Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective: To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education...
Importance: The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide crit...
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Her...
Background: Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods: In this modelling study, we included people with mild cognitive impairment (MCI) fro...
Background Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods In this modelling study, we included people with mild cognitive impairment (MCI) from ...
Importance: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as meas...