Living Alone With Mild-to-Moderate Dementia Over a Two-Year Period: Longitudinal Findings From the IDEAL Cohort.

OBJECTIVES: To compare the experiences of people with dementia living alone or with others and how these may change over two years. DESIGN: We analysed longitudinal data from three assessment waves, one year apart, in the British IDEAL cohort. SETTING: Participants with mild-to-moderate dementia were recruited through National Health Service providers, where possible with a family caregiver, and interviewed at home. PARTICIPANTS: The current analyses include 281 people with dementia living alone and 1,244 living with others at baseline; follow-up data were available for 200 and 965 respectively at time 2 and 144 and 696 respectively at time 3. For those living alone, 140 nonresident caregivers contributed at baseline, 102 at time 2 and 81 at time 3. For those living with others, 1,127 family caregivers contributed at baseline, 876 at time 2 and 670 at time 3. MEASUREMENTS: Assessments covered: cognitive and functional ability; self-reported perceptions of health, mood, social engagement, quality of life, satisfaction with life and well-being; use of in-home and community care; and transitions into residential care. RESULTS: People living alone tended to have better cognitive and functional ability and were more frequent users of in-home care. However, they experienced poorer physical, social, and psychological health and reduced quality of life, satisfaction with life, and well-being. These differences persisted over time and rates of transition into residential care were higher. CONCLUSIONS: To facilitate continuing in place for people with dementia living alone, a dual focus on supporting functional ability and addressing psychosocial needs is essential in the context of an enabling policy framework.

Differences in trajectories of quality of life according to type of dementia: 6-year longitudinal findings from the IDEAL programme.

BACKGROUND: People with different types of dementia may have distinct symptoms and experiences that affect their quality of life. This study investigated whether quality of life varied across types of dementia and over time. METHODS: The participants were 1555 people with mild-to-moderate dementia and 1327 carers from the IDEAL longitudinal cohort study, recruited from clinical services. As many as possible were followed for up to 6 years. Diagnoses included were Alzheimer's disease, vascular dementia, mixed Alzheimer's and vascular dementia, Parkinson's disease dementia, dementia with Lewy bodies, and frontotemporal dementia. Self- and informant-rated versions of the Quality of Life in Alzheimer's Disease scale were used. A joint model, incorporating a mixed effects model with random effects and a survival model to account for dropout, was used to examine whether quality of life varied by dementia type at the time of diagnosis and how trajectories changed over time. RESULTS: The strongest associations between dementia type and quality of life were seen around the time of diagnosis. For both self-ratings and informant ratings, people with Parkinson's disease dementia or dementia with Lewy bodies had lower quality of life scores. Over time there was little change in self-rated scores across all dementia types (- 0.15 points per year). Informant-rated scores declined over time (- 1.63 points per year), with the greatest decline seen in ratings by informants for people with dementia with Lewy bodies (- 2.18 points per year). CONCLUSIONS: Self-rated quality of life scores were relatively stable over time whilst informant ratings showed a steeper decline. People with Parkinson's disease dementia or dementia with Lewy bodies report particularly low levels of quality of life, indicating the importance of greater attention to the needs of these groups.

The Microglial Transcriptome of Age-Associated Deep Subcortical White Matter Lesions Suggests a Neuroprotective Response to Blood-Brain Barrier Dysfunction.

Age-associated deep-subcortical white matter lesions (DSCLs) are an independent risk factor for dementia, displaying high levels of CD68+ microglia. This study aimed to characterize the transcriptomic profile of microglia in DSCLs and surrounding radiologically normal-appearing white matter (NAWM) compared to non-lesional control white matter. CD68+ microglia were isolated from white matter groups (n = 4 cases per group) from the Cognitive Function and Ageing Study neuropathology cohort using immuno-laser capture microdissection. Microarray gene expression profiling, but not RNA-sequencing, was found to be compatible with immuno-LCM-ed post-mortem material in the CFAS cohort and identified significantly differentially expressed genes (DEGs). Functional grouping and pathway analysis were assessed using the Database for Annotation Visualization and Integrated Discovery (DAVID) software, and immunohistochemistry was performed to validate gene expression changes at the protein level. Transcriptomic profiling of microglia in DSCLs compared to non-lesional control white matter identified 181 significant DEGs (93 upregulated and 88 downregulated). Functional clustering analysis in DAVID revealed dysregulation of haptoglobin-haemoglobin binding (Enrichment score 2.5, p = 0.017), confirmed using CD163 immunostaining, suggesting a neuroprotective microglial response to blood-brain barrier dysfunction in DSCLs. In NAWM versus control white matter, microglia exhibited 347 DEGs (209 upregulated, 138 downregulated), with significant dysregulation of protein de-ubiquitination (Enrichment score 5.14, p < 0.001), implying an inability to maintain protein homeostasis in NAWM that may contribute to lesion spread. These findings enhance understanding of microglial transcriptomic changes in ageing white matter pathology, highlighting a neuroprotective adaptation in DSCLs microglia and a potentially lesion-promoting phenotype in NAWM microglia.

Associations between multimorbidity and neuropathology in dementia: consideration of functional cognitive disorders, psychiatric illness and dementia mimics.

BACKGROUND: Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.g. Parkinson's disease, vascular disease), in others, conditions may reflect a prodromal stage of dementia (e.g. depression, anxiety and psychosis). AIMS: To assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy. METHOD: We examined ante-mortem and autopsy data from 767 brain tissue donors from the UK, identifying physical multimorbidity in later life and specific brain-related conditions. We assessed associations between these purported risk factors and dementia-related neuropathological changes at autopsy (Alzheimer's-disease related neuropathology, Lewy body pathology, cerebrovascular disease and limbic-predominant age-related TDP-43 encephalopathy) with logistic models. RESULTS: Physical multimorbidity was not associated with greater dementia-related neuropathological changes. In the presence of physical multimorbidity, clinical dementia was less likely to be associated with Alzheimer's disease pathology. Conversely, conditions which may be clinical or prodromal manifestations of dementia-related neuropathology (Parkinson's disease, cerebrovascular disease, depression and other psychiatric conditions) were associated with dementia and neuropathological changes. CONCLUSIONS: Physical multimorbidity alone is not associated with greater dementia-related neuropathological change; inappropriate inclusion of brain-related conditions in multimorbidity measures and misdiagnosis of neurodegenerative dementia may better explain increased rates of clinical dementia in multimorbidity.

Health conditions in spousal caregivers of people with dementia and their relationships with stress, caregiving experiences, and social networks: longitudinal findings from the IDEAL programme.

OBJECTIVES: Longitudinal evidence documenting health conditions in spousal caregivers of people with dementia and whether these influence caregivers' outcomes is scarce. This study explores type and number of health conditions over two years in caregivers of people with dementia and subgroups based on age, sex, education, hours of care, informant-rated functional ability, neuropsychiatric symptoms, cognition of the person with dementia, and length of diagnosis in the person with dementia. It also explores whether over time the number of health conditions is associated with caregivers' stress, positive experiences of caregiving, and social networks METHODS: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used. Participants comprised spousal caregivers (n = 977) of people with dementia. Self-reported health conditions using the Charlson Comorbidity Index, stress, positive experiences of caregiving, and social network were assessed over two years. Mixed effect models were used RESULTS: On average participants had 1.5 health conditions at baseline; increasing to 2.1 conditions over two years. More health conditions were reported by caregivers who were older, had no formal education, provided 10 + hours of care per day, and/or cared for a person with more neuropsychiatric symptoms at baseline. More baseline health conditions were associated with greater stress at baseline but not with stress over time. Over two years, when caregivers' health conditions increased, their stress increased whereas their social network diminished DISCUSSION: Findings highlight that most caregivers have their own health problems which require management to avoid increased stress and shrinking of social networks.

Living well with dementia: An exploratory matched analysis of minority ethnic and white people with dementia and carers participating in the IDEAL programme.

OBJECTIVES: The increasing heterogeneity of the population of older people is reflected in an increasing number of people with dementia and carers drawn from minority ethnic groups. Data from the IDEAL study are used to compare indices of 'living well' among people with dementia and carers from ethnic minority groups with matched white peers. METHODS: We used an exploratory cross-sectional case-control design to compare 'living well' for people with dementia and carers from minority ethnic and white groups. Measures for both groups were quality of life, life satisfaction, wellbeing, loneliness, and social isolation and, for carers, stress, relationship quality, role captivity and caring competence. RESULTS: The sample of people with dementia consisted of 20 minority ethnic and 60 white participants and for carers 15 and 45 respectively. People with dementia from minority ethnic groups had poorer quality of life (-4.74, 95% CI: -7.98 to -1.50) and higher loneliness (1.72, 95% CI: 0.78-2.66) whilst minority ethnic carers had higher stress (8.17, 95% CI: 1.72-14.63) and role captivity (2.00, 95% CI: 0.43-3.57) and lower relationship quality (-9.86, 95% CI: -14.24 to -5.48) than their white peers. CONCLUSION: Our exploratory study suggests that people with dementia from minority ethnic groups experience lower quality of life and carers experience higher stress and role captivity and lower relationship quality than their white peers. Confirmatory research with larger samples is required to facilitate analysis of the experiences of specific minority ethnic groups and examine the factors contributing to these disadvantages.

Relationships of brain cholesterol and cholesterol biosynthetic enzymes to Alzheimer's pathology and dementia in the CFAS population-derived neuropathology cohort.

Altered cholesterol metabolism is implicated in brain ageing and Alzheimer's disease. We examined whether key genes regulating cholesterol metabolism and levels of brain cholesterol are altered in dementia and Alzheimer's disease neuropathological change (ADNC). Temporal cortex (n = 99) was obtained from the Cognitive Function and Ageing Study. Expression of the cholesterol biosynthesis rate-limiting enzyme HMG-CoA reductase (HMGCR) and its regulator, SREBP2, were detected using immunohistochemistry. Expression of HMGCR, SREBP2, CYP46A1 and ABCA1 were quantified by qPCR in samples enriched for astrocyte and neuronal RNA following laser-capture microdissection. Total cortical cholesterol was measured using the Amplex Red assay. HMGCR and SREBP2 proteins were predominantly expressed in pyramidal neurones, and in glia. Neuronal HMGCR did not vary with ADNC, oxidative stress, neuroinflammation or dementia status. Expression of HMGCR neuronal mRNA decreased with ADNC (p = 0.022) and increased with neuronal DNA damage (p = 0.049), whilst SREBP2 increased with ADNC (p = 0.005). High or moderate tertiles for cholesterol levels were associated with increased dementia risk (OR 1.44, 1.58). APOE ε4 allele was not associated with cortical cholesterol levels. ADNC is associated with gene expression changes that may impair cholesterol biosynthesis in neurones but not astrocytes, whilst levels of cortical cholesterol show a weak relationship to dementia status.

Comorbid health conditions and their impact on social isolation, loneliness, quality of life, and well-being in people with dementia: longitudinal findings from the IDEAL programme.

BACKGROUND: Most people with dementia have multiple health conditions. This study explores (1) number and type of health condition(s) in people with dementia overall and in relation to age, sex, dementia type, and cognition; (2) change in number of health conditions over two years; and (3) whether over time the number of health conditions at baseline is related to social isolation, loneliness, quality of life, and/or well-being. METHODS: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used. Participants comprised people with dementia (n = 1490) living in the community (at baseline) in Great Britain. Health conditions using the Charlson Comorbidity Index, cognition, social isolation, loneliness, quality of life, and well-being were assessed over two years. Mixed effects modelling was used. RESULTS: On average participants had 1.8 health conditions at baseline, excluding dementia; increasing to 2.5 conditions over two years. Those with vascular dementia or mixed (Alzheimer's and vascular) dementia had more health conditions than those with Alzheimer's disease. People aged ≥ 80 had more health conditions than those aged < 65 years. At baseline having more health conditions was associated with increased loneliness, poorer quality of life, and poorer well-being, but was either minimally or not associated with cognition, sex, and social isolation. Number of health conditions had either minimal or no influence on these variables over time. CONCLUSIONS: People with dementia in IDEAL generally had multiple health conditions and those with more health conditions were lonelier, had poorer quality of life, and poorer well-being.

Trajectories of cognitive and perceived functional decline in people with dementia: Findings from the IDEAL programme.

INTRODUCTION: Impaired cognition and instrumental activities of daily living (iADL) are key diagnostic features of dementia; however, few studies have compared trajectories of cognition and iADL. METHODS: Participants from the IDEAL study comprised 1537, 1183, and 851 people with dementia, and 1277, 977, and 749 caregivers at baseline, 12 and 24 months, respectively. Addenbrooke's Cognitive Examination-III and Functional Activities Questionnaire were used to measure cognition and iADL, respectively. Scores were converted to deciles. RESULTS: Self-rated iADL declined on average by -0.08 (-0.25, 0.08) decile points per timepoint more than cognition. Informant-rated iADL declined on average by -0.31 (-0.43, -0.18) decile points per timepoint more than cognition. DISCUSSION: Cognition and self-rated iADL declined at a similar rate. Informant-rated iADL declined at a significantly greater rate than cognition. Therefore, either cognition and perceived iADL decline at different rates or informants overestimate increasing iADL difficulties compared to both cognition and self-ratings. HIGHLIGHTS: Self-ratings of the degree of functional difficulties were consistent with cognition Decline in self-rated everyday activities was consistent with cognitive decline Informant-ratings of everyday activities declined more than cognition.

Dyadic perspectives on loneliness and social isolation among people with dementia and spousal carers: findings from the IDEAL programme.

OBJECTIVES: This study aims to investigate the impact of self and partner experiences of loneliness and social isolation on life satisfaction in people with dementia and their spousal carers. METHODS: We used data from 1042 dementia caregiving dyads in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) programme cohort. Loneliness was measured using the six-item De Jong Gierveld loneliness scale and social isolation using the six-item Lubben Social Network Scale. Data were analysed using the Actor-Partner Interdependence Model framework. RESULTS: Self-rated loneliness was associated with poorer life satisfaction for both people with dementia and carers. The initial partner effects observed between the loneliness of the carer and the life satisfaction of the person with dementia and between social isolation reported by the person with dementia and life satisfaction of the carer were reduced to nonsignificance once the quality of the relationship between them was considered. DISCUSSION: Experiencing greater loneliness and social isolation is linked with reduced life satisfaction for people with dementia and carers. However, having a positive view of the quality of the relationship between them reduced the impact of loneliness and social isolation on life satisfaction. Findings suggest the need to consider the experiences of both the person with dementia and the carer when investigating the impact of loneliness and social isolation. Individual interventions to mitigate loneliness or isolation may enhance life satisfaction for both partners and not simply the intervention recipient.

Insights into the pathological basis of dementia from population-based neuropathology studies.

The epidemiological neuropathology perspective of population and community-based studies allows unbiased assessment of the prevalence of various pathologies and their relationships to late-life dementia. In addition, this approach provides complementary insights to conventional case-control studies, which tend to be more representative of a younger clinical cohort. The Cognitive Function and Ageing Study (CFAS) is a longitudinal study of cognitive impairment and frailty in the general United Kingdom population. In this review, we provide an overview of the major findings from CFAS, alongside other studies, which have demonstrated a high prevalence of pathology in the ageing brain, particularly Alzheimer's disease neuropathological change and vascular pathology. Increasing burdens of these pathologies are the major correlates of dementia, especially neurofibrillary tangles, but there is substantial overlap in pathology between those with and without dementia, particularly at intermediate burdens of pathology and also at the oldest ages. Furthermore, additional pathologies such as limbic-predominant age-related TDP-43 encephalopathy, ageing-related tau astrogliopathy and primary age-related tauopathies contribute to late-life dementia. Findings from ageing population-representative studies have implications for the understanding of dementia pathology in the community. The high prevalence of pathology and variable relationship to dementia status has implications for disease definition and indicate a role for modulating factors on cognitive outcome. The complexity of late-life dementia, with mixed pathologies, indicates a need for a better understanding of these processes across the life-course to direct the best research for reducing risk in later life of avoidable clinical dementia syndromes.

Predicting cognitive decline using neuropsychiatric symptoms in prodromal Lewy body dementia: A longitudinal study.

INTRODUCTION: Neuropsychiatric symptoms (NPS) in Lewy body dementias (LBD) occur frequently and early in disease progression. Such symptoms are associated with worse quality of life, caregiver burden and functional limitations. Limited evidence exists, however, outlining the longitudinal relationship between NPS and cognitive decline in prodromal LBD. METHODS: 123 participants were derived from three cohort studies. Patients with mild cognitive impairment (MCI) relating to probable dementia with Lewy bodies (MCI-LB, n = 67) and Parkinson's disease (PD-MCI, n = 56) completed comprehensive cognitive and neuropsychiatric assessment and were followed up longitudinally. Linear regression and mixed effects models assessed the relationship between baseline NPS and cognition at baseline and over time. RESULTS: In MCI-LB, overall NPS burden was associated with declines over time in executive function (p = 0.026) and processing speed (p = 0.028) and baseline aberrant motor behaviour was associated with declines in attention (p < 0.025). Anxiety was significantly associated with poorer visuospatial functioning (p = 0.016) at baseline and poorer attention both at baseline (p = 0.017) and across time points (p = 0.024). In PD-MCI, psychosis was associated with poorer executive functioning at baseline (p = 0.008) and across time points (p = 0.002) but had no association with changes longitudinally. CONCLUSIONS: Core neuropsychiatric components of LBD are not strongly associated with cognition in prodromal disease. This may suggest that neuropathological mechanisms underlying NPS may not be the same as those underlying cognitive impairment. Non-core NPS, however, may be more directly associated with cognitive change. Future studies utilising neuroimaging techniques are needed to explore the neuropathological basis of NPS in prodromal LBD.

The prevalence, correlation, and co-occurrence of neuropathology in old age: harmonisation of 12 measures across six community-based autopsy studies of dementia.

BACKGROUND: Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population. METHODS: We combined data from six community-based autopsy cohorts in the US and the UK in a coordinated cross-sectional analysis. Among all decedents aged 80 years or older, we assessed 12 neuropathologies known to be associated with dementia: arteriolosclerosis, atherosclerosis, macroinfarcts, microinfarcts, lacunes, cerebral amyloid angiopathy, Braak neurofibrillary tangle stage, Consortium to Establish a Registry for Alzheimer's disease (CERAD) diffuse plaque score, CERAD neuritic plaque score, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and Lewy body pathology. We divided measures into three groups describing level of confidence (low, moderate, and high) in harmonisation. We described the prevalence, correlations, and co-occurrence of neuropathologies. FINDINGS: The cohorts included 4354 decedents aged 80 years or older with autopsy data. All cohorts included more women than men, with the exception of one study that only included men, and all cohorts included decedents at older ages (range of mean age at death across cohorts 88·0-91·6 years). Measures of Alzheimer's disease neuropathological change, Braak stage and CERAD scores, were in the high confidence category, whereas measures of vascular neuropathologies were in the low (arterioloscerosis, atherosclerosis, cerebral amyloid angiopathy, and lacunes) or moderate (macroinfarcts and microinfarcts) categories. Neuropathology prevalence and co-occurrence was high (2443 [91%] of 2695 participants had more than one of six key neuropathologies and 1106 [41%] of 2695 had three or more). Co-occurrence was strongly but not deterministically associated with dementia status. Vascular and Alzheimer's disease features clustered separately in correlation analyses, and LATE-NC had moderate associations with Alzheimer's disease measures (eg, Braak stage ρ=0·31 [95% CI 0·20-0·42]). INTERPRETATION: Higher variability and more inconsistency in the measurement of vascular neuropathologies compared with the measurement of Alzheimer's disease neuropathological change suggests the development of new frameworks for the measurement of vascular neuropathologies might be helpful. Results highlight the complexity and multi-morbidity of the brain pathologies that underlie dementia in older adults and suggest that prevention efforts and treatments should be multifaceted. FUNDING: Gates Ventures.

Are there socioeconomic inequalities in polypharmacy among older people? A systematic review and meta-analysis.

BACKGROUND: Socioeconomic status (SES) may influence prescribing, concordance and adherence to medication regimens. This review set out to investigate the association between polypharmacy and an individual's socioeconomic status. METHODS: A systematic review and meta-analyses of observational studies was conducted across four databases. Older people (≥ 55 years) from any healthcare setting and residing location were included. The search was conducted across four databases: Medline (OVID), Web of Science, Embase (OVID) and CINAHL. Observational studies from 1990 that reported polypharmacy according to SES were included. A random-effects model was undertaken comparing those with polypharmacy (≥ 5 medication usage) with no polypharmacy. Unadjusted odds ratios (ORs), 95% confidence intervals (CIs) and standard errors (SE) were calculated for each study. RESULTS: Fifty-four articles from 13,412 hits screened met the inclusion criteria. The measure of SES used were education (50 studies), income (18 studies), wealth (6 studies), occupation (4 studies), employment (7 studies), social class (5 studies), SES categories (2 studies) and deprivation (1 study). Thirteen studies were excluded from the meta-analysis. Lower SES was associated with higher polypharmacy usage: individuals of lower educational backgrounds displayed 21% higher odds to be in receipt of polypharmacy when compared to those of higher education backgrounds. Similar findings were shown for occupation, income, social class, and socioeconomic categories. CONCLUSIONS: There are socioeconomic inequalities in polypharmacy among older people, with people of lower SES significantly having higher odds of polypharmacy. Future work could examine the reasons for these inequalities and explore the interplay between polypharmacy and multimorbidity.

Household wealth, neighbourhood deprivation and frailty amongst middle-aged and older adults in England: a longitudinal analysis over 15 years (2002-2017).

BACKGROUND: frailty is a condition of reduced function and health due to ageing processes and is associated with a higher risk of falls, hospitalisation, disability and mortality. OBJECTIVE: to determine the relationship between household wealth and neighbourhood deprivation with frailty status, independently of demographic factors, educational attainment and health behaviours. DESIGN: population-based cohort study. SETTING: communities in England. SUBJECTS: in total 17,438 adults aged 50+ from the English Longitudinal Study of Ageing. METHODS: multilevel mixed-effects ordered logistic regression was used in this study. Frailty was measured using a frailty index. We defined small geographic areas (neighbourhoods) using English Lower layer Super Output Areas. Neighbourhood deprivation was measured by the English Index of Multiple Deprivation, grouped into quintiles. Health behaviours included in this study are smoking and frequency of alcohol consumption. RESULTS: the proportion of respondents who were prefrail and frail were 33.8% [95% confidence interval (CI) 33.0-34.6%] and 11.7 (11.1-12.2)%, respectively. Participants in the lowest wealth quintile and living in the most deprived neighbourhood quintile had 1.3 (95% CI = 1.2-1.3) and 2.2 (95% CI = 2.1-2.4) times higher odds of being prefrail and frail, respectively, than the wealthiest participants living in the least deprived neighbourhoods Living in more deprived neighbourhood and poorer wealth was associated with an increased risk of becoming frail. Those inequalities did not change over time. CONCLUSIONS: in this population-based sample, living in a deprived area or having low wealth was associated with frailty in middle-aged and older adults. This relationship was independent of the effects of individual demographic characteristics and health behaviours.

Assessment of Alzheimer-related pathologies of dementia using machine learning feature selection.

Although a variety of brain lesions may contribute to the pathological assessment of dementia, the relationship of these lesions to dementia, how they interact and how to quantify them remains uncertain. Systematically assessing neuropathological measures by their degree of association with dementia may lead to better diagnostic systems and treatment targets. This study aims to apply machine learning approaches to feature selection in order to identify critical features of Alzheimer-related pathologies associated with dementia. We applied machine learning techniques for feature ranking and classification to objectively compare neuropathological features and their relationship to dementia status during life using a cohort (n=186) from the Cognitive Function and Ageing Study (CFAS). We first tested Alzheimer's Disease and tau markers and then other neuropathologies associated with dementia. Seven feature ranking methods using different information criteria consistently ranked 22 out of the 34 neuropathology features for importance to dementia classification. Although highly correlated, Braak neurofibrillary tangle stage, beta-amyloid and cerebral amyloid angiopathy features were ranked the highest. The best-performing dementia classifier using the top eight neuropathological features achieved 79% sensitivity, 69% specificity and 75% precision. However, when assessing all seven classifiers and the 22 ranked features, a substantial proportion (40.4%) of dementia cases was consistently misclassified. These results highlight the benefits of using machine learning to identify critical indices of plaque, tangle and cerebral amyloid angiopathy burdens that may be useful for classifying dementia.

Are profiles of social, cultural, and economic capital related to living well with dementia? Longitudinal findings from the IDEAL programme.

RATIONALE: Research exploring social, cultural, and economic capital among people with dementia is scarce. OBJECTIVE: We describe levels of social, cultural, and economic capital in people with dementia at baseline and levels of social and cultural capital 12 and 24 months later. We identify groups of people with dementia having different combinations of capital and explore whether the identified groups differ in personal characteristics at baseline and in quality of life (QoL), satisfaction with life (SwL), and well-being over time. METHOD: Baseline, 12-months, and 24-months data from 1537 people with dementia (age, mean = 76.4 years; SD = 8.5; Alzheimer's Disease = 55.4%) enrolled in the IDEAL cohort were analyzed. Social (interactions with friends, civic participation, social participation, neighborhood trust, social network), cultural (education, cultural participation) and economic (annual income) capital, QoL, SwL, well-being, and personal characteristics were assessed. RESULTS: Compared to people their age, people with dementia reported slightly lower frequency of interactions with friends, social networks and social support, civic and cultural participation, education, and annual income. However, social engagement, cultural participation, and annual income are low among British older adults. Latent profile analysis identified four groups that, based on their levels of social, cultural, and economic capital were named socially and economically privileged (18.0% of participants); financially secure (21.0% of participants); low capital (36.9% of participants); and very low capital (24.1% of participants). Latent growth curve models showed that over time QoL, SwL, and well-being remained largely stable for all groups. Compared to the low capital group, the socially and economically privileged and financially secure groups had higher QoL and well-being whereas the group with very low capital had poorer QoL, SwL, and well-being. CONCLUSIONS: New policies and efforts from the government, philanthropic foundations, the voluntary and primary care sectors are needed to address social, cultural, and economic disadvantage among people with dementia.

Could Country-Level Factors Explain Sex Differences in Dementia Incidence and Prevalence? A Systematic Review and Meta-Analysis.

BACKGROUND: Despite rising interest in sex differences in dementia, it is unclear whether sex differences in dementia incidence and prevalence are apparent globally. OBJECTIVE: We examine sex differences in incidence and prevalence of Any dementia, Alzheimer's disease (AD), and vascular dementia (VaD), and evaluate whether country-level indicators of gender inequality account for differences. METHODS: Systematic review with meta-analysis was used to obtain estimates of incidence and prevalence of Any dementia, AD, and VaD using random effects meta-analysis, and population-based studies with clinical or validated dementia measures. Meta-regression was used to evaluate how country-specific factors of life expectancy, education, and gender differences in development, unemployment, and inequality indices influenced estimates. RESULTS: We identified 205 eligible studies from 8,731 articles, representing 998,187 participants across 43 countries. There were no sex differences in the incidence of Any dementia, AD, or VaD, except in the 90+ age group (women higher). When examined by 5-year age bands, the only sex difference in prevalence of Any dementia was in the 85+ group and there was no sex difference in VaD. AD was more prevalent in women at most ages. Globally, the overall prevalence of dementia in adults 65 + was higher for women (80.22/1000, 95% CI 62.83-97.61) than men (54.86/1000, 95% CI 43.55-66.17). Meta-regression revealed that sex differences in Any dementia prevalence were associated with gender differences in life expectancy and in education. CONCLUSION: Globally, there are no sex differences in age-specific dementia incidence, but prevalence of AD is higher in women. Country-level factors like life expectancy and gender differences in education may explain variability in sex differences.

Profiles of social, cultural, and economic capital as longitudinal predictors of stress, positive experiences of caring, and depression among spousal carers of people with dementia.

OBJECTIVE: We explored (1) social, cultural, and economic capital in spousal carers of people with dementia; (2) profiles of carers with different levels of capital; (3) whether the identified profiles differ in levels of stress and positive experiences of caring, and likelihood of depression over time. METHODS: Baseline (2014-2016), 12-month, and 24-month follow-up data were analyzed for 984 coresident spousal carers of people with dementia. We assessed social, cultural, and economic capital, stress, positive experiences of caring, depression. RESULTS: On average, carers reported infrequent social and cultural participation. Most carers were not socially isolated, trusted their neighbours, had education at least to age 16, and had an income aligned with the 2014 UK average. We identified four groups of carers with different levels of capital. Although on average stress was low, depression was infrequent, and positive experiences of caring were moderately frequent, the group of carers with lowest capital was the least stressed and reported the most positive experiences of caring over time. Compared to the two groups with better capital, those with poorer capital were more likely to be depressed over time. CONCLUSION: Social, cultural, and economic resources may decrease likelihood of depression, but not stress, in carers of people with dementia.