To determine changes in the incidence of dementia between 1988 and 2015.
This analysis was performed in aggregated data from individuals >65 years of age in 7 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 nonoverlapping 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.
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% confidence interval CI, 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% 95% CI 14%-32% vs 8% 0%-15%).
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.
Cardiovascular risk factors are closely linked with dementia risk, but whether heart disease predisposes to dementia is uncertain.
We systematically reviewed the literature and meta-analyzed risk ...estimates from longitudinal studies reporting the association of coronary heart disease (CHD) or heart failure (HF) with risk of dementia.
We identified 16 studies (1,309,483 individuals) regarding CHD, and seven studies (1,958,702 individuals) about HF. A history of CHD was associated with a 27% increased risk of dementia (pooled relative risk RR 95% confidence interval, CI: 1.27 1.07–1.50), albeit with considerable heterogeneity across studies (I2 = 80%). HF was associated with 60% increased dementia risk (pooled RR 1.60 1.19–2.13) with moderate heterogeneity (I2 = 59%). Among prospective population-based cohorts, pooled estimates were similar (for CHD, RR 1.26 1.06–1.49, nine studies; and HF, RR 1.80 1.41–2.31, four studies) and highly consistent (I2 = 0%).
CHD and HF are associated with an increased risk of dementia.
Inflammatory markers are often elevated in patients with dementia, including Alzheimer's disease (AD). However, it remains unclear whether inflammatory markers are associated with the risk of ...developing dementia.
We searched PubMed, Embase, and Cochrane library for prospective population-based studies reporting associations between inflammatory markers and all-cause dementia or AD. We used random effects meta-analyses to obtain pooled hazard ratios (HRs) and 95% confidence intervals of inflammatory markers (highest vs. lowest quantile) for all-cause dementia and AD.
Fifteen articles from 13 studies in six countries reported data that could be meta-analyzed. C-reactive protein (HR = 1.37 1.05; 1.78), interleukin-6 (HR = 1.40 1.13; 1.73), α1-antichymotrypsin (HR = 1.54 1.14; 2.80), lipoprotein-associated phospholipase A2 activity (HR = 1.40 1.03; 1.90), and fibrinogen were each associated with all-cause dementia, but neither was significantly associated with AD.
Several inflammatory markers are associated with an increased risk of all-cause dementia; however, these markers are not specific for AD. Whether inflammatory markers closely involved in AD pathology are associated with the risk of AD remains to be elucidated.
Sleep disturbances may signal presence of prodromal parkinsonism, including Parkinson's disease. Whether general sleep quality or duration in otherwise healthy subjects is related to the risk of ...parkinsonism remains unclear. We hypothesized that both worse self-reported sleep quality and duration, as well as a longitudinal deterioration in these measures, are associated with the risk of parkinsonism, including Parkinson's disease. In the prospective population-based Rotterdam Study, we assessed sleep quality and duration with the Pittsburgh Sleep Quality Index in 7726 subjects (mean age 65 years, 57% female) between 2002 and 2008, and again in 5450 subjects between 2009 and 2014. Participants were followed until 2015 for a diagnosis of parkinsonism and Parkinson's disease. Outcomes were assessed using multiple modalities: interviews, physical examination, and continuous monitoring of pharmacy records and medical records of general practitioners. We used Cox regression to associate sleep, and changes in sleep over time, with incident parkinsonism and Parkinson's disease, adjusting for age, sex, education and smoking status. Over 64 855 person-years in 13 years of follow-up (mean: 8.4 years), 75 participants developed parkinsonism, of whom 47 developed Parkinson's disease. We showed that within the first 2 years of follow-up, worse sleep quality {hazard ratio (HR) 2.38 per standard deviation increase 95% confidence interval (CI 0.91-6.23)} and shorter sleep duration HR 0.61 per standard deviation increase (95% CI 0.31-1.21) related to a higher risk of parkinsonism. Associations of worse sleep quality HR 3.86 (95% CI 1.19-12.47) and shorter sleep duration HR 0.48 (95% CI 0.23-0.99) with Parkinson's disease were more pronounced, and statistically significant, compared to parkinsonism. This increased risk disappeared with longer follow-up duration. Worsening of sleep quality HR 1.76 per standard deviation increase (95% CI 1.12-2.78), as well as shortening of sleep duration HR 1.72 per standard deviation decrease (95% CI 1.08-2.72), were related to Parkinson's disease risk in the subsequent 6 years. Therefore, we argue that in the general population, deterioration of sleep quality and duration are markers of the prodromal phase of parkinsonism, including Parkinson's disease.
Parkinson’s disease (PD) research is beginning to focus on early disease modification and prevention. The therapeutic pipeline includes a growing range of pharmacological interventions that could ...theoretically intervene with the underlying disease process. It is hoped that applying such interventions in a very early stage of the disease pathology, before the onset of motor symptoms or during its early stages, may prevent or delay further disease progression. To identify people in this early disease stage, criteria for ‘prodromal PD’ have been proposed—describing people with one or more specific features that jointly constitute a variably increased risk of developing clinically manifest PD. Here, we aim to draw lessons from the field of Alzheimer’s research, which has followed a similar strategy over the last decade, including the expansion of the disease label to ‘prodromal’ stages. Importantly, none of the large and costly randomized-controlled trials aiming to slow down or prevent Alzheimer’s dementia by targeting the alleged disease pathology, i.e., amyloid-β aggregation, resulted in detectable clinical effects. Lack of sufficiently robust phase 2 trial results before moving to phase 3 studies, suboptimal participant selection, insensitive outcomes, a too narrow target focus, and trial design flaws contributed to this disappointing outcome. We discuss the various similarities between these Alzheimer’s and PD approaches, and review the design of prevention or early disease modification trials for both diseases including the potential for immunotherapy. Finally, we offer considerations to optimize the design of such trials in PD, benefiting from the lessons learned in Alzheimer’s prevention research.
Background
There is a growing recognition that sex characteristics and gender-related aspects can have a substantial impact on the health-related quality of life (HRQoL) of persons with Parkinson’s ...disease (PD). Gender is a multidimensional construct, including dynamic social norms and relations that influence health and impact quality of life. Even when gender is investigated in the field of PD, it is frequently conceptualized as gender identity while other dimensions, such as roles or relations, are generally ignored. The aim of this study was to explore the impact of several gender dimensions on HRQoL among people with PD.
Methods
We performed a survey-based, cross-sectional study in the Netherlands to explore the impact of several gender dimensions, namely; gender identity, gender roles and gender relations on HRQoL (PDQ-39) of people with PD.
Results
In our study population (
N
= 307), including 127 (41%) women, we did not observe an association between gender identity and overall HRQoL. In contrast, an androgynous gender role and higher engagement in household tasks were associated with better overall HRQoL among people with PD.
Conclusions
This study offers the first detailed description of the impact of different gender dimensions on the HRQoL of people with PD and highlights the need for more precise gender-measures to inform actionable gender-sensitive health interventions for people with PD.
Context: Choline is a precursor of both betaine and acetylcholine and might, therefore, influence cardiovascular and cognitive outcomes. There has been concern, however, that it may influence blood ...lipid levels because it is an essential component of very-low-density lipoproteins. Objective: The aim was to systematically review, using PRISMA guidelines, the literature pertaining to the effects of choline on body composition and on metabolic, cardiovascular, respiratory, and neurological outcomes in different life stages. Data Sources: The MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar databases were searched up to July 2014. Data Extraction: Fifty relevant articles were identified. These comprised trials and cohort, case-control, and cross-sectional studies that assessed blood levels of choline, dietary intake of choline, and supplementation with choline in a population free of diseases at baseline. Data Synthesis: There is some observational evidence that choline during pregnancy may be beneficial for the neurological health of the child. In adults, choline may have beneficial effects on cognition, but high-quality (intervention) studies are lacking. Results on the effects of choline on body composition, blood lipids, and cardiovascular health were inconsistent. Conclusions: Evidence to confirm the suggested effects of choline on health in different stages of life is scarce. Potential effects of choline need to be confirmed by intervention studies. Possible harmful effects on cardiometabolic health need careful evaluation.
Cerebral small vessel disease is increasingly linked to dementia.
We systematically searched Medline, Embase, and Cochrane databases for prospective population-based studies addressing associations ...of white matter hyperintensities, covert brain infarcts (i.e., clinically silent infarcts), and cerebral microbleeds with risk of all-dementia or Alzheimer's disease and performed meta-analyses.
We identified 11 studies on white matter hyperintensities, covert brain infarcts, or cerebral microbleeds with risk of all-dementia or Alzheimer's disease. Pooled analyses showed an association of white matter hyperintensity volume and a borderline association of covert brain infarcts with risk of all-dementia (hazard ratio: 1.39 95% confidence interval: 1.00; 1.94, N = 3913, and 1.47 95% confidence interval: 0.97; 2.22, N = 8296). Microbleeds were not statistically significantly associated with an increased risk of all-dementia (hazard ratio: 1.25 95% confidence interval: 0.66; 2.38, N = 8739).
White matter hyperintensities are associated with an increased risk of all-dementia and Alzheimer's disease in the general population. However, studies are warranted to further determine the role of markers of cerebral small vessel disease in dementia.
Background and purpose
This study was undertaken to compare risk factors, neuroimaging characteristics and prognosis between two clinical prodromes of dementia, namely, the motoric cognitive risk ...syndrome (MCRS) and mild cognitive impairment (MCI).
Methods
Between 2009 and 2015, dementia‐free participants of the population‐based Rotterdam Study were classified with a dementia prodrome if they had subjective cognitive complaints and scored >1 SD below the population mean of gait speed (MCRS) or >1.5 SD below the population mean of cognitive test scores (MCI). Using multinomial logistic regression models, we determined cross‐sectional associations of risk factors and structural neuroimaging markers with MCRS and MCI, followed by subdistribution hazard models, to determine risk of incident dementia until 2016.
Results
Of 3025 included participants (mean age = 70.4 years, 54.7% women), 231 had MCRS (7.6%), 132 had MCI (4.4%), and 62 (2.0%) fulfilled criteria for both. Although many risk factors were shared, a higher body mass index predisposed to MCRS, whereas male sex and hypercholesterolemia were associated with MCI only. Gray matter volumes, hippocampal volumes, white matter hyperintensities, and structural white matter integrity were worse in both MCRS and MCI. During a mean follow‐up of 3.9 years, 71 individuals developed dementia and 200 died. Five‐year cumulative risk of dementia was 7.0% (2.5%–11.5%) for individuals with MCRS, versus 13.3% (5.8%–20.8%) with MCI and only 2.3% (1.5%–3.1%) in unaffected individuals.
Conclusions
MCRS is associated with imaging markers of neurodegeneration and risk of dementia, even in the absence of MCI, highlighting the potential of motor function assessment in early risk stratification for dementia.
Individuals with motoric cognitive risk syndrome are at increased risk of dementia and mortality in the absence of mild cognitive impairment. Risk factors and neuroimaging markers were similar between the two dementia prodromes.
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