity are associated with later EAOA across three cohort studies including: the Biomarkers of Cognitive Decline among Normal Individuals (BIOCARD) study, the Baltimore Longitudinal Study of Aging (BLSA), and the Wisconsin Registry for Alzheimer’s Prevention (WRAP) study. Cognitively unimpaired participants from BIOCARD (N = 133), BLSA (N = 117), and WRAP (N = 115) who completed accelerometer-measured physical activity monitoring over 7 days and underwent 11 C-Pittsburgh compound B PET imaging were included. Total daily physical activity was measured through wrist-worn (BIOCARD, BLSA) or waist-worn (WRAP) accelerometers and EAOA was estimated using sampled Iterative Local Approximation. Proportional Hazard Cox regression models assessed whether physical activity is associated with EAOA, using right-censoring for participants who did not develop amyloid positivity, adjusting for sex and APOE status. Potential interactions between physical activity and APOE status were also assessed. Participant demographics are displayed in Table 1. Across all three cohorts, APOE status was associated with EAOA (all p<.05), such that APOE -e4 carriers had an earlier amyloid onset. We did not observe associations between physical activity and EAOA among BIOCARD (z-score HR = 1.27, p = 0.27), BLSA (z-score HR = 1.01, p = 0.97), or WRAP participants (z-score HR = 0.96, p = 0.85). Furthermore, no significant interactions between physical activity and APOE status were observed (all p>.05). Across three separate studies of community-dwelling middle- age and older adults, we did not observe an association between accelerometer-measured physical activity and EAOA. Further research is needed to i) determine if alternate methods for assessing physical activity are associated with AD biomarkers and ii) investigate non-AD pathways through which physical activity may impact cognitive function and AD risk.

Impairments in sensory and motor function are common and have been independently linked with higher risk of dementia in older adults. Yet, there is limited information associated with the increasing number of such impairments and dementia risk. This study investigated longitudinal associations between sensory and motor impairment and dementia in older adults. We used data from the US National Health and Aging Trends Study (NHATS), a nationally representative cohort study of community-living Medicare beneficiaries aged 65 years and older. Baseline sensory impairments were defined based on self-reported vision and hearing loss indicators. Baseline motor impairments were defined based on performance in gait, repeated chair stands, standing balance, and grip strength tests. Multivariable Cox regression models were used to evaluate the hazard ratio of incident dementia from baseline (2011) to 2022. A total of 3847 participants without dementia at baseline were included (weighted mean age 73.9 (95% CI: 73.7-74.1) years old and 56% (95% CI: 54.1-57.9) female). Compared to those without impairment in each specific domain, hazard ratios for incident dementia were 1.02 (95% CI 0.89-1.16, p = 0.82) for hearing impairment, 1.34 (95% CI 1.13-1.60, p = 0.001) for vision impairment, 1.31 (95% CI 1.18-1.47, p<0.001) for chair stand impairment, 1.23 (95% CI 1.10-1.39, p<0.001) for standing balance impairment, 1.49 (95% CI 1.34-1.67, p<0.001) for gait speed impairment, and 1.31 (95% CI 1.13-1.51, p<0.001) for grip strength impairment (Table 1). Additionally, compared to participants with no impairments, the hazard ratio for incident dementia for those with three impairments was 1.44 (95% CI 1.14-1.82, p = 0.003), with four impairments was 1.92 (95% CI 1.50-2.47, p<0.001) and with 5-6 impairments was 1.96 (95% CI 1.50-2.56, p<0.001) (Table 1, Figure 1). In this cohort study of US Medicare beneficiaries, vision and motor impairment as well as a higher number of impairments were associated with elevated risk of dementia. These findings underscore the cumulative burden of sensory and motor impairments on incident dementia. A better understanding of the temporality and longitudinal effect of sensory and motor impairments on incident dementia may help inform future targeted interventions.

BACKGROUND:Alzheimer's disease (AD) is characterized by the abnormal accumulation of amyloid-beta (Aβ) and tau that can be quantified in vivo through cerebrospinal fluid (CSF) sampling. Physical activity has emerged as a possible modifier of AD risk; however, its impact on CSF biomarkers and cognitive function is not yet fully understood. We examined whether higher levels of physical activity modifies associations between AD CSF biomarkers and cognitive function. METHODS:One hundred and seventeen adults free of dementia from the BIOCARD study (mean age 72.2 ± 8.0 years, 70% women) wore a wrist accelerometer for 1 week, underwent lumbar puncture to collect CSF, and completed a comprehensive neuropsychological exam. Multivariable linear regression analyses were used to examine whether physical activity (total activity counts over the 10 most active hours of the day) moderates the association between AD CSF biomarkers [Aβ42/40, phosphorylated tau (p-tau181), and total tau] and cognitive composite scores (episodic memory, executive function). RESULTS:There were significant interactions between physical activity and p-tau181 (p = 0.016) as well as between physical activity and total tau (p = 0.004) in relation to the executive function composite score. Among participants with higher levels of physical activity, the adverse relationship between CSF-measured tau and executive function was diminished. In contrast, there were no significant interactions for episodic memory, and physical activity did not interact with Aβ42/40 (all interactions p > 0.05). CONCLUSION:A physically active lifestyle may provide protection against AD-related cognitive decline by reducing the impact of tau pathology. Highlights:Older age was associated with lower levels of physical activity, worse CSF biomarker profiles, and poorer cognition.Physical activity moderates the impact of tau pathology on executive function but shows no significant effect on amyloid-beta pathology.Physical activity may enhance cognitive reserve, thereby attenuating the influence of accumulating AD pathology on cognition.

Background:Large population-based studies are crucial for dementia research; yet variation in cognitive tests and dementia classification approaches can lead to inconsistent findings. We harmonized cognitive data from two nationally representative US studies of aging to facilitate comparisons. Methods:We examined 2016 data for individuals aged ≥70 years from the National Health and Aging Trends Study (NHATS) (n = 5696) and the Harmonized Cognitive Assessment Protocol (HCAP) of the Health and Retirement Study (HRS) (n = 2731). We derived factor scores for general cognitive performance in the NHATS cognitive test battery that were co-calibrated to the HRS-HCAP battery and identified cutpoints for dementia that returned the expected prevalence in each study. We evaluated diagnostic characteristics of the cutpoints against study-specific dementia algorithms with Area Under the Curve analysis. Results:Study-specific algorithms yielded comparable dementia prevalence estimates: 10.8 % in NHATS and 11.1 % in HRS-HCAP. Co-calibrated scores showed similar distributions and had acceptable reliability, with similar dementia cutpoints. In both studies, sensitivity was higher among lower-educated (vs. higher educated) and non-White (vs. non-Hispanic White) groups. Co-calibrated populations with dementia in both studies had similar age and gender distributions but differed somewhat in education levels and race/ethnicity profiles. Conclusions:NHATS and HRS-HCAP both provide reliable cognitive function measures and dementia prevalence estimates for older Americans. Co-calibrated scores based on each study's cognitive test battery provide a valid and feasible approach for comparative US research. Better aligned algorithmic approaches across studies could strengthen opportunities for comparative studies of disparities in the US context using the co-calibration approach.

BACKGROUND AND OBJECTIVES:Aging is associated with changes in circadian rhythms. Rest-activity rhythms (RARs) measured using accelerometers are markers of circadian rhythms. Altered circadian rhythms may be risk factors of neurocognitive outcomes; however, results are mixed, and previous studies were often conducted in homogeneous populations. We aimed to assess the association between circadian RARs and incident dementia in a racially diverse sample of older adults. METHODS:This was a retrospective examination of data from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort study conducted at 4 US centers. ARIC participants who wore the Zio XT® long-term continuous monitoring patch in 2016-17 for ≥3 days and were free of prevalent dementia were included. RARs were derived from investigational accelerometer data from the patch. Nonparametric RARs included relative amplitude (rhythm strength), intradaily variability (rhythm fragmentation), and interdaily stability (rhythm consistency). Cosinor RARs included measures of rhythm strength (amplitude, mesor) and circadian timing (acrophase). Dementia cases were adjudicated through 2020 using in-person and phone assessments, hospitalization codes, and death certifications. Cox proportional hazards models were used. RESULTS:Of the 2,183 participants (mean ± SD age 79 ± 4.5 years, 58% female, 24% Black), 176 (8%) developed dementia. The median follow-up time was 3 years, and the mean Zio XT Patch wear time was 12 days. After multivariable adjustment, each 1-SD decrement in relative amplitude and 1-SD increment in intradaily variability were associated with 54% (95% CI 32%-78%) and 19% (95% CI 2%-38%) greater risk of dementia, respectively. Amplitude and mesor were associated with elevated dementia risk after multivariable adjustment (hazard ratios per 1-SD decrement: 1.43 [95% CI 1.15-1.78] and 1.33 [95% CI 1.08-1.63], respectively). A later acrophase was associated with 1.45 times (95% CI 1.01-2.07) greater risk of dementia compared with a normal acrophase. DISCUSSION:Using accelerometer data from a commonly used ambulatory ECG monitor, weaker and more fragmented circadian RARs and later peak activity time were prospectively associated with elevated dementia risk in older Black and White adults. Limitations of our study include the lack of dementia subtype data and objective sleep disorder measurements. Further research to determine whether circadian rhythm interventions can reduce dementia risk is warranted.

INTRODUCTION:Physical activity is a modifiable risk factor for dementia. However, the potential reverse effect of adverse cognitive change on physical activity remains underexplored. METHODS:Cross-sectional analysis of a subset of National Health and Aging Trends Study (NHATS; N = 706) U.S. Medicare beneficiaries. Dementia status (dementia vs. no dementia) was classified per NHATS protocol. Cognitive performance was assessed in executive function, orientation, and memory domains. Daily physical activity was assessed using wrist-worn accelerometers (Actigraph Insight). RESULTS:Compared with participants living without dementia, participants living with dementia had lower daily activity counts (×1000) (-319.3; 95% confidence interval (CI), -471.0 - -167.5), lower activity intensity (-1129.2 maximum counts per day; 95% CI, -1518.4 - -740.0 counts per day), less time spent active (64.3 min/day; 95% CI, 28.1-100.4 min/day), and more fragmented patterns of activity (6.1%; 95% CI, 3.0%-9.2%). One-unit higher cognitive performance in executive function was associated with higher daily activity counts (×1000) (67.9; 95% CI, 19.7-116.0), higher activity intensity (375.4; 95% CI, 232.0-518.7), more time spent active (12.4 min; 95% CI, 2.1-22.7 min), and lower fragmentation (-1.4%; 95% CI, -2.2% - -0.5%). One-unit higher orientation score was associated with higher daily activity counts (×1000) (61.0; 95% CI, 31.9-90.0), higher activity intensity (266.6; 95% CI, 197.9-335.2), more time spent active (11.6 min; 95% CI, 5.2-18.0 more active minutes), greater stability of daily activities (1.1; 95% CI, 0.3-1.9), and lower fragmentation (-1.2%; 95% CI, -1.7% - -0.7%). One-unit higher memory score was associated with higher daily activity counts (×1000) (28.1; 95% CI, 15.0-41.2), higher activity intensity (113.5; 95% CI, 77.0-150.1), and more time spent active (5.2 min; 95% CI, 2.4-8.0 min), as well as lower fragmentation (-0.5%; 95% CI, -0.7% - -0.3%). CONCLUSIONS:In a nationally representative sample of older US adults, dementia and lower cognitive performance were associated with lower volume and intensity of daily physical activity, as well as more fragmented and less consistent patterns of physical activity. These associations emphasize the need for considering the impact of cognition on individuals' ability to engage in and maintain regular physical activity and suggest shifts in daily quantities and patterns of activity consistent with cognitive decline and dementia.

INTRODUCTION:Age-related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI). METHODS:Six hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function and ECI was examined using structural equation modeling with three latent factors corresponding to multisensory, fine motor, and gross motor function. RESULTS:The multisensory, fine, and gross motor factors were all correlated (r = 0.74 to 0.81). The odds of ECI were lower for each additional unit improvement in the multisensory (32%), fine motor (30%), and gross motor factors (12%). DISCUSSION:The relationship between sensory and motor impairment and emerging cognitive impairment may guide future intervention studies aimed at preventing and/or treating ECI. HIGHLIGHTS:Sensorimotor function and early cognitive impairment (ECI) prevalence were assessed via structural equation modeling. The degree of fine and gross motor function is associated with indicators of ECI. The degree of multisensory impairment is also associated with indicators of ECI.

BACKGROUND:Daily physical activity patterns differ by Alzheimer's disease (AD) status and might signal cognitive risk. It is critical to understand whether patterns are disrupted early in the AD pathological process. Yet, whether established AD risk markers (β-amyloid [Aβ] or apolipoprotein E-ε4 [APOE-ε4]) are associated with differences in objectively measured activity patterns among cognitively unimpaired older adults is unclear. METHODS:Wrist accelerometry, brain Aβ (+/-), and APOE-ε4 genotype were collected in 106 (Aβ) and 472 (APOE-ε4) participants (mean age 76 [standard deviation{SD}: 8.5) or 75 [SD: 9.2] years, 60% or 58% women) in the Baltimore Longitudinal Study of Aging. Adjusted linear and function-on-scalar regression models examined whether Aβ or APOE-ε4 status was cross-sectionally associated with activity patterns (amount, variability, or fragmentation) overall and by time of day, respectively. Differences in activity patterns by combinations of Aβ and APOE-ε4 status were descriptively examined (n = 105). RESULTS:There were no differences in any activity pattern by Aβ or APOE-ε4 status overall. Aβ+ was associated with lower total amount and lower within-day variability of physical activity overnight and early evening, and APOE-ε4 carriers had higher total amount of activity in the evening and lower within-day variability of activity in the morning. Diurnal curves of activity were blunted among those with Aβ+ regardless of APOE-ε4 status, but only when including older adults with mild cognitive impairment/dementia. CONCLUSIONS:Aβ+ in cognitively unimpaired older adults might manifest as lower amount and variability of daily physical activity, particularly during overnight/evening hours. Future research is needed to examine changes in activity patterns in larger samples and by other AD biomarkers.

Introduction: Alterations in circadian rest/activity rhythms (RARs) are common among older adults. RARs can be derived from accelerometry data and are routinely used as proxy measures. Evidence suggests that altered (e.g., fragmented, delayed) RARs may be risk factors for dementia. However, results have been mixed. Using data from the ARIC Study, a community-based cohort, we assessed the association between RARs and incident dementia. Methods: ARIC participants without dementia who wore the Zio XT ECG Patch in 2016-17 for > 3 days were included. RARs were obtained from an accelerometer within the Zio XT ECG Patch and measures of interdaily stability (IS; consistency), intradaily variability (IV; fragmentation), and relative amplitude (RA; strength) were derived. Dementia cases were identified through 2020 using in-person and phone-based cognitive assessments, hospitalization discharge codes, or death certificates. Cox proportional hazards models were used. Results: Of the 2,183 participants (mean [SD] age 79 [4.5] years, 58% female, 24% identified as Black), 176 (8%) developed dementia. Median follow-up time was 3 years and mean Zio XT ECG Patch wear time was 12 days. After multivariable adjustment, lower RA and higher IV were associated with incident dementia (HRs [95% CIs] per 1-SD increment: 0.65 [0.56-0.76], 1.19 [1.02-1.38]). No significant association between IS and dementia was noted; however, there was an interaction by race (p=0.03). Stratified results were not significant, but effect estimates were in opposite directions: (HRs [95% CIs] per 1-SD increment in IS: 0.78 [0.59-1.02] in Black participants and 1.17 [0.96-1.41] in white participants, respectively). No interactions by sex or APOEε4 were noted (p>0.10). Conclusion: In this community-based cohort of older adults, weaker circadian rhythm strength and fragmentation were associated with dementia risk. The association between IS and dementia may differ by race; however, this needs to be further examined in future research. Overall, measures of circadian RARs may be risk factors for dementia. Additional research is warranted to determine whether they can be novel targets for dementia prevention.

Abstract Alzheimer’s disease (AD) is characterized by the abnormal accumulation of amyloid-β (plaques), and tau (neurofibrillary tangles) that can be quantified in vivo through cerebrospinal fluid (CSF) sampling. Physical activity has emerged as a possible modifier of AD risk; however, the influence of physical activity on CSF biomarkers and cognitive function remains unclear. We examined whether higher levels of physical activity favorably modify associations between AD CSF biomarkers and cognitive function. One hundred and seventeen adults free of dementia from the BIOCARD study (mean age 72.2±8.0 years, 70% women) wore a wrist accelerometer for one week, underwent lumbar puncture to collect CSF, and completed a comprehensive neuropsychological exam. Covariate-adjusted linear regression analyses were used to examine whether physical activity (total activity counts over the 10 most active hours of the day) moderates the association between AD CSF biomarkers [amyloid-β (Aβ42/40), total tau, phosphorylated tau (p-tau181)] and cognitive composite scores (episodic memory, executive function). There were significant interactions between physical activity and total tau (p=.004) as well as physical activity and p-tau181 (p=.016) for the executive function composite score. Among those with elevated total tau or p-tau181, participants with greater levels of physical activity exhibited significantly higher executive function composite scores compared to participants with lower levels of physical activity. In contrast, there were no significant interactions for episodic memory, and physical activity did not interact with Aβ42/40 (all interactions p>.05). These findings suggest that a physically active lifestyle may play a protective role against cognitive decline through tau pathways.

INTRODUCTION:Regular participation in aerobic physical activity is associated with a reduced risk of dementia. It is currently unclear whether this association is due to the total volume or intensity of physical activity. METHODS:This prospective cohort study analyzed 386,486 adults from the UK Biobank who were free of dementia and self-reported >0 minutes of moderate-to-vigorous intensity physical activity (MVPA) at baseline (2007-2010). Participants were categorized as performing 0%, >0%-30%, or >30% of their total MVPA in vigorous activity (VPA). Cox proportional hazards regression models were used to examine the associations between categories of VPA and incident dementia while adjusting for sociodemographic and lifestyle factors including total MVPA. Analyses were performed in 2022. RESULTS:Over an average follow-up of 12.0 (1.7) years, there were 5,177 (1.3%) cases of dementia. Compared to the group reporting 0% VPA, the hazard ratios (95% confidence intervals) of dementia for the groups reporting >0%-30% and >30% VPA were 0.73 (0.68-0.78) and 0.81 (0.75-0.87), respectively, in the fully adjusted model. In a joint analysis, reporting some VPA was associated with a reduced risk of dementia regardless of meeting the aerobic physical activity guidelines (HR=0.78 [0.72-0.85]) or not (HR=0.76 [0.60-0.98]), while meeting the aerobic physical activity guidelines alone without VPA was not associated with incident dementia (HR=0.98 [0.90-1.07]), compared to the group that did not meet the guidelines and reported no VPA. CONCLUSIONS:These results suggest that engaging in VPA as part of MVPA is associated with a lower risk of dementia.