Affiliations: [a] Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA, USA | [b] Department of Neurology, School of Medicine, University of Pittsburgh, PA, USA | [c] Departments of Psychiatry and Psychology, School of Medicine, University of Pittsburgh, PA, USA
Correspondence:
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Correspondence to: Timothy M. Hughes, PhD, MPH, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 N. Bellefield Street, Room 463, Pittsburgh, PA 15213, USA. Tel.: +1 412 383 1066; Fax: +1 412 383 1308; E-mail: tmh57@pitt.edu.
Abstract: Cholesterol metabolism is believed to play a role in the development of Alzheimer's disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with AD. We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age: 80 ± 4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual cognitive assessment for incident AD and mild cognitive impairment made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities, and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process.
Keywords: 24S-hydroxycholesterol, cerebrovascular disease, dementia and Alzheimer's disease, oxysterols
