The long-term effects of a polygenetic predisposition to general cognition on healthy cognitive ageing: evidence from the English Longitudinal Study of Ageing.

BACKGROUND: As an accelerated cognitive decline frequently heralds onset of severe neuropathological disorders, understanding the source of individual differences in withstanding the onslaught of cognitive ageing may highlight how best cognitive abilities may be retained into advanced age. METHODS: Using a population representative sample of 5088 adults aged •50 years from the English Longitudinal Study of Ageing, we investigated relationships of polygenic predisposition to general cognition with a rate of change in cognition during a 10-year follow-up period. Polygenic predisposition was measured with polygenic scores for general cognition (GC-PGS). Cognition was measured employing tests for verbal memory and semantic fluency. RESULTS: The average baseline memory score was 11.1 (s.d. = 2.9) and executive function score was 21.5 (s.d. = 5.8). An increase in GC-PGS by one standard deviation (1-s.d.) was associated with a higher baseline verbal memory by an average 0.27 points (95% CI 0.19-0.34, p < 0.001). Similarly, 1-s.d. increase in GC-PGS was associated with a higher semantic fluency score at baseline in the entire sample (ß = 0.45, 95% CI 0.27-0.64, p < 0.001). These associations were significant for women and men, and all age groups. Nonetheless, 1-s.d. increase in GC-PGS was not associated with decreases in verbal memory nor semantic fluency during follow-up in the entire sample, as well stratified models by sex and age. CONCLUSION: Although common genetic variants associated with general cognition additively are associated with a stable surplus to cognition in adults, a polygenic predisposition to general cognition is not associated with age-related cognitive decline during a 10-year follow-up.

Role of inflammation in the socioeconomic inequalities of neurocognitive disorders.

BACKGROUND: Socioeconomic position has been shown to be associated with inflammation. However, little is known about the role of inflammation in socioeconomic inequalities in relation to neurocognitive disorders in later life and the potential underlying inflammatory mechanisms. This study has used longitudinal data to investigate the mediation effects of inflammation in the relationship between socioeconomic position and neurocognitive disorders in older adults. METHODS: Using data from the English Longitudinal Study of Ageing (ELSA, n = 4,815), we ascertained neurocognitive disorders using a recognised consensus criterion and included the following categories: (1) No Cognitive Impairment (NOCI) (2) Cognitive Impairment No Dementia (CIND) and (3) Dementia. We examined whether socioeconomic position (education, occupation, and wealth) measured in 2008/09 was associated with neurocognitive disorders measured in 2018/19. Mediation analyses were carried out to investigate the role of inflammatory markers [C-Reactive Protein (CRP), plasma fibrinogen and white blood cells (WBC)] in the association between socioeconomic inequalities and subsequent neurocognitive disorders. Sensitivity analyses were conducted to assess the mediating role of lifestyle behaviours and body mass index (BMI). RESULTS: Higher education, occupation and wealth were longitudinally associated with a lower likelihood of cognitive impairment and dementia. WBC mediated the association between latent socioeconomic position and CIND [ß = -0.037 (CI: -0.06 to -0.01)], but not the association with dementia. Indirect effects were attenuated but remained significant when other mediators, such as lifestyle behaviours and BMI were considered. In a separate analysis accounting for main confounders, CRP and fibrinogen mediated the association between education and CIND, all three inflammatory biomarkers mediated the association of occupation and CIND, while WBC mediated the association between wealth and CIND. CONCLUSION: These findings emphasise that socioeconomic inequalities in mid and later life could contribute to the prevalence of neurocognitive disorders in later life. Our results provide some evidence for the biological embedding of WBC in the association between socioeconomic inequalities and cognitive impairment via elevated inflammation. Future studies should explore other plausible biological mechanisms.

Excess body weight and specific types of depressive symptoms: Is there a mediating role of systemic low-grade inflammation?

OBJECTIVES: Obesity is associated with an increased risk of depression. Systemic low-grade inflammation, a plausible consequence of obesity, has also been linked to depression. However, the potential mediating effects of systemic low-grade inflammation on the association between excess body weight and specific symptom domains of depression remain uncertain. This study examined whether systemic low-grade inflammation mediated the associations of excess body weight (overweight and obesity) with subsequent overall, cognitive-affective, and somatic depressive symptoms. DESIGN: This study used a prospective cohort design. METHODS: The final analytical sample included 4,942 adults aged ≥50 years drawn from the English Longitudinal Study of Ageing (ELSA). Body mass index (BMI) and covariates were ascertained at baseline (wave 4, 2008/09). Continuous BMI scores were divided into four categories: 'normal weight' (18.5 ≤ BMI <25 kg/m2); 'overweight' (25 ≤ BMI <30 kg/m2); 'obesity' (BMI ≥30 kg/m2); in addition to 'excess body weight' ('overweight' and 'obesity' combined). Covariates included sociodemographic variables, behavioural factors, and chronic physical conditions. Serum concentrations of CRP were measured at wave 6 (2012/13). Depressive symptoms were assessed at baseline and ten years later (wave 9, 2018/19), using the 8-item Centre for Epidemiological Studies Depression (CES-D) Scale. Two symptom domains were constructed, distinguishing between cognitive-affective (depressed mood, loneliness, sadness, enjoyment in life, and happiness) and somatic (sleep problems, low energy levels, and fatigue) symptoms. Mediation analyses were performed to examine whether CRP statistically mediated the associations between BMI categories and depressive symptoms. RESULTS: In multivariable-adjusted analyses, excess body weight was associated with elevated somatic (OR = 1.231, 95% CI: 1.029, 1.473), but not cognitive-affective or overall depressive symptoms at follow-up. Higher CRP was associated with elevated somatic (OR = 1.156, 95% CI: 1.061, 1.259), but not cognitive-affective or overall depressive symptoms. CRP acted as a partial mediator (14.92%) of the association between excess body weight and elevated somatic, but not cognitive-affective, or overall depressive symptoms. CONCLUSION: Systemic low-grade inflammation may partially explain the association of excess body weight with somatic depressive symptoms, but not the associations with cognitive-affective or overall depressive symptoms.

Linear linking for related traits (LLRT): A novel method for the harmonization of cognitive domains with no or few common items.

Harmonization means to make data comparable. Recent efforts to generate comparable data on cognitive performance of older adults from many different countries around the world have presented challenges for direct comparison. Neuropsychological instruments vary in many respects, including language, administration techniques and cultural differences, which all present important obstacles to assumptions regarding the presence of linking items. Item response theory (IRT) methods have been previously used to harmonize cross-national data on cognition, but these methods rely on linking items to establish the shared metric. We introduce an alternative approach for linking cognitive performance across two (or more) groups when the fielded assessments contain no items that can be reasonably considered linking items: Linear Linking for Related Traits (LLRT). We demonstrate this methodological approach in a sample from a single United States study split by educational attainment, and in two sets of cross-national comparisons (United States to England, and United States to India). All data were collected as part of the Harmonized Cognitive Assessment Protocol (HCAP) and are publicly available. Our method relies upon strong assumptions, and we offer suggestions for how the method can be extended to relax those assumptions in future work.

The Impact of Long-Term Conditions and Comorbidity Patterns on COVID-19 Infection and Hospitalisation: A Cohort Study.

INTRODUCTION: Older adults are more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher risk of COVID-19 infection. This study investigated the role of long-term conditions or comorbidity patterns on COVID-19 infection and related hospitalisations. METHODS: This study included 4,428 individuals from Waves 8 (2016-2017) and 9 (2018-2019) of the English Longitudinal Study of Ageing (ELSA) who also participated in the ELSA COVID-19 Substudy in 2020. Comorbidity patterns were identified using an agglomerative hierarchical clustering method. The relationships between comorbidity patterns or long-term conditions and COVID-19-related outcomes were examined using multivariable logistic regression. RESULTS: Among a representative sample of community-dwelling older adults in England, those with cardiovascular disease (CVD) and complex comorbidities had an almost double risk of COVID-19 infection (OR = 1.87, 95% CI = 1.42-2.46) but not of COVID-19-related hospitalisation. A similar pattern was observed for the heterogeneous comorbidities cluster (OR = 1.56, 95% CI = 1.24-1.96). The individual investigations of long-term conditions with COVID-19 infection highlighted primary associations with CVD (OR = 1.46, 95% CI = 1.23-1.74), lung diseases (OR = 1.40, 95% CI = 1.17-1.69), psychiatric conditions (OR = 1.40, 95% CI = 1.16-1.68), retinopathy/eye diseases (OR = 1.39, 95% CI = 1.18-1.64), and arthritis (OR = 1.27, 95% CI = 1.09-1.48). In contrast, metabolic disorders and diagnosed diabetes were not associated with any COVID-19 outcomes. CONCLUSION: This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and hospitalisations, highlighting the vulnerability of those with CVD and other complex comorbidities. These findings facilitate crucial new evidence that should be considered for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak.

Pneumonia and subsequent risk of dementia: Evidence from the Japan Gerontological evaluation study.

BACKGROUND: Recently, several studies reported that pneumonia might increase the risk of cognitive decline and dementia due to increased frailty. OBJECTIVES: This study aims to examine the association between a history of pneumonia and subsequent dementia risk. METHODS: Participants were 9952 aged 65 years or older Japanese men and women from the Japan Gerontological Evaluation Study prospective cohort study, followed up from 2013 to 2019. Dementia was identified by public long-term care insurance registration. A history of pneumonia contracted 1 year before the baseline questionnaire in 2013. A cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia risk, adjusted for potential confounding variables. We conducted competing risk analyses using a cause-specific hazard model. RESULTS: During the follow-up period of 6 years, 939 persons developed dementia. There was no association between having a prior history of pneumonia with dementia risk (HR 1.20, 95% CI:0.81-1.78). However, we observed an increased risk of dementia in persons with pre-frailty and frailty; the multivariable HR (95% CI) was 1.75 (1.48-2.07) and 2.42 (2.00-2.93) for pre-frailty and frailty, respectively. When pneumonia and frailty were combined, the risk of dementia was the highest for the persons with a history of pneumonia and frailty; the multivariable HR (95% CI) was 2.30 (1.47-3.62). The multivariable HR (95% CI) for those without pneumonia with frailty was 1.95 (1.66-2.28). Meanwhile, the multivariable HR (95% CI) for those with pneumonia without frailty was 1.64 (0.68-3.99). CONCLUSION: Our findings imply that a prior history of pre-frailty and frailty with or without pneumonia, but not a history of pneumonia per se, was associated with an increased risk of dementia among population-based-cohort of older Japanese people.

Interplay between polygenic propensity for ageing-related traits and the consumption of fruits and vegetables on future dementia diagnosis.

BACKGROUND: Understanding how polygenic scores for ageing-related traits interact with diet in determining a future dementia including Alzheimer's diagnosis (AD) would increase our understanding of mechanisms underlying dementia onset. METHODS: Using 6784 population representative adults aged ≥50 years from the English Longitudinal Study of Ageing, we employed accelerated failure time survival model to investigate interactions between polygenic scores for AD (AD-PGS), schizophrenia (SZ-PGS) and general cognition (GC-PGS) and the baseline daily fruit and vegetable intake in association with dementia diagnosis during a 10-year follow-up. The baseline sample was obtained from waves 3-4 (2006-2009); follow-up data came from wave 5 (2010-2011) to wave 8 (2016-2017). RESULTS: Consuming < 5 portions of fruit and vegetables a day was associated with 33-37% greater risk for dementia in the following 10 years depending on an individual polygenic propensity. One standard deviation (1-SD) increase in AD-PGS was associated with 24% higher risk of dementia and 47% higher risk for AD diagnosis. 1-SD increase in SZ-PGS was associated with an increased risk of AD diagnosis by 66%(95%CI = 1.05-2.64) in participants who consumed < 5 portions of fruit or vegetables. There was a significant additive interaction between GC-PGS and < 5 portions of the baseline daily intake of fruit and vegetables in association with AD diagnosis during the 10-year follow-up (RERI = 0.70, 95%CI = 0.09-4.82; AP = 0.36, 95%CI = 0.17-0.66). CONCLUSION: A diet rich in fruit and vegetables is an important factor influencing the subsequent risk of dementia in the 10 years follow-up, especially in the context of polygenetic predisposition to AD, schizophrenia, and general cognition.

Adverse Childhood Experiences and Rate of Memory Decline From Mid to Later Life: Evidence From the English Longitudinal Study of Ageing.

Evidence on the role of early-life adversity in later-life memory decline is conflicting. We investigated the relationships between adverse childhood experiences (ACEs) and memory performance and rate of decline over a 10-year follow-up among middle-aged and older adults in England. Data were from biennial interviews with 5,223 participants aged 54 years or older in the population-representative English Longitudinal Study of Ageing from 2006/2007 to 2016/2017. We examined self-reports of 9 ACEs prior to age 16 years that related to abuse, household dysfunction, and separation from family. Memory was assessed at each time point as immediate and delayed recall of 10 words. Using linear mixed-effects models with person-specific random intercepts and slopes and adjusted for baseline age, participants' baseline age squared, sex, ethnicity, and childhood socioeconomic factors, we observed that most individual and cumulative ACE exposures had null to weakly negative associations with memory function and rate of decline over the 10-year follow-up. Having lived in residential or foster care was associated with lower baseline memory (adjusted ß = -0.124 standard deviation units; 95% confidence interval: -0.273, -0.025) but not memory decline. Our findings suggest potential long-term impacts of residential or foster care on memory and highlight the need for accurate and detailed exposure measures when studying ACEs in relation to later-life cognitive outcomes.

Markers of cognitive reserve and dementia incidence in the English Longitudinal Study of Ageing.

BACKGROUND: In the current climate of an ageing population, it is imperative to identify preventive measures for dementia. AIMS: We implemented a multifaceted index of cognitive reserve markers and investigated dementia incidence over 15 years of follow-up in a representative sample of the English population. METHOD: Data were 12 280 participants aged ≥50 years from the English Longitudinal Study of Ageing, free from dementia at their baseline assessments during wave 1 (2002-2003), 3 (2006-2007) or 4 (2008-2009), and followed up until wave 8 (2016-2017). The Cognitive Reserve Index was constructed as a composite measure of education, occupation and leisure activities, using a standardised questionnaire. Cox proportional hazards regression models were used to estimate the hazard ratios of dementia in relation to cognitive reserve levels (low, medium and high) and its components (education, occupation and leisure activities). RESULTS: During the follow-up period, 602 participants aged 56-99 years developed dementia. Higher levels of cognitive reserve (hazard ratio 0.65, 95% CI 0.48-0.89, P = 0.008) were associated with a lower risk of dementia. An individual analysis of its components showed that higher levels of education (hazard ratio 0.56, 95% CI 0.36-0.88, P = 0.012), occupation (hazard ratio 0.72, 95% CI 0.56-0.91, P = 0.008) and leisure activities (hazard ratio 0.74, 95% CI 0.56-0.99, P = 0.047) were predictive of a reduced dementia risk, with the first two components particularly protective in younger participants (<85 years). CONCLUSIONS: This study showed a reduced risk of dementia for individuals with a higher level of cognitive reserve, represented by higher education, complex occupations and multifaceted level of leisure activities.

Association of inflammatory markers with hearing impairment: The English Longitudinal Study of Ageing.

BACKGROUND: Hearing impairment is common at an older age and has considerable social, health and economic implications. With an increase in the ageing population, there is a need to identify modifiable risk factors for hearing impairment. A shared aetiology with cardiovascular disease (CVD) has been advanced as CVD risk factors (e.g. obesity, type 2 diabetes) are associated with a greater risk of hearing impairment. Moreover, low-grade inflammation is implicated in the aetiology of CVD. Accordingly, our aim was to investigate the association between several markers of inflammation - C-reactive protein, fibrinogen and white blood cell count - and hearing impairment. METHODS: Participants of the English Longitudinal Study of Ageing aged 50-93 were included. Inflammatory marker data from both wave 4 (baseline, 2008/09) and wave 6 (2012/13) were averaged to measure systemic inflammation. Hearing acuity was measured with a simple handheld tone-producing device at follow-up (2014/15). RESULTS: Among 4879 participants with a median age of 63 years at baseline, 1878 (38.4%) people presented hearing impairment at follow-up. All three biomarkers were positively and linearly associated with hearing impairment independent of age and sex. After further adjustment for covariates, including cardiovascular risk factors (smoking, physical activity, obesity, diabetes, hypertension, cholesterol), memory and depression, only the association with white blood cell count remained significant: odds ratio per log-unit increase; 95% confidence interval = 1.46; 1.11, 1.93. CONCLUSIONS: While white blood cell count was positively associated with hearing impairment in older adults, no relationships were found for two other markers of low-grade inflammation.

Systemic low-grade inflammation and subsequent depressive symptoms: Is there a mediating role of physical activity?

OBJECTIVE: Systemic low-grade inflammation has been associated with the onset of depression, but the exact mechanisms underlying this relationship remain elusive. This study examined whether physical activity (PA) explained the association between elevated serum levels of inflammatory markers and subsequent depressive symptoms. DESIGN: Prospective cohort design. METHOD: The sample consisted of 3809 non-depressed men and women (aged 50+) recruited from the English Longitudinal Study of Ageing (ELSA). Serum levels of inflammatory markers (C-reactive protein (CRP), fibrinogen) and covariates (age, sex, education, wealth, body mass index, smoking, cholesterol, triglycerides) were measured at baseline (wave 4, 2008/09). Self-reported weekly moderate/vigorous (high) PA versus no weekly moderate/vigorous (low) PA was examined at a four-year follow-up (wave 6, 2012/13), using a single-item question. Depressive symptoms were assessed at baseline, four years (wave 6, 2012/13) and six years post baseline (wave 7, 2014/15), using the 8-item version of the Centre for Epidemiological Studies Depression Scale (CES-D). RESULTS: Participants with higher baseline concentrations of inflammatory markers were significantly more likely to report low PA levels four years later (CRP: OR: 1.25; 95% CI, 1.05-1.48; fibrinogen: OR: 1.18; 95% CI, 1.05-1.39). Moreover, low PA was associated with higher odds of elevated depressive symptoms at follow-up (OR: 1.59; 95% CI, 1.15-2.19). Mediation analyses revealed that low PA explained a total of 36.71% of the relationship between high CRP and elevated depressive symptoms, and 33.26% between higher levels of fibrinogen and elevated depressive symptoms six years later. No direct association was found between systemic low-grade inflammation and future depressive symptoms. CONCLUSION: These results suggest that low PA is a significant partial mediator of the relationship between systemic low-grade inflammation and subsequent elevated depressive symptoms in a nationally representative cohort of older adults.

Cultural engagement and cognitive reserve: museum attendance and dementia incidence over a 10-year period.

Theories of cognitive reserve, disuse syndrome and stress have suggested that activities that are mentally engaging, enjoyable and socially interactive could be protective against the development of dementia. Using data from the English Longitudinal Study of Ageing, this study shows that for adults aged 50 and older visiting museums every few months or more was associated with a lower incidence rate of dementia over a 10-year follow-up period compared with less-frequent visiting. This association was independent of demographics, socioeconomic status, health-related variables including sensory impairment, depression, vascular conditions and other forms of community engagement. Visiting museums may be a promising psychosocial activity to support the prevention of dementia.Declaration of interestNone.

Effect of retirement on cognitive function: the Whitehall II cohort study.

According to the 'use it or lose it' hypothesis, a lack of mentally challenging activities might exacerbate the loss of cognitive function. On this basis, retirement has been suggested to increase the risk of cognitive decline, but evidence from studies with long follow-up is lacking. We tested this hypothesis in a cohort of 3433 civil servants who participated in the Whitehall II Study, including repeated measurements of cognitive functioning up to 14 years before and 14 years after retirement. Piecewise models, centred at the year of retirement, were used to compare trajectories of verbal memory, abstract reasoning, phonemic verbal fluency, and semantic verbal fluency before and after retirement. We found that all domains of cognition declined over time. Declines in verbal memory were 38% faster after retirement compared to before, after taking account of age-related decline. In analyses stratified by employment grade, higher employment grade was protective against verbal memory decline while people were still working, but this 'protective effect' was lost when individuals retired, resulting in a similar rate of decline post-retirement across employment grades. We did not find a significant impact of retirement on the other cognitive domains. In conclusion, these findings are consistent with the hypothesis that retirement accelerates the decline in verbal memory function. This study points to the benefits of cognitively stimulating activities associated with employment that could benefit older people's memory.

An International Evaluation of Cognitive Reserve and Memory Changes in Early Old Age in 10 European Countries.

BACKGROUND: Cognitive reserve was postulated to explain individual differences in susceptibility to ageing, offering apparent protection to those with higher education. We investigated the association between education and change in memory in early old age. METHODS: Immediate and delayed memory scores from over 10,000 individuals aged 65 years and older, from 10 countries of the Survey of Health, Ageing and Retirement in Europe, were modeled as a function of time in the study over an 8-year period, fitting independent latent growth models. Education was used as a marker of cognitive reserve and evaluated in association with memory performance and rate of change, while accounting for income, general health, smoking, body mass index, gender, and baseline age. RESULTS: In most countries, more educated individuals performed better on both memory tests at baseline, compared to those less educated. However, education was not protective against faster decline, except for in Spain for both immediate and delayed recall (0.007 [SE = 0.003] and 0.006 [SE = 0.002]), and Switzerland for immediate recall (0.006 [SE = 0.003]). Interestingly, highly educated Italian respondents had slightly faster declines in immediate recall (-0.006 [SE = 0.003]). CONCLUSIONS: We found weak evidence of a protective effect of education on memory change in most European samples, although there was a positive association with memory performance at individuals' baseline assessment.

The role of cognitive reserve on terminal decline: a cross-cohort analysis from two European studies: OCTO-Twin, Sweden, and Newcastle 85+, UK.

OBJECTIVE: Cognitive performance shows a marked deterioration in close proximity to death, as postulated by the terminal decline hypothesis. The effect of education on the rate of terminal decline in the oldest people (i.e. persons 85+ years) has been controversial and not entirely understood. In the current study, we investigated the rate of decline prior to death with a special focus on the role of education and socioeconomic position, in two European longitudinal studies of ageing: the Origins of Variance in the Old-Old: Octogenarian Twins (OCTO-Twin) and the Newcastle 85+ study. METHODS: A process-based approach was used in which individuals' cognitive scores were aligned according to distance to death. In a coordinated analysis, multilevel models were employed to examine associations between different markers of cognitive reserve (education and socioeconomic position) and terminal decline using the mini-mental state examination (MMSE), controlling for age at baseline, sex, dementia incidence and time to death from the study entry to the time of death within each cohort. RESULTS: The current findings suggest that education was positively associated with higher MMSE scores prior to death in the OCTO-Twin, but not in the Newcastle 85+ study, independent of socioeconomic position and other factors such as baseline age, sex and time to death from the study entry. However, education was not associated with the rate of terminal decline in both of these studies. CONCLUSIONS: Our results offer only partial support to the cognitive reserve hypothesis and cognitive performance prior to death.

Bidirectional Associations of Depressive Symptoms and Cognitive Function Over Time.

Importance: Cognitive decline and depressive symptoms often co-occur among older adults, and they share several mechanisms. Despite the fact that cognitive dysfunction has been linked to increased depressive symptoms, the directionality of this association remains unclear. Objective: To examine whether there is a bidirectional association between depressive symptoms and cognitive function in English adults aged 50 years or older throughout a 16-year follow-up period. Design, Setting, and Participants: This cohort study included a nationally representative sample of community-dwelling English adults aged 50 years or older. The current analysis included 8268 eligible participants with relevant data. These participants were examined every other year from 2002 and 2003 until 2018 and 2019, resulting in a follow-up period of up to 16 years. Data were analyzed from July to November 2023. Main Outcomes and Measures: The bivariate dual change score models were used to estimate the multivariable associations between depressive symptoms and cognitive function, which were interchangeably used as exposures and outcomes. Cognitive measures include memory and verbal fluency tests, while the Center for Epidemiologic Studies Depression Scale evaluated depressive symptoms. Results: The study population of 8268 participants had a mean (SD) age of 64 (10) years at the study baseline, and 4517 participants (55%) were female. Higher depressive symptoms were cross-sectionally associated with poorer memory (ß intercept, -0.018; standard error [SE], 0.004; P < .001) and verbal fluency (ß intercept, -0.009; SE, 0.004; P = .02) at study baseline. A steeper linear change in depressive symptoms was associated with an accelerated memory change (ß intercept, -0.253; SE, 0.079; P = .001), and a linear change in memory was associated with an acceleration in depressive symptoms over time (ß intercept, 0.016; SE, 0.006; P = .005). This bidirectional change was not observed with verbal fluency. Conclusions and Relevance: In this study, greater depressive symptoms were associated with poorer memory at the study baseline and steeper memory change over time. A gradual linear change in depressive symptoms contributed to accelerated memory loss and vice versa, suggesting that psychological mood and memory performance are intrinsically associated.

Systemic inflammation, lifestyle behaviours and dementia: A 10-year follow-up investigation.

Objectives: Lifestyle behaviours have been linked to dementia incidence, but their cumulative impact on dementia and the underlying mechanisms remain poorly understood. This study investigated the association of co-occurring lifestyle behaviours with dementia incidence and the mediating role of systemic inflammation in this association. Methods: The sample comprised 3131 participants (55.2% female) from the English Longitudinal Study of Ageing aged 52-92 years at baseline (2008/09). Self-reported baseline lifestyle behaviours (alcohol intake, fruit and vegetable consumption, smoking, physical activity, sleep duration, social engagement, and cognitive activity) were summed to derive an index of lifestyle behaviours, ranging from 0 to 7, with higher scores denoting a higher number of health-risk behaviours. Incident dementia cases (n = 130, 4.2%) were identified through doctor-diagnosed dementia, informant interviews, and health records between 2014/15 and 2018/19. Systemic inflammation was measured through fasting plasma concentrations of C-reactive protein in 2012/13. Results: Binary logistic regression models indicated that the odds of subsequent dementia increased by 1.19 for each additional health-risk behaviour (95% confidence intervals: 1.04, 1.37, p = 0.014) after adjusting for age, sex, ethnicity, wealth, education, marital status, body mass index, coronary heart disease, hypertension, stroke, and depression. However, this association was not mediated by C-reactive protein. Conclusions: Co-occurring health-risk behaviours were associated with higher dementia incidence up to 10 years later, underscoring the importance of modifying health-risk behaviours for the prevention of dementia. Systemic inflammation did not explain the association between behaviours and dementia.

Life-Course Socioeconomic Position and Mild Cognitive Impairment in Midlife: Evidence from the 1958 British Birth Cohort.

BACKGROUND: Dementia has been the leading cause of death in the UK since 2015. Increasing evidence supports an association between socioeconomic position (SEP) and dementia onset in later life. However, limited studies have examined how life-course SEP influences the development of mild cognitive impairment (MCI), an intermediate state potentially preceding dementia. Therefore, the present study aims to examine the relationship between life-course SEP and MCI amongst adults aged 50 years in Great Britain. METHODS: We employed data from the National Child Development Study (NCDS), also known as the 1958 British Birth Cohort, to determine the associations between SEP and MCI in 6590 participants. We categorised life-course measures of SEP as stable high/low or moving upward/downward over the life course. We assessed MCI at age 50 using one standard deviation below the averaged combined scores from all cognitive tests available. We then used binary logistic regression to estimate the longitudinal associations between life-course SEP and MCI. RESULTS: Relative to those of a high SEP across the life course, participants who moved upward, downward, or remained at a low SEP were significantly associated with 25% (95% CI 1.02-1.54, p = 0.035), 70% (95% CI 1.27-2.27, p < 0.001), and 85% (95% CI 1.50-2.29, p < 0.001), respectively, higher odds of MCI, independent of all selected covariates. CONCLUSIONS: Lower life-course SEP was associated with significantly higher odds of MCI onset in middle life within the NCDS cohort. Public health policies targeting cognitive impairment should encompass a life-course approach to reduce socioeconomic inequalities.

Impact of sleep duration and sleep disturbances on the incidence of dementia and Alzheimer's disease: A 10-year follow-up study.

The nature of the relationship between sleep problems and dementia remains unclear. This study investigated the relationship between sleep measures and dementia in older adults (≥ 65) using data from the English Longitudinal Study of Ageing (ELSA) and further investigated the causal association in Mendelian randomization (MR) analysis. In total of 7,223 individuals, 5.7 % developed dementia (1.7 % Alzheimer's disease (AD)) within an average of 8 (± 2.9) years. Cox regression models and MR were employed. Long sleep duration (>8 h) was associated with 64 % increased risk of incident dementia and 2-fold high risk of AD compared to ideal sleep duration (7-8 h). This association was particularly evident in older-older adults (≥70 years) and those who consumed alcohol. Short sleep duration (<7 h) was associated with lower risk of incident dementia among older-older but higher risk among younger-older adults. Sleep disturbances and perceived sleep quality were not associated with dementia or AD. The MR study did not reveal causal associations between sleep duration and dementia. These findings suggest that self-reported short sleep in younger-older and long sleep in older-older adults and those with frequent alcohol consumption are associated with dementia. Early detection of these sleep patterns may help identify individuals at higher dementia risk.

Operationalization of Intrinsic Capacity in Older People and Its Association With Subsequent Disability, Hospital Admission and Mortality: Results From The English Longitudinal Study of Ageing.

BACKGROUND: Intrinsic capacity (IC) is a new concept in the healthy aging field and has many operationalized definitions. In this study, we operationalized IC using item response theory in the English Longitudinal Study of Ageing (ELSA) and tested the predictive value of the scale using a subsequent functional ability, mortality, and hospital admission. METHODS: IC was measured at baseline (2004, Wave 2) using 14 dichotomous indicators: word recall, orientation in time, balance, chair rises, walking speed, upper mobility, lower mobility, eyesight, hearing, grip strength, body mass index, waist circumference, depressive symptoms, and life satisfaction. A 2-parameter item response theory model was used to generate a scale of IC at baseline. Logistic regression was used for the prediction of subsequent difficulties, measured by difficulties with ≥1 activities of daily living (ADLs) and ≥1 instrumental activities of daily living (IADLs) at 4 and 8 years after baseline. Competing risk and Cox regressions were employed to test the prediction of hospital admission and mortality, respectively, over a 14-year follow-up. RESULTS: IC scores were generated for 4 545 individuals aged on average 70.8 years (standard deviation [SD] 7.93). Better baseline IC scores were associated with reduced risk of subsequent difficulties with ADLs and IADLs, hospital admission (subdistribution hazard ratios [SHR] = 0.99, 95% confidence interval [CI] 0.98-0.99), and mortality (hazard ratios [HR] = 0.98, 95% CI 0.98-0.99), when adjusted for sociodemographic and health-related covariates. CONCLUSION: These results suggest the utility of this IC score as a measure of risk for future adverse outcomes in older people, potentially above that indicated by other sociodemographic and health-related factors.