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BACKGROUND: US studies suggest that leptin, a fat-derived hormone, may be protective against the development of dementia. OBJECTIVE: To investigate the complex relationship between leptin levels and cognitive decline in elderly Italians. METHODS: We studied circulating fasting leptin levels in 809 elderly adults free from dementia who participated in the prospective Italian population-based InCHIANTI study between 1998 and 2009 (mean follow-up of 8.0 years). Global cognitive decline was defined as a reduction of ≥5 points on the Mini-Mental State Examination (MMSE). Trail-Making Tests A and B were also incorporated, with cognitive decline defined as discontinued testing or the worst 10% of change from baseline. We also investigated whether any association could be explained by midlife weight and whether cognitive decline was associated with changing leptin levels. RESULTS: The multivariate adjusted relative risk ([RR]; 95% confidence interval [CI]) of cognitive decline on the MMSE was 0.84 (95% CI 0.73-0.97) in relation to baseline sex-standardized log-leptin levels. High leptin levels showed a non-significant trend toward a reduced risk of decline on the Trail-Making Tests A (RR = 0.85, 95% CI 0.71-1.02) and B (RR = 0.90, 0.79-1.02). Adjusting for midlife weight or change in weight did not alter the pattern of results, and cognitive decline was not associated with changing leptin levels. CONCLUSIONS: High leptin levels were independently associated with a reduced risk of cognitive decline in elderly Italians.

Original publication




Journal article


J Alzheimers Dis

Publication Date





1231 - 1239


Adipokines, cognitive decline, cohort analysis, epidemiology, leptin, Aged, Aged, 80 and over, Aging, Cognition Disorders, Female, Humans, Italy, Leptin, Longitudinal Studies, Male, Mental Status Schedule, Neuropsychological Tests, Sex Factors, Statistics as Topic