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Background Studies investigating the association between hypercholesterolemia in the elderly and cognitive decline report discrepant outcomes. We determined in a prospective population-based cohort (NEDICES) in elders whether hypercholesterolemia was associated with slower cognitive decline. Methods Participants were evaluated at baseline and 3 years later. Baseline demographic variables were recorded. Hypercholesterolemia was defined by total cholesterol of > 200 mg/dl or current use of lipid-lowering drugs. At baseline and at follow-up, a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered. Results The final sample, 2015 participants (72.9 ± 6.1 years), comprised 1166 (57.9%) hypercholesterolemic and 849 (42.1%) non-hypercholesterolemic participants (reference category). The mean follow-up was 3.4 ± 0.5 years. During the three year follow-up period, the 37-MMSE declined by 0.7 ± 4.3 points (median = 0 point) in non-hypercholesterolemic participants vs. 0.3 ± 3.9 points in hypercholesterolemic participants (median = 0 points) (Mann–Whitney test, p = 0.007). In analyses adjusted for baseline age and other potential confounders, this difference remained robust. We also assessed the cognitive decline per unit time (i.e., the rate of cognitive decline). The rate of cognitive decline was 0.2 ± 1.3 (median = 0.0) points/year for non-hypercholesterolemic participants and 0.1 ± 1.2 (median = 0.0) points/year for hypercholesterolemic participants (Mann–Whitney test, p = 0.028). Conclusions In this prospective population-based cohort study, cognitive test scores among hypercholesterolemic elders declined more slowly than observed in their non-hypercholesterolemic counterparts. Additional studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]