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Introduction: Plasma proteins affect biological processes and are common drug targets but their role in the development of Alzheimer's disease and related dementias remains unclear. We examined associations between 4953 plasma proteins and cognitive decline and risk of dementia in two cohort studies with 20‐year follow‐ups. Methods: In the Whitehall II prospective cohort study proteins were measured using SOMAscan technology. Cognitive performance was tested five times over 20 years. Linkage to electronic health records identified incident dementia. The results were replicated in the Atherosclerosis Risk in Communities (ARIC) study. Results: Fifteen non‐amyloid/non‐tau–related proteins were associated with cognitive decline and dementia, were consistently identified in both cohorts, and were not explained by known dementia risk factors. Levels of six of the proteins are modifiable by currently approved medications for other conditions. Discussion: This study identified several plasma proteins in dementia‐free people that are associated with long‐term risk of cognitive decline and dementia. [ABSTRACT FROM AUTHOR]

Introduction: Conventional risk factors targeted by prevention (e.g., low education, smoking, and obesity) are associated with a 1.2‐ to 2‐fold increased risk of dementia. It is unclear whether having a physical disease is an equally important risk factor for dementia. Methods: In this exploratory multicohort study of 283,414 community‐dwelling participants, we examined 22 common hospital‐treated physical diseases as risk factors for dementia. Results: During a median follow‐up of 19 years, a total of 3416 participants developed dementia. Those who had erysipelas (hazard ratio = 1.82; 95% confidence interval = 1.53 to 2.17), hypothyroidism (1.94; 1.59 to 2.38), myocardial infarction (1.41; 1.20 to 1.64), ischemic heart disease (1.32; 1.18 to 1.49), cerebral infarction (2.44; 2.14 to 2.77), duodenal ulcers (1.88; 1.42 to 2.49), gastritis and duodenitis (1.82; 1.46 to 2.27), or osteoporosis (2.38; 1.75 to 3.23) were at a significantly increased risk of dementia. These associations were not explained by conventional risk factors or reverse causation. Discussion: In addition to conventional risk factors, several physical diseases may increase the long‐term risk of dementia. [ABSTRACT FROM AUTHOR]