Objective:To determine changes in the incidence of dementia between 1988 and 2015.Methods:This analysis was performed in aggregated data from individuals >65 years in seven population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined non-overlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex.Results:Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person years in individuals aged 65-69 years, to 65 per 1,000 person years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% CI: 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] versus 8% [0%-15%]).Conclusion:The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations.

SummaryBackgroundLittle is known about how the proportions of dependency states have changed between generational cohorts of older people. We aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011, and new projections of future demand for care.MethodsIn this population-based study, we compared two Cognitive Function and Ageing Studies (CFAS I and CFAS II) of older people (aged ≥65 years) who were permanently registered with a general practice in three defined geographical areas (Cambridgeshire, Newcastle, and Nottingham; UK). These studies were done two decades apart (1991 and 2011). General practices provided lists of individuals to be contacted and were asked to exclude those who had died or might die over the next month. Baseline interviews were done in the community and care homes. Participants were stratified by age, and interviews occurred only after written informed consent was obtained. Information collected included basic sociodemographics, cognitive status, urinary incontinence, and self-reported ability to do activities of daily living. CFAS I was assigned as the 1991 cohort and CFAS II as the 2011 cohort, and both studies provided prevalence estimates of dependency in four states: high dependency (24-h care), medium dependency (daily care), low dependency (less than daily), and independent. Years in each dependency state were calculated by Sullivan's method. To project future demands for social care, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections.FindingsBetween 1991 and 2011, there were significant increases in years lived from age 65 years with low dependency (1·7 years [95% CI 1·0–2·4] for men and 2·4 years [1·8–3·1] for women) and increases with high dependency (0·9 years [0·2–1·7] for men and 1·3 years [0·5–2·1] for women). The majority of men's extra years of life were spent independent (36·3%) or with low dependency (36·3%) whereas for women the majority were spent with low dependency (58·0%), and only 4·8% were independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71 215 care home places by 2025.InterpretationOn average older men now spend 2·4 years and women 3·0 years with substantial care needs, and most will live in the community. These findings have considerable implications for families of older people who provide the majority of unpaid care, but the findings also provide valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations.FundingMedical Research Council (G9901400) and (G06010220), with support from the National Institute for Health Research Comprehensive Local research networks in West Anglia and Trent, UK, and Neurodegenerative Disease Research Network in Newcastle, UK.

Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.

To systematically review the literature for dementia prediction models for use in the general population and externally validate their performance in a head-to-head comparison. We selected four prediction models for validation: CAIDE, BDSI, ANU-ADRI and DRS. From the Rotterdam Study, 6667 non-demented individuals aged 55 years and older were assessed between 1997 and 2001. Subsequently, participants were followed for dementia until 1 January, 2015. For each individual, we computed the risk of dementia using the reported scores from each prediction model. We used the C-statistic and calibration plots to assess the performance of each model to predict 10-year risk of all-cause dementia. For comparisons, we also evaluated discriminative accuracy using only the age component of these risk scores for each model separately. During 75,581 person-years of follow-up, 867 participants developed dementia. C-statistics for 10-year dementia risk prediction were 0.55 (95% CI 0.53–0.58) for CAIDE, 0.78 (0.76–0.81) for BDSI, 0.75 (0.74–0.77) for ANU-ADRI, and 0.81 (0.78–0.83) for DRS. Calibration plots showed that predicted risks were too extreme with underestimation at low risk and overestimation at high risk. Importantly, in all models age alone already showed nearly identical discriminative accuracy as the full model (C-statistics: 0.55 (0.53–0.58) for CAIDE, 0.81 (0.78–0.83) for BDSI, 0.77 (0.75–0.79) for ANU-ADRI, and 0.81 (0.78–0.83) for DRS). In this study, we found high variability in discriminative ability for predicting dementia in an elderly, community-dwelling population. All models showed similar discriminative ability when compared to prediction based on age alone. These findings highlight the urgent need for updated or new models to predict dementia risk in the general population.Electronic supplementary materialThe online version of this article (10.1007/s10654-018-0403-y) contains supplementary material, which is available to authorized users.

ObjectiveHigh blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.MethodsTo identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.ResultsOver 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.ConclusionOur findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.Clinical trials registrationThe review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.