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Data collected from clinical trials and cohort studies, such as dementia studies, are often high-dimensional, censored, heterogeneous and contain missing information, presenting challenges to traditional statistical analysis. There is an urgent need for methods that can overcome these challenges to model this complex data. At present there is no cure for dementia and no treatment that can successfully change the course of the disease. Machine learning models that can predict the time until a patient develops dementia are important tools in helping understand dementia risks and can give more accurate results than traditional statistical methods when modelling high-dimensional, heterogeneous, clinical data. This work compares the performance and stability of ten machine learning algorithms, combined with eight feature selection methods, capable of performing survival analysis of high-dimensional, heterogeneous, clinical data. We developed models that predict survival to dementia using baseline data from two different studies. The Sydney Memory and Ageing Study (MAS) is a longitudinal cohort study of 1037 participants, aged 70–90 years, that aims to determine the effects of ageing on cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal study aimed at identifying biomarkers for the early detection and tracking of Alzheimer's disease. Using the concordance index as a measure of performance, our models achieve maximum performance values of 0.82 for MAS and 0.93 For ADNI.

BackgroundThe global epidemiological shift of disease burden towards long-term conditions means understanding long-term outcomes of cardiovascular disease is increasingly important. More people are surviving stroke to experience its long-term consequences, but outcomes in people living more >10 years after stroke have not been described in detail.MethodsData were collected for the population-based South London Stroke Register, with participants followed up annually until death. Outcomes were survival, disability, activity, cognitive impairment, quality of life, depression and anxiety.FindingsOf 2625 people having first-ever stroke, 262 (21%) survived to 15 years. By 15 years, 61% (95% CI 55% to 67%) of the survivors were male, with a median age of stroke onset of 58 years (IQR 48–66). 87% of the 15-year survivors were living at home and 33.8% (26.2% to 42.4%) had mild disability, 14.3% (9.2% to 21.4%) moderate disability and 15.0% (9.9% to 22.3%) severe disability. The prevalence of disability increased with time but 1 in 10 of the 15-year survivors had lived with moderate-severe disability since their stroke. At 15 years, the prevalence of cognitive impairment was 30.0% (19.5% to 43.1%), depression 39.1% (30.9% to 47.9%) and anxiety 34.9% (27.0% to 43.8%), and survivors reported greater loss of physical than mental quality of life.ConclusionsOne in five people live at least 15 years after a stroke and poor functional, cognitive and psychological outcomes affect a substantial proportion of these long-term survivors. As the global population of individuals with cardiovascular long-term conditions grows, research and health services will need to increasingly focus on preventing and managing the long-term consequences of stroke.

Understanding patterns of multimorbidity in the US older adult population and their relationship with mortality is important for reducing healthcare utilization and improving health. Previous investigations measured multimorbidity as counts of conditions rather than specific combination of conditions. This cross-sectional study with longitudinal mortality follow-up employed latent class analysis (LCA) to develop clinically meaningful subgroups of participants aged 50 and older with different combinations of 13 chronic conditions from the National Health Interview Survey 2002-2014. Mortality linkage with National Death Index was performed through December 2015 for 166,126 participants. Survival analyses were conducted to assess the relationships between LCA classes and all-cause mortality and cause specific mortalities. LCA identified five multimorbidity groups with primary characteristics: \"healthy\" (51.5%), \"age-associated chronic conditions\" (33.6%), \"respiratory conditions\" (7.3%), \"cognitively impaired\" (4.3%) and \"complex cardiometabolic\" (3.2%). Covariate-adjusted survival analysis indicated \"complex cardiometabolic\" class had the highest mortality with a Hazard Ratio (HR) of 5.30, 99.5% CI [4.52, 6.22]; followed by \"cognitively impaired\" class (3.34 [2.93, 3.81]); \"respiratory condition\" class (2.14 [1.87, 2.46]); and \"age-associated chronic conditions\" class (1.81 [1.66, 1.98]). Patterns of multimorbidity classes were strongly associated with the primary underlying cause of death. The \"cognitively impaired\" class reported similar number of conditions compared to the \"respiratory condition\" class but had significantly higher mortality (3.8 vs 3.7 conditions, HR = 1.56 [1.32, 1.85]). We demonstrated that LCA method is effective in classifying clinically meaningful multimorbidity subgroup. Specific combinations of conditions including cognitive impairment and depressive symptoms have a substantial detrimental impact on the mortality of older adults. The numbers of chronic conditions experienced by older adults is not always proportional to mortality risk. Our findings provide valuable information for identifying high risk older adults with multimorbidity to facilitate early intervention to treat chronic conditions and reduce mortality.

Hypertension is a risk factor for cardiovascular disease, but the evidence for treatment and blood pressure (BP) targets in the elderly is less robust. Orthostatic hypertension is a potential risk factor for cardiovascular mortality and cognitive decline. All 85-years-olds in Linköping municipality, Sweden, were invited to a prospective birth cohort study including questionnaires, cognitive testing and physical examinations, including supine and orthostatic BP measurements. Logistic regression and Cox proportional hazard models were used to assess the impact of baseline supine and orthostatic BP on cognitive decline and all-cause mortality after 5- and 7.2 years respectively. Of 650 invited 85-year-olds, 322 were included. During follow-up, 190 persons died, and 28 persons developed cognitive decline. Neither elevated supine BP nor orthostatic hypertension were associated with cognitive decline. After adjustments, elevated supine BP was not associated with mortality in all participants, but was associated with lower all-cause mortality in participants with previously diagnosed hypertension, HR 0.59 (95% CI 0.41–0.85). Orthostatic hypertension was not associated with all-cause mortality, HR 0.56 (95% CI 0.26–1.22) after multiple adjustments. In 85-year-olds with known hypertension, elevated supine BP was associated with lower all-cause mortality. Orthostatic hypertension was not associated with cognitive decline but trended towards a lower all-cause mortality.

Objectives: Intraindividual variability (IIV) in reaction time refers to the trial-to-trial fluctuations in responding across a given cognitive task. Cross-sectional research suggests that IIV increases with normal and neuropathological ageing and it may serve as a marker of neurobiological integrity. This raises the possibility that IIV may also predict future cognitive decline and, indeed, neuropathology. Therefore, we conducted a systematic review to address these issues. Methods: A search of electronic databases Embase, Medline, PsycINFO, and Web of Science was completed on May 17, 2016 that identified longitudinal investigations of IIV in middle-aged or older adults. Results: A total of 688 studies were initially identified of which 22 met the inclusion criteria. Nine included longitudinal IIV measures and 17 predicted subsequent outcome (cognitive decline or impairment, dementia, mortality) from baseline IIV. The results suggested IIV increased over time, particularly in participants aged over 75 years. Greater baseline IIV was consistently associated with increased risk of adverse outcomes including cognitive decline or impairment, and mortality. Conclusions: Increased IIV over time is associated with normal ageing. However, further increases in IIV over and above those found in normal ageing may be a risk factor for future cognitive impairment or mortality. Measures of IIV may, therefore, have considerable potential as a supplement to existing clinical assessment to aid identification of individuals at risk of adverse outcomes such as dementia or death. (JINS, 2017, 23, 431–445)

Background The global aging trend exacerbates the challenge of frailty and cognitive impairment in older adults, yet their combined impact on health outcomes remains under-investigated. This study aims to explore how frailty and psychometric mild cognitive impairment (pMCI) jointly affect all-cause and cardiovascular disease (CVD) mortality. Methods The cohort study we examined 2,442 participants aged ≥ 60, is the secondary analysis from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Frailty was quantified using a 49-item frailty index, while pMCI was determined by three composite cognition scores one standard deviation (SD) below the mean. The associations between frailty, pMCI, comorbidity, and mortality were assessed using weighted Cox proportional hazards models. Results Of the participants, 31.37% were frail, 17.2% had pMCI, and 8.64% exhibited both conditions. The cohort was stratified into four groups based on frailty and pMCI status. After a median follow-up period of 6.5 years, frail individuals with pMCI had the highest all-cause (75.23 per 1,000 person-years) and CVD (32.97 per 1,000 person-years) mortality rates. Adjusted hazard ratios (HRs) for all-cause (3.06; 95% CI, 2.05–4.56) and CVD (3.8; 95% CI, 2.07–6.96) mortality were highest in frail older adults with pMCI compared to those who were non-frail without pMCI. Conclusion Our study highlights the ubiquity of frailty and cognitive impairment in older adults and underscores the heightened risk of mortality associated with their coexistence. These findings suggest the critical need for proactive screening and management of frailty and cognitive function in clinical practice to improve outcomes for the older adults.

Evidence on the association between cognitive activities and mortality among older adults with cognitive impairment is limited. Therefore, the study aimed to assess the association and examine whether baseline cognitive function mediates the association. A total of 10477 older participants with cognitive impairment (median age: 95.0 [IQR: 88.0-100.0], males: 27.9%, Mini-Mental State Examination score ≤24 points) from the Chinese Longitudinal Healthy Longevity Survey conducted between 1998 and 2014 were included, with follow-up until 2018. Exposures were three prevalent cognitive activities among older adults in China: reading books/newspapers, playing cards/mah-jong, and watching TV or listening to radio, and the outcome was all-cause mortality within a 10-year follow-up period. We evaluated the association between these activities and mortality using Cox regression models and also conducted a mediation analysis to examine the role of baseline cognitive function in this association. During a follow-up period of totaling 33632.1 person-years, there were 8763 recorded deaths (83.6%). For each cognitive activity, the risk of mortality decreased with an increased frequency of engagement in these activities. Moreover, the risk of mortality significantly decreased with a greater number of cognitive activities. With zero activities as reference, adjusted hazard ratios were 0.83 (95% CI: 0.79-0.87) for one activity, 0.76 (95% CI: 0.69-0.83) for two activities, and 0.67 (95% CI: 0.53-0.86) for three activities, respectively. Stratified and sensitivity analyses confirmed the robustness of these findings. Additionally, baseline cognitive function partially mediated the association between cognitive activities and mortality; compared to zero activities, the mediated proportions were 15.2% (95% CI: 10.9%-22.4%) for one activity, 13.4% (95% CI: 8.9%-21.3%) for two activities, and 9.3% (95% CI: 4.2%-23.4%) for three activities, respectively. Among older adults with cognitive impairment in China, the risk of all-cause mortality significantly decreased as both the frequency and number of cognitive activities increased. Baseline cognitive function only mediated a small proportion of the benefits of cognitive activities in longevity.

INTRODUCTION The association between cognitive function, healthy lifestyle, and mortality remains understudied in large Chinese cohorts. METHODS In this nationwide 10‐year prospective study of 24,657 older adults, we assessed Mini‐Mental State Examination (MMSE) categories (<18, 18 to 23, 24 to 27, 28 to 30) and a seven‐component lifestyle score (0 to 7) for their relationships with all‐cause, cardiovascular, and cerebrovascular mortality. RESULTS Compared with individuals scoring 28 to 30 on the MMSE, lower scores were linked to elevated all‐cause and cerebrovascular mortality but not cardiovascular mortality. Participants with lifestyle scores of 4 or 5 had a higher risk of all‐cause mortality. Even optimal lifestyle practices did not fully mitigate the heightened mortality risk associated with declining cognitive performance. DISCUSSION A healthy lifestyle is beneficial but cannot fully offset the impact of cognitive impairment. Therefore, integrating routine cognitive assessments and targeted interventions with healthy lifestyle practices is crucial for effectively reducing mortality risk. Highlights A nationally representative, 10‐year prospective cohort in China was employed to investigate the combined effects of lifestyle behaviors and cognitive function on all‐cause, cardiovascular, and cerebrovascular mortality. Both healthy lifestyle and better cognitive function were associated with a reduced risk of all‐cause mortality. Even among individuals practicing optimal lifestyle behaviors, cognitive impairment significantly elevated the risk of all‐cause and cerebrovascular mortality. These findings underscore the necessity of incorporating routine cognitive assessments and targeted interventions with healthy lifestyle practices aimed at reducing mortality risk in aging populations.

Background Cognitive impairment, including dementia, and hip fracture are both common among older patients. Both conditions are associated with increased morbidity and mortality. Cognitive impairment is often underdiagnosed and may remain undetected in hip fracture patients. Little is known about the prevalence, specific characteristics, and outcomes of hip fracture patients with cognitive impairment. This analysis aimed to compare hip fracture patients with and without cognitive impairments regarding their health conditions, hospital care, and the risk of complications and mortality. Methods This study used data derived from the EMAAge project, a prospective multi-center cohort study conducted in Berlin, Germany. Patients aged 40 years and older with hip fracture were stratified into three cognitive status groups: no cognitive impairment (NCI), moderate cognitive impairment (MCI), and severe cognitive impairment (SCI). Categorization was based on patients’ ability to engage in interviews and their performance on the 6-item Cognitive Impairment Test (6-CIT). Standardized mean differences were used to compare various health-related parameters and health care utilization measures. Regression models, both adjusted and unadjusted, were calculated for the number of complications and the mortality rate. Results Cognitive impairment was present in 37% of the 310 hip fracture patients in the study cohort. Patients with cognitive impairment had a worse baseline health profile, delayed admission to the emergency department, a longer time to surgery, and were less likely to be referred to a rehabilitation program. In the adjusted regression model for the number of complications, the incidence rate ratio was 1.237 ( p  = 0.292) for MCI patients and 2.065 ( p  < 0.001) for SCI patients compared with NCI patients. The adjusted odds ratio for mortality was 1.046 ( p  = 0.942) for MCI patients and 2.875 ( p  = 0.060) for SCI patients. Conclusions Hip fracture patients with cognitive impairment, particularly severe impairment, arrive at the ED in a considerably poorer state of health and are at a higher risk of adverse outcomes, including complications and mortality. Timely identification of this at-risk group upon arrival appears to be essential to providing adequate care. This study highlights the need for interventions and research aimed at improving prevention, emergency care and outcomes for this vulnerable group, addressing their specific risk factors, and promoting the quality of care in hospital and after discharge.

Research on socioeconomic position (SEP) and mild neurocognitive impairment, considered a transient state between normal cognitive function and dementia is limited. The purpose of this study was to determine the role of SEP in transitioning between different cognitive states and mortality risk. Using nationally representative English data and utilising a multistate model association between SEP and the risk of transitioning from no cognitive impairment (NOCI) to Cognitive impairment no dementia (CIND), dementia and death were investigated. The potential reverse transition from CIND to NOCI was also explored. The probabilities of transitioning between cognitive states and time spent in each state differed significantly between those with lower and higher levels of SEP. Higher wealth was associated with a reverse transition from CIND to NOCI [HR = 1.56, CI (1.42,1.72)]. Socioeconomic advantage might protect against the progression to the early stages of neurocognitive disorders (CIND) and facilitate the potential reversion from mild cognitive impairment to a healthy cognitive state in later life. Lower levels of education affect the risk of mortality after the onset of dementia.