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From the Department of Neuroscience and Neurology, University of Kuopio, Finland (A.S., T.N., H.S., M.K.); Department of Clinical Geriatrics (A.S., B.W., M.K.) and Aging Research Center (I.K., T.N., B.W., M.K.), Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland (I.K., A.N., J.T.); Department of Social Work, Stockholm University, Sweden (I.K.); Department of Public Health, University of Helsinki, Finland (J.T.); and South Ostrobothnia Central Hospital, Seinäjoki, Finland (J.T.).
Address correspondence and reprint requests to Dr. Miia Kivipelto, Aging Research Center, Karolinska Institutet, Gävlegatan 16, 11330 Stockholm, Sweden; e-mail: Miia.Kivipelto{at}ki.se
Background: Longitudinal studies have shown that high serum total cholesterol (TC) at midlife is a risk factor for dementia/Alzheimer disease. The significance of TC later in life is unclear.
Objective: To investigate changes in serum TC from midlife to late life and their relationship with late-life cognition.
Methods: Participants of the Cardiovascular Risk Factors, Aging and Dementia study were derived from random, population-based samples previously studied in a survey in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1,449 individuals aged 65 to 79 were reexamined in 1998.
Results: Serum TC levels decreased in most individuals. High midlife TC represented a risk factor for more severe cognitive impairment later in life, and the values were significantly different between the control, mild cognitive impairment, and dementia groups. There were no significant differences in serum TC at reexamination. A moderate decrease in serum TC from midlife to late life (0.5 to 2 mmol/L) was significantly associated with the risk of a more impaired late-life cognitive status, even after adjusting for age, follow-up time, sex, years of formal education, midlife cholesterol, changes in body mass index, APOE 
4 genotype, history of myocardial infarction/stroke/diabetes, and lipid-lowering treatment.
Conclusions: The relationship between serum total cholesterol (TC) and dementia seems to be bidirectional. High midlife serum TC is a risk factor for subsequent dementia/Alzheimer disease, but decreasing serum TC after midlife may reflect ongoing disease processes and may represent a risk marker for late-life cognitive impairment.
The study is supported by Alzheimer Association, USA, Grant IIRG-04-1345, Marie-Curie EST Program, MEST-CT-2005-019217, EVO-grant 5772720 from Kuopio University Hospital, the Gamla Tjänarinnor Foundation and the Swedish Council for Working Like and Social Research (2004-1200).
Disclosure: The authors report no conflicts of interest.
Contributors: M.K. has been the principal investigator in diagnosing dementia. A.S. analyzed the data and drafted the paper. M.K., I.K., and T.N. assisted in analyses and writing. M.K., A.N., J.T., and H.S. contributed to the conception and design of the study; J.T. and A.N. were involved in the baseline surveys for the study. A.S., T.N., I.K., B.W., H.S., J.T., A.N., and M.K. took part in planning the study and interpreting the data and commented on the manuscript. M.K. is the guarantor.
Received July 4, 2006. Accepted in final form November 9, 2006.
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