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.

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.

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.

Shaping care home COVID-19 testing policy: a protocol for a pragmatic cluster randomised controlled trial of asymptomatic testing compared with standard care in care home staff (VIVALDI-CT).

INTRODUCTION: Care home residents have experienced significant morbidity, mortality and disruption following outbreaks of SARS-CoV-2. Regular SARS-CoV-2 testing of care home staff was introduced to reduce transmission of infection, but it is unclear whether this remains beneficial. This trial aims to investigate whether use of regular asymptomatic staff testing, alongside funding to reimburse sick pay for those who test positive and meet costs of employing agency staff, is a feasible and effective strategy to reduce COVID-19 impact in care homes. METHODS AND ANALYSIS: The VIVALDI-Clinical Trial is a multicentre, open-label, cluster randomised controlled, phase III/IV superiority trial in up to 280 residential and/or nursing homes in England providing care to adults aged >65 years. All regular and agency staff will be enrolled, excepting those who opt out. Homes will be randomised to the intervention arm (twice weekly asymptomatic staff testing for SARS-CoV-2) or the control arm (current national testing guidance). Staff who test positive for SARS-CoV-2 will self-isolate and receive sick pay. Care providers will be reimbursed for costs associated with employing temporary staff to backfill for absence arising directly from the trial.The trial will be delivered by a multidisciplinary research team through a series of five work packages.The primary outcome is the incidence of COVID-19-related hospital admissions in residents. Secondary outcomes include the number and duration of outbreaks and home closures. Health economic and modelling analyses will investigate the cost-effectiveness and cost consequences of the testing intervention. A process evaluation using qualitative interviews will be conducted to understand intervention roll out and identify areas for optimisation to inform future intervention scale-up, should the testing approach prove effective and cost-effective. Stakeholder engagement will be undertaken to enable the sector to plan for results and their implications and to coproduce recommendations on the use of testing for policy-makers. ETHICS AND DISSEMINATION: The study has been approved by the London-Bromley Research Ethics Committee (reference number 22/LO/0846) and the Health Research Authority (22/CAG/0165). The results of the trial will be disseminated regardless of the direction of effect. The publication of the results will comply with a trial-specific publication policy and will include submission to open access journals. A lay summary of the results will also be produced to disseminate the results to participants. TRIAL REGISTRATION NUMBER: ISRCTN13296529.

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.

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.

The impact of long-term conditions and comorbidity patterns on COVID-19 infection and hospitalisation: a cohort study.

Introduction: Older adults are usually more vulnerable to COVID-19 infections; however, little is known about which comorbidity patterns are related to a higher probability 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 of chronic conditions 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. Discussion/Conclusion: This study provides novel insights into the comorbidity patterns that are more vulnerable to COVID-19 infections and highlights the importance of CVD and complex comorbidities.These findings facilitate crucial new evidence for appropriate screening measures and tailored interventions for older adults in the ongoing global outbreak.

Socioeconomic and Contextual Differentials in Memory Decline: A Cross-Country Investigation Between England and China.

OBJECTIVES: Although cognitive functioning is strongly associated with biological changes in the brain during the aging process, very little is known about the role of sociocultural differentials between the western and eastern parts of the world. We examined the associations between individual socioeconomic markers (e.g., education, household wealth) and contextual levels characteristics (e.g., urbanicity) with memory performance and memory decline over up to 8 years of follow-up in England and China. METHODS: The analytical samples included participants aged 50+ from the English Longitudinal Study of Aging (n = 6,687) and the China Health and Retirement Longitudinal Study (n = 10,252). Mixed linear models were employed to examine the association between baseline individual socioeconomic markers (education, wealth) and contextual-level characteristics (urbanicity) on the change in memory over time. RESULTS: Our analyses showed that higher education and wealth were associated with better baseline memory in both England and China. Still, the impact of contextual-level characteristics such as urbanicity differed between the 2 countries. For English individuals, living in a rural area showed an advantage in memory, while the opposite pattern was observed in China. Memory decline appeared to be socioeconomically patterned by higher education, wealth, and urbanicity in China but not in England. DISCUSSION: Our findings highlight substantial socioeconomic and contextual inequity in memory performance in both England and China, as well as in the rate of memory decline primarily in China. Public health strategies for preventing memory decline should target the socioeconomic gaps at the individual and contextual levels to protect those particularly disadvantaged.

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.

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.

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.

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.

Moderating Role of Cognitive Reserve Markers Between Childhood Cognition and Cognitive Aging: Evidence From the 1946 British Birth Cohort.

BACKGROUND AND OBJECTIVES: As the population ages, differences in cognitive abilities become more evident. We investigated key genetic and life course influences on cognitive state at age 69 years, building on previous work using the longitudinal Medical Research Council National Survey of Health and Development (the British 1946 birth cohort). METHODS: Multivariable regressions investigated the association between 4 factors: (1) childhood cognition at age 8 years; (2) a Cognitive Reserve Index (CRI) composed of 3 markers: (i) educational attainment by age 26 years, (ii) engagement in leisure activities at age 43 years, and (iii) occupation up to age 53 years; (3) reading ability assessed by the National Adult Reading Test (NART) at age 53 years; and (4) APOE genotype in relation to cognitive state measured at age 69 years with Addenbrooke's Cognitive Examination, third edition (ACE-III). We then investigated the modifying role of the CRI, NART, and APOE in the association between childhood cognition and the ACE-III. RESULTS: The analytical sample comprised 1,184 participants. Higher scores in childhood cognition, CRI, and NART were associated with higher scores in the ACE-III. We found that the CRI and NART modified the association between childhood cognition and the ACE-III: for 30 additional points in the CRI or 20 additional points in the NART, the simple slope of childhood cognition decreased by approximately 0.10 points (CRI = 70: marginal effects (MEs) 0.22, 95% CI 0.12-0.32, p < 0.001 vs CRI = 100: MEs 0.12, 95% CI 0.06-0.17, p < 0.001; NART = 15: MEs 0.22, 95% CI 0.09-0.35, p = 0.001, vs NART = 35: MEs 0.11, 95% CI 0.05-0.17, p < 0.001). The association between childhood cognition and the ACE-III was nonsignificant at high levels of the CRI or NART. Furthermore, the e4 allele of the APOE gene was associated with lower scores in the ACE-III (ß = -0.71, 95% CI -1.36 to -0.06, p = 0.03) but did not modify the association between childhood cognition and cognitive state in later life. DISCUSSION: The CRI and NART are independent measures of cognitive reserve because both modify the association between childhood cognition and cognitive state.

Occasions for laughter and dementia risk: Findings from a six-year cohort study.

AIM: Currently, there is little evidence on the relationship between laughter and the risk of dementia, and since laughter is mainly a social behavior, we aimed to examine the association between various occasions for laughter and the risk of dementia in Japanese older adults. METHODS: We draw upon 6-year follow-up data from the Japan Gerontological Evaluation Study, including 12 165 independent older adults aged 65 years or over. Occasions for laughter were assessed using a questionnaire, while dementia was diagnosed using the standardized dementia scale of the long-term care insurance system in Japan. Cox proportional hazards models were estimated, yielding hazard ratios and 95% confidence intervals (CIs). RESULTS: The multivariable hazard ratio of dementia incidence for all participants in the groups for high versus low variety of occasions for laughter was 0.84 (95% CI: 0.72-0.98, P for trend <0.001). A greater variety of occasions for laughter was associated with a lower risk of dementia 0.78 (95% CI: 0.63-0.96, P for trend <0.001) among women, but was less pronounced for men, with significant associations only for the medium group. Laughing during conversations with friends, communicating with children or grandchildren, and listening to the radio were primarily associated with decreased risk. CONCLUSION: A greater variety of laughter occasions in individual and social settings was associated with a reduced risk of dementia. Geriatr Gerontol Int 2022; 22: 392-398.

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.

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.

Bi-directional associations between religious attendance and mental health: findings from a British birth cohort study.

BACKGROUND: There is evidence that religious attendance is associated with positive outcomes for mental health; however, there are few longitudinal studies, and even fewer, which take into account the possibility of bi-directional associations. This study aimed to investigate bi-directional associations between religious attendance and mental health. METHODS: Participants were 2125 study members who provided data at age 68-69 from the Medical Research Council National Survey of Health and Development (1946 British birth cohort study). Mental health was assessed using the 28-item General Health Questionnaire at ages 53, 60-64 and 68-69. Religious attendance was measured using a 4-point scale (weekly=3, monthly=2, less than monthly=1 or never=0) at ages 43, 60-64 and 68-69. Cross-lagged path analysis was used to assess reciprocal associations between mental health and religious attendance, adjusting for gender and education. RESULTS: Previous religious attendance was strongly related to later attendance (r=0.62-0.74). Similarly, mental health at baseline was strongly associated with subsequent mental health scores (r=0.46-0.54). Poor mental health at age 53 and 60-64 was associated with more frequent religious attendance at age 60-64 (b=0.04; 95% CI: 0.02 to 0.06; p<0.05), and 68-69 (b=0.03; 95% CI: 0.02 to 0.06; p<0.05), respectively. There was no evidence that religious attendance at age 43, 60-64 or 68-69 was associated with later or concurrent mental health. CONCLUSION: Using birth cohort data from the UK, it was found that poor mental health was associated with later religious attendance but not vice versa. Future research should confirm these novel findings and explore the underlying mechanisms between religious attendance and mental health.

Systemic inflammation and emotional responses during the COVID-19 pandemic.

The impact of the COVID-19 pandemic on population mental health is of global concern. Inflammatory processes are thought to contribute to mental ill-health, but their role in experiences of psychological distress during the pandemic has not been investigated. We tested the hypothesis that elevated inflammatory biomarkers (high-sensitivity plasma C-reactive protein [CRP] and plasma fibrinogen) measured pre-pandemic would be positively predictive of increased depressive symptoms experienced during the pandemic. Data were analysed from the English Longitudinal Study of Ageing (ELSA), with 3574 individuals aged >50 for CRP and 3314 for fibrinogen measured in waves 8 (2016/17) or 9 (2018/19). Depressive symptoms were measured with a short version of the Centre for Epidemiological Studies Depression Scale (CES-D) pre-pandemic (2016-2019) and during the pandemic (June/July 2020). Participants with higher baseline CRP concentrations had 40% higher odds of developing depressive symptoms during the pandemic (ORadjusted = 1.40, 95% CI 1.12-1.73, p = 0.003) after full adjustment. Fibrinogen concentrations were also associated with depressive symptoms during the pandemic (ORadjusted = 1.23, 95% CI 1.04-1.46, p = 0.019), but this association was no longer significant after controlling for lifestyle factors (smoking status, alcohol consumption and physical activity). In this large population study, systemic inflammation measured 1-3 years pre-pandemic was associated with greater depressed mood during the early months of the pandemic. This finding is consistent with the hypothesis that higher levels of inflammation increase the vulnerability of older people to impaired mental health in the presence of the widespread stress of the COVID-19 pandemic.