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Background: The Eatwell guide reflects the UK government's recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associations between the Eatwell Guide and risk for future dementia. Methods: Data from the PREVENT dementia cohort study baseline visit was used in this analysis. Binary and graded Eatwell Guide scores (BEWG, GEWG) were created from a self-reported Food Frequency Questionnaire. The CAIDE score was included as the primary outcome measure to represent risk for future Alzheimer's disease. Secondary outcome measures included cardiometabolic health measures and brain health measures. Generalised additive models were run in R. Results: A total of 517 participants were included in the analysis, with a mean BEWG score of 4.39 (± 1.66) (out of a possible 12 points) and GEWG score of 39.88 (± 6.19) (out of a possible 60 points). There was no significant association between either Eatwell Guide score and the CAIDE score (BEWG β: 0.07, 95% confidence interval (CI): -0.07, 0.22; GEWG β: 0.02, 95% CI: -0.02, 0.06) or any measures of brain health. There was a significant association between higher GEWG score and lower systolic and diastolic blood pressure and body mass index (BMI) (systolic β: -0.24, 95% CI: -0.45, -0.03; diastolic β: -0.16, 95% CI: -0.29, -0.03; BMI β: -0.09, 95% CI: -0.16, -0.01). Conclusions: Although not directly associated with the CAIDE score, the Eatwell Guide dietary pattern may be beneficial for dementia prevention efforts through the modification of hypertension and obesity, which are both known risk factors for dementia. Future work could replicate these findings in other UK-based cohorts as well as further development of Eatwell Guide scoring methodologies. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to estimate the association between anticholinergic burden, general cognitive ability and various measures of brain structural MRI in relatively healthy middle‐aged and older individuals. Methods: In the UK Biobank participants with linked health‐care records (n = 163,043, aged 40–71 at baseline), of whom about 17 000 had MRI data available, we calculated the total anticholinergic drug burden according to 15 different anticholinergic scales and due to different classes of drugs. We then used linear regression to explore the associations between anticholinergic burden and various measures of cognition and structural MRI, including general cognitive ability, 9 separate cognitive domains, brain atrophy, volumes of 68 cortical and 14 subcortical areas and fractional anisotropy and median diffusivity of 25 white‐matter tracts. Results: Anticholinergic burden was modestly associated with poorer cognition across most anticholinergic scales and cognitive tests (7/9 FDR‐adjusted significant associations, standardised betas (β) range: −0.039, −0.003). When using the anticholinergic scale exhibiting the strongest association with cognitive functions, anticholinergic burden due to only some classes of drugs exhibited negative associations with cognitive function, with β‐lactam antibiotics (β = −0.035, PFDR < 0.001) and opioids (β = −0.026, PFDR < 0.001) exhibiting the strongest effects. Anticholinergic burden was not associated with any measure of brain macrostructure or microstructure (PFDR > 0.08). Conclusions: Anticholinergic burden is weakly associated with poorer cognition, but there is little evidence for associations with brain structure. Future studies might focus more broadly on polypharmacy or more narrowly on distinct drug classes, instead of using purported anticholinergic action to study the effects of drugs on cognitive ability. [ABSTRACT FROM AUTHOR]

Background: The use of prescription drugs with anticholinergic properties has been associated with multiple negative health outcomes in older people. Moreover, recent evidence suggests that associated adverse effects may occur even decades after stopping anticholinergic use. Despite the implicated importance of examining longitudinal patterns of anticholinergic prescribing for different age groups, few such data are available. Methods: We performed an age‐period‐cohort (APC) analysis to study trends in an aggregate measure of anticholinergic burden between the years 1990 and 2015, utilising data from >220 000 UK Biobank participants with linked prescription data from primary care. Results: Anticholinergic burden in the sample increased up to 9‐fold over 25 years and was observed for both period and age effects across most classes of drugs. The greatest increase was seen in the prescribing of antidepressants. Female sex, lower education and greater deprivation were associated with greater anticholinergic burden. Conclusions: The increase in anticholinergic prescribing is mostly due to an increase in polypharmacy and is attributable to both ageing of participants and period‐related changes in prescribing practices. Research is needed to clarify the implications of rising anticholinergic use for public health and to contextualise this rise in light of other relevant prescribing practices. [ABSTRACT FROM AUTHOR]

Background: Previous studies on the relationship between anticholinergic drugs and dementia have reported heterogeneous results. This variability could be due to different anticholinergic scales and differential effects of distinct classes of drugs. Methods: Using Cox proportional hazards models, we computed the association between annual anticholinergic burden (AChB) and the risk of dementia inUK Biobank with linked general practitioner prescription records between the years 2000 and 2015 (n = 171,775). Results:AChB according to most anticholinergic scales (standardized odds ratio range: 1.027-1.125) and the slope of the AChB trajectory (hazard ratio = 1.094; 95% confidence interval: 1.068-1.119) were predictive of dementia. However, the association between AChB and dementia held only for some classes of drugs, especially antidepressants, antiepileptics, and antidiuretics. Discussion: The heterogeneity in previous findings may partially be due to different effects for different classes of drugs. Future studies should establish differences in more detail and further examine the practicality of a general measure of AChB relating to the risk of dementia. [ABSTRACT FROM AUTHOR]

Background: The genetic variant rs9923231 (VKORC1) is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has been linked in a gene-based test to dementia/Alzheimer's disease in the parents of participants, with suggestive evidence for an association for rs9923231 (p = 1.8×10-7), which was included in the genome-wide significant KAT8 locus.Objective: Our study aimed to investigate whether the relationship between rs9923231 and dementia persists only for certain dementia sub-types, and if those taking warfarin are at greater risk.Methods: We used logistic regression and data from 238,195 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use.Results: Parental history of dementia, APOE variant, atrial fibrillation, diabetes, hypertension, and hypercholesterolemia all had strong associations with vascular dementia (p < 4.6×10-6). The T-allele in rs9923231 was linked to a lower warfarin dose (βperT - allele = -0.29, p < 2×10-16) and risk of vascular dementia (OR = 1.17, p = 0.010), but not other dementia sub-types. However, the risk of vascular dementia was not affected by warfarin use in carriers of the T-allele.Conclusion: Our study reports for the first time an association between rs9923231 and vascular dementia, but further research is warranted to explore potential mechanisms and specify the relationship between rs9923231 and features of vascular dementia. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity including physical and mental illness is increasing in prevalence. We aimed to investigate the associations between physical conditions and medication use with anxiety and depression in midlife. Methods: We conducted an observational cross-sectional study of volunteers in the PREVENT Dementia study. Using logistic and linear regression, we investigated the association between increasing numbers of self-reported chronic physical conditions and medications with self-reported depression and anxiety disorder, and scores on the Center for Epidemiologic Studies Depression (CES-D) scale and Spielberger State-Trait Anxiety Inventory (STAI) state subtest. Results: Of the 210 participants, 148 (71%) were women and 188 (90%) Caucasian. The mean age was 52 (standard deviation (SD) = 5.5) years. The mean number of physical conditions was 2.2 (SD = 1.9) and medications 1.7 (SD = 2.2). Each additional physical condition was associated with increased odds of self-reported depression (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.11–1.80; p = 0.004, adjusted for age and gender) and anxiety disorder (OR 1.70, 95% CI 1.30–2.37; p < 0.001). Increasing medication use was associated with self-reported depression (adjusted OR per additional medication 1.35, 95% CI 1.08–1.71; p = 0.008) but not anxiety disorder. For each additional condition, CES-D scores increased by 0.72 (95% CI 0.11–1.33; p = 0.020) and for each extra medication, by 0.88 (95% CI 0.32–1.44; p = 0.002). There was no significant association between increasing conditions and medications with STAI scores. In models accounting for antidepressant use, all associations were attenuated. Conclusions: Having more physical conditions is associated with anxiety and depression in midlife, and taking more medications is associated with depression but not anxiety. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is recognized as one of the greatest global public health challenges. There is increasing consensus that optimal disease modification using pharmaceuticals may best be achieved earlier in the disease continuum before symptoms occur. However, more needs to be understood about what outcomes are meaningful to potential participants in clinical trials within this preventative paradigm and how people make trade‐offs between risks and benefits. The Electronic Person‐Specific Outcome Measure (ePSOM) programme is developing an app to capture person‐specific outcomes and preferences in clinical trials. Objective: As one phase in the ePSOM programme, this study explored what matters when developing new treatments to prevent AD and how trade‐offs are made between risks and benefits, from three perspectives. Design: Focus groups were conducted with people living with memory problems (n = 21) and healthy volunteers (n = 10), and telephone interviews with health and social care professionals (n = 10). Differences and overlap between the three groups were explored. Results: Outcomes that matter lie in five key domains in relation to what matters in everyday life: Everyday Functioning; Relationships and Social Connections; Enjoying Life; Sense of Identity; and Alleviating  Symptoms. Insights were gained into the significance of reducing the risk of developing dementia with drugs and the processes of weighing up risks versus benefits. Discussion and conclusions: The key domains identified are being used to inform the next stage of the ePSOM programme which is to develop a survey to be distributed nationally in the UK to explore these issues further. [ABSTRACT FROM AUTHOR]

Given the aging population in the UK, statistical modelling of cognitive function in the older population is of interest. Joint models are formulated for survival and cognitive function in the older population. Because tests of cognitive function often result in discrete outcomes, binomial and beta--binomial mixed effects regression models are applied to analyse longitudinal measurements. Dropout due to death is accounted for by parametric survival models, where the choice of a Gompertz baseline hazard and the specification of the random-effects structure are of specific interest. The measurement model and the survival model are combined in a shared parameter joint model. Estimation is by marginal likelihood. The methods are used to analyse data from the Cambridge City over-75s cohort study and the English Longitudinal Study of Ageing. [ABSTRACT FROM AUTHOR]

Background: criteria for mild cognitive impairment (MCI) capture an intermediate cognitive state between normal ageing and dementia, associated with increased dementia risk. Whether criteria for MCI are applicable in the context of stroke and can be used to predict dementia in stroke cases is not known.Objectives: to determine the prevalence of MCI in individuals with stroke and identify predictors of 2-year incident dementia in stroke cases.Methods: individuals were from the Medical Research Council Cognitive Function and Ageing Study. MCI prevalence in individuals with stroke was determined. Logistic regression, with receiver operating characteristic curve analysis, was used to identify variables associated with risk of dementia in stroke cases including MCI criteria, demographic, health and lifestyle variables.Findings: of 2,640 individuals seen at the first assessment, 199 reported stroke with no dementia. In individuals with stroke, criteria for MCI are not appropriate, with less than 1% of stroke cases being classified as having MCI. However, in individuals with stroke two components of the MCI definition, subjective memory complaint and cognitive function (memory and praxis scores) predicted 2-year incident dementia (area under the curve = 0.85, 95% CI: 0.77–0.94, n = 113).Conclusion: criteria for MCI do not appear to capture risk of dementia in the context of stroke in the population. In stroke cases, subjective and objective cognitive performance predicts dementia and these variables could possibly be incorporated into dementia risk models for stroke cases. Identifying individuals with stroke at greatest risk of dementia has important implications for treatment and intervention. [ABSTRACT FROM PUBLISHER]

Social integration in older age is a key quality of life component and is associated with reduced mortality and morbidity risk. There are socio-economic differences in social integration, but the influence of different indicators of socio-economic position on long-term change in social integration at older ages is not known. This study aimed to identify profiles of social integration across adulthood and explore the impact of various socio-economic indicators at different ages. Data were drawn from the MRC National Survey of Health and Development. A latent class analysis used measures of contact with friends and family, participation in group activities and marital status at ages 36, 43 and 60-64 to identify profiles of change in social integration for men and women. One-step analyses related profiles to father's occupation-based socio-economic position, own educational attainment and head of household occupation-based socio-economic position. Four profiles of social integration were identified for men: high and maintained, married; medium and maintained, married; declining, married; and declining, unmarried. Higher head of household occupation and educational attainment were associated with greater likelihood of maintained integration. Four profiles of social integration were also identified for women: high and maintained, married; high and maintained, unmarried; declining group participation, unmarried; and declining group participation, married. Higher socio-economic position on all indicators was associated with greater likelihood of maintained integration. Lower socio-economic groups are more likely to experience declining social integration by early old age. Support to promote social integration may be particularly important for those with lower occupational grade or education. [ABSTRACT FROM AUTHOR]

The terminal decline hypothesis states that in the proximity of death, an individual's decline in cognitive abilities accelerates. We aimed at estimating the onset of faster rate of decline in global cognition using Mini Mental State Examination (MMSE) scores from participants of the Cambridge City over 75 Cohort Study (CC75C), a U.K. population-based longitudinal study of aging where almost all participants have died. The random change point model fitted to MMSE scores structured as a function of distance to death allowed us to identify a potentially different Onset of change in rate of decline before death for each individual in the sample. Differences in rate of change before and after the onset of change in rate of decline by sociodemographic variables were investigated. On average, the onset of a faster rate of change occurred about 7.7 years before death and varied across individuals. Our results show that most individuals experience a period of slight decline followed by a much sharper decline. Education, age at death, and cognitive impairment at study entry were identified as modifiers of rate of change before and after change in rate of decline. Gender differences were found in rate of decline in the final stages of life. Our study suggests that terminal decline is a heterogeneous process, with its Onset varying between individuals. [ABSTRACT FROM AUTHOR]

Objectives: To explore whether it is possible to detect decline in global scores of cognitive function in the proximity of death whilst simultaneously investigating potential risk profiles. Methods: Using the Mini Mental State Examination in a population study of the oldest old in which 99% of participants have died, a linear and quadratic time-to-death repeated measures random effects models were used to detect decline and potential factors which might indicate individual variation. Results: Decline and acceleration of this decline were detectable in the period before death. Some between person variation was detected in this pattern, which included differences in cognitive performance by age at death (-0.2 (SE=0.02)), sex (-1.2 (SE=0.2)), initial cognitive impairment (-7.5 (SE=0.2)) and mobility (-0.6 (SE=0.2)), in rate of decline by age at death (-0.04 (SE=0.005)), sex (-0.1 (SE=0.06)), initial cognitive impairment (-0.3 (SE=0.07)) and mobility (-0.1 (SE=0.05)) and differences in change in rate of decline by sex (-0.008 (SE=0.004)), initial cognitive impairment (-0.02 (SE=0.04)) and mobility (-0.01 (SE=0.003)). Conclusion: Using an extension of existing methods for exploring terminal decline, the phenomenon of decline in global cognition measures in the proximity of death was clearly detected as well as potential variables which could influence that pattern. Further work is required to explore whether similar methods can be used to detect the onset of the acceleration of this decline in each individual together with the potential to identify individual level factors that can allow clinicians to distinguish between the normal and preterminal phases of change in extreme old age. [ABSTRACT FROM AUTHOR]

Background: Much of our understanding of the age-related progression of systolic blood pressure (SBP) comes from crosssectional data, which do not directly capture within-individual change. We estimated life course trajectories of SBP using longitudinal data from seven population-based cohorts and one predominantly white collar occupational cohort, each from the United Kingdom and with data covering different but overlapping age periods. Methods and Findings: Data are from 30,372 individuals and comprise 102,580 SBP observations spanning from age 7 to 80+y. Multilevel models were fitted to each cohort. Four life course phases were evident in both sexes: a rapid increase in SBP coinciding with peak adolescent growth, a more gentle increase in early adulthood, a midlife acceleration beginning in the fourth decade, and a period of deceleration in late adulthood where increases in SBP slowed and SBP eventually declined. These phases were still present, although at lower levels, after adjusting for increases in body mass index though adulthood. The deceleration and decline in old age was less evident after excluding individuals who had taken antihypertensive medication. Compared to the population-based cohorts, the occupational cohort had a lower mean SBP, a shallower annual increase in midlife, and a later midlife acceleration. The maximum sex difference was found at age 26 (+8.2 mm Hg higher in men, 95% CI: 6.7, 9.8); women then experienced steeper rises and caught up by the seventh decade. Conclusions: Our investigation shows a general pattern of SBP progression from childhood in the UK, and suggests possible differences in this pattern during adulthood between a general population and an occupational population. [ABSTRACT FROM AUTHOR]

Importance: Traumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI., Objective: To assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals., Design, Setting, and Participants: This cross-sectional analysis used baseline data from the PREVENT Dementia program collected across 5 sites in the UK and Ireland between 2014 and 2020. Eligible participants were cognitively healthy midlife adults aged between 40 and 59 years. Data were analyzed between January 2023 and April 2024., Exposure: Lifetime TBI history was assessed using the Brain Injury Screening Questionnaire., Main Outcomes and Measures: Cerebral microbleeds and other markers of cerebral small vessel disease (white matter hyperintensities [WMH], lacunes, perivascular spaces) were assessed on 3T magnetic resonance imaging. Clinical measures were cognition, sleep, depression, gait, and cardiovascular disease (CVD) risk, assessed using Computerized Assessment of Information Processing (COGNITO), Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies Depression Scale, clinical interviews, and the Framingham Risk Score, respectively., Results: Of 617 participants (median [IQR] age, 52 [47-56] years; 380 female [61.6%]), 223 (36.1%) had a history of TBI. TBI was associated with higher microbleed count (β = 0.10; 95% CI, 0.01-0.18; P = .03), with a dose-response association observed with increasing number of TBI events (β = 0.05; 95% CI, 0.01-0.09; P = .03). Conversely, TBI was not associated with other measures of small vessel disease, including WMH. Furthermore, TBI moderated microbleed associations with vascular risk factors and clinical outcomes, such that associations were present only in the absence of TBI. Importantly, observations held when analyses were restricted to individuals reporting only mild TBI., Conclusions and Relevance: In this cross-sectional study of healthy middle-aged adults, detectable changes in brain imaging and clinical features were associated with remote, even mild, TBI in the general population. The potential contribution of vascular injury to TBI-related neurodegeneration presents promising avenues to identify potential targets, with findings highlighting the need to reduce TBI through early intervention and prevention in both clinical care and policymaking.

Current mortality prediction indexes are mainly based on functional morbidity and comorbidity, with limited information for risk prevention. This study aimed to develop and validate a modifiable lifestyle-based mortality predication index for older adults. Data from 51,688 participants (56% women) aged ≥50 years in 2002 Health and Retirement Study, 2002 English Longitudinal Study of Ageing and 2004 Survey of Health Ageing and Retirement in Europe were used to estimate coefficients of the index with cohort-stratified Cox regression. Models were validated across studies and compared to the Lee index (having comorbid and morbidity predictors). Over an average of 11-year follow-up, 10,240 participants died. The lifestyle index includes smoking, drinking, exercising, sleep quality, BMI, sex and age; showing adequate model performance in internal validation (C-statistic 0.79; D-statistic 1.94; calibration slope 1.13) and in all combinations of internal-external cross-validation. It outperformed Lee index (e.g. differences in C-statistic = 0.01, D-statistic = 0.17, P < 0.001) consistently across health status. The lifestyle index stratified participants into varying mortality risk groups, with those in the top quintile having 13.5% excess absolute mortality risk over 10 years than those in the bottom 50th centile. Our lifestyle index with easy-assessable behavioural factors and improved generalizability may maximize its usability for personalized risk management.

Background: Cognitive capabilities change in later life, although their onset and rate of decline, and how they are shaped by lifetime socioeconomic position, childhood cognition and adult health status are all unclear., Methods: From the Medical Research Council National Survey of Health and Development, we analysed 3,192 participants undergoing one or more cognitive assessments at ages 43, 53, 60-64 and 69. Linear mixed models described cognitive trajectories, adjusting for factors across the life course., Results: For both search speed and verbal memory, better performance at age 43 (the intercept) was associated with higher paternal and own education, childhood cognition, and adult occupational class. For search speed, the trajectory was best described as a quadratic function (decline of 45.6 letters/5-years + 4.6 letters). Verbal memory showed a linear decline of 0.20 words/5-years between ages 43 and 60 and a steeper linear decline of 0.95 words/5-years between ages 60 and 69. Decline in verbal memory in the latter period was steeper in those with higher educational achievements at age 26 (additional 0.28 words/5-years for highest attainment)., Conclusions: Decline in verbal memory and search speed across midlife is evident, though with different non-linear trajectories. By implication, pathways to cognitive impairment and dementia in older age may have their origins in this period., (© 2017 The Author(s) Published by S. Karger AG, Basel.)