Importance:Blood-based biomarkers for Alzheimer disease, particularly plasma phosphorylated tau 217 (p-tau217), accurately reflect early Alzheimer disease brain pathology in cognitively unimpaired individuals, but estimates of absolute risk of progression to cognitive impairment across multiple cohorts are needed. Objective:To estimate absolute risk of progression to cognitive impairment and rates of cognitive decline based on plasma p-tau217 across cognitively unimpaired older adults. Design, Setting, and Participants:Longitudinal cohort study using harmonized data from 2684 cognitively unimpaired older adults (defined within cohort) across 6 observational and clinical trial cohorts based in North America, Japan, and Australia. The earliest enrollment was in 2004, with most recent follow-up in 2025. Exposure:Baseline plasma p-tau217. Main Outcomes and Measures:The primary outcome was time to progression to cognitive impairment (mild cognitive impairment, dementia, or 2 consecutive global Clinical Dementia Rating scores ≥0.5). The secondary outcome was longitudinal change on the latent Preclinical Alzheimer Cognitive Composite (PACC; higher values indicate better performance). Results:Among the 2684 participants (median [IQR] age, 69.6 [66.2-74.2] years; 1697 [63%] female), there were 478 events of progression to cognitive impairment over a median follow-up of 5.4 years (maximum follow-up of 13.5 years). Each 1-SD increase in baseline p-tau217 level was associated with an increased risk of progression to cognitive impairment (hazard ratio, 1.38 [95% CI, 1.30-1.46]), and the association remained significant after adjustment, including β-amyloid positron emission tomography scan Centiloids (hazard ratio, 1.32 [95% CI, 1.24-1.41]). Participants with high (1.1-2.4 SD) and very high (>2.5 SD) baseline p-tau217 had 24% (95% CI, 20%-28%) and 38% (95% CI, 33%-43%) absolute risk of progression over 5 years, respectively, and risk was markedly higher over 10 years, although longer-term estimates were constrained by limited data. Elevated p-tau217 was also associated with faster cognitive decline based on change in latent PACC score. Among the overall sample, baseline latent PACC scores ranged from -0.8 to 2.7. The 5-year annualized decline for the very high p-tau217 group was -0.07 latent PACC units/y (95% CI, -0.10 to -0.05), relative to 0.03 units/y (95% CI, 0.02-0.04) in the low p-tau217 group. Conclusions and Relevance:In a pooled sample of multiple selected cohorts of cognitively unimpaired older adults, higher plasma p-tau217 levels were consistently associated with increased risk of clinical progression and accelerated cognitive decline. By providing time-specific absolute risk estimates, these findings support the potential of p-tau217 for prognostic model development, with direct implications for future trial design. Further validation in unselected populations is needed to inform individual prognosis and clinical decision-making in cognitively unimpaired individuals.

BACKGROUND:Neurodevelopmental conditions (NDC), including attention deficit/hyperactivity disorder (ADHD) and autism, are associated with increased rates of neurodegenerative diseases, including Alzheimer's disease and related dementias (ADRD) and Parkinson's disease. Such associations are unstudied in diverse populations and while controlling for a range of important covariates. The purpose of this study was to examine the association of ADRD and Parkinson's disease with NDCs in a diverse sample of adults. METHODS:This case-control study used data from the United States All of Us Research Program 2018-2023 from approximately 600 000 adults in the United States. We matched on ADRD and Parkinson's disease status to examine the association of these conditions with NDCs. RESULTS:NDC was more prevalent in ADRD cases than in non-ADRD controls (7.8% vs 2.4%) and among Parkinson's disease cases than non-Parkinson's disease controls (4.5% vs 1.8%). After adjustment for sex, age, education level, body mass index, cardiometabolic conditions, and psychiatric conditions, individuals with ADRD had significantly higher odds of having an NDC compared with controls (adjusted odds ratio, 2.68; 95% CI, 2.40-2.99). Similarly, Parkinson's disease cases had 2.09 times the odds of having an NDC as non-Parkinson's disease controls (95% CI 1.66, 2.59) in adjusted models. CONCLUSIONS:As the population of individuals with NDCs ages, and more older adults find themselves in the care of clinicians with expertise in ADRD and Parkinson's disease, it is imperative to understand the support needs of this population, and to provide targets for reducing ADRD prevalence in younger or middle adulthood.

BACKGROUND:Rapid growth in Medicare Advantage (MA) enrollment has spurred dementia research using diagnoses in MA encounter data. However, the validity of MA-encounter-based dementia diagnoses is uncertain. METHODS:Using four cohort studies at the Rush Alzheimer's Disease Center linked to Medicare data from 2017-19, we validated prevalent dementia indicators in MA encounter data, based on the Bynum-Standard algorithm, against dementia status determined by rigorous cognitive assessment in cohort studies. We replicated analyses among participants in Traditional Medicare (TM). RESULTS:Of the 508 eligible MA enrollees, mean age was 82.8 (SD = 7.2) years, 81% were female, and 49% were non-Latino White; 62 participants (12%) were classified as having dementia by the cohort assessment. MA-encounter-based dementia indicators performed reasonably well in identifying participants with cohort-assessed dementia: using encounters alone, positive predictive value was 63% (95% CI: 52-75%), negative predictive value was 96% (95% CI: 94-98%), and accuracy was 92% (95% CI: 89-94%). Inclusion of chart reviews did not impact performance. Compared to TM-based indicators during the same period, MA-based indicators yielded similar validity metrics but identified a less functionally impaired group as having dementia. In secondary validation analysis of MCI, sensitivity was low. CONCLUSIONS:As one of the first studies to validate dementia diagnoses in MA encounter data, indicators based on the Bynum-Standard algorithm can be a valid tool for identifying prevalent dementia. Findings support the use of MA-encounter-based dementia indicators for research within MA. However, observed health differences between MA- and TM-identified dementia groups suggest potential for selection bias in MA plans.

Loneliness and social isolation are associated with numerous adverse physical and psychological health outcomes in older adulthood, including cognitive impairment and mortality risk. Yet, how the individual and joint effects of loneliness and social isolation contribute to these outcomes remains unclear, particularly given the interplay between individual differences (loneliness) and environmental factors (social isolation) in shaping these important health outcomes in older adulthood (i.e., person-environment interactions). We used Cox regression, logistic regression, and multistate survival models to systematically investigate the individual and adjusted associations among loneliness, social isolation, cognitive aging outcomes, and mortality risk. Further, extensive between-study variability in operational definitions, modeling approaches, and covariate adjustments may be contributing to mixed results in the existing literature. In this registered report, we applied a multistudy approach (i.e., coordinated data analysis) in which independent but identical models were fit across 11 longitudinal studies representing participants from 18 countries (Ntotal = 175,070). Random effects meta-analyses synthesized results across studies, showing that loneliness was consistently associated with an elevated risk of cognitive impairment and mortality across statistical approaches, even after adjusting for social isolation. Conversely, social isolation was not consistently associated with cognitive impairment and showed weaker associations with mortality risk. Together, our findings suggest that loneliness is a robust, proximal predictor of major aging outcomes and highlight avenues for theory development, strategies to strengthen cognitive resilience and independence in older adulthood, and more efficient resource allocation of public health resources. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Plasma p-tau217 closely tracks amyloid-β (Aβ) pathology, yet its ability to predict long-term clinical progression in cognitively unimpaired (CU) adults remains uncertain. We analyzed harmonized data from 2,705 CU participants (Agemean=69.8±7years; Female=63%) across six longitudinal cohorts with up to 13.5 years of follow-up. Cox models evaluated associations between p-tau217 and progression to a clinical diagnosis of cognitive impairment, while natural cubic spline models assessed associations with longitudinal decline on a cognitive composite. Higher p-tau217 was associated with increased risk of progression (hazard-ratio[HR]=1.38; 95%CI:1.31-1.44), independent of demographics and APOEε4, and in models with Aβ-PET (HR=1.30; 95%CI:1.23-1.38). Very high p-tau217 levels (>2.5SD) were associated with 61%[95%CI:53-68%] absolute risk of progression over 10 years. Elevated p-tau217 associated with accelerated cognitive decline, both independent of, and synergistic with, greater Aβ-PET. These findings establish plasma p-tau217 as a robust prognostic marker in preclinical AD and support its value in future individualized risk prediction.

Background: Others have examined heterogeneity in Alzheimer's disease (AD); however, few have used longitudinal data while accounting for variation in disease stage. We used latent classes to model heterogeneity in the trajectories of three cognitive domains (memory, language, and executive functioning) starting at AD dementia diagnosis. Objective: Our aim was to describe the patterns of heterogeneity in cognitive decline across cognitive domains during the course of AD and to contextualize our findings by assessing associations with demographic factors and neuropathological measures. Methods: We used cognitive data from the Religious Orders Study, the Rush Memory and Aging Project, and the Minority Aging Research Study in a multi-dimensional joint latent class mixed model, which allowed us to estimate cognitive trajectories that varied across cognitive domains and latent classes. We accounted for the uncertainty in latent class assignment and corrected for multiple hypotheses when assessing the association of the latent classes with demographic and neuropathological variables. Results: We identified five latent classes differentiated by level of impairment (high to low) and rate of decline (slow to fast). Within each latent class, the pattern of decline did not differ substantially across cognitive domains. Classes were associated with APOE genotype, sex, race, education, and neuritic plaque and neurofibrillary tangle burden. Conclusions: Our results highlight global differences in the level of cognitive impairment at diagnosis and the rate of decline rather than differences between domains of cognition. Examination of patterns in the global rate of cognitive decline may improve understanding of heterogeneity in AD.

Alzheimer’s disease (AD) and total joint arthroplasty are prevalent and often concomitant in older adults, but an etiologic link is debated. Since wear particles are an inevitable side product of total joint arthroplasty (TJA), we hypothesized that older adults with TJA agglomerate higher-than-normal concentrations of implant alloy elements caused by the dissemination of debris from the implants, resulting in a pathological reaction. A cross-sectional analysis was conducted among 701 autopsied participants of an ongoing longitudinal cohort (Memory and Aging Project (MAP)) of whom postmortem neuropathologic data was available and implant-related metals (cobalt, titanium) were quantified in four brain regions by inductively coupled mass-spectrometry. MAP participants are enrolled without known dementia at baseline and followed annually for cognitive assessments using 19-test battery. In the analytical sample, 229 had TJA (total hip arthroplasty, total knee arthroplasty, and total shoulder arthroplasty) and n=472 had no total joint. Due to a higher likelihood of cobalt release in total hip arthroplasty, the TJA group was subdivided into a hip (n=146) and a knee/shoulder (n=83) group. We used regression and linear mixed-effects models, adjusted for demographics and apolipoprotein E ε4 status, to examine associations between metals, AD pathology and cognitive decline. Cobalt content of brain tissue was 8.9% higher in the total hip arthroplasty group than in the no-TJA group (p=0.003). Cobalt-containing particles were identified within brain tissue using scanning electron microscopy. In the inferior temporal cortex, cobalt was positively associated (p=0.0004) and titanium was negatively associated (p=0.038) with amyloid-beta load, but had no association with cognition. These results warrant monitoring the potential impact of metal implant debris on brain health. Statement of Significance This study is of great clinical significance because Alzheimer’s disease (AD) and total joint arthroplasty (TJA)—the end-stage treatment of osteoarthritis—affect large and overlapping groups in our aging population. There is limited knowledge about the relationship between the prominent TJA implant metals cobalt and titanium and the pathogenesis of AD. This study shows that Co28Cr6Mo and Ti6Al4V implant alloy particles—most likely from a subset of total hip replacements with accelerated wear or tribocorrosion—can disseminate to the brain and be associated with increased cobalt and titanium concentrations. Cobalt was associated with greater AD pathology in the inferior-temporal cortex, even after correction for other known AD risk factors. However, there was no correlation with cognitive decline. Titanium was negatively associated with AD pathology, but titanium oxide appeared to be abundant in the brain from sources other than joint replacements.

BACKGROUND:Residing in a formerly redlined community is often associated with worse health. Few studies have studied redlining and late-life cognition; none have examined multiple cognitive domains. METHODS:Black older adults (N = 676, mean baseline age 74.1 [SD: 6.5] years, 78.2% female) from two cohorts in Chicago, IL completed annual cognitive assessments of episodic, semantic, and working memory, perceptual speed, and visuospatial ability. Baseline geocoded addresses were matched to historic Home Owners' Loan Corporation grades ("best," "still desirable," "definitely declining," and "redlined" [first two combined in analyses]). Grades served as place-based proxies for the culmination of decades of policies that heavily impacted redlined communities. Linear mixed-effects models tested associations between grade and change in global and domain-specific cognition, adjusting for age, sex, and years of education. RESULTS:Compared to those in communities graded as "best/still desirable," participants in redlined communities had lower initial global cognition (β = 0.14, SE = 0.05, p = 0.01), though there were no differences for those in "definitely declining" communities, or differences in the rate of longitudinal change. For cognitive domains, those in redlined communities had lower initial episodic and working memory (β = -0.13, SE = 0.07, p = 0.04 and β = -0.17, SE = 0.08, p = 0.03, respectively), but slower decline in semantic memory (β = 0.03, SE = 0.01, p = 0.04) compared to those in "best/still desirable" communities. Results remained consistent when considering potential mediators related to health status, present-day community resources characteristics, and spatial correlations. CONCLUSIONS:Residing in a historically redlined community is associated with cognition in older Black adults, indicating importance of historical community context, though these results are nuanced.

BACKGROUND:The COVID-19 pandemic disrupted older adults' daily lives, particularly concerning social interaction, physical activity, and sleep quality. Older African Americans were disproportionately affected yet remain underrepresented in research documenting the impact of the COVID-19 pandemic. OBJECTIVE:This study investigated changes in self-reported health, survey engagement, physical activity, and sleep duration among older African American adults in the Minority Aging Research Study (MARS) before and after Illinois' March 21, 2020, COVID-19 stay-at-home order, using online surveys and actigraphy watch data. METHODS:MARS is a longitudinal observational cohort study of older African American adults who enroll initially without dementia. We examined a subset of MARS participants enrolled in the Collaborative Aging Research Using Technology initiative. Weekly online health survey responses to binary (yes/no) questions (eg, away from home overnight, overnight visitors, blue mood, loneliness, medication changes, falls, accidents, hospitalizations, health limitations, living space change, or assistance change) were analyzed for 32 weeks (November 30, 2019, to July 11, 2020) and actigraphy data for over 10 weeks (February 15, 2020, to April 15, 2020). Generalized linear mixed models with a logit link function for binary outcomes and linear mixed models for continuous outcomes, adjusted for age, sex, and education, were used to assess changes in self-reported experiences and actigraphy-derived daily steps and nightly sleep and reported as odds ratios (ORs) with 95% credible intervals (CrIs). RESULTS:Of 59 participants (mean age 76.6, SD 6.1 years; male: 11/59, 19%) included in the survey data analysis, 43 (73%) were classified as high-engagement (completed at least 50% of the weekly surveys) and 16 (27%) as low-engagement; these participants were more likely to have mild cognitive impairment (3/43, 7% vs 5/16, 31%; P=.03) and lower mean Mini-Mental State Examination scores (28.1, SD 1.4 vs 28.9, SD 1.0; P=.04). Generalized linear mixed models on the full analytic sample (N=59) showed significant reductions post-COVID-19 in being away from home overnight (OR 0.30, 95% CrI 0.20-0.46), having overnight visitors (OR 0.44, 95% CrI 0.31-0.64), a medication change (OR 0.60, 95% CrI 0.42-0.86), and a health limitation (OR 0.70, 95% CrI 0.52-0.95). COVID-19 and study-related technical disruptions limited actigraphy data availability. Among 15 participants with valid data, mean daily step count decreased significantly (20.1%; 1646, SD 1306 to 1315, SD 1149 steps; P<.001); nightly sleep duration decreased but not significantly (2.8%; 7.1, SD 2.3 hours to 6.9, SD 2.3 hours; P=.49). CONCLUSIONS:Despite widespread COVID-19 disruptions, older African American MARS participants maintained stable survey engagement. Participants with low survey engagement were more likely to have cognitive impairment, suggesting that mild cognitive challenges may hinder sustained participation with online responses. A subset with valid actigraphy data showed reduced physical activity. Although technical issues limited data availability, findings support the value of objective monitoring and highlight the challenges associated with public health disruptions to research infrastructure.

Multiple brain pathologies contribute to dementia. It remains unknown if certain neuropathologies are associated with susceptibility to diagnostic delays in dementia; delays are common and may result in missed opportunities for treatment and support. This study investigates relationships between presence of specific neuropathologies and timeliness of dementia diagnosis in healthcare settings. Using five cohorts at Rush Alzheimer's Disease Center, we selected participants who had incident dementia based on annual cohort assessments, linkage to Medicare records, and later had postmortem brain autopsy. Neuropathologic examinations identified presence of Alzheimer's disease (AD), Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), vascular, and Lewy bodies (LB) pathologies. In linked Medicare data, we defined timely dementia diagnoses as claims diagnoses received within 3 years prior to or 1 year after cohort dementia onset. We used logistic regression to assess associations of pathology with timely diagnosis versus underdiagnosis. Among 548 participants (29% male, 95% non-Latino White, mean[SD] age at dementia onset = 87.6[6.6] years, mean[SD] years from dementia onset to death = 3.8[3.2]), only 54% received a timely diagnosis in the healthcare settings. Adjusting for demographics, other pathologies, and time to death, we found AD (OR = 1.91, 95% CI = 1.21-3.00) and LATE-NC pathologies (OR = 1.83, 95% CI = 1.25-2.68) were independently associated with higher odds of timely diagnosis. Vascular (OR=0.94, 95% CI = 0.55-1.59) and LB pathologies (OR = 1.00, 95% CI = 0.64-1.55) were not significantly associated with timely diagnosis. We observed no multiplicative interaction of coexisting AD and LATE-NC pathologies (interaction term OR = 0.66, 95% CI = 0.26-1.68). In deceased older adults with incident dementia, the healthcare system was twice as likely to capture those with AD and LATE-NC pathologies in a timely manner. The reasons for this are unknown but may be related to differences in clinical manifestations. These findings provide some reassurance that those with AD pathology may be recognized in a timely window, which is believed to be necessary for effectively treating AD. The lack of association between vascular pathology and timely diagnosis may be concerning, given that treatments to improve vascular health (e.g. blood pressure control) can reduce cognitive impairment.

Background Previous studies investigating associations between genetic variants and late-onset Alzheimer's disease (LOAD)-related cognitive functions included primarily European-ancestry individuals and utilized linear models on neuropsychological test scores with ceiling effects.Objective Investigate associations between LOAD-related single nucleotide polymorphisms (SNPs) and neuropsychological test scores by applying the superior approach, Tobit (versus linear) regression models, to identify population-specific SNPs associated with cognitive performance across multiple genetic ancestry groups.Methods National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) and Alzheimer's Disease Genetics Consortium (ADGC) provided phenotype and genotype data on Alzheimer's Disease Research Center (ADRC) participants, respectively. Using the ADGC genotype data, genetic ancestry groups were identified for ADRC participants, including non-Hispanic White (NHW), African American (AA), Hispanic, and Asian. Tobit and linear models were applied to examine genetic associations of 84 LOAD-related SNPs with cognitive performance at the most recent visit, utilizing the NACC UDS data.Results Genetic architectures varied across genetic ancestry groups. The Tobit model detected the association of TMEM106B-rs13237518(A) missed by the linear model. APOE-rs429358(C) was negatively associated with global cognitive function across ancestry groups. Subgroup analyses recognized associations among participants with a cognitive status of dementia: ADAMTS1-rs2830489(T) for Asians and SHARPIN-rs34173062(A) for Hispanics.Conclusions Tobit models demonstrated superior model fit for genetic association analyses of global cognition and language test scores exhibiting ceiling effects.

Objectives As medical interventions for cognitive decline and dementia continue to evolve, the identification of modifiable psychosocial factors has become increasingly important. Sense of purpose and loneliness represent potential targets for intervention. In this study, we aimed to understand the potentially reciprocal relationship between sense of purpose, loneliness, and cognitive function.Methods The current project draws upon data from the Memory and Aging Project and Minority and Aging Research Study led by the Rush Alzheimer's Disease Center, 2 longitudinal cohort studies of 3,118 older adults (Mage=78.4 years; 75% female; 31% Black) without dementia at enrollment. Participants completed annual assessments of cognitive function and completed self-report measures on sense of purpose and loneliness every year for up to 12 years. Using trivariate random intercept cross-lagged panel models, we examined between-person, prospective within-person, and concurrent within-person associations among sense of purpose, loneliness, and cognitive function.Results At the between-person level, a higher sense of purpose and lower loneliness were associated with better cognitive function. At the prospective within-person level, decreases in sense of purpose and increases in loneliness predicted subsequent cognitive decline, independent of ApoE genotype, race, sex, education, depressive symptoms, and social activity.Discussion Changes in both sense of purpose and loneliness independently predicted cognitive decline in older adults, suggesting these constructs are unique targets for potential interventions to promote cognitive health.

Background: The Multiracial population is the fastest-growing racial group in the United States but remains underrepresented in cognitive aging research. No national estimates exist for subjective cognitive decline (SCD)-a self-reported indicator of worsening memory associated with dementia risk-among older Multiracial adults. Methods: We used 2019-2023 Behavioral Risk Factor Surveillance System data from states that administered the optional cognitive decline module (n = 599,874 adults aged ≥45). We estimated crude and age/sex-adjusted SCD prevalence by race and Hispanic ethnicity using survey-weighted logistic regression with predictive marginal standardization. Results: Adjusted SCD prevalence was highest among American Indian or Alaska Native (16.3%) and Multiracial (16.0%) adults, twice that of Asian adults (7.9%). Among Multiracial adults, state-level adjusted prevalence showed low variation (IQR: 18.5%-19.2%). Conclusions: These are the first national estimates of SCD for the Multiracial population, highlighting the need for inclusion in cognitive aging and dementia research.

The recent approval of two anti-amyloid antibodies, Aducanamab and Lecanamab, have set the stage for the next generation of anti-amyloid treatments. Despite the capability of these treatments to lower Aβ brain levels, there is thus far limited clinical efficacy on cognitive outcomes. Because eligibility for treatment includes individuals with MCI or mild dementia, that often harbor mixed pathologies, the cognitive impact of other brain pathologies may be important. This study investigated mixed brain pathologies from autopsied persons that would be considered eligible for anti-amyloid treatment and the association of pathologies with rate of decline in global cognition and five cognitive domains. Eligibility was defined based on having an MMSE score ≥ 20, a clinical diagnosis of MCI or Alzheimer’s dementia, and a level of Aβ pathology that would be indicative of having a positive amyloid PET scan (CERAD score≥moderate). We examined the number and types of co-pathologies. Mixed-effect models were employed to examine association of pathologies (β-amyloid, tangles, LATE-NC, infarcts, and LB) with rate of decline in global cognition and across 5 cognitive domains. Among 428 older autopsied persons (mean age at death = 90 years) considered possibly eligible for anti-amyloid treatment, 58% had MCI and 42% had mild dementia. The majority (94%) had a pathologic diagnosis for AD, of which most had ≥ 1 co-pathology; 43% had +1 co-pathology, 22% had +2 co-pathologies, and 3% had +3 co-pathologies. Regarding type of co-pathologies, 37% had AD + infarcts, 36% had AD + LATE, and 24% had AD + LB. In mixed-effect models, tangles were associated with a faster rate of global cognitive decline, specifically in the domains of episodic (estimate = -0.04; SE = 0.01; p<0.001) and semantic memory (estimate = -0.02; SE = 0.01; p = 0.001). Independent of tangles, LATE-NC and β-amyloid were also associated with decline in episodic (estimate = -0.03, SE = 0.01; p = 0.004) and semantic memory (estimate = -0.02; SE = 0.01, p = 0.04), respectively. Infarcts and LB were not associated with decline in global cognition or any cognitive domains. Mixed pathologies are common in this group of community-dwelling older persons possibly eligible for anti-amyloid treatments. Tangles and LATE-NC pathologies drive late-life cognitive decline, especially episodic memory.

Life satisfaction is an important component of well-being to consider in relation to cognitive function due to its modifiability, potential utility in public health policy, and associations with cognitive health outcomes. However, little is known about the directionality of the association between life satisfaction and cognitive function, and past longitudinal work has yielded mixed findings. Using a coordinated data analytic approach, the current research used data from five longitudinal studies with at least three co-occurring waves of life satisfaction and cognitive function assessments, including over 60,000 individuals aged 50 years and older across multiple countries. Bivariate latent growth curve models and random intercept cross-lagged panel models were used to model between- and within-person associations and to test the potentially bidirectional association between life satisfaction and cognitive function over time. Findings revealed modest between- and within-person associations between life satisfaction and cognitive function. At the between-person level, individuals with higher life satisfaction also had higher cognitive function, and the two constructs changed together across time. However, initial levels of one did not predict long-term change trajectories in the other. At the within-person level, declines in life satisfaction predicted subsequent declines in cognitive function, and vice versa. The current research advances our understanding of the relationship between life satisfaction and cognitive function, suggesting that these constructs change together in the long term and predict changes in each other in the short term. Findings provide observational evidence for the potential utility of life satisfaction in promoting healthy cognitive aging. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

The relationship between Alzheimer’s disease (AD) pathology and the associated clinical syndrome a patient presents with remains indeterminate. Cognitively-defined subgroups of AD have revealed distinctions based on relative cognitive impairments, including AD-Language, where challenges in language are substantial, and AD-No Domain, where no relative asymmetries across cognitive domains occur. Pathological features of AD have been associated as the primary neuropathology of the logopenic variant of primary progressive aphasia (lvPPA). Hallmark clinical features of lvPPA include relatively spared comprehension in the face of decline in naming and repetition abilities. This work aimed to test the hypothesis that the lvPPA language profile was overrepresented in AD-Language when compared to AD-No Domain. Measures of verbal comprehension, confrontation naming, and phrase-level repetition were obtained from all participants from the Religious Orders Study (ROS), the RUSH Memory and Aging Project (MAP) and the Minority Aging Research Study (MARS) using confirmatory factor analyses. We subsetted the data to include participants belonging to the AD-Language and AD-No Domain groups at their initial AD diagnosis visit. We compared patterns of language profiles based on strengths and weaknesses in comprehension, naming, and repetition. Pearson’s Chi-squared tests with Yates continuity correction was used to test if the language patterns were statistically different between the two AD subgroups. We analyzed language performance in 642 participants across AD-Language (31.8%) and AD-No Domain (68.2%) groups (Table 1). Thresholds were based on AD-No Domain and set as the median for each subdomain (comprehension = -.101, naming = -.957, repetition = .233) to establish whether a score represented a relative strength or weakness in the language profile. Eight patterns of language profiles based on strengths and weaknesses in comprehension, naming, and repetition were formed (Figure 1). The distribution of language patterns differed significantly between AD-Language and AD-No Domain (χ2 = 97.6, p <.001). Furthermore, the lvPPA pattern was found more frequently in AD-Language (χ2 = 28.1, p <.001). Heterogeneity within the AD-Language spectrum includes a significant proportion that is consistent with the language profile of lvPPA. Relative performance in domains of verbal comprehension, confrontation naming, and phrase-level repetition varied by AD subgroup.

Both genetic and social factors contribute to Alzheimer's disease and related dementia (ADRD) risk. Genetic risk may be modified by social factors, such as neighborhood characteristics. While previous studies have commonly constructed social factor scores by summing item scores, item response theory (IRT) can estimate more precise composite scores by modeling observable items. This study aimed to 1) construct perceived neighborhood disorder (PND) scores using IRT models across diverse populations, and 2) examine their interaction with genetic risk in ADRD. Using All of Us data, we constructed four cohorts (aged 65+ years): non-Hispanic White (NHW), Black or African American (AA), Hispanic, and Asian. We applied an IRT-based generalized partial credit model to constructed PND scores within each cohort, using the 13-item Ross-Mirowsky Perceived Neighborhood Disorder Scale. Higher scores indicated greater neighborhood disadvantage. APOE ε4 status as a measure of genetic risk for ADRD. Clinically diagnosed dementia or memory impairment was the phenotype: case (diagnosed) and control (non-diagnosed). Logistic regression was employed to estimate joint associations among PND scores and APOE ε4 status with dementia, adjusting for age and sex. In this analysis, we applied random sampling to balance sample sizes between cases and controls. 7∼8% of participants reported clinically diagnosed dementia or memory impairment (Table 1A). APOE ε4 burden was highest among AA (38%), followed by NHW (25%), Hispanic (21%), and Asian (17%). PND item scores varied across groups. For instance, AA and Hispanic participants perceived greater neighborhood safety disadvantages compared to NHW and Asian cohorts (Table 1B). PND scores were approximately normally distributed (Figure 1A). Crime, drug use, alcohol use, and vandalism were the most informative items (Figure 1B). Among NHW participants without ε4 or with one copy of ε4, a 1-point PND score increase raised dementia odds by 1.11 (-/-) and 1.18 (ε4/-). In Hispanics, as 1-point PND score increased, odds of dementia increased by 1.34 (-/-), 1.78 (ε4/-), and 2.39 (ε4/ε4), respectively (Table 1C). APOE and PND were jointly associated with dementia risk. Future research should include additional social measures, more genes, ADRD subtypes, and larger sample sizes to understand gene-environment interaction in dementia.

INTRODUCTION:US Medicare claims can be used to identify dementia cases for research. Our objective was to evaluate the performance of International Classification of Diseases, 10th Revision (ICD-10) code definitions versus research-based dementia ascertainment. METHODS:Participants of five Rush Alzheimer's Disease Center (RADC) cohorts with study visits between October 2015 and December 2019 and fee-for-service Medicare contributed observations. For each observation, we compared research-based dementia status to dementia status based on six ICD-10 code definitions. RESULTS:A total of 1869 participants contributed 5309 observations (mean age 82.9 years, 21.0% Black, 9.3% met research-based dementia criteria). The accuracy of ICD-10 code definitions was high (87%-90%); five of six code definitions favored specificity over sensitivity. All ICD-10 code definitions were less accurate among subgroups defined by older age, minoritized race, increased depressive symptoms, and history of stroke. DISCUSSION:Performance of ICD-10 code definitions mirrored that of ICD-9 code definitions. Awareness of differential performance by participant characteristics can improve the robustness of research. HIGHLIGHTS:We report the performance of the International Classification of Diseases, 10th Revision (ICD-10) code versus research-based dementia ascertainment. ICD-10 performed worse with age, depressive symptoms, minoritized race, and stroke. Awareness of accuracy and differential performance can improve research robustness.

BACKGROUND:Ambulatory care is critical in delivering interventions for dementia and mild cognitive impairment (MCI), from basic services to novel therapeutics. Yet, little is known regarding how community-dwelling persons with dementia/MCI interact with clinicians in outpatient ambulatory settings. We assessed associations of dementia/MCI with outpatient ambulatory evaluation and management (E&M) visits. METHODS:We included 2116 community-dwelling participants in Rush Alzheimer's Disease Center cohorts, with linked fee-for-service Medicare claims. Annually from 2011 to 2019, cohort neuropsychologic evaluations classified participants as dementia, MCI, or no cognitive impairment (NCI). Across groups, we compared annual probability of visiting providers and number of E&M visits, using repeated measures logistic or generalized Poisson mixed effects models. RESULTS:Across 8672 person-years (PY) of follow-up, the mean age was 82 (SD 7.6) years; 77% of PYs were among females and 24% among Black participants. Controlling for demographics and comorbidity, the annual predicted probability of primary care visits was high in all groups (86%-92%). Although there were few visits with dementia-related specialists, we found a higher probability of these visits among those with dementia (15%) and MCI (17%) than NCI (12%; p = 0.009, dementia vs. NCI; p < 0.001, MCI vs. NCI). There were striking differences in visits to other medical specialties: the mean number of annual visits was 40% lower for those with dementia (p < 0.001) and 10% lower for MCI (p < 0.001) than NCI. Overall, dementia and MCI were associated with 19% (p < 0.001) and 4% (p = 0.005) fewer E&M visits, respectively, compared to NCI. CONCLUSIONS:Older adults with dementia and MCI interact with primary care providers regularly and are more likely to use dementia-related specialists than those with NCI. Yet, we found lower utilization of other medical specialties, without compensatory increases in primary care, leading to fewer overall E&M visits, even in MCI. Together, the findings may suggest lost opportunities to address the scope of health issues in vulnerable groups.

Previous research suggests dementia is undetected in healthcare settings for more than half of those with dementia. Most research on underdiagnosis of dementia has focused on the presence or absence of a clinical diagnosis in claims or the medical record without addressing differences in the timeliness of a diagnosis. Little is known about factors that may be related to the timeliness of clinical dementia diagnosis. In five longitudinal cohorts at Rush Alzheimer’s Disease Center, we identified participants with incident dementia based on annual research assessments from 1994 to 2019 and examined the timing of dementia diagnoses in Medicare claims. Receiving a claims diagnosis within three years prior to or one year following incident dementia was considered a “timely diagnosis”; the remaining were categorized as “underdiagnosis”, including late or missed diagnosis. We assessed correlates of timely versus under- diagnosis, including sociodemographic characteristics, health, and psychosocial factors, using bivariate analyses and adjusted logistic regressions. Of the 710 participants with incident dementia, 54% (n = 385) received a timely diagnosis. In logistic regressions adjusting for demographic characteristics, we found Black older adults had twice the odds of underdiagnosis versus timely diagnosis (OR = 2.15, 95% CI: 1.21-3.82). Higher mid-life income (on 10-level scale) was related to 11% lower odds of underdiagnosis (OR = 0.89, 95% CI: 0.81-0.97). Better cognitive function (OR = 1.48, 95% CI: 1.10-1.98 for one standard-deviation higher cognitive function), and fewer comorbidities (OR = 0.94, 95% CI: 0.89-0.98 for one-unit increase in Elixhauser Comorbidity Index) at the time of dementia onset were associated with diagnostic delay. The number of encounters with the healthcare system, disability, frailty, social network, psychosocial factors, and APOE-4 genotype were not associated with diagnostic timing. When considering the timeliness of dementia diagnosis, two socio-demographic characteristics (Black race and lower income) and two health characteristics (better cognitive function and fewer comorbidities) were related to receiving a late/missed diagnosis. Observed correlates of timeliness may have implications for improving dementia diagnosis and care.