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BACKGROUND AND AIMS: Increased parathyroid activity has been associated with impaired cognitive function, although the predictive value of parathyroid hormone (PTH) for cognitive decline has not yet been fully investigated. This association was evaluated in random persons of age cohorts of 75, 80 and 85 years in a 10- year longitudinal prospective study. METHODS: Cognition of patients (n=514) was assessed with the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) at baseline and at intervals of one, five and ten years. Clinical data were collected and serum PTH, ionized calcium (Ca2+) and creatinine as well as apolipoprotein E (APOE) alleles were determined at baseline. RESULTS: Impaired cognition (MMSE<24 or CDR>/=1) was associated with older age, impaired renal function, and elevated PTH (>/=62 ng/L, IV-quartile) at baseline. Elevated PTH indicated a 2-fold risk of an at least 4-point decrease in MMSE (OR 2.20) and a 3-fold risk of an increase in CDR-class (OR 3.20) within the first year of follow- up. The risk remained significantly elevated even after controlling for age, gender, baseline cognition, serum Ca2+, creatinine, and APOE4 (OR 2.24 for MMSE; OR 2.12 for CDR). High PTH also predicted cognitive decline within a five-year follow-up (OR 3.20), but the association disappeared at ten years. CONCLUSIONS: Elevated PTH concentrations are associated with a five-year cognitive decline in a general aged population, independently of Ca2+ and renal function. The role of vitamin D deficiency, the most common cause of elevated PTH in the elderly, needs to be further investigated. [ABSTRACT FROM AUTHOR]