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.

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.

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.

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.

Cardiometabolic multimorbidity and incident dementia: the Swedish twin registry.

AIMS: Cardiometabolic diseases (CMDs), including diabetes, heart disease, and stroke, are established risk factors for dementia, but their combined impact has been investigated only recently. This study aimed to examine the association between mid- and late-life cardiometabolic multimorbidity and dementia and explore the role of genetic background in this association. METHODS AND RESULTS: Within the Swedish Twin Registry, 17 913 dementia-free individuals aged ≥60 were followed for 18 years. CMDs [including age of onset in mid (60) or late (≥60) life] and dementia were ascertained from medical records. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. Cox regression was used to estimate the CMD-dementia association in (i) a classical cohort study design and (ii) a co-twin study design involving 356 monozygotic and dizygotic pairs. By comparing the strength of the association in the two designs, the contribution of genetic background was estimated. At baseline, 3,312 (18.5%) participants had 1 CMD and 839 (4.7%) had ≥2 CMDs. Over the follow-up period, 3,020 participants developed dementia. In the classic cohort design, the hazard ratio (95% confidence interval) of dementia was 1.42 (1.27-1.58) for 1 CMD and 2.10 (1.73-2.57) for ≥2 CMDs. Dementia risk was stronger with mid-life as opposed to late-life CMDs. In the co-twin design, the CMD-dementia association was attenuated among monozygotic [0.99 (0.50-1.98)] but not dizygotic [1.55 (1.15-2.09)] twins, suggesting that the association was in part due to genetic factors common to both CMDs and dementia. CONCLUSION: Cardiometabolic multimorbidity, particularly in mid-life, is associated with an increased risk of dementia. Genetic background may underpin this association.

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.

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.

The age-dependent association of Life's Simple 7 with transitions across cognitive states after age 60.

BACKGROUND: Life's Simple 7 (LS7) aims to promote ideal cardiovascular health (CVH). Its association with different cognitive states in the older old is unclear. OBJECTIVES: To assess the associations of LS7 with transitions across normal cognition, cognitive impairment, no dementia (CIND), and dementia and evaluate cognitive impairment-free years of life by LS7-defined CVH levels in older adults. METHODS: This cohort study included 2746 participants from the Swedish National Study on Aging and Care in Kungsholmen, regularly examined over 15 years. Total LS7 scores were created and dichotomized into worse and better CVH categories. The associations of LS7 total scores and CVH categories with cognitive states were assessed with multistate models in the whole sample and in younger old (<78 years) and older old adults (≥78 years) separately. Cognitive impairment-free life years by CVH categories were then predicted. RESULTS: A 1-point increment in the LS7 total score was associated with lower dementia risk in younger old adults (hazard ratio: 0.87 [0.78-0.97]) but not in older old adults (1.04 [0.97-1.13]). Better CVH was also associated with a lower risk of transition from normal cognition to CIND (0.76 [0.61-0.95]) and from normal cognition to dementia (0.42 [0.21-0.82]) in younger old adults. In younger old adults, those with better CVH were predicted to have two-to-three more cognitive impairment-free life years than those with worse CVH. CONCLUSION: Maintaining LS7-defined ideal CVH seems relevant in younger old adults but not in older old adults when considering the potential protective effects against cognitive impairment.

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.

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.

Markers of olfactory dysfunction and progression to dementia: A 12-year population-based study.

INTRODUCTION: We evaluated markers of olfactory dysfunction (OD) for estimating hazard of dementia in older adults. METHODS: Mild (hyposmia) and severe (anosmia) OD was classified in a population-based study of dementia-free persons (SNAC-K; n = 2473; mean age = 70 years) using the Sniffin sticks odor identification task. Combined variables were created for objective and subjective OD and for OD and APOE status. Hazard of dementia across 12 years was estimated with Cox regression. RESULTS: OD was associated with increased hazard of dementia (2.01; 95% confidence interval [CI] 1.60-2.52), with the strongest association for anosmia (2.92; 95% CI 2.14-3.98). Results remained consistent after adjusting for potential confounders and across age and sex subgroups. APOE ε4 carriers with anosmia had the highest hazard of dementia (ε4: 6.95; 95% CI 4.16-11.62; ε4/ε4: 19.84; 95% CI 6.17-63.78). DISCUSSION: OD is associated with increased risk of dementia, especially severe impairment in combination with genetic risk of Alzheimer's disease.

Association of ischemic heart disease with long-term risk of cognitive decline and dementia: A cohort study.

INTRODUCTION: The independent and joint effect of ischemic heart disease (IHD) and coexisting atrial fibrillation (AF) and heart failure (HF) on dementia risk is largely unknown. METHODS: This population-based cohort study included 2568 dementia-free participants (age ≥60 years) in SNAC-K, who were regularly examined from 2001-2004 through 2013-2016. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. Global cognitive function was assessed using a global cognitive composite z-score derived from five cognitive domains. Data were analyzed using Cox, Fine-Gray, and linear mixed-effects models. RESULTS: Overall, IHD at baseline was associated with multivariable-adjusted hazard ratio (HR) of 1.39 (95% confidence interval = 1.06-1.82) for dementia and multivariable-adjusted ß-coefficient of -0.02 (-0.03 to -0.01) for annual changes in global cognitive z-score, independent of AF, HF, and cerebrovascular disease. Coexisting AF or HF did not add further risk to dementia and cognitive decline. DISCUSSION: IHD is independently associated with dementia and cognitive decline in older adults, whereas coexisting AF/HF is not associated with an increased risk. HIGHLIGHTS: Is a history of ischemic heart disease (IHD) associated with a risk for dementia? How do coexisting heart diseases affect this association? IHD was an independent risk factor for dementia in older adults. This association was independent of coexisting heart and cerebrovascular diseases. The coexistence of heart diseases did not confer additional risk for dementia.

Associations of pre-pandemic levels of physical function and physical activity with COVID-19-like symptoms during the outbreak.

BACKGROUND: One's physical function and physical activity levels can predispose or protect from the development of respiratory infections. We aimed to explore the associations between pre-pandemic levels of physical function and physical activity and the development of COVID-19-like symptoms in Swedish older adults. METHODS: We analyzed data from 904 individuals aged ≥ 68 years from the population-based Swedish National study on Aging and Care in Kungsholmen. COVID-19-like symptoms were assessed by phone interview (March-June 2020) and included fever, cough, sore throat and/or a cold, headache, pain in muscles, legs and joints, loss of taste and/or odor, breathing difficulties, chest pain, gastrointestinal symptoms, and eye inflammation. Muscle strength, mobility, and physical activity were examined in 2016-2018 by objective testing. Data were analyzed using logistic regression models in the total sample and stratifying by age. RESULTS: During the first outbreak of the pandemic, 325 (36%) individuals from our sample developed COVID-19-like symptoms. Those with slower performance in the chair stand test had an odds ratio (OR) of 1.5 (95% confidence interval [CI] 1.1-2.1) for presenting with COVID-19-like symptoms compared to better performers, after adjusting for potential confounders. The association was even higher among people aged ≥ 80 years (OR 2.6; 95% CI 1.5-4.7). No significant associations were found between walking speed or engagement in moderate-to-vigorous physical activity and the likelihood to develop COVID-19-like symptoms. CONCLUSION: Poor muscle strength, a possible indicator of frailty, may predispose older adults to higher odds of developing COVID-19-like symptoms, especially among the oldest-old.

Association of resting heart rate with cognitive decline and dementia in older adults: A population-based cohort study.

INTRODUCTION: Resting heart rate (RHR) predicts future risk for cardiovascular disease (CVD). However, longitudinal studies investigating the relationship of RHR with cognitive decline are scarce. METHODS: This population-based cohort study included 2147 participants (age≥60) in SNAC-K who were free of dementia and regularly followed from 2001-2004 to 2013-2016. RHR was assessed with electrocardiogram. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders 4th Revision criteria. Global cognitive function was assessed using Mini-Mental State Examination (MMSE). Data were analyzed using Cox and linear mixed-effects models. RESULTS: RHR≥80 (vs. 60-69) bpm was associated with a multi-adjusted hazard ratio of 1.55 (95% confidence interval 1.06-2.27) for dementia. The association remained significant after excluding participants with prevalent and incident CVDs. Similarly, RHR≥80 bpm was associated with a multi-adjusted ß-coefficient of -0.13 (-0.21 to -0.04) for MMSE score. DISCUSSION: Higher RHR is associated with increased risk for dementia and faster cognitive decline independent of CVDs in a general population of elderly people.

Trajectories of cognitive decline and dementia development: A 12-year longitudinal study.

INTRODUCTION: Mapping the preclinical dementia phase is important for early detection and evaluation of interventions. We assessed the trajectories of cognitive decline in preclinical dementia over 12 years and investigated whether being a fast decliner across 6 years is associated with increased risk of dementia the following 6 years. METHODS: Rates of cognitive decline were determined using mixed-effects models for 1646 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) cohort. Cox regression was used to assess the future likelihood of dementia for fast decliners (declining ≥1.5 standard deviations [SDs] faster than the age-specific rates). RESULTS: Participants in a preclinical phase of dementia showed increased rates of decline in all cognitive tests compared to the no-dementia group, particularly closer (0-6 years) to diagnosis. Participants declining fast in three or more cognitive tests 12-6 years before diagnosis demonstrated a high risk of dementia 6 years later (hazard ratio [HR] 3.90, 95% confidence interval [CI] 2.28-6.69). DISCUSSION: Being a fast decliner is linked to increased risk of future dementia.

Cardiometabolic multimorbidity accelerates cognitive decline and dementia progression.

INTRODUCTION: Cardiometabolic diseases (CMDs) have been individually associated with adverse cognitive outcomes, but their combined effect has not been investigated. METHODS: A total of 2577 dementia-free participants 60 years of age or older were followed for 12 years to observe changes in cognitive function and to detect incident cognitive impairment, no dementia (CIND) and dementia. CMDs (including type 2 diabetes, heart disease, and stroke) were assessed at baseline through medical records and clinical examinations. Cardiometabolic multimorbidity was defined as the presence of two or more CMDs. Data were analyzed using multi-adjusted linear mixed-effects models, Cox regression, and Laplace regression. RESULTS: CMD multimorbidity was associated with cognitive decline, CIND (hazard ratio [HR] 1.73; 95% confidence interval CI 1.23 to 2.44), and its progression to dementia (HR 1.86; 95% CI 1.17 to 2.97). CMD multimorbidity accelerated the onset of CIND by 2.3 years and dementia by 1.8 years. CONCLUSIONS: CMD multimorbidity accelerates cognitive decline and increases the risk of both CIND and its conversion to dementia. HIGHLIGHTS: We explored the combined impact of cardiometabolic diseases (CMDs) on cognition. An increasing number of CMDs dose-dependently accelerated cognitive decline. CMD multimorbidity increased the risk of both cognitive impairment and dementia. Co-morbid CMDs could be ideal targets for interventions to protect cognitive health.

Cerebral Small Vessel Disease Associated With Atrial Fibrillation Among Older Adults: A Population-Based Study.

Background and Purpose: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults. Methods: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001­2004) and follow-ups (2004­2007 and 2007­2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models. Results: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (ß coefficient=0.45 [95% CI, 0.04­0.86]) and lateral ventricular volume (0.58 [0.13­1.02]). There was no significant association of AF with annual changes in perivascular spaces number (ß coefficient=0.53 [95% CI, −0.27 to 1.34]) or lacune number (−0.01 [−0.07 to 0.05]). Conclusions: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.

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.