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Brain Imaging Links Cholesterol Levels in Midlife to Alzheimer’s Disease Risk
SAN DIEGO—Brain imaging studies suggest that cholesterol may contribute to both the genetic and nongenetic risk for Alzheimer’s disease, according to Eric Reiman, MD, and colleagues. Dr. Reiman presented his team’s findings at the 37th Annual Meeting of the Society for Neuroscience.
Dr. Reiman’s group originally found strong correlations between the number of e4 alleles in a person’s APOE genotype and lower rates of glucose metabolism in Alzheimer’s disease–affected brain regions. They subsequently found correlations between a risk score generated using information from several cholesterol-related genes and lower glucose metabolism in some of the same Alzheimer’s disease regions. In their latest study, the research group hypothesized a correlation between higher serum total cholesterol levels in late middle-aged people with normal cognition and lower glucose metabolism in the same regions. A brain mapping algorithm (SPM99) was used to quantify the association between higher cholesterol levels and lower cerebral glucose metabolism, according to Dr. Reiman, Executive Director of the Banner Alz-heimer’s Institute in Phoenix and Director of the Arizona Alzheimer’s Consortium.
The study included 117 people in their 50s and 60s with normal cognition. Participants were classified into three levels of genetic risk for Alzheimer’s disease: 24 APOE e4 homozygotes, 37 APOE e4 heterozygotes, and 56 APOE e4 noncarriers. The homozygote group had modestly elevated total cholesterol levels (210 mg/dL), compared with the other groups, which had mean total serum cholesterol levels of 194 mg/dL. The homozygote group also had modestly higher LDL cholesterol levels (130 vs 115 mg/dL).
The investigators found that higher cholesterol levels were significantly correlated with lower cerebral metabolic rate for glucose in the precuneus, parietotemporal, and prefrontal regions that have shown predisposition to Alzheimer’s disease, and in extensive frontal regions known to be affected by normal aging. Although significant associations were evident in the three groups, the correlations were stronger in the Alzheimer’s disease–related temporal regions of the homozygote and heterozygote group members, compared with the noncarriers.
Dr. Reiman commented that “higher midlife cholesterol levels are associated with hypometabolism in brain regions affected by Alzheimer’s disease and normal aging,” and he postulated that “higher cholesterol levels might accelerate certain aging processes, conspiring with other Alz-heimer’s risk factors in the predisposition to Alzheimer’s disease.” Based on these and other findings, Dr. Reiman suggested that initiating statin therapy before age 70 could potentially reduce the risk for Alzheimer’s disease. The next step would be to use PET in a randomized clinical trial to evaluate the effects of midlife statin treatment in the primary prevention of Alzheimer’s disease, investigating the treatment’s ability to slow down the brain changes associated with Alzheimer’s disease without having to wait many years to determine whether study participants develop Alzheimer’s disease symptoms.
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—Kathlyn Stone
Suggested Reading
Reiman EM. Genetics, cholesterol, and the risk of Alzheimer’s disease. J Clin Psychiatry. 2005;66(7):938-939.
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