Social Health and Cognitive Change in Old Age: Role of Brain Reserve.

OBJECTIVE: Individual aspects of social health (SH; eg, network, engagement, support) have been linked to cognitive health. However, their combined effect and the role of the structural properties of the brain (brain reserve [BR]) remain unclear. We investigated the interplay of SH and BR on cognitive change in older adults. METHODS: Within the Swedish National Study on Aging and Care-Kungsholmen, 368 dementia-free adults aged ≥60 years with baseline brain magnetic resonance imaging were followed over 12 years to assess cognitive change. A measure of global cognition was computed at each of the 5 waves of assessment by averaging domain-specific Z scores for episodic memory, perceptual speed, semantic memory, and letter and category fluency. An SH composite score was computed at baseline by combining leisure activities and social network. BR was proxied by total brain tissue volume (TBTV). Linear mixed models (adjusted for sociodemographic, vascular, and genetic factors) were used to estimate cognitive trajectories in relation to SH and TBTV. Interaction analysis and stratification were used to examine the interplay between SH and TBTV. RESULTS: Moderate-good SH (n = 245; vs poor, ß-slope = 0.01, 95% confidence interval [CI] = 0.002-0.02, p = 0.018) and moderate-to-large TBTV (n = 245; vs small, ß-slope = 0.03, 95% CI = 0.02-0.04, p < 0.001) were separately associated with slower cognitive decline. In stratified analysis, moderate-good SH was associated with higher cognitive levels (but not change) only in participants with moderate-to-large TBTV (ß-intercept = 0.21, 95% CI = 0.06-0.37, p < 0.01; interaction SH * TBTV, p < 0.05). INTERPRETATION: Our findings highlight the interplay between SH and BR that likely unfolds throughout the entire life course to shape old-age cognitive outcomes. ANN NEUROL 2023;93:844-855.

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.

Association of cognitive reserve with transitions across cognitive states and death in older adults: A 15-year follow-up study.

INTRODUCTION: We investigated the association of cognitive reserve (CR) with transitions across cognitive states and death. METHODS: This population-based cohort study included 2631 participants (age ≥60 years) who were dementia-free at baseline and regularly examined up to 15 years. Data were analyzed using the Markov multistate models. RESULTS: Each 1-point increase in the composite CR score (range: -4.25 to 3.46) was significantly associated with lower risks of transition from normal cognition to cognitive impairment, no dementia (CIND) (multivariable-adjusted hazards ratio = 0.78; 95% confidence interval = 0.72-0.85) and death (0.85; 0.79-0.93), and from CIND to death (0.82; 0.73-0.91), but not from CIND to normal cognition or dementia. A greater composite CR score was associated with a lower risk of transition from CIND to death in people aged 60-72 but not in those aged ≥ 78 years. DISCUSSION: CR contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. HIGHLIGHTS: We use Markov multistate model to examine the association between cognitive reserve and transitions across cognitive states and death. A great cognitive reserve contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. A great cognitive reserve is associated with a lower risk of transition from cognitive impairment, no dementia to death in people at the early stage of old age, but not in those at the late stage of old age.

Association of Lifelong Cognitive Reserve with Dementia and Mild Cognitive Impairment among Older Adults with Limited Formal Education: A Population-Based Cohort Study.

INTRODUCTION: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. METHODS: This population-based cohort study included 2,127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. RESULTS: During the total of 8,330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with Alzheimer's disease (AD) and 26 with vascular dementia (VaD). The high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratios (95% confidence interval) of 0.28 (0.14-0.55) for dementia and 0.18 (0.07-0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60-74 but not in those aged ≥75 years (p for interaction = 0.011). Similarly, among MCI-free people at baseline (n = 1,635), the high (vs. low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratios of 0.51 (0.38-0.69) for MCI and 0.46 (0.33-0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. DISCUSSION: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in maintaining late-life cognitive health even among people with no or limited education.

Socioeconomic differences in older adults' unplanned hospital admissions: the role of health status and social network.

BACKGROUND: the socioeconomic distribution of unplanned hospital admissions in older adults is poorly understood. We compared associations of two life-course measures of socioeconomic status (SES) with unplanned hospital admissions while comprehensively accounting for health, and examined the role of social network in this association. METHODS: in 2,862 community-dwelling adults aged 60+ in Sweden, we derived (i) an aggregate life-course SES measure grouping individuals into Low, Middle or High SES based on a summative score, and (ii) a latent class measure that additionally identified a Mixed SES group, characterised by financial difficulties in childhood and old age. The health assessment combined measures of morbidity and functioning. The social network measure included social connections and support components. Negative binomial models estimated the change in hospital admissions over 4 years in relation to SES. Stratification and statistical interaction assessed effect modification by social network. RESULTS: adjusting for health and social network, unplanned hospitalisation rates were higher for the latent Low SES and Mixed SES group (incidence rate ratio [IRR] = 1.38, 95% confidence interval [CI]: 1.12-1.69, P = 0.002; IRR = 2.06, 95% CI: 1.44-2.94, P < 0.001; respectively; ref: High SES). Mixed SES was at a substantially greater risk of unplanned hospital admissions among those with poor (and not rich) social network (IRR: 2.43, 95% CI: 1.44-4.07; ref: High SES), but the statistical interaction test was non-significant (P = 0.493). CONCLUSION: socioeconomic distributions of older adults' unplanned hospitalisations were largely driven by health, although considering SES dynamics across life can reveal at-risk sub-populations. Financially disadvantaged older adults might benefit from interventions aimed at improving their social network.

Late-life depression and multimorbidity trajectories: the role of symptom complexity and severity.

INTRODUCTION: as late-life depression is associated with poor somatic health, we aimed to investigate the role of depression severity and symptom phenotypes in the progression of somatic multimorbidity. METHODS: we analysed data from 3,042 dementia-free individuals (60+) participating in the population-based Swedish National Study on Aging and Care in Kungsholmen. Using the baseline clinical assessment of 21 depressive symptoms from the Comprehensive Psychopathological Rating Scale, we: (i) diagnosed major, minor (in accordance with DSM-IV-TR) and subsyndromal depression; (ii) extracted symptom phenotypes by applying exploratory network graph analysis. Somatic multimorbidity was measured as the number of co-occurring chronic diseases over a 15-year follow-up. Linear mixed models were used to explore somatic multimorbidity trajectories in relation to baseline depression diagnoses and symptom phenotypes, while accounting for sociodemographic and behavioural factors. RESULTS: in multi-adjusted models, relative to individuals without depression, those with major (ß per year: 0.33, 95% confidence interval [CI]: 0.06-0.61) and subsyndromal depression (ß per year: 0.21, 95%CI: 0.12-0.30) experienced an accelerated rate of somatic multimorbidity accumulation, whereas those with minor depression did not. We identified affective, anxiety, cognitive, and psychomotor symptom phenotypes from the network analysis. When modelled separately, an increase in symptom score for each phenotype was associated with faster multimorbidity accumulation, although only the cognitive phenotype retained its association in a mutually adjusted model (ß per year: 0.07, 95%CI: 0.03-0.10). CONCLUSIONS: late-life major and subsyndromal depression are associated with accelerated somatic multimorbidity. Depressive symptoms characterised by a cognitive phenotype are linked to somatic health change in old age.

Social Health and Change in Cognitive Capability among Older Adults: Findings from Four European Longitudinal Studies.

INTRODUCTION: In this study, we examine whether social health markers measured at baseline are associated with differences in cognitive capability and the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. METHODS: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. RESULTS: Pooled estimates show distinct relationships between markers of social health and cognitive domains, e.g., a large network size (≥6 people vs. none) was associated with higher executive function (0.17 standard deviation [SD] [95% CI: 0.00, 0.34], I2 = 27%) but not with memory (0.08 SD [95% CI: -0.02, 0.18], I2 = 19%). We also observed pooled associations between being married or cohabiting, having a large network size, and participating in social activities with slower decline in cognitive capability. However, estimates were close to zero, e.g., 0.01 SD/year (95% CI: 0.01, 0.02) I2 = 19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous, and results for average memory were the most heterogeneous. CONCLUSION: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between-study differences and considering the context specificity of findings in developing and deploying interventions.

Mobility and muscle strength trajectories in old age: the beneficial effect of Mediterranean diet in combination with physical activity and social support.

INTRODUCTION: Decline in physical function varies substantially across older individuals due to several extrinsic modifiable factors such as dietary patterns, physical activity and social support. We aimed to determine the association of these factors and their interaction with mobility and muscle strength decline. METHODS: We analyzed data from 1686 functionally healthy individuals aged 60 + from the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K). The Mediterranean Diet Score (MDS) was calculated based on a validated food frequency questionnaire. Self-reported physical activity was categorized based on current recommendations, and social support was measured according to participants' perceived material and psychological support from relatives and friends. Participants' physical function was assessed over 12 years through changes in walking speed (m/s) and chair stand time (s). Linear mixed models adjusted for socio-demographic and clinical factors were used. In order to explore the combined effect of the different exposures, two indicator variables were created by cross-classifying individuals' levels of Mediterranean diet adherence and social support or physical activity. RESULTS: Participants with a high adherence to Mediterranean diet were primarily < 78 years (82.3%), women (56.1%), married (61.1%), with university education (52.8%), high levels of social support (39.3%) and health-enhancing levels of physical activity (51.5%). A one-point increase in MDS (score range 0-9) was associated with less annual deterioration in walking speed (ß*time[year] = 0.001; p = 0.024) and chair-stand time (ß*time[year] = -0.014; p = 0.008). The potential protective effect of Mediterranean diet was highest among participants reporting high social support (ß*time[year] = -0.065, p = 0.026 for chair stands) and high physical activity (ß*time[year] = 0.010, p = 0.001 for walking speed), beyond the effect of each exposure individually. CONCLUSION: A higher adherence to Mediterranean diet, especially in combination with recommended levels of physical activity and high social support, may contribute to delay the decline in physical function observed with aging.

Genetic risk of dementia mitigated by cognitive reserve: A cohort study.

OBJECTIVE: We investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein ε4 (APOE-ε4), a well-known genetic risk factor for dementia. METHODS: We followed 2,556 cognitively intact participants aged ≥60 years from the ongoing prospective community-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE-ε4 was assessed on multiplicative and additive scales. RESULTS: After an average of 6.3 years (range = 2.1-10.7) of follow-up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE-ε4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE-ε4 carriers with low cognitive reserve, ε4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13-0.59). The magnitude of risk reduction was similar in ε4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15-0.40). INTERPRETATION: Lifelong engagement in reserve-enhancing activities attenuates the risk of dementia attributable to APOE-ε4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019.

Can active life mitigate the impact of diabetes on dementia and brain aging?

INTRODUCTION: We investigated whether lifelong exposure to stimulating activities (active life, AL) mitigates diabetes-associated dementia risk and brain aging. METHODS: In the Swedish National Study on Aging and Care-Kungsholmen, 2286 dementia-free older adults (407 with MRI volumetric measures) were followed over 12 years to detect incident dementia. AL index (low, moderate, high) combined education, work complexity, leisure activities, and social network. RESULTS: Participants with diabetes and low AL had higher dementia risk (hazard ratio [HR] = 2.36, 95% confidence interval [CI] 1.45-3.87) than patients who were diabetes-free with moderate-to-high AL (reference). Dementia risk in participants with diabetes and moderate-to-high AL did not differ from the reference. People with diabetes and low AL had the smallest brain volume, but those with diabetes and moderate-to-high AL exhibited total brain and gray-matter volumes that were similar to those of diabetes-free participants. AL did not modify the diabetes microvascular lesions association. DISCUSSION: AL could mitigate the deleterious impact of diabetes on dementia, potentially by limiting the loss of brain tissue volume.

Psychosocial working conditions, trajectories of disability, and the mediating role of cognitive decline and chronic diseases: A population-based cohort study.

BACKGROUND: Unfavorable psychosocial working conditions have been associated with cognitive decline and chronic diseases, both of which may subsequently accelerate functional dependence. This study aimed to investigate the association between job demand-control-support combinations and trajectories of disability in later life and to further explore the role of cognitive decline and the co-occurrence of chronic diseases in mediating this association. METHODS AND FINDINGS: In this cohort study, 2,937 community dwellers aged 60+ years (mean age 73 ± 10.6; 62.9% female) residing in the Kungsholmen District of Stockholm, Sweden, participated in the baseline survey (2001-2004) and were followed up to 12 years. Lifelong occupational history was obtained through a standardized interview; job demands, job control, and social support at work in the longest-held occupation were graded with a psychosocial job-exposure matrix. Job control, demands, and social support were dichotomized using the median values from the matrix, respectively, to further generate demand-control-support combinations. Disability was measured by summing the number of impaired basic and instrumental activities of daily living. Global cognitive function was assessed by Mini-Mental State Examination. Chronic conditions were ascertained by clinical examinations, medical history, and patient clinical records; the total number of chronic diseases was summed. Data were analyzed using linear mixed-effects models and mediation analysis. Age, sex, education, alcohol consumption, smoking, leisure activity engagement, early-life socioeconomic status, occupational characteristic and physical demands, and baseline cognitive function and number of chronic diseases were adjusted for in the analyses. Compared with active jobs (high control/high demands; n = 1,807), high strain (low control/high demands; n = 328), low strain (high control/low demands; n = 495), and passive jobs (low control/low demands; n = 307) were all associated with a faster rate of disability progression (ß = 0.07, 95% CI 0.02-0.13, p = 0.01; ß = 0.10, 95% CI 0.06-0.15, p < 0.001; ß = 0.11, 95% CI 0.05-0.18, p < 0.001). The association between high strain and disability progression was only shown in people with low social support at work (ß = 0.13, 95% CI 0.07-0.19, p < 0.001), but not in those with high social support (ß = 0.004, 95% CI -0.09 to 0.10, p = 0.93). Moreover, we estimated that the association between demand-control status and disability trajectories was mediated 38.5% by cognitive decline and 18.4% by accumulation of chronic diseases during the follow-up period. The limitations of this study include unmeasured confounding, self-reported work experience, and the reliance on a psychosocial job-exposure matrix that does not consider variabilities in individuals' perception on working conditions or job characteristics within occupations. CONCLUSIONS: Our findings suggest that negative psychosocial working conditions during working life may accelerate disability progression in later life. Notably, social support at work may buffer the detrimental effect of high strain on disability progression. Cognitive decline and chronic-disease accumulation, and especially the former, partially mediate the association of psychosocial working conditions with trajectories of disability. Further studies are required to explore more mechanisms that underlie the association between psychosocial working conditions and disability trajectories.

Association Between Speed of Multimorbidity Accumulation in Old Age and Life Experiences: A Cohort Study.

Rapidly accumulating multiple chronic conditions (multimorbidity) during aging are associated with many adverse outcomes. We explored the association between 4 experiences throughout life-childhood socioeconomic circumstances, early-adulthood education, midlife occupational stress, and late-life social network-and the speed of chronic disease accumulation. We followed 2,589 individuals aged ≥60 years from the Swedish National Study on Aging and Care in Kungsholmen for 9 years (2001-2013). Information on life experiences was collected from detailed life-history interviews. Speed of disease accumulation was operationalized as the change in the count of chronic conditions obtained from clinical examinations, medical histories, laboratory data, drug use, and register linkages over 9 years. Linear mixed models were used to analyze the data. Speed of disease accumulation was lower in individuals with more than elementary education (for secondary, ß × time = -0.065, 95% CI: -0.126, -0.004; for university, ß × time = -0.118, 95% CI: -0.185, -0.050); for active occupations compared with high-strain jobs (ß × time = -0.078, 95% CI: -0.138, -0.017); and for richer social networks (for moderate tertile, ß × time = -0.102, 95% CI: -0.149, -0.055; for highest tertile, ß × time = -0.135, 95% CI: -0.182, -0.088). The association between childhood circumstances and speed of disease accumulation was attenuated by later-life experiences. Diverse experiences throughout life might decelerate chronic disease accumulation during aging.

Psychological correlates of multimorbidity and disability accumulation in older adults.

BACKGROUND/OBJECTIVES: attitudes toward life and health are emerging as important psychological contributors to health heterogeneity in ageing. We aimed to explore whether different psychological factors were associated with the rate of chronic disease and disability accumulation over time. DESIGN: population-based cohort study between 2001 and 2010. SETTING: Swedish National study on aging and care in Kungsholmen. SUBJECTS: adults aged 60 and older (N = 2293). METHODS: linear mixed models were employed to study the association of life satisfaction, health outlook, resistance to illness, sickness orientation, and health worry with the rate of accumulation of chronic diseases and impaired basic and instrumental activities of daily living. Models were adjusted for demographic, clinical, social, personality and lifestyle factors. Analyses were repeated after excluding individuals with multimorbidity or disability at baseline. RESULTS: high life satisfaction and positive health outlook were consistently associated with a lower rate of accumulation and progression of multimorbidity (ß -0.064 95% confidence interval [CI] -0.116, -0.011; ß -0.065 95% CI -0.121, -0.008, respectively) and disability (ß -0.063 95% CI -0.098, -0.028; ß -0.042 95% CI -0.079, -0.004, respectively) over time. This was true even for people without multimorbidity or disability at baseline and after adjusting for all covariates. CONCLUSIONS: positive attitudes toward life in general and health in particular may be especially important in old age, when the cumulative effects of biological and environmental deficits lead to accelerated health decline. These findings should encourage researchers to use measures of psychological well-being to better understand the multifactorial and diverse process of ageing.

Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study.

BACKGROUND: Variation in the clinical manifestation of dementia has been associated with differences in cognitive reserve, although less is known about the cumulative effects of exposure to cognitive reserve factors over the life course. We examined the association of cognitive reserve-related factors over the lifespan with the risk of dementia in a community-based cohort of older adults. METHODS AND FINDINGS: Information on early-life education, socioeconomic status, work complexity at age 20, midlife occupation attainment, and late-life leisure activities was collected in a cohort of dementia-free community dwellers aged 75+ y residing in the Kungsholmen district of Stockholm, Sweden, in 1987-1989. The cohort was followed up to 9 y (until 1996) to detect incident dementia cases. To exclude preclinical phases of disease, participants who developed dementia at the first follow-up examination 3 y after the baseline were excluded (n = 602 after exclusions). Structural equation modelling was used to generate latent factors of cognitive reserve from three periods over the life course: early (before 20 y), adulthood (around 30-55 y), and late life (75 y and older). The correlation between early- and adult-life latent factors was strong (γ = 0.9), whereas early-late (γ = 0.27) and adult-late (γ = 0.16) latent factor correlations were weak. One hundred forty-eight participants developed dementia during follow-up, and 454 remained dementia-free. The relative risk (RR) of dementia was estimated using Cox models with life-course cognitive reserve-enhancing factors modelled separately and simultaneously to assess direct and indirect effects. The analysis was repeated among carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele. A reduced risk of dementia was associated with early- (RR 0.57; 95% CI 0.36-0.90), adult- (RR 0.60; 95% CI 0.42-0.87), and late-life (RR 0.52; 95% CI 0.37-0.73) reserve-enhancing latent factors in separate multivariable Cox models. In a mutually adjusted model, which may have been imprecisely estimated because of strong correlation between early- and adult-life factors, the late-life factor preserved its association (RR 0.65; 95% CI 0.45-0.94), whereas the effect of midlife (RR 0.73; 95% CI 0.50-1.06) and early-life factors (RR 0.76; 95% CI 0.47-1.23) on the risk of dementia was attenuated. The risk declined progressively with cumulative exposure to reserve-enhancing latent factors, and having high scores on cognitive reserve-enhancing composite factors in all three periods over the life course was associated with the lowest risk of dementia (RR 0.40; 95% CI 0.20-0.81). Similar associations were detected among APOE ε4 allele carriers and noncarriers. Limitations include measurement error and nonresponse, with both biases likely favouring the null. Strong correlation between early- and adult-life latent factors may have led to a loss in precision when estimating mutually adjusted effects of all periods. CONCLUSIONS: In this study, cumulative exposure to reserve-enhancing factors over the lifespan was associated with reduced risk of dementia in late life, even among individuals with genetic predisposition.

A Life-Course Study of Cognitive Reserve in Dementia--From Childhood to Old Age.

OBJECTIVE: To test a life-course model of cognitive reserve in dementia and examine if school grades around age 10 years, formal educational attainment, and lifetime occupational complexity affect the risk of dementia in old age. METHODS: 7,574 men and women from the Uppsala Birth Cohort Multigenerational Study were followed for 21 years. Information on school performance, formal education, and occupational attainment was collected prospectively from elementary school archives and population censuses. Dementia diagnosis was extracted from the two Swedish registers. Discrete-time Cox proportional hazard models were estimated. RESULTS: Dementia was diagnosed in 950 individuals (12.5%). Dementia risk was lower among individuals with higher childhood school grades (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.68 to 0.93) and was lower among individuals in data-complex occupations (HR: 0.77; 95% CI: 0.64 to 0.92). Professional/university education predicted lower risk of dementia in minimally adjusted models (HR: 0.74; 95% CI: 0.60 to 0.91), although the effect faded with adjustment for occupational complexity. Lowest risk was found in the group with both higher childhood school performance and high occupational complexity with data (HR: 0.61; 95% CI: 0.50 to 0.75). Importantly, high occupational complexity could not compensate for the effect of low childhood grades. In contrast, dementia risk was reduced in those with higher school grades, irrespective of occupational complexity. CONCLUSION: Higher childhood school performance is protective of dementia risk, particularly when preserved through complex work environments in adulthood, although it will remain protective even in the absence of later-life educational or occupational stimulation.

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.

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.

Early growth, stress, and socioeconomic factors as predictors of the rate of multimorbidity accumulation across the life course: a longitudinal birth cohort study.

BACKGROUND: Early growth, stress, and socioeconomic factors are associated with future risk of individual chronic diseases. It is uncertain whether they also affect the rate of multimorbidity accumulation later in life. This study aimed to explore whether early life factors are associated with the rate at which chronic diseases are accumulated across older age. METHODS: In this national birth cohort study, we studied people born at Helsinki University Central Hospital, Helsinki, Finland between Jan 1, 1934, and Dec 31, 1944, who attended child welfare clinics in the city, and were living in Finland in 1971. Individuals who had died or emigrated from Finland before 1987 were excluded, alongside participants without any registry data and who died before the end of the registry follow-up on Dec 31, 2017. Early anthropometry, growth, wartime parental separation, and socioeconomic factors were recorded from birth, child welfare clinic, or school health-care records, and Finnish National Archives. International Classification of Diseases codes of diagnoses for chronic diseases were obtained from the Care Register for Health Care starting from 1987 (when participants were aged 42-53 years) until 2017. Linear mixed models were used to study the association between early-life factors and the rate of change in the number of chronic diseases over 10-year periods. FINDINGS: From Jan 1, 1934, to Dec 31, 2017, 11 689 people (6064 [51·9%] men and 5625 [48·1%] women) were included in the study. Individuals born to mothers younger than 25 years (ß 0·09; 95% CI 0·06-0·12), mothers with a BMI of 25-30 kg/m2 (0·08; 0·05-0·10), and mothers with a BMI more than 30 kg/m2 (0·26; 0·21-0·31) in late pregnancy accumulated chronic diseases faster than those born to older mothers (25-30 years) and those with a BMI of less than 25 kg/m2. Individuals with a birthweight less than 2·5 kg (0·17; 0·10-0·25) and those with a rapid growth in height and weight from birth until age 11 years accumulated chronic diseases faster during their life course. Additionally, paternal occupational class (manual workers vs upper-middle class 0·27; 0·23-0·30) and wartime parental separation (0·24; 0·19-0·29 for boys; 0·31; 0·25-0·36 for girls) were associated with a faster rate of chronic disease accumulation. INTERPRETATION: Our findings suggest that the foundation for accumulating chronic diseases is established early in life. Early interventions might be needed for vulnerable populations, including war evacuee children and children with lower socioeconomic status. FUNDING: Finska Läkaresällskapet, Liv och Hälsa rf, the Finnish Pediatric Research Foundation, and Folkhälsan Research Center. TRANSLATIONS: For the Finnish and Swedish translations of the abstract see Supplementary Materials section.

Social health and subsequent cognitive functioning in people aged 50 years and older: examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies.

BACKGROUND: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. METHODS: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). FINDINGS: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001-0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000-0·002]) and in delayed recall (PIE 0·001 [0·000-0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000-0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. INTERPRETATION: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. FUNDING: EU Joint Programme-Neurodegenerative Disease Research (JPND) and Alzheimer's Society. TRANSLATION: For the Swedish translation of the abstract see Supplementary Materials section.

Association between personality traits, leisure activities, and cognitive levels and decline across 12 years in older adults.

The engagement in cognitively stimulating activities has been found to be associated with slower rates of cognitive decline in old age. In which type of activities people engage in may depend on their personality traits, which thus might have an impact on later cognitive fitness. To study these potential links, we examined the associations between Neuroticism, Extraversion, and Openness; different types of leisure activities (e.g., social, mental, physical); and cognitive ability levels and decline in older adults. Analyses were based on a sample of young-old (60-72 years old; n = 1,609) and old-old (78 years or older; n = 1,085) adults from the Swedish National Study on Aging and Care in Kungsholmen, who participated in up to five repeated measurements of cognitive abilities spanning 12 years. We used latent growth curve models to estimate cognitive levels and decline, as well as the correlations with initial personality trait levels and leisure activity engagement. In both groups, lower Neuroticism, higher Extraversion, and higher Openness levels were moderately associated with stronger engagement in all types of activities. Lower Neuroticism, higher Extraversion, and a more activity lifestyle were weakly to moderately associated with slower cognitive decline in the old-old age group. There, personality traits and activities explained 9.3% of the variance in cognitive decline after controlling for age, sex, education, and chronic diseases (which explained 9.0%). Taken together, this study provides further evidence for the connection between personality traits, activity engagement, and later cognitive decline in old age. (PsycInfo Database Record (c) 2023 APA, all rights reserved).