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.

The relationship between frailty and social vulnerability: a systematic review.

Both frailty (reduced physiological reserve) and social vulnerability (scarcity of adequate social connections, support, or interaction) become more common as people age and are associated with adverse consequences. Analyses of the relationships between these constructs can be limited by the wide range of measures used to assess them. In this systematic review, we synthesised 130 observational studies assessing the association between frailty and social vulnerability, the bidirectional longitudinal relationships between constructs, and their joint associations with adverse health outcomes. Frailty, across assessment type, was associated with increased loneliness and social isolation, perceived inadequacy of social support, and reduced social participation. Each of these social vulnerability components was also associated with more rapid progression of frailty and lower odds of improvement compared with the absence of that social vulnerability component (eg, more rapid frailty progression in people with social isolation vs those who were not socially isolated). Combinations of frailty and social vulnerability were associated with increased mortality, decline in physical function, and cognitive impairment. Clinical and public health measures targeting frailty or social vulnerability should, therefore, account for both frailty and social vulnerability.

Patterns of multimorbidity in primary care electronic health records: A systematic review.

Background: Multimorbidity, the coexistence of multiple chronic conditions in an individual, is a complex phenomenon that is highly prevalent in primary care settings, particularly in older individuals. This systematic review summarises the current evidence on multimorbidity patterns identified in primary care electronic health record (EHR) data. Methods: Three databases were searched from inception to April 2022 to identify studies that derived original multimorbidity patterns from primary care EHR data. The quality of the included studies was assessed using a modified version of the Newcastle-Ottawa Quality Assessment Scale. Results: Sixteen studies were included in this systematic review, none of which was of low quality. Most studies were conducted in Spain, and only one study was conducted outside of Europe. The prevalence of multimorbidity (i.e. two or more conditions) ranged from 14.0% to 93.9%. The most common stratification variable in disease clustering models was sex, followed by age and calendar year. Despite significant heterogeneity in clustering methods and disease classification tools, consistent patterns of multimorbidity emerged. Mental health and cardiovascular patterns were identified in all studies, often in combination with diseases of other organ systems (e.g. neurological, endocrine). Discussion: These findings emphasise the frequent coexistence of physical and mental health conditions in primary care, and provide useful information for the development of targeted preventive and management strategies. Future research should explore mechanisms underlying multimorbidity patterns, prioritise methodological harmonisation to facilitate the comparability of findings, and promote the use of EHR data globally to enhance our understanding of multimorbidity in more diverse populations.

Potentially inappropriate prescribing in multimorbid and polymedicated older adults with AF: A Systematic Review and Meta-Analysis.

AIM: Polypharmacy in multimorbid older patients with atrial fibrillation (AF) is a risk factor for potentially inappropriate prescribing (PIP). We aimed to systematically assess the evidence on the prevalence of PIP and its impact on adverse health outcomes in this patient group. METHODS: A systematic search of the published peer-reviewed literature describing the prevalence of PIP and/or its association with adverse health outcomes in multimorbid (AF plus one comorbidity) and polymedicated (≥ 2 drugs) adults ≥ 65 years was done up to March 2023. A meta-analysis of the prevalence of PIP of (direct) oral anticoagulants ((D)OACs) was conducted using a random-effects model. Leave-one-out analysis was performed with R (version 4.2.2) and RStudio (version 2022.12.0+353). RESULTS: Of the 12 studies included, only one reported on the prevalence of overall PIP (65%). The meta-analysis of 10 studies assessing PIP of (D)OACs produced a pooled prevalence [95% confidence interval (CI)] of 35% [30-40%], with significant heterogeneity between the included studies (I2 95%). No statistically significant association was reported in three studies between PIP of (D)OACs, cardiovascular (CV) and all-cause mortality, hospital readmission, CV hospitalisation and stroke. Reported associations between PIP and major bleeding differed, with one study demonstrating a significant association (odds ratio 2.17; 95% CI 1.14-4.12) and the other study not showing such association. CONCLUSION: This systematic review highlights the scarce evidence regarding the prevalence of PIP and its association with adverse health outcomes in multimorbid older adults with AF. Large, prospective and better-designed studies are needed.

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.

Recent developments in frailty identification, management, risk factors and prevention: A narrative review of leading journals in geriatrics and gerontology.

Frailty is an age-related clinical condition characterised by an increased susceptibility to stressors and an elevated risk of adverse outcomes such as mortality. In the light of global population ageing, the prevalence of frailty is expected to soar in coming decades. This narrative review provides critical insights into recent developments and emerging practices in frailty research regarding identification, management, risk factors, and prevention. We searched journals in the top two quartiles of geriatrics and gerontology (from Clarivate Journal Citation Reports) for articles published between 01 January 2018 and 20 December 2022. Several recent developments were identified, including new biomarkers and biomarker panels for frailty screening and diagnosis, using artificial intelligence to identify frailty, and investigating the altered response to medications by older adults with frailty. Other areas with novel developments included exercise (including technology-based exercise), multidimensional interventions, person-centred and integrated care, assistive technologies, analysis of frailty transitions, risk-factors, clinical guidelines, COVID-19, and potential future treatments. This review identified a strong need for the implementation and evaluation of cost-effective, community-based interventions to manage and prevent frailty. Our findings highlight the need to better identify and support older adults with frailty and involve those with frailty in shared decision-making regarding their care.

Epidemiology of invasive meningococcal disease and its sequelae: a population-based study in Italian primary care, 2000-2019.

BACKGROUND: Invasive meningococcal disease (IMD) is a severe infectious disease. Although effective preventive and therapeutical strategies are available, the fatality rate remains high in the general population, with an occurrence of meningococcal-related severe sequelae involving 10-20% of survivors. Given the crucial role of general practitioners in recognizing and preventing IMD and its related sequelae, we aim to assess the burden of these conditions in primary care. METHODS: Using an Italian primary care database, the incidence rate of IMD was calculated in the period 2000-2019 by capturing the first diagnosis registered during follow-up. As far as meningococcal-related sequelae are concerned, we identified and clinically evaluated each potential sequela during the first 3 months, from 3 to 12 months, and up to 36 months. RESULTS: Among 508 patients diagnosed with IMD, 403 (incidence rate: 0.24 per 10,000 person-years) comprised those diagnosed with IMD in patients aged 15 years or older. We ascertained 104 sequelae (20.4%); 76% of them occurred in those aged 25 or older; 42, 27, and 35 were assessed as short-, medium-, or long-term sequelae, respectively. Overall, 4.7% of IMD patients reported physical sequelae, while 12.2% and 5.7% of patients reported neurological and psychological sequelae, respectively. CONCLUSION: Our study showed that a substantial proportion of IMD and related sequelae occur in individuals aged over 25, with a non-negligible burden for healthcare systems. As for the paediatric population, effective communication on the relevance of meningococcal vaccination in adults should be proficiently fostered.

Optimising the care for older persons with complex chronic conditions in home care and nursing homes: design and protocol of I-CARE4OLD, an observational study using real-world data.

INTRODUCTION: In ageing societies, the number of older adults with complex chronic conditions (CCCs) is rapidly increasing. Care for older persons with CCCs is challenging, due to interactions between multiple conditions and their treatments. In home care and nursing homes, where most older persons with CCCs receive care, professionals often lack appropriate decision support suitable and sufficient to address the medical and functional complexity of persons with CCCs. This EU-funded project aims to develop decision support systems using high-quality, internationally standardised, routine care data to support better prognostication of health trajectories and treatment impact among older persons with CCCs. METHODS AND ANALYSIS: Real-world data from older persons aged ≥60 years in home care and nursing homes, based on routinely performed comprehensive geriatric assessments using interRAI systems collected in the past 20 years, will be linked with administrative repositories on mortality and care use. These include potentially up to 51 million care recipients from eight countries: Italy, the Netherlands, Finland, Belgium, Canada, USA, Hong Kong and New Zealand. Prognostic algorithms will be developed and validated to better predict various health outcomes. In addition, the modifying impact of pharmacological and non-pharmacological interventions will be examined. A variety of analytical methods will be used, including techniques from the field of artificial intelligence such as machine learning. Based on the results, decision support tools will be developed and pilot tested among health professionals working in home care and nursing homes. ETHICS AND DISSEMINATION: The study was approved by authorised medical ethical committees in each of the participating countries, and will comply with both local and EU legislation. Study findings will be shared with relevant stakeholders, including publications in peer-reviewed journals and presentations at national and international meetings.

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

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

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.

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.

Association of Comorbidity With Healthcare Utilization in People Living With Dementia, 2010-2019: A Population-Based Cohort Study.

Evidence on the healthcare utilization associated with comorbidity in people with dementia is lacking in Chinese societies. This study aimed to quantify healthcare utilization associated with comorbidity that is common in people living with dementia. We conducted a cohort study using population-based data from Hong Kong public hospitals. Individuals aged 35+ with a dementia diagnosis between 2010 and 2019 were included. Among 88,151 participants, people with at least two comorbidities accounted for 81.2%. Estimates from negative binomial regressions showed that compared to those with one or no comorbid condition other than dementia, adjusted rate ratios of hospitalizations among individuals with six or seven and eight or more conditions were 1.97 [98.75% CI, 1.89-2.05] and 2.74 [2.63-2.86], respectively; adjusted rate ratios of Accident and Emergency department visits among individuals with six or seven and eight or more conditions were 1.53 [1.44-1.63] and 1.92 [1.80-2.05], respectively. Comorbid chronic kidney diseases were associated with the highest adjusted rate ratios of hospitalizations (1.81 [1.74-1.89]), whereas comorbid chronic ulcer of the skin was associated with the highest adjusted rate ratios of Accident and Emergency department visits (1.73 [1.61-1.85]). Healthcare utilization for individuals with dementia differed substantially by both the number of comorbid chronic conditions and the presence of some specific comorbid conditions. These findings further highlight the importance of taking account of multiple long-term conditions in tailoring the care approach and developing healthcare plans for people with dementia.

Concordance and Discrepancies Among 5 Creatinine-Based Equations for Assessing Estimated Glomerular Filtration Rate in Older Adults.

Importance: There is uncertainty as to which estimated glomerular filtration rate (eGFR) equation should be used among older adults. Objective: To compare the 5 most commonly used creatinine-based eGFR equations in older adults, quantifying the concordance among the equations, comparing their discriminative capacity in regards to 15-year mortality, and identifying sources of potential discrepancies. Design, Setting, and Participants: This cohort study used data from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal study of adults aged 60 years or older in Sweden. Participants were recruited between 2001 and 2004 and followed up for mortality until December 2016. Participants missing creatinine values were excluded. Data were originally analyzed March through July 2022, and were rerun in January 2023. Exposures: Five creatinine-based equations were considered: Modification of Diet in Renal Disease (MDRD), 2009 Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI), Revised Lund-Malmö (RLM), Berlin Initiative Study (BIS), and European Kidney Function Consortium (EKFC). Main Outcomes and Measures: Concordance between equations was quantified using Cohen κ. Discriminative capacity for mortality was quantified using area under the receiver operating characteristic curve (AUC) and the Harrel C statistic. Calf circumference, body mass index (BMI), and age were explored as correlates of discrepancies. Results: The study sample consisted of 3094 older adults (1972 [63.7%] female; median [IQR] age, 72 [66-81] years). Cohen κ between dyads of equations ranged from 0.42 to 0.91, with poorest concordance between MDRD and BIS, and best between RLM and EKFC. MDRD and CKD-EPI provided higher estimates of GFR compared with the other equations. The best mix of AUC and Harrel C statistic was observed for BIS (0.80 and 0.73, respectively); however, the prognostic accuracy for death decreased among those aged over 78 years and those with low calf circumference. Differences between equations were inconsistent across levels of calf circumference, BMI, and age. Conclusions and Relevance: In this cohort study, we found that eGFR equations were not interchangeable when assessing kidney function. BIS outperformed other equations in predicting mortality; however, its discriminative capacity was reduced in subgroup analyses. Clinicians should consider these discrepancies when monitoring kidney function in old age.

Social network and severe lower respiratory tract infections in older adults: findings from a Swedish longitudinal population-based study.

OBJECTIVES: To investigate the association between social network and the risk and prognosis of severe lower respiratory tract infections (LRTIs) in older adults. METHODS: Data from Swedish hospital records were matched with the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Social network was operationalized as social connections and social support, based on different self-reported variables, and categorized as low, medium, and high. The risk of severe LRTI and related outcomes were assessed using Cox, Poisson, and logistic regression models where appropriate. RESULTS: A total of 362 individuals experienced LRTI-related hospitalizations between 2001 and 2016 (479 total hospitalizations). High levels of social support decreased the hazard of incident LRTI by 29% (hazard ratio 0.71, 95% confidence interval [CI] 0.52-0.96), the hospital length of stay by 21% (incidence rate ratio 0.79, 95% CI 0.65-0.97), and the risk of 30-day mortality by 92% (odds ratio 0.08, 95% CI 0.01-0.68), but was a risk factor for 30-day readmission (odds ratio 3.16, 95% CI 1.38-7.24). High levels of social connections were associated with a higher risk of incident LRTI in women and those with dementia and/or slow walking speed (Pinteraction <0.05). CONCLUSION: Older individuals' quality of social support seems to be a stronger determinant of LRTI incidence and prognosis than the quantity of their social connections. These findings may inform evidence-based policies aimed at preventing LRTIs in older adults.

Associations of Cardiac Ventricular Repolarization with Serum Adhesion Molecules and Cognitive Function in Older Adults: The MIND-China Study.

BACKGROUND: Emerging evidence has linked electrocardiographic parameters with serum adhesion molecules and cognition; however, their interrelationship has not been explored. OBJECTIVE: We sought to investigate the associations of ventricular depolarization and repolarization intervals with serum adhesion molecules and cognitive function among rural-dwelling older adults. METHODS: This population-based study engaged 4,886 dementia-free participants (age ≥60 years, 56.2% women) in the baseline examination (March-September 2018) of MIND-China. Of these, serum intercellular and vascular adhesion molecules (ICAM-1 and VCAM-1) were measured in 1591 persons. We used a neuropsychological test battery to assess cognitive function. Resting heart rate, QT, JT intervals, and QRS duration were assessed with electrocardiogram. Data were analyzed using general linear models adjusting for multiple confounders. RESULTS: Longer JT interval was significantly associated with lower z-scores of global cognition (multivariable-adjusted ß= -0.035; 95% confidence interval = -0.055, -0.015), verbal fluency (-0.035; -0.063, -0.007), attention (-0.037; -0.065, -0.010), and executive function (-0.044; -0.072, -0.015), but not with memory function (-0.023; -0.054, 0.009). There were similar association patterns of QT interval with cognitive functions. In the serum biomarker subsample, longer JT and QT intervals remained significantly associated with poorer executive function and higher serum adhesion molecules. We detected statistical interactions of JT interval with adhesion molecules (pinteraction <0.05), such that longer JT interval was significantly associated with a lower executive function z-score only among individuals with higher serum ICAM-1 and VCAM-1. CONCLUSION: Longer ventricular depolarization and repolarization intervals are associated with worse cognitive function in older adults and vascular endothelial dysfunction may play a part in the associations.

Impact of Pneumonia on Cognitive Aging: A Longitudinal Propensity-Matched Cohort Study.

BACKGROUND: Acute clinical events, such as pneumonia, may impact physical functionality but their effect on cognition and the possible duration of this effect remains to be quantified. This study investigated the impact of pneumonia on cognitive trajectories and dementia development in older people. METHODS: Data were obtained from 60+ years old individuals, who were assessed from 2001 to 2018 in the population-based SNAC-K study (Sweden). Participants were eligible if they were not institutionalized, had no dementia, and did not experience pneumonia 5 years prior to baseline (N = 2 063). A propensity score was derived to match 1:3 participants hospitalized with a diagnosis of pneumonia (N = 178), to nonexposed participants (N = 534). Mixed linear models were used to model cognitive decline. The hazard of dementia, clinically diagnosed by physicians following Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV, was estimated using Cox regression models. RESULTS: We found a transient impact of pneumonia on cognitive decline in the first 2.5 years (B = -0.94, 95% confidence interval [CI] -1.75, -0.15). The hazard ratio (HR) for dementia was not statistically significantly increased in pneumonia participants (HR = 1.17, 95%CI 0.82, 1.66). CONCLUSIONS: The transient impact of pneumonia on cognitive function suggests an increased need of health care for patients after a pneumonia-related hospitalization and reinforces the relevance of pneumonia prevention.

Beyond Chronological Age: A Multidimensional Approach to Survival Prediction in Older Adults.

BACKGROUND: There is a growing interest in generating precise predictions of survival to improve the assessment of health and life-improving interventions. We aimed to (a) test if observable characteristics may provide a survival prediction independent of chronological age; (b) identify the most relevant predictors of survival; and (c) build a metric of multidimensional age. METHODS: Data from 3 095 individuals aged ≥60 from the Swedish National Study on Aging and Care in Kungsholmen. Eighty-three variables covering 5 domains (diseases, risk factors, sociodemographics, functional status, and blood tests) were tested in penalized Cox regressions to predict 18-year mortality. RESULTS: The best prediction of mortality at different follow-ups (area under the receiver operating characteristic curves [AUROCs] 0.878-0.909) was obtained when 15 variables from all 5 domains were tested simultaneously in a penalized Cox regression. Significant prediction improvements were observed when chronological age was included as a covariate for 15- but not for 5- and 10-year survival. When comparing individual domains, we find that a combination of functional characteristics (ie, gait speed, cognition) gave the most accurate prediction, with estimates similar to chronological age for 5- (AUROC 0.836) and 10-year (AUROC 0.830) survival. Finally, we built a multidimensional measure of age by regressing the predicted mortality risk on chronological age, which displayed a stronger correlation with time to death (R = -0.760) than chronological age (R = -0.660) and predicted mortality better than widely used geriatric indices. CONCLUSIONS: Combining easily accessible characteristics can help in building highly accurate survival models and multidimensional age metrics with potentially broad geriatric and biomedical applications.

Specific multimorbidity patterns modify the impact of an exercise intervention in older hospitalized adults.

Background: Different multimorbidity patterns present with different prognoses, but it is unknown to what extent they may influence the effectiveness of an individualized multicomponent exercise program offered to hospitalized older adults. Methods: This study is a secondary analysis of a randomized controlled trial conducted in the Department of Geriatric Medicine of a tertiary hospital. In addition to the standard care, an exercise-training multicomponent program was delivered to the intervention group during the acute hospitalization period. Multimorbidity patterns were determined through fuzzy c-means cluster analysis, over 38 chronic diseases. Functional, cognitive and affective outcomes were considered. Results: Three hundred and six patients were included in the analyses (154 control; 152 intervention), with a mean age of 87.2 years, and 58.5% being female. Four patterns of multimorbidity were identified: heart valves and prostate diseases (26.8%); metabolic diseases and colitis (20.6%); psychiatric, cardiovascular and autoimmune diseases (16%); and an unspecific pattern (36.6%). The Short Physical Performance Battery (SPPB) test improved across all patterns, but the intervention was most effective for patients in the metabolic/colitis pattern (2.48-point difference between intervention/control groups, 95% CI 1.60-3.35). Regarding the Barthel Index and the Mini Mental State Examination (MMSE), the differences were significant for all multimorbidity patterns, except for the psychiatric/cardio/autoimmune pattern. Differences concerning quality of life were especially high for the psychiatric/cardio/autoimmune pattern (16.9-point difference between intervention/control groups, 95% CI 4.04, 29.7). Conclusions: Patients in all the analyzed multimorbidity patterns improved with this tailored program, but the improvement was highest for those in the metabolic pattern. Understanding how different chronic disease combinations are associated with specific functional and cognitive responses to a multicomponent exercise intervention may allow further tailoring such interventions to older patients' clinical profile.

12-year evolution of multimorbidity patterns among older adults based on Hidden Markov Models.

BACKGROUND: The evolution of multimorbidity patterns during aging is still an under-researched area. We lack evidence concerning the time spent by older adults within one same multimorbidity pattern, and their transitional probability across different patterns when further chronic diseases arise. The aim of this study is to fill this gap by exploring multimorbidity patterns across decades of age in older adults, and longitudinal dynamics among these patterns. METHODS: Longitudinal study based on the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) on adults ≥60 years (N=3,363). Hidden Markov Models were applied to model the temporal evolution of both multimorbidity patterns and individuals' transitions over a 12-year follow-up. FINDINGS: Within the study population (mean age 76.1 years, 66.6% female), 87.2% had ≥2 chronic conditions at baseline. Four longitudinal multimorbidity patterns were identified for each decade. Individuals in all decades showed the shortest permanence time in an Unspecific pattern lacking any overrepresented diseases (range: 4.6-10.9 years), but the pattern with the longest permanence time varied by age. Sexagenarians remained longest in the Psychiatric-endocrine and sensorial pattern (15.4 years); septuagenarians in the Neuro-vascular and skin-sensorial pattern (11.0 years); and octogenarians and beyond in the Neuro-sensorial pattern (8.9 years). Transition probabilities varied across decades, sexagenarians showing the highest levels of stability. INTERPRETATION: Our findings highlight the dynamism and heterogeneity underlying multimorbidity by quantifying the varying permanence times and transition probabilities across patterns in different decades. With increasing age, older adults experience decreasing stability and progressively shorter permanence time within one same multimorbidity pattern.

Frailty, multimorbidity patterns and mortality in institutionalized older adults in Italy.

BACKGROUND: Little is known on how frailty influences clinical outcomes in persons with specific multimorbidity patterns. AIMS: To investigate the interplay between multimorbidity and frailty in the association with mortality in older individuals living in nursing homes (NH). METHODS: We considered 4,131 NH residents aged 60 years and over, assessed through the interRAI LTCF instrument between 2014 and 2018. Follow-up was until 2019. Considering four multimorbidity patterns identified via principal component analysis, subjects were stratified in tertiles (T) with respect to their loading values. Frailty Index (FI) considered 23 variables and a cut-off of 0.24 distinguished between high and low frailty levels. For each pattern, all possible combinations of tertiles and FI were evaluated. Their association (Hazard Ratio [HR] and 95% confidence interval) with mortality was tested in Cox regression models. RESULTS: In the heart diseases and dementia and sensory impairments patterns, the hazard of death increases progressively with patterns expression and frailty severity (being HR T3 vs. T1 = 2.36 [2.01-2.78]; HR T3 vs. T1 = 2.12 [1.83-2.47], respectively). In heart, respiratory and psychiatric diseases and diabetes, musculoskeletal and vascular diseases patterns, frailty seems to have a stronger impact on mortality than patterns' expression. DISCUSSION: Frailty increases mortality risk in all the patterns and provides additional prognostic information in NH residents with different multimorbidity patterns. CONCLUSIONS: These findings support the need to routinely assess frailty. Older people affected by specific groups of chronic diseases need a specific care approach and have high risk of negative health outcomes.