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PMID: 19631758 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Higher serum total cholesterol levels in late middle age are associated with glucose hypometabolism in brain regions affected by Alzheimer's disease and normal aging.

NeuroImage ·Vol. 49 ·No. 1 ·2010-01-01 ·Pages 169-76

Reiman EM, Chen K, Langbaum JB, Lee W, Reschke C, Bandy D, Alexander GE, Caselli RJ

Abstract

Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer's disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late middle-aged people, we demonstrated an association between apolipoprotein E (APOE) epsilon4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a pre-symptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE epsilon4 homozygotes, heterozygotes and non-carriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE epsilon4 carriers than non-carriers in some of the AD-affected brain regions. We postulate that higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD.

MeSH Terms
Aged Aging/metabolism Alzheimer Disease/diagnostic imaging,genetics,metabolism Anticholesteremic Agents/therapeutic use Apolipoprotein E4/genetics Brain Chemistry/physiology Brain Mapping Cholesterol/blood Female Glucose/metabolism Heterozygote Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use Hypercholesterolemia/blood Lipid Metabolism/genetics,physiology Magnetic Resonance Imaging Male Middle Aged Neuropsychological Tests Positron-Emission Tomography Risk
Chemicals
Anticholesteremic Agents Apolipoprotein E4 Hydroxymethylglutaryl-CoA Reductase Inhibitors Cholesterol Glucose
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Reiman Eric M
Banner Alzheimer's Institute and Banner Good Samaritan PET Center, 901 East Willetta Street, Phoenix, AZ 85006, USA. eric.reiman@bannerhealth.com
Chen Kewei
Langbaum Jessica B S
Lee Wendy
Reschke Cole
Bandy Daniel
Alexander Gene E
Caselli Richard J
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Article Info
Journal
NeuroImage
Abbr.
Neuroimage
ISSN
1095-9572
DOI
10.1016/j.neuroimage.2009.07.025
Email
eric.reiman@bannerhealth.com
Published
2010-01-01
Epub
2009-00-23
Pages
169-76
Language
English
Region
United States
NLM ID
9215515
PMCID
PMC2888804
Subset
IM
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NIA NIH HHS · R01 AG031581-11 · United States
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PubMed source DOI: 10.1016/j.neuroimage.2009.07.025 PMC Full Text View journal details
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