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Background. The search for preventable and remediable risk conditions of cognitive decline is ongoing, but results have thus far been inconsistent. According to the hypothesis of our 10-year prospective study, the predictive values of different risk indicators change over time in a general 75+ population. Methods. A population-based sample of 75-, 80-, and 85-year-old individuals (n = 650) underwent comprehensive clinical examinations in 1990 in Helsinki, Finland. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and/or Clinical Dementia Rating (CDR) at baseline and after 1, 5, and 10 years. Results. At baseline, a low MMSE score was associated with age, history of stroke, apolipoprotein E allele [epsilon]4 (APOE4), and intermittent claudication. After 1 year, cognitive decline was typical of participants suffering from vascular diseases, e.g., heart failure and intermittent claudication. Five-year decline was predicted by the presence of atrial fibrillation (RR [relative risk] 2.8), APOE4 (RR 2.4), elevated C-reactive protein (CRP) (RR 2.3). diabetes mellitus (RR 2.2), and heart failure (RR 1.8). They also tended to increase 5-year all-cause mortality. At 10 years, the decline associated with APOE4 (RR 3.3), slightly elevated serum ionized calcium (RR 3.3), and feelings of loneliness (RR 3.0). Conclusions. Long follow-up of a general aged population explains several inconsistencies of earlier reports. In 75+ individuals, general ill health is a strong associate of cognitive deficits. The strongest predictors of both cognitive decline and mortality are age, APOE4, manifest vascular diseases, and diabetes. The role of new potential predictors, feelings of loneliness and hypercalcemia, needs clinical testing.