Neighborhood disadvantage in later life is associated with poorer cognition and increased vulnerability to dementia. Cognitive reserve (CR), an individual's total cognitive resources, may foster cognitive resilience against dementia in the face of neighborhood disadvantage. However, whether the neighborhood disadvantage-cognition association varies across older adults remains understudied and its moderators remain underexplored. We examined associations between late midlife neighborhood disadvantage and five domain-specific cognitive functions as well as the moderating role of young adult CR on these associations. In 1149 community-dwelling men age 61-73 living across the United States, we assessed neighborhood-level socioeconomic disadvantage using the area deprivation index and cognitive performance in executive function, episodic memory, processing speed, verbal fluency, and visual-spatial ability. General cognitive ability assessed at average age 20 was used as a measure of young adult CR. Years of education was included as another potential moderator for comparison. Greater late midlife neighborhood disadvantage was associated with poorer executive function (β = -.09, p < .05) and processing speed (β = -.12, p < .05). Moreover, those with higher young adult CR showed a weaker association between neighborhood disadvantage and executive function (β = .07, p < .02). The same moderation effect was not observed for years of education. Findings are consistent with the idea that neighborhood disadvantage negatively associates with executive function, albeit less so among those with higher young adult CR. Fostering cognitive development to enhance CR earlier in life may buffer against environmental threats to later-life executive function, which is among the earliest cognitive functions affected in aging, and may, in turn, decrease vulnerability to dementia.

INTRODUCTION:Educational attainment (EA) is negatively associated with body mass index (BMI), but less is known about the association between EA and adult BMI change. We analysed the role of genetic and environmental factors in the associations between EA and BMI trajectory components over adulthood. DATA AND METHODS:Pooled data from 59,490 twins aged 31-99 years (49% women) across 11 cohorts with EA and repeated measures of BMI were used. BMI trajectory components (baseline BMI and BMI change per decade) were estimated using linear mixed-effects (LME) and delta slope methods. EA was derived by regressing years of education on birth year and cohort. Associations between EA and BMI trajectories were evaluated with LME models in both cohort-specific and pooled data. Genetic and environmental contributions were evaluated using structural equation modelling. RESULTS:EA was more strongly negatively associated with baseline BMI and BMI change (mean of 1.31 and 1.32 kg/m2 per decade in men and women, respectively) in women (β = -0.14 kg/m², 95% CI: -0.15 to -0.12; β = -0.02 kg/m²/decade, 95% CI: -0.03 to -0.01, respectively) than in men (β = -0.07, 95% CI: -0.08 to -0.06; β = -0.01, 95% CI: -0.02 to -0.001, respectively). The associations between baseline BMI and EA were explained by genetic factors in men (rA = -0.10) and by both genetic (rA = -0.17) and unique environmental factors (rE = -0.07) in women. For BMI change, the associations with EA were explained by genetic factors (rA = -0.04 in men; -0.06 in women). CONCLUSION:Individuals with higher EA tend to have lower baseline BMI and slower BMI increases across adulthood. These associations are primarily genetically mediated.

Subjective cognitive decline (SCD) refers to cognitive concerns that may occur with or without objective impairment on standardized testing. Studies suggest that SCD may be an early clinical marker of Alzheimer's disease and related dementias, and that it can predict future objective cognitive decline and progression to dementia. However, the research that supports these conclusions is primarily based on samples with homogeneous socioeconomic and cultural backgrounds. The limited studies in samples with more diverse representations of racial, ethnic, gender, and sexual orientation characteristics show varying SCD prevalence, correlates, and outcomes. Here, we review this literature, focusing on how to apply the findings to advance our understanding of SCD. We further evaluate how our findings inform a roadmap for future research. Overall, we conclude that broader investigations across more diverse populations enhance our understanding of the factors that may differentially contribute to SCD and shape its utility as a clinical metric.

INTRODUCTION:Ambient air pollution increases Alzheimer's disease (AD) risk, yet exposure associations with cortical thickness (CTh) in AD-vulnerable brain regions is unclear. Here we examined the associations between PM2.5 and NO2 with CTh in an AD meta-region of interest (ROI), and across the cortex, in participants from the Vietnam Era Twin Study of Aging (VETSA) and Women's Health Initiative Memory Study (WHIMS). METHODS:We conducted a cross-sectional study using data from 387 VETSA men (Mage=61.9 ± 2.6) and 1097 WHIMS women (Mage=77.9 ± 3.7) without dementia or stroke prior to MRI. Long-term residential exposures to PM2.5 and NO2 were quantified as the 3-year average of monthly estimates prior to MRI that were derived from spatiotemporal models with regionalized universal kriging. Brain MRI scans were processed using FreeSurfer-v.5.3.0 to estimate CTh in 34 bilateral regions parcellated with the Desikan-Killiany atlas. An AD meta-ROI was calculated as the surface-area weighted average of CTh in four bilateral regions (entorhinal, fusiform, inferior temporal, and middle temporal cortices) that are vulnerable to AD. Linear mixed models were conducted separately in each cohort with appropriate covariates. RESULTS:In WHIMS, exposures were negatively associated with CTh in the AD meta-ROI (pPM2.5<0.001; pNO2=0.018) and diffusely across the cortex. In VETSA, exposures were positively associated with CTh in the AD meta-ROI (pPM2.5=0.017; pNO2=0.021) and temporal pole, but effects were age-dependent, becoming negative (though nonsignificant) after age 64. DISCUSSION:Positive associations in younger VETSA men, coupled with negative associations in older WHIMS women, may suggest nonmonotonic AD-related neurodegeneration.

INTRODUCTION:Evidence regarding the association between physical activity (PA) and Alzheimer's disease (AD)-related biomarkers is scarce and inconsistent. METHODS:At ages 56 and 67, 564 men from the Vietnam Era Twin Study of Aging reported their PA during the preceding week from which metabolic equivalent of energy expenditure (MET) hours were determined. At age 67 we assayed plasma AD-related biomarkers (phosphorylated tau [p-tau]217, neurofilament light chain [NfL], amyloid beta (Aβ)42/40 ratio, and glial fibrillary acidic protein [GFAP]). We used generalized estimating equations to test whether PA at ages 56 or 67 was associated with these biomarkers at 67. RESULTS:Age 56 MET hours were inversely associated with NfL and GFAP at 67 (NfL: B = -0.10, 95% confidence interval [CI]: -0.17 to -0.03, GFAP: B = -0.08, 95% CI: -0.15 to -0.01) but were not significantly associated with p-tau217 or Aβ42/40 ratio. DISCUSSION:Our NfL and GFAP results suggest that midlife PA may reduce risk for neurodegeneration in older age via amyloid-independent mechanisms.

OBJECTIVES:Early-life rural-urban residence has been linked to differences in later-life cognitive functioning and dementia risk. However, the contextual pathways underlying these associations, particularly emergent associations later in life, remain underexplored. We examined the associations between young adult urbanicity and domain-specific cognition in older adulthood and whether late midlife neighborhood socioeconomic disadvantage may mediate such associations. METHODS:Participants were 881 community-dwelling men aged 61-73 from across the United States. Young adult urbanicity (rural, suburban, and urban) was assessed at a mean age of 20 based on the Rural-Urban Continuum Codes. Late midlife neighborhood disadvantage was indexed by the area deprivation index (ADI), and cognitive performance in older adulthood was assessed in five domains: executive function, episodic memory, processing speed, verbal fluency, and visual-spatial ability. RESULTS:Compared to those in rural areas, participants who resided in urban areas during young adulthood had lower late midlife ADI (β = -0.85, p < .05), and better executive function (β = 0.19), processing speed (β = 0.24), and verbal fluency (β = 0.30) (ps < .05) in older adulthood. ADI partially mediated these associations, such that urban residence was associated with lower ADI, which was then associated with better performance in these three domains (indirect effects: βs = 0.02 to 0.03). DISCUSSION:Late midlife neighborhood disadvantage represents a contextual pathway linking early-life rural-urban residence to cognitive function in older adulthood. Reducing socioeconomic disadvantage through health policies and interventions at both the community-level early in life and the neighborhood-level later in life may help reduce the risk of cognitive impairment and dementia.

Background Living in a country with a large gap between high and low earners has been linked to poor health, including depression. Less studied is gene-by-environment interplay with income inequality as the environmental exposure. Here, we examine the association between childhood exposure to inequality and individual differences in adult depressive symptoms, testing for moderation of genetic influences by inequality using polygenic indices for major depressive disorder, as well as twin models.Methods The research participants were 69,924 members of twin studies from four developed countries, born between 1893 and 1979, aged 22-103 years at depressive symptom assessment. Genotyping was available for 6,256 participants. Income inequality was operationalized as share of income accruing to the top 1% for each country when the participants were between age 5 and 15 years.Results Childhood income inequality was associated with depressive symptom scores in adulthood, adjusting for covariates. Each 1% rise in inequality was associated with 0.295 higher depressive symptoms (scaled on T-score units). In genetic analyses, interaction effects showed that men who faced more inequality as children and had higher genetic risk for depression reported modestly higher depressive symptoms compared to other men. For women, both genetic risk and inequality mattered, with each independently associated with depressive symptoms. Twin models showed that inequality moderated genetic variance underlying depressive symptoms; heritability of depressive symptoms was higher where exposure to income inequality was higher.Conclusions Findings illustrate the long reach of childhood exposure to income inequality and suggest that advantaged environments may help protect against the effects of deleterious genes.

Background The process by which aging leads to increased risk for Alzheimer’s disease and related dementias is not entirely understood, but one hypothesized contributor is the occurrence of low-grade inflammation in older age. Associations between peripheral C-reactive protein (CRP), a marker of systemic inflammation, and brain structure have been widely studied, but fewer studies have examined CRP in relation to diffusion measures, particularly using newer techniques such as restriction spectrum imaging (RSI). In the current study, we examined how high sensitivity CRP (hsCRP) relates to diffusion metrics and global brain tissue volumes among a group of older adult men. Methods We analyzed a sample of 372 cognitively unimpaired men from VETSA, who were assessed at average age 67 for plasma hsCRP and underwent diffusion and structural brain imaging. Linear mixed models examined associations of hsCRP with global and regional measures of restricted normalized directional (RND) and free normalized isotropic (FNI) diffusion in white matter and hindered normalized total diffusion (HNT) and FNI diffusion in gray matter derived from RSI. Similarly, the relationship of hsCRP to global and regional fractional anisotropy (FA) in white matter and mean diffusivity (MD) in white and gray matter was examined. Finally, we examined hsCRP relationships with global gray and white matter volumes as well as global abnormal white matter (AWM; white matter hyperintensities), to attempt quasi-replication of previous findings. Results Higher hsCRP was associated with lower global white matter RND, with several tract-level associations. hsCRP was also associated with greater entorhinal cortex FNI. Conventional DTI metrics showed no associations with hsCRP. In structural analyses, higher hsCRP was associated with lower global gray matter volume but not white matter volume or abnormalities. Conclusion In this sample of older males, higher hsCRP was associated with differences in white matter microstructure measured using multi-shell RSI metrics and with lower global gray matter volume. Conventional DTI metrics showed few associations with hsCRP. These findings suggest that systemic inflammation may be reflected in subtle differences in brain microstructure and macrostructure and highlight the potential value of more sensitive multi-shell diffusion approaches for detecting inflammation-related brain differences in aging populations.

BACKGROUND:Cumulative deficit frailty (CDF) is a syndrome characterized by the accumulation of negative physical, functional and psychosocial insults. Accumulation of CDF and changes in brain structure both occur during the transition to older age and are associated with the development of Alzheimer's disease (AD) and related dementias. However, how these phenomena are temporally related to each other during the aging process is not well understood. METHODS:We examined bidirectional relationships between CDF and brain structure using structural MRI-based brain-predicted age difference and an AD brain signature. Longitudinal MRI and questionnaire-based data were collected from men in the Vietnam Era Twin Study of Aging at three study waves (average ages 56, 62, and 68). RESULTS:Best-fitting longitudinal random intercepts cross-lagged panel models support the strong overall association between CDF and brain structural integrity with significant covariance between random intercepts for CDF and brain-predicted age difference (r = 0.36, p < .001) and between CDF and AD brain signature (r = -0.16, p = .005) after controlling for chronological age, smoking, race/ethnicity, and education. Significant bidirectional negative cross-lagged associations suggested attenuation over time of the association between CDF and nonspecific brain aging (βs = -0.33 to -0.23, p ≤ .012) but not between CDF and AD brain signature. CONCLUSIONS:CDF was associated with age-related brain structure via strong time-invariant common variance as well as weaker across-time factors. By contrast, the association between CDF and AD-related brain structure was via moderate common variance and was not temporally dynamic. Together, this suggests that CDF is differentially associated with age-related and AD-related brain changes and may be a clinically relevant risk factor for pathological brain aging.

Motor dysfunction in different subtypes of mild cognitive impairment (MCI) and dementia have been widely reported. Whether motor profiles could differentiate between MCI subtypes such as amnestic MCI (aMCI) and non-amnestic MCI (naMCI) has not been systematically studied, but could augment the diagnostic process to improve diagnostic accuracy early on in the disease process. Here, we compare motor function across the motor domain between cognitively unimpaired (CU; n = 878), aMCI (n = 89) and naMCI (n = 63) subjects from the Vietnam Era Twin Study of Aging (VETSA). Subjects completed measures of left and right grip strength, simple reaction time, gait at normal and fast pace, gait turn time, chair rises, and graphomotor speed. Linear mixed-effects models, adjusted for multiple comparisons, were used to compare groups. The combined MCI group performed worse on measures in all domains except on the grip strength tests. Multiple comparisons corrected analyses showed that, compared to CU, aMCI had larger reaction time variability, slower normal gait speed and walk turn, and slower graphomotor speed, while naMCI had weaker grip strength, slower walking at fast pace, and slower graphomotor speed. MCI is associated with motor behavioral deficits across several motor domains beyond the well documented domain of gait. Precursors to different types of dementia present with different patterns of motor dysfunction, that can potentially be leveraged to improve diagnostic accuracy in a clinical setting. Early classification of dementia subtype could help with timely assigning appropriate care.

OBJECTIVE:Poor social relations of older adults have been linked to cognitive decline, dementia risk, morbidity, and mortality. We investigated how characteristic ways people relate to romantic partners (adult attachment) might function as risk/protective factors for overall health or dementia risk. Specifically, we evaluated whether attachment anxiety and/or attachment avoidance at midlife predicted cumulative deficit frailty (CDF) and mild cognitive impairment (MCI) in early old age. METHOD:Participants were 1,608 men in the Vietnam Era Twin Study of Aging. Participants' attachment was assessed at a mean age of 56 (starting 2003) and health mediators at a mean age of 62 (2009-2014; e.g., perceived stress, doctor visits, smoking, alcohol consumption, and social isolation). Outcomes at a mean age of 68 (2016-2019) included CDF based on a 37-item scale and MCI. Structural equation modeling assessed associations between attachment, mediators, and outcomes. RESULTS:The effect of attachment anxiety on CDF was indirect, mediated by perceived stress, doctor visits, and smoking at age 62 (total indirect effect: β = .147, p < .001). Its effect on MCI was also indirect, mediated by its association with perceived stress (total indirect effect (β = .090, p = .001). Attachment avoidance did not predict CDF, but it directly predicted MCI (β = .134, p = .033). CONCLUSIONS:Attachment anxiety and attachment avoidance predict frailty and cognitive function through different pathways in older adults. Viewing others as trustworthy and dependable in midlife may be protective against frailty and dementia risk in old age. Focusing on improving the quality of interpersonal relationships may thus help to reduce risk. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Growing evidence supports chronic pain (CP) as a risk factor for Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). We examined whether CP is associated with longitudinal worsening of AD-related biomarkers, brain structure, and cognition, and whether effects differ by APOE-ε4 status. Data were drawn from 1,493 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) without baseline dementia (mean age = 72.4 ± 7.19 years; 48

Plasma phosphorylated tau at threonine 231 (pTau231) is a promising Alzheimer's disease biomarker, especially for preclinical stages, though early measurements often fall below detection limits. Assay detection limits create left-censored data that can bias biomarker heritability estimates and associations with other variables. Standard approaches such as treating values as continuous, setting censored values to zero, or coding them as missing can bias results. We developed a model to estimate heritability that integrates censored and uncensored observations, providing a framework for analyzing left-censored biomarker data. We analyzed plasma pTau231 data from Quanterix Simoa assays of 1,071 male twins aged 60-73 years within the Vietnam Era Twin Study of Aging. Our Integrated Censored and Uncensored (ICU) model treats observations below the limit of detection (LOD=0.621 pg/mL) as ordinal data and above-limit values as continuous measures before decomposing variance into additive genetic effects, shared environmental factors common to twins, and unique environmental influences specific to each twin. Using our ICU model adjusted for site and storage time covariates, we found that plasma pTau231 was moderately heritable, with additive genetic influences explaining 38% of the variance (95% CI: 0.26-0.48), while unique environmental influences explained the remaining 62%. Different approaches to handling censored data produced varying results, with some methods suggesting no genetic influence. Simulation studies will demonstrate conditions where the ICU maintains reliable performance while other approaches may produce biased estimates. Our ICU modeling strategy offers a theoretically grounded approach for estimating heritability from left-censored biomarker data without requiring arbitrary decisions about censored values. These findings have implications for genetic association studies and other biomarker analyses - appropriate handling of censored values is crucial since different approaches can substantially alter estimates of genetic influence, potentially leading to spurious or missed genetic associations. The moderate heritability of plasma pTau231 supports its potential as an AD biomarker while suggesting substantial environmental influence on individual differences. Reference 1. Snieder, H., Boomsma, D.I., Van Doornen, L.J., Neale, M.C. (1999) Bivariate genetic analysis of fasting insulin and glucose levels. Genet Epidemiol . 16:426-446.

Sleep quality (SQ) is associated with cognitive performance; however, it remains unclear if this association is causal, and consequently, whether SQ is a modifiable risk factor for cognitive aging. Leveraging data from the Vietnam Era Twin Study of Aging (VETSA; N =1036, Mage =67.46, range=61.37-72.13, 304 monozygotic (MZ) pairs, 214 dizygotic (DZ) pairs), we investigated the causal relationship between sleep and cognition, accounting for genetic and shared environmental confounding. Using a Co-Twin Control (CTC) design, we examined whether sleep-cognition associations reflect causal effects versus genetic and environmental confounding, leveraging that MZ twins share 100% of genes while DZ twins share 50%. Measures included sleep quality (Pittsburgh Sleep Quality Index total score), general cognitive ability (GCA), and factor scores across episodic memory, visual-spatial memory, executive function, fluency, and processing speed. SQ-cognition associations were decomposed into between-pair effects (comparing twin pair averages) and within-pair effects (comparing co-twins) to capture familial confounding versus potential causal effects. At the individual level, poorer SQ predicted worse performance (β = -0.02 to -0.03, all ps <.05). Within-pair effects (β = -0.02 to -0.05, all ps <.05) indicated the twin with poorer SQ performed worse, showing stronger effects in DZ (β = -0.02 to -0.06) than MZ twins (β = -0.001 to -0.02), except for processing speed. Weaker within- than between-pair effects suggested partial genetic confounding. Potential causation was observed for SQ-GCA and SQ-visual-spatial relationships as effects persisted regardless of genetic relatedness. SQ-episodic memory and SQ-semantic fluency associations suggested both sources of confounding as effects were only observed in the full sample. The remaining domains suggested genetic confounding as effects dissipated with increasing genetic relatedness. Poorer SQ is associated with worse cognitive performance, though the relationship is complex. In some domains, poorer sleep may causally impact cognition, independent of genetic relatedness, albeit effects are small. In others, associations may reflect sources of confounding, with disrupted sleep and cognition representing symptoms of shared neurodegenerative or pathological processes. These findings emphasize the need for a nuanced approach to determine when sleep interventions may be most effective. NIH/NIA grants R01AG050595 & R01AG076838.

Genetic and environmental factors contribute to weight gain, but how these effects change over adulthood is largely unknown. We examined how genetic factors influence BMI changes from young adulthood to old age and how this change relates to BMI in early adulthood. Data from 16 longitudinal twin cohorts, including 111,370 adults (56

Concerns about memory often increase with age and have been suggested as a precursor to impending memory impairment or dementia. However, subjective memory concern (SMC) has also been shown to reflect an individual’s trait-like tendency to worry about memory, which is more strongly linked to negative affect than to objective memory performance. Despite behavioral evidence supporting a trait-like dimension of SMC, its neuroanatomical underpinnings remain underexplored. In 477 community-dwelling dementia-free men (56–72 years old), we investigated the association between SMC and cortical mean diffusivity (cMD)—a diffusion MRI-based metric of gray matter microstructural integrity—generating a brain-wide map of their association. Self-report trait anxiety and depressive symptoms were collected, along with objective memory scores based on three neuropsychological tasks for which brain maps of their association with cMD were also generated. Finally, we conducted spatial correlational analyses to compare the spatial patterns of these brain association maps to assess whether there were significant spatial resemblances between each. We found that the gray matter integrity correlates of SMC spatially resembled those of depressive symptoms and trait anxiety but not those of objective memory. The spatial correspondences between gray matter integrity correlates of negative affect measures and SMC were significantly stronger than those between SMC and objective memory. Together, these results suggest a neuroanatomical basis of trait-like SMC, which should be distinguished from state-related SMC that may be a precursor of objective memory deficits in research and clinical settings.

The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causation between Aβs and t-Tau. No clear evidence that Aβ40 or Aβ42 directly causes t-Tau was observed. Instead, the alternative causal hypotheses also fit the data well. In contrast, exploratory analyses suggested a causal impact of the Aβ biomarkers on NFL. Separately, reciprocal causation was observed between t-Tau and NFL. Plasma Aβ40 or Aβ42 do not appear to have a direct causal impact on t-Tau, though our use of total rather than phosphorylated tau was a limitation. In contrast, Aβ biomarkers appeared to causally impact NFL in cognitively unimpaired men in their late 60 s.

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA successfully analyzed a large-n dataset of several thousand participants and revealed findings in brain regions that some traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.

BACKGROUND:The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain. METHODS:Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI. RESULTS:Moderate-to-severe, but not mild, chronic pain intensity (β = -.10) and interference (β = -.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = -.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05). DISCUSSION:Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.