Lung function in relation to brain aging and cognitive transitions in older adults: A population-based cohort study.

BACKGROUND: We investigated the association of peak expiratory flow (PEF) with dementia; cognitive impairment, no dementia (CIND); and transition from CIND to dementia, and possible underlying neuropathological mechanisms. METHODS: A population-based cohort of adults aged 60+ was followed over 15 years to detect dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria), CIND (assessed through a cognitive battery), and progression from CIND to dementia, in relation to baseline PEF observations. A subsample (n = 462) had 6-year follow-up data on brain magnetic resonance imaging markers of neurodegeneration and small vessel disease. RESULTS: In fully adjusted models, poor PEF performance (< 10th vs. ≥ 80th percentile) was associated with increased hazards for dementia (hazard ratio [HR] = 1.89; 95% confidence interval [CI] = 1.23-2.92) and CIND (HR = 1.55; 95% CI = 1.01-2.38) and CIND progression to dementia, although not statistically significantly (HR = 2.44; 95% CI = 0.78-6.88). People with poor PEF also experienced the fastest ventricular enlargement (ß coefficient = 0.67 mL/year; 95% CI = 0.13-1.21) and had the highest likelihood of developing lacunes (odds ratio = 5.05; 95% CI = 1.01-25.23). DISCUSSION: Poor lung function contributes to cognitive deterioration possibly through accelerated brain atrophy and microvascular damage. HIGHLIGHTS: Poor lung function increased the risk of dementia and mild cognitive impairment (MCI). Poor lung function accelerated the progression from MCI to dementia. Poor lung function was linked to brain microvascular damage and global brain atrophy.

Stimulating leisure-time activities and the risk of dementia: a multi-cohort study.

BACKGROUND: Stimulating activities are associated with a decreased risk of dementia. However, the extent to which this reflects a protective effect of activity or non-participation resulting from dementia is debated. We investigated the association of stimulating leisure-time activity in late adulthood with the risk of dementia across up to two decades' follow-up. METHODS: We used data from five prospective cohort studies from Finland and Sweden. Mental, social, outdoor, consumptive and physical leisure-time activities were self-reported. Incident dementia was ascertained from clinical diagnoses or healthcare and death registers. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Of the 33 263 dementia-free individuals aged ≥50 years at baseline, 1408 had dementia during a mean follow-up of 7.0 years. Active participation in mental (HR: 0.52, 95% CI: 0.41 to 0.65), social (HR: 0.56 95% CI: 0.46 to 0.72), outdoor (HR: 0.70, 95% CI: 0.58 to 0.85), consumptive (HR: 0.67, 95% CI: 0.53 to 0.94) and physical (HR: 0.62, 95% CI: 0.51 to 0.75) activity, as well as variety (HR: 0.54, 95% CI: 0.43 to 0.68) and the overall frequency of activity (HR: 0.41, 95% CI: 0.34 to 0.49) were associated with a reduced risk of dementia in <10 years' follow-up. In ≥10 years' follow-up all associations attenuated toward the null. CONCLUSION: Stimulating leisure-time activities are associated with a reduced risk of dementia in short-term but not long-term follow-up. These findings may reflect a reduction in leisure-time activity following preclinical dementia or dilution of the association over time.

Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia.

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10-12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10-12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10-8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.

Validation of the Health Assessment Tool (HAT) based on four aging cohorts from the Swedish National study on Aging and Care.

BACKGROUND: As global aging accelerates, routinely assessing the functional status and morbidity burden of older patients becomes paramount. The aim of this study is to assess the validity of the comprehensive clinical and functional Health Assessment Tool (HAT) based on four cohorts of older adults (60 + years) from the Swedish National study on Aging and Care (SNAC) spanning urban, suburban, and rural areas. METHODS: The HAT integrates five health indicators (gait speed, global cognition, number of chronic diseases, and basic and instrumental activities of daily living), providing an individual-level score between 0 and 10. The tool was constructed using nominal response models, first separately for each cohort and then in a harmonized dataset. Outcomes included all-cause mortality over a maximum follow-up of 16 years and unplanned hospital admissions over a maximum of 3 years of follow-up. The predictive capacity was assessed through the area under the curve (AUC) using logistic regressions. For time to death, Cox regressions were performed, and Harrell's C-indices were reported. Results from the four cohorts were pooled using individual participant data meta-analysis and compared with those from the harmonized dataset. RESULTS: The HAT demonstrated high predictive capacity across all cohorts as well as in the harmonized dataset. In the harmonized dataset, the AUC was 0.84 (95% CI 0.81-0.87) for 1-year mortality, 0.81 (95% CI 0.80-0.83) for 3-year mortality, 0.80 (95% CI 0.79-0.82) for 5-year mortality, 0.69 (95% CI 0.67-0.70) for 1-year unplanned admissions, and 0.69 (95% CI 0.68-0.70) for 3-year unplanned admissions. The Harrell's C for time-to-death throughout 16 years of follow-up was 0.75 (95% CI 0.74-0.75). CONCLUSIONS: The HAT is a highly predictive, clinically intuitive, and externally valid instrument with potential for better addressing older adults' health needs and optimizing risk stratification at the population level.

Blood biomarkers of Alzheimer's disease in the community: Variation by chronic diseases and inflammatory status.

INTRODUCTION: We explored the variations of blood biomarkers of Alzheimer's disease (AD) by chronic diseases and systemic inflammation. METHODS: We explored the association of AD blood biomarkers with chronic diseases and systemic inflammation (interleukin-6 [IL-6]), in 2366 dementia-free participants of the Swedish National Study on Aging and Care-in Kungsholmen, using quantile regression models. RESULTS: A greater number of co-occurring chronic diseases was associated with higher concentrations of phosphorylated-tau 181 (p-tau181), total-tau (t-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) (p < 0.01). Anemia, kidney, cerebrovascular, and heart diseases were associated with variations in the levels of AD blood biomarkers. Participants in the highest (vs. lowest) interleukin-6 (IL-6) tertile had higher NfL concentration. Systemic inflammation amplified the associations between several chronic diseases and p-tau181, t-tau, NfL, and GFAP. DISCUSSION: In the community, the concentration of AD blood biomarkers varies in relation to medical conditions and systemic inflammation. Recognizing these influences is crucial for the accurate interpretation and clinical implementation of blood biomarkers. HIGHLIGHTS: Participants with a complex clinical profile (i.e., multiple co-occurring diseases or specific disease combinations) display elevated levels of AD blood-biomarkers. Anemia, heart, cerebrovascular, and kidney diseases are associated with variations is the levels of AD blood biomarkers in cognitively intact older adults. Systemic inflammation amplifies the association between several chronic diseases and AD blood biomarkers.

Mapping 15-year depressive symptom transitions in late life: population-based cohort study.

BACKGROUND: The longitudinal course of late-life depression remains under-studied. AIMS: To describe transitions along the depression continuum in old age and to identify factors associated with specific transition patterns. METHOD: We analysed 15-year longitudinal data on 2745 dementia-free persons aged 60+ from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression (minor and major) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; subsyndromal depression (SSD) was operationalised as the presence of ≥2 symptoms without depression. Multistate survival models were used to map depression transitions, including death, and to examine the association of psychosocial (social network, connection and support), lifestyle (smoking, alcohol consumption and physical activity) and clinical (somatic disease count) factors with transition patterns. RESULTS: Over the follow-up, 19.1% had ≥1 transitions across depressive states, while 6.5% had ≥2. Each additional somatic disease was associated with a higher hazard of progression from no depression (No Dep) to SSD (hazard ratio 1.09; 1.07-1.10) and depression (Dep) (hazard ratio 1.06; 1.04-1.08), but also with a lower recovery (HRSSD-No Dep 0.95; 0.93-0.97 [where 'HR' refers to 'hazard ratio']; HRDep-No Dep 0.96; 0.93-0.99). Physical activity was associated with an increased hazard of recovery to no depression from SSD (hazard ratio 1.49; 1.28-1.73) and depression (hazard ratio 1.20; 1.00-1.44), while a richer social network was associated with both higher recovery from (HRSSD-No Dep 1.44; 1.26-1.66; HRDep-No Dep 1.51; 1.34-1.71) and lower progression hazards to a worse depressive state (HRNo Dep-SSD 0.81; 0.70-0.94; HRNo Dep-Dep 0.58; 0.46-0.73; HRSSD-Dep 0.66; 0.44-0.98). CONCLUSIONS: Older people may present with heterogeneous depressive trajectories. Targeting the accumulation of somatic diseases and enhancing social interactions may be appropriate for both depression prevention and burden reduction, while promoting physical activity may primarily benefit recovery from depressive disorders.

Effectiveness of integrated person-centered interventions for older people's care: Review of Swedish experiences and experts' perspective.

Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers' scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field.

Somatic disease burden and depression risk in late life: a community-based study.

AIMS: Co-occurring somatic diseases exhibit complex clinical profiles, which can differentially impact the development of late-life depression. Within a community-based cohort, we aimed to explore the association between somatic disease burden, both in terms of the number of diseases and their patterns, and the incidence of depression in older people. METHODS: We analysed longitudinal data of depression- and dementia-free individuals aged 60+ years from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression diagnoses were clinically ascertained following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision over a 15-year follow-up. Somatic disease burden was assessed at baseline through a comprehensive list of chronic diseases obtained by combining information from clinical examinations, medication reviews and national registers and operationalized as (i) disease count and (ii) patterns of co-occurring diseases from latent class analysis. The association of somatic disease burden with depression incidence was investigated using Cox models, accounting for sociodemographic, lifestyle and clinical factors. RESULTS: The analytical sample comprised 2904 people (mean age, 73.2 [standard deviation (SD), 10.5]; female, 63.1%). Over the follow-up (mean length, 9.6 years [SD, 4 years]), 225 depression cases were detected. Each additional disease was associated with the occurrence of any depression in a dose-response manner (hazard ratio [HR], 1.16; 95% confidence interval [CI]: 1.08, 1.24). As for disease patterns, individuals presenting with sensory/anaemia (HR, 1.91; 95% CI: 1.03, 3.53), thyroid/musculoskeletal (HR, 1.90; 95% CI: 1.06, 3.39) and cardiometabolic (HR, 2.77; 95% CI: 1.40, 5.46) patterns exhibited with higher depression hazards, compared to those without 2+ diseases (multimorbidity). In the subsample of multimorbid individuals (85%), only the cardiometabolic pattern remained associated with a higher depression hazard compared to the unspecific pattern (HR, 1.71; 95% CI: 1.02, 2.84). CONCLUSIONS: Both number and patterns of co-occurring somatic diseases are associated with an increased risk of late-life depression. Mental health should be closely monitored among older adults with high somatic burden, especially if affected by cardiometabolic multimorbidity.

Cardiovascular health and rate of cognitive decline in preclinical dementia: A 12-year population-based study.

OBJECTIVE: We investigated whether vascular risk factors (VRFs), assessed with Life's Simple 7 (LS7), are associated with the rate of cognitive decline in the years preceding a dementia diagnosis. METHOD: This study included 1,449 stroke-free participants aged ≥60 years from the Swedish National Study on Aging and Care in Kungsholmen, who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, perceptual speed) across 12 years. The LS7 score, assessed at baseline, included smoking, diet, physical activity, body mass index, plasma glucose, total cholesterol, and blood pressure. Preclinical dementia was defined as being dementia-free at baseline and diagnosed with dementia during follow-up. Level and change in cognitive performance as a function of LS7 category (poor vs. intermediate to optimal) and future dementia status were estimated using linear mixed-effect models. RESULTS: Participants who later developed dementia had, on average, a poorer LS7 score compared to those who remained dementia-free. For individuals aged 60-72 years, poor diet was associated with accelerated decline in perceptual speed (ß = -0.05, 95% CI [-0.08, -0.02]), and a poor glucose score was associated with faster rates of verbal fluency (ß = -0.019, 95% CI [-0.09, -0.01]) and global cognitive (ß = -0.028, 95% CI [-0.06, 0.00]) decline in the preclinical dementia group. CONCLUSIONS: VRFs exacerbate rate of cognitive decline in the years preceding a dementia diagnosis. This effect was most pronounced in young-old age and primarily driven by diet and glucose. The effect of VRFs may be especially detrimental for cognitive decline trajectories of individuals with impending dementia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Associations of Orthostatic Hypotension and Frailty With Dementia and Mortality in Older Adults: A Population-Based Cohort Study.

BACKGROUND: This study aimed to assess the associations of orthostatic hypotension (OH), in the presence or absence of frailty, with dementia and mortality in older adults. METHODS: We conducted a 15-year population-based cohort study including 2 703 baseline dementia-free individuals from the Swedish National Study on Aging and Care in Kungsholmen. At baseline, OH was defined as a decline in systolic/diastolic blood pressure ≥20/10 mm Hg 1 minute after standing up from a supine position. Frailty status was defined following Fried's frailty phenotype. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders-fourth edition criteria. Multistate flexible parametric survival models were used to estimate associations of OH and frailty with dementia and mortality. RESULTS: Robust people with OH (adjusted hazard ratio [HR] = 2.28; 95% confidence interval [CI] = 1.47-3.54) and frail people without OH (HR = 1.98; 95% CI = 1.40-2.82) or with OH (HR = 2.73; 95% CI = 1.82-4.10) had a higher dementia risk than OH-free and robust people. Moreover, frail people, independently of the presence of OH, had higher mortality rate than OH-free and robust people. In individuals who developed dementia during the follow-up period, neither OH nor frailty was significantly associated with mortality. CONCLUSIONS: Older adults with OH, whether robust or frail, may have a higher dementia risk than those without OH. Older adults with OH, when having frailty, may have a higher mortality rate than those without OH. The concurrent assessments of OH and frailty may provide prognostic values in terms of dementia and mortality risk in older adults.

Living Longer But Frailer? Temporal Trends in Life Expectancy and Frailty in Older Swedish Adults.

BACKGROUND: This study aims to examine temporal trends in frailty state transitions, and years spent frail, in older Swedish adults. METHODS: We followed the Swedish National Study on Aging and Care in Kungsholmen participants from baseline (2001-2004) for 15 (median: 9.6) years. A 40-deficit frailty index (FI) was constructed to identify 3 frailty states: robust (FI ≤ 0.125), mild frailty (0.125 < FI ≤ 0.25), and moderate and severe frailty (FI  > 0.25). Multistate survival analyses were implemented to obtain hazard ratios (HRs) for frailty state transitions, with birth year and sex as predictors. To examine temporal trends, frailty state-specific life expectancies at age 60 were forecasted for robust persons born in different years (1900, 1910, 1920, 1930, and 1940), also by sex. RESULTS: At baseline, the 2 941 participants' mean age was 75 years and 65% were women. Predicted life expectancy and time spent frail from age 60 followed an increasing trend by birth year. Hazards of transitioning from mild frailty to death (HR: 0.89; 95% confidence interval [CI]: 0.83-0.97) and moderate and severe frailty to death (HR: 0.98; 95% CI: 0.97-1.00) were lower for those born later. Women were less likely to transition from robust to mild frailty (HR: 0.81; 95% CI: 0.70-0.93), mild frailty to moderate and severe frailty (HR: 0.80; 95% CI: 0.68-0.93), and moderate and severe frailty to death (HR: 0.68; 95% CI: 0.59-0.78), but spent more time frail. CONCLUSIONS: Our results point to an expansion of time spent frail among older Swedish adults over time.

Association of Long-term Exposure to Air Pollution and Dementia Risk: The Role of Homocysteine, Methionine, and Cardiovascular Burden.

BACKGROUND AND OBJECTIVES: Growing evidence links air pollution with dementia risk, but the biological mechanisms are largely unknown. We investigated the role played by homocysteine (tHcy) and methionine in this association and explored whether this could be explained by cardiovascular diseases (CVDs). METHODS: Data were extracted from the ongoing Swedish National study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal population-based study. At baseline, 2,512 dementia-free participants were examined up to 2013 (mean follow-up: 5.18 ± 2.96 years). Two air pollutants (particulate matter ≤2.5 µm [PM2.5] and nitrogen oxides [NOx]) were assessed yearly from 1990 until 2013 using dispersion models at residential addresses. The hazard ratio of dementia over air pollution levels was estimated using Cox models adjusted for age, sex, education, smoking, socioeconomic status, physical activity, retirement age, creatinine, year of assessment, and the use of supplements. The total effect of air pollutants on dementia was decomposed into 4 pathways involving tHcy/methionine: (1) direct effect; (2) indirect effect (mediation); (3) effect due to interaction; and (4) effect due to both mediation and interaction. To test whether the association was independent from CVDs (ischemic heart disease, atrial fibrillation, heart failure, and stroke), we repeated the analyses excluding those individuals who developed CVDs. RESULTS: The mean age of the study participants was 73.4 years (SD: 10.4), and 62.1% were female individuals. During an average period of 5 years (mean: 5.18; SD: 2.96 years), 376 cases with incident dementia were identified. There was a 70% increased hazard of dementia per unit increase of PM2.5 during the 5 years before baseline (hazard ratio [HR]: 1.71; 95% CI 1.33-2.09). Overall, 50% (51.6%; 95% CI 9.0-94.1) of the total effect of PM2.5 on dementia was due to mediation of tHcy (6.6%; 95% CI 1.6-11.6) and/or interaction (47.8%; 95% CI 4.9-91.7) with tHcy and 48.4% (p = 0.03) to the direct effect of PM2.5 on dementia. High levels of methionine reduced the dementia hazard linked to PM2.5 by 31% (HR: 0.69; 95% CI 0.56-0.85) with 24.8% attributable to the interaction with methionine and 25.9% (p = 0.001) to the direct effect of PM2.5. No mediation effect was found through methionine. Attenuated results were obtained for NOx. Findings for tHcy were attenuated after excluding those who developed CVDs, while remained similar for methionine. DISCUSSION: High levels of homocysteine enhanced the dementia risk attributed to air pollution, while high methionine concentrations reduced this risk. The impact of homocysteine on cardiovascular conditions partly explains this association. Alternative pathways other than cardiovascular mechanisms may be at play between methionine and dementia.

Multimorbidity patterns and 18-year transitions from normal cognition to dementia and death: A population-based study.

BACKGROUND: Several chronic diseases accelerate cognitive decline; however, it is still unknown how different patterns of multimorbidity influence individuals' trajectories across the cognitive continuum. OBJECTIVES: We aimed to investigate the impact of multimorbidity and of specific multimorbidity patterns on the transitions across cognitive stages (normal cognition, cognitive impairment, no dementia [CIND], dementia) and death. METHODS: We included 3122 dementia-free individuals from the Swedish National study on Aging and Care in Kungsholmen. Using fuzzy c-means cluster analysis, multimorbid participants were classified into mutually exclusive groups characterized by commonly coexisting chronic diseases. Participants were followed up to 18 years to detect incident CIND, dementia, or death. Transition hazard ratios (HRs), life expectancies, and time spent in different cognitive stages were estimated using multistate Markov models. RESULTS: At baseline, five multimorbidity patterns were identified: neuropsychiatric, cardiovascular, sensory impairment/cancer, respiratory/metabolic/musculoskeletal, and unspecific. Compared to the unspecific pattern, the neuropsychiatric and sensory impairment/cancer ones showed reduced hazards of reverting from CIND to normal cognition (HR 0.53, 95% CI 0.33-0.85 and HR 0.60, 95% CI 0.39-0.91). Participants in the cardiovascular pattern exhibited an increased hazard of progression from CIND to dementia (HR 1.70, 95% CI 1.15-2.52) and for all transitions to death. Subjects with the neuropsychiatric and cardiovascular patterns showed reduced life expectancy at age 75, with an anticipation of CIND (up to 1.6 and 2.2 years, respectively) and dementia onset (up to 1.8 and 3.3 years, respectively). CONCLUSIONS: Multimorbidity patterns differentially steer individual trajectories across the cognitive continuum of older adults and may be used as a risk stratification tool.

Trajectories of Physical Function and Behavioral, Psychological, and Social Well-Being in a Cohort of Swedish Older Adults.

Background and Objectives: Successful aging has been described as a multifactorial and dynamic process. The aims of the study were to detect aging trajectories of physical function and behavioral, psychological, and social well-being; and to explore the correlations between functional versus well-being trajectories by age group. Research Design and Methods: Data were gathered from the Swedish National Study on Aging and Care in Kungsholmen (N = 1,375). Subjects' physical function was assessed through walking speed and chair-stand tests, behavioral well-being through participation in mental and physical activities, psychological well-being through life satisfaction and positive affect, and social well-being through social connections and support. All exposures were standardized (z-scores). Linear mixed models were used to estimate trajectories of physical function and well-being over a 12-year follow-up. Results: The steepest declines were seen for physical function (relative change [RC] in z-scores across ages; RC = 3.01), followed by behavioral well-being (RC = 2.15), psychological well-being (RC = 2.01), and social well-being (RC = 0.76). Correlations between physical function and the different well-being domains were weak, especially for slopes. Stronger intercept correlations were observed among the oldest-compared to the youngest-old, especially with behavioral (r = 0.39 vs r = 0.24) and psychological (r = 0.33 vs r = 0.22) well-being. Discussion and Implications: Physical function declines the fastest throughout aging. The different well-being domains decline at a slower rate, which may be a possible sign of compensation against age-related functional decline, especially among the youngest-old, for whom discordances between physical function and the different well-being domains were more common.

Role of Orthostatic Hypotension in the Development of Dementia in People With and Without Cardiovascular Disease.

BACKGROUND: Orthostatic hypotension (OH) has been associated with elevated risk of cardiovascular diseases (CVDs) and dementia risk. To better understand the OH-dementia association, we assessed the associations of OH with CVD and subsequent dementia in older adults and considered the temporality of CVD and dementia onset. METHODS: This 15-year population-based cohort study included, at baseline, 2703 dementia-free participants (mean age, 73.7 years) who were divided into a CVD-free cohort (n=1986) and a CVD cohort (n=717). OH was defined as a systolic/diastolic blood pressure decline of ≥20/10 mm Hg after standing up from a supine position. CVDs and dementia were ascertained by physicians or identified from registers. Multistate Cox regressions were applied to assess the associations of OH with CVD and subsequent dementia in the CVD-free and dementia-free cohort. The OH-dementia association in the CVD cohort was examined with Cox regressions. RESULTS: OH was present in 434 (21.9%) individuals in the CVD-free cohort and 180 (25.1%) individuals in the CVD cohort. OH was associated with a hazard ratio of 1.33 (95% CI, 1.12-1.59) for CVD. OH was not significantly associated with incident dementia in the absence of CVD occurring before dementia diagnosis (hazard ratio, 1.22 [95% CI, 0.83-1.81]). In the CVD cohort, individuals with OH had a higher dementia risk than those without OH (hazard ratio, 1.54 [95% CI, 1.06-2.23]). CONCLUSIONS: The association between OH and dementia may partly be explained by the intermediate development of CVD. In addition, in people with CVD, those with OH may have a poorer cognitive prognosis.