Cholesterol, Statins and the Risk of Dementia in the Oldest-Old: The 90+ Study (S58.003)

Abstract

OBJECTIVE: To determine if hypercholesterolemia or statin use are related to dementia risk in the oldest-old, people aged 90 years and over. BACKGROUND: Midlife hypercholesterolemia has been associated with increased dementia risk. Some studies, however, suggest that the association changes with age and high cholesterol may be associated with decreased dementia risk at very advanced ages. Cholesterol-lowering medications (statins) have also been associated with decreased dementia risk, although some studies report no association. It is unknown how cholesterol and statins affect dementia in the oldest-old. DESIGN/METHODS: We assessed 563 non-demented participants of The 90+ Study, a longitudinal population-based study of people aged 90 and older. Dementia (DSM-IV criteria) was assessed biannually. Participants were classified into three mutually exclusive groups based on statin use and hypercholesterolemia: no hypercholesterolemia+no statins (59%), hypercholesterolemia+no statins (17%), hypercholesterolemia+statins (24%). We estimated the hazard ratio (HR) of incident dementia using Cox regression with age as the time scale adjusting for gender and education. RESULTS: Participants at baseline were on average 93 years (range=90-103), Caucasian (99%), women (69%), and college educated (77%). After an average follow-up of 2.6 years (range=0.06-9.0), 222 individuals (39%) developed dementia. Compared to the no hypercholesterolemia+no statin group, people in the hypercholesterolemia+statin group were less likely to develop dementia (HR=0.58, 95%CI=0.39-0.85, p=0.005), whereas individuals in the hypercholesterolemia+no statin group were not different in their risk of dementia (HR=0.88, 95%CI=0.61-1.28, p=0.51). CONCLUSIONS: Contrary to studies reporting that high cholesterol is associated with decreased dementia in the oldest-old, we report that hypercholesterolemia was not associated with dementia while statin users were at decreased dementia risk. There are a variety of mechanisms by which statins may be neuroprotective including effects on amyloid production, neurofibrillary tangles, secondary stroke prevention, and other anti-inflammatory pleiotropic effects. Additional research is needed to explore other potential explanations for our results along with assessment of the effect of serum cholesterol levels and statin lipophilicity. Study Supported by: NIA grants R01AG042444, R01AG21055

Disclosure: Dr. Evans has nothing to disclose. Dr. Kawas has received personal compensation for activities with Biogen Idec. Dr. Kawas has received personal compensation in an editorial capacity for Continuum. Dr. Corrada has nothing to disclose.