Protein Intake and Mortality in Older Adults With Chronic Kidney Disease.

Importance: Avoiding high protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of kidney function decline, but whether it can be suboptimal for survival is not well known. Objective: To estimate the associations of total, animal, and plant protein intake with all-cause mortality in older adults with mild or moderate CKD and compare the results to those of older persons without CKD. Design, Setting, and Participants: Data from 3 cohorts (Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain 1 and 2 and the Swedish National Study on Aging and Care in Kungsholmen [in Sweden]) composed of community-dwelling adults 60 years or older were used. Participants were recruited between March 2001 and June 2017 and followed up for mortality from December 2021 to January 2024. Those with no information on diet or mortality, with CKD stages 4 or 5, or undergoing kidney replacement therapy and kidney transplant recipients were excluded. Data were originally analyzed from June 2023 to February 2024 and reanalyzed in May 2024. Exposures: Cumulative protein intake, estimated via validated dietary histories and food frequency questionnaires. Main Outcomes and Measures: The study outcome was 10-year all-cause mortality, ascertained with national death registers. Chronic kidney disease was ascertained according to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from medical records. Results: The study sample consisted of 8543 participants and 14 399 observations. Of the 4789 observations with CKD stages 1 to 3, 2726 (56.9%) corresponded to female sex, and mean (SD) age was 78.0 (7.2) years. During the follow-up period, 1468 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD; adjusted hazard ratio (HR) for 1.00 vs 0.80 g/kg/d was 0.88 (95% CI, 0.79-0.98); for 1.20 vs 0.80 g/kg/d, 0.79 (95% CI, 0.66-0.95); and for 1.40 vs 0.80 g/kg/d, 0.73 (95% CI, 0.57-0.92). Associations with mortality were comparable for plant and animal protein (HRs, 0.80 [95% CI, 0.65-0.98] and 0.88 [95% CI, 0.81-0.95] per 0.20-g/kg/d increment, respectively) and for total protein intake in participants younger than 75 years vs 75 years or older (HRs, 0.94 [95% CI, 0.85-1.04] and 0.91 [95% CI, 0.85-0.98] per 0.20-g/kg/d increment in total protein intake, respectively). However, the hazards were lower among participants without CKD than in those with CKD (HRs, 0.85 [95% CI, 0.79-0.92] and 0.92 [95% CI, 0.86-0.98] per 0.20-g/kg/d increment, respectively; P = .02 for interaction). Conclusions and Relevance: In this multicohort study of older adults, higher intake of total, animal, and plant protein was associated with lower mortality in participants with CKD. Associations were stronger in those without CKD, suggesting that the benefits of proteins may outweigh the downsides in older adults with mild or moderate CKD.

Differential interplay between multimorbidity patterns and frailty and their mutual mediation effect on mortality in old age.

BACKGROUND: Multimorbidity and frailty often concurrently occur among older adults. OBJECTIVES: To assess the reciprocal association between multimorbidity (condition count and patterns) and frailty and examine the mutual mediation effect of multimorbidity and frailty in their associations with mortality among Chinese older adults. METHODS: This nationwide population-based longitudinal study included 16,563 participants aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey who were surveyed in 2008 and followed up in 2011, 2014, and 2018. Frailty phenotype was assessed by the modified Fried criteria and vital status was ascertained from family members. Cross-lagged panel model (CLPM) was used to test bidirectional associations between multimorbidity and frailty. The direct and indirect effects of multimorbidity and frailty on mortality were evaluated using the combined CLPM with survival analysis. RESULTS: Three multimorbidity patterns were identified: cardiometabolic diseases, cognitive-sensory disorder, and arthritis-digestive-respiratory diseases. The number of chronic conditions and cognitive-sensory disease pattern showed bidirectional associations with frailty across waves (range for ß: 0.046-0.109; all P < 0.001), while cardiometabolic and arthritis-digestive-respiratory patterns unidirectionally predicted frailty change. Furthermore, frailty mediated 23%-27% of the association between multimorbidity and mortality. Only the number of conditions and cognitive-sensory disease pattern were significant mediators in the association between frailty and mortality, with the proportion of mediation ranging 4%-12%. CONCLUSIONS: Multimorbidity measures including condition count and cognitive-sensory disease pattern are bi-directionally associated with frailty in older adults. These multimorbidity measures and frailty partially mediated each other's association with mortality, with frailty acting as a more prominent pathway in the association between multimorbidity and mortality.

Frailty and socioeconomic position: A systematic review of observational studies.

BACKGROUND: Frailty, an age-related state of reduced physiological reserve, is often associated with lower socio-economic position (SEP). This systematic review synthesised observational studies assessing (i) the association between SEP and frailty prevalence; (ii) how changes in frailty status over time vary by SEP; and (iii) whether the association between frailty and clinical outcomes is modified by SEP. METHODS: We searched three electronic databases from 2001 to 2023. We included observational studies measuring early-, mid-, and late-life indicators of SEP (education, income, wealth, housing, occupation, and area-based measures of multiple deprivation) and frailty (assessed using any validated measure). Screening and extraction were performed in duplicate. Findings were synthesised using narrative synthesis. RESULTS: We included 383 studies reporting findings from 265 independent samples/cohorts across 64 countries. Lower SEP was associated with higher frailty prevalence across all indicators (childhood deprivation 7/8 studies, education 227/248, occupation 28/32, housing 8/9, income 98/108, wealth 39/44 and area-based deprivation 32/34). Lower SEP was also associated with higher frailty incidence (27/30), with greater odds of transitioning towards a more severe frailty state (35/43), lower odds of frailty reversion (7/11), and (in some studies) with more rapid accumulation of deficits (7/15). The relationship between frailty and mortality was not modified by SEP. INTERPRETATION: Preventative measures across multiple levels of individual and structural inequality are likely to be required to reduce the rising levels of frailty. Resourcing of interventions and services to support people living with frailty should be proportionate to needs in the population to avoid widening existing health inequalities.

High cognitive reserve attenuates the risk of dementia associated with cardiometabolic diseases.

BACKGROUND: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs. METHODS: Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts. RESULTS: At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p < 0.001) among people with CMDs and moderate-to-high compared to low CR. On brain MRI, CMDs were associated with smaller GMV (ß -0.18 [-0.22, -0.13]) and HV (ß -0.13 [-0.18, -0.08]) as well as significantly larger WMHV (ß 0.06 [0.02, 0.11]) and MD (ß 0.08 [0.02, 0.13]). People with CMDs and moderate-to-high compared to low CR had significantly larger GMV and HV, but no differences in WMHV, MD, or FA. CONCLUSIONS: Among people with CMDs, having a higher level of CR was associated with lower dementia risk and larger gray matter and hippocampal volumes. The results highlight a mentally and socially active life as a modifiable factor that may support cognitive and brain health among people with CMDs.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Atrial fibrillation accelerates functional decline in older adults: a 15-year follow-up population-based study.

AIMS: Atrial fibrillation (AF) has been associated with functional impairment. However, the role exerted by AF on the long-term trajectories of functional mobility remains to be elucidated. This study aimed to evaluate the impact of AF on functional mobility by tracing walking speed (WS) trajectories over 15 years of follow-up in a population-based cohort of individuals aged 60+ years. METHODS AND RESULTS: This population-based cohort study included 3141 community-dwelling participants (mean age 73.7 years; 63.6% women) from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001-2004 to 2016-2019. Functional mobility was assessed by measuring WS in a standardized way. The association between AF and WS trajectories was assessed by multivariable joint models accounting for the longitudinal dropouts due to death. Stratified analyses by demographic and clinical factors were performed. The effect-modifying role of oral anticoagulant therapy (OAC), incident heart failure (HF), and incident stroke was finally investigated. At baseline, 285 (9.1%) participants were ascertained to have AF. A faster annual WS decline was observed in persons with AF than in non-AF peers (adjusted ß coefficient per year = -0.011, 95% confidence interval: -0.016 to -0.005). Incident HF and stroke were associated with greater WS decline in participants with AF. OAC use was not associated with a slower functional decline. CONCLUSION: Atrial fibrillation is associated with a faster physical function decline in older individuals. Incident HF and stroke possibly accelerate WS decline over time in AF participants.

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.

Applicability of STOPP/START prescribing criteria in integrated Swedish administrative health registries and a Swedish population-based cohort.

PURPOSE: The STOPP/START criteria are frequently applied in observational studies to assess potentially inappropriate prescribing in older adults. This study aimed to assess the applicability of the three available STOPP/START versions in two distinct data sources. METHODS: To evaluate the applicability of the three versions of STOPP/START criteria, we used two observational data sources: (i) Integrated Swedish administrative health registries (ISHR) encompassing routinely collected health data and (ii) the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K), based on health professional-led clinical assessments. The Anatomical Therapeutic Classification code (ATC) was used to categorise medications. Diseases were categorised using the international classification of diseases version 10 (ICD10). RESULTS: The first STOPP/START version demonstrated an applicability rate of 80% in ISHR and 84% in SNAC-K. The second version demonstrated an applicability of 64% in ISHR and 74% in SNAC-K. The third version showed an applicability of 66% in ISHR and 77% in SNAC-K. Challenges in applicability included broad definitions, vague terminology, and the lack of information on disease severity, symptomatic traits, and stability of certain conditions. CONCLUSION: The applicability of the STOPP/START criteria in observational studies seems to have decreased in more recent versions of the tool. Population-based studies with comprehensive clinical assessments may offer higher applicability compared to studies based on administrative data. Future versions of the STOPP/START criteria should prioritise clear and unambiguous definitions to improve their applicability in research and promote result generalisability and comparability.

Cardiometabolic disease, cognitive decline, and brain structure in middle and older age.

INTRODUCTION: The presence of multiple cardiometabolic diseases (CMDs) has been linked to increased dementia risk, but the combined influence of CMDs on cognition and brain structure across the life course is unclear. METHODS: In the UK Biobank, 46,562 dementia-free participants completed a cognitive test battery at baseline and a follow-up visit 9 years later, at which point 39,306 also underwent brain magnetic resonance imaging. CMDs (diabetes, heart disease, and stroke) were ascertained from medical records. Data were analyzed using age-stratified (middle age [< 60] versus older [≥ 60]) mixed-effects models and linear regression. RESULTS: A higher number of CMDs was associated with significantly steeper global cognitive decline in older (ß = -0.008; 95% confidence interval: -0.012, -0.005) but not middle age. Additionally, the presence of multiple CMDs was related to smaller total brain volume, gray matter volume, white matter volume, and hippocampal volume and larger white matter hyperintensity volume, even in middle age. DISCUSSION: CMDs are associated with cognitive decline in older age and poorer brain structural health beginning already in middle age. Highlights: We explored the association of CMDs with cognitive decline and brain MRI measures.CMDs accelerated cognitive decline in older (≥60y) but not middle (<60) age.CMDs were associated with poorer brain MRI parameters in both middle and older age.Results highlight the connection between CMDs and cognitive/brain aging.

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.

Enhancing routine immunization efforts for older adults and frail individuals: Good practices during the SARS-CoV-2 pandemic in Italy.

Infectious diseases pose a significant burden on the general population, particularly older adults who are more susceptible to severe complications. Immunization plays a crucial role in preventing infections and securing a healthier aging, but actual vaccination rates among older adults and frail individuals (OAFs) remains far from recommended targets. This study aims to collect and share good practices implemented in several Italian local health districts during the SARS-CoV-2 pandemic to ease routine immunization for OAFs. A 28-items questionnaire has been developed to collect information on organization aspect of immunization services and local good practices implemented before and during the SARS-CoV-2 pandemic. Twelve Public Health managers representative of 9 Italian Regions were further interviewed between January and March 2021. Despite literature suggests several effective interventions to increase vaccine demand, improve vaccine access, and enhance healthcare providers' performance, our survey highlighted substantial heterogeneity in their implementation at local level. Seven good local practices have been identified and described: mass vaccination centers; vaccination mobile units; drive-through vaccination; co-administration; tailored pathways; cooperation among providers involved in vaccination; digitization. Our survey pointed out valuable strategies for enhancing routine immunization for OAFs. Providers should combine effective interventions adequate to their specific context and share good practices.

How to support general practitioners to better detect sarcopenia among older adults: a nested case-control analysis.

PURPOSE: This study explores correlations of sarcopenia and its proxies, such as history of falls, asthenia, and ambulation issues, with frailty levels among older adults in primary care. METHODS: In a cohort of 546,590 patients aged 60 years or older, "definite" sarcopenia cases were operationally defined through the use of non-specific diagnostic codes coupled with inspection of free-texts. Proxies of sarcopenia, such as falls history, asthenia, and ambulation issues were considered as well. Frailty was calculated using an Index intended to primary care. RESULTS: Overall, 171 definite sarcopenia cases were found, rising to 51,520 cases when including proxies (9.4% prevalence). There was a significant association between severe frailty and increased odds of sarcopenia, consistently observed across different event definitions. CONCLUSIONS: Sarcopenia was strongly associated with severe frailty in primary care. The history of falls, asthenia, and ambulation issues were reliable proxies to raise the suspect of sarcopenia. Improved strategies for sarcopenia detection, focusing on specific indicators within severely frail individuals, are warranted.

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.

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.

Association of mild and complex multimorbidity with structural brain changes in older adults: A population-based study.

INTRODUCTION: We quantified the association of mild (ie, involving one or two body systems) and complex (ie, involving ≥3 systems) multimorbidity with structural brain changes in older adults. METHODS: We included 390 dementia-free participants aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen who underwent brain magnetic resonance imaging at baseline and after 3 and/or 6 years. Using linear mixed models, we estimated the association between multimorbidity and changes in total brain tissue, ventricular, hippocampal, and white matter hyperintensities volumes. RESULTS: Compared to non-multimorbid participants, those with complex multimorbidity showed the steepest reduction in total brain (ß*time -0.03, 95% CI -0.05, -0.01) and hippocampal (ß*time -0.05, 95% CI -0.08, -0.03) volumes, the greatest ventricular enlargement (ß*time 0.03, 95% CI 0.01, 0.05), and the fastest white matter hyperintensities accumulation (ß*time 0.04, 95% CI 0.01, 0.07). DISCUSSION: Multimorbidity, particularly when involving multiple body systems, is associated with accelerated structural brain changes, involving both neurodegeneration and vascular pathology. HIGHLIGHTS: Multimorbidity accelerates structural brain changes in cognitively intact older adults These brain changes encompass both neurodegeneration and cerebrovascular pathology The complexity of multimorbidity is associated with the rate of brain changes' progression.

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.

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population-based study.

INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults. METHODS: This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aß), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS: The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aß and NfL (p < 0.05). DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults. HIGHLIGHTS: We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

Risk factors for multimorbidity in adulthood: A systematic review.

BACKGROUND: Multimorbidity, the coexistence of multiple chronic diseases in an individual, is highly prevalent and challenging for healthcare systems. However, its risk factors remain poorly understood. OBJECTIVE: To systematically review studies reporting multimorbidity risk factors. METHODS: A PRISMA-compliant systematic review was conducted, searching electronic databases (MEDLINE, EMBASE, Web of Science, Scopus). Inclusion criteria were studies addressing multimorbidity transitions, trajectories, continuous disease counts, and specific patterns. Non-human studies and participants under 18 were excluded. Associations between risk factors and multimorbidity onset were reported. RESULTS: Of 20,806 identified studies, 68 were included, with participants aged 18-105 from 23 countries. Nine risk factor categories were identified, including demographic, socioeconomic, and behavioral factors. Older age, low education, obesity, hypertension, depression, low pysical function were generally positively associated with multimorbidity. Results for factors like smoking, alcohol consumption, and dietary patterns were inconsistent. Study quality was moderate, with 16.2% having low risk of bias. CONCLUSIONS: Several risk factors seem to be consistently associated with an increased risk of accumulating chronic diseases over time. However, heterogeneity in settings, exposure and outcome, and baseline health of participants hampers robust conclusions.

Ventricular Electrocardiographic Signatures Associated with Dementia and Plasma Alzheimer's Disease Biomarkers in Older Adults: A Population-Based Study.

BACKGROUND: Evidence has emerged that altered ventricular electrocardiogram profiles are associated with dementia, but the neuropathological mechanisms underlying their associations are poorly understood. OBJECTIVE: To investigate the interrelationships of ventricular electrocardiogram profiles with dementia and plasma Alzheimer's disease (AD) biomarkers among older adults. METHODS: This population-based cross-sectional study included 5,153 participants (age ≥65 years; 57.3% women) living in rural communities in China; of these, 1,281 had data on plasma amyloid-ß (Aß)40, Aß42, total-tau, and neurofilament light chain (NfL) protein. The QT, QTc, JT, JTc, QRS intervals, and QRS axis were derived from the 10-second electrocardiogram recording. The DSM-IV criteria were followed for clinical diagnosis of dementia, the NIA-AA criteria for AD, and the NINDS-AIREN criteria for vascular dementia (VaD). Data were analyzed using general linear models, multinomial logistic models, and restricted cubic splines. RESULTS: Of the 5,153 participants, 299 (5.8%) were diagnosed with dementia, including 194 with AD and 94 with VaD. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with all-cause dementia, AD, and VaD (p < 0.05). Left QRS axis deviation was significantly associated with all-cause dementia and VaD (p < 0.01). In the subsample of plasma biomarkers (n = 1,281), prolonged QT, JT, and JTc intervals were significantly associated with a lower Aß42/Aß40 ratio and higher plasma NfL concentrations (p < 0.05). CONCLUSION: Alterations in ventricular repolarization and depolarization are independently associated with all-cause dementia, AD, VaD, and AD plasma biomarkers in older adults (age ≥65 years). Ventricular electrocardiogram parameters may be valuable clinical markers for dementia and the underlying AD pathologies and neurodegeneration.