Hypometabolism in Alzheimer-Affected Brain Regions in Cognitively Healthy Latino Individuals Carrying the Apolipoprotein E ε4 Allele
Open accessAbstract
OBJECTIVE: To investigate with fluorodeoxyglucose positron emission tomography whether regional reductions in the cerebral metabolic rate for glucose (CMRgl) previously found in cognitively healthy late-middle-aged apolipoprotein E (APOE) epsilon4 carriers extend to members of the Latino Mexican American community. DESIGN: Prospective cohort study. SETTING: Banner Alzheimer's Institute, Phoenix, Arizona. PATIENTS OR OTHER PARTICIPANTS: Eleven APOE epsilon4 carriers and 16 noncarriers from Arizona's Latino community (mean [SD] age, 54.6 [6.4] years) matched for sex, mean age, and educational level and who were predominantly of self-designated Mexican origin. MAIN OUTCOME MEASURE: A brain mapping algorithm was used to compare cross-sectional regional CMRgl in Latino APOE epsilon4 carriers vs noncarriers. RESULTS: Participant groups had similar distributions for age, sex, education, family history of dementia, clinical ratings, and neuropsychological test scores. Latino APOE epsilon4 carriers had lower CMRgl than the noncarriers in the posterior cingulate, precuneus, and parietal regions previously found to be preferentially affected in patients with Alzheimer disease (AD) and cognitively healthy non-Latino APOE epsilon4 carriers. Additionally, the Latino APOE epsilon4 carriers had lower CMRgl in the middle and anterior cingulate cortex, hippocampus, and thalamus. CONCLUSIONS: This study provides support for the relationship between APOE epsilon4 and risk of AD in Latino individuals. It illustrates the role of positron emission tomography as a presymptomatic endophenotype for the assessment of AD risk factors and supports the inclusion of Latino APOE epsilon4 carriers in proof-of-concept studies using fluorodeoxyglucose PET to evaluate promising presymptomatic treatments in cognitively healthy carriers of this common AD susceptibility gene.
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Thalamic atrophy in MCI and hypometabolism in APOE4 carriers have been observed.
“The role of thalamic structure and function in AD appears complex and perhaps nonlinear, as thalamic atrophy in MCI [48] and hypometabolism in APOE4 carriers [49] have been observed, whereas others have reported increased thalamic volume [50] and hypermetabolism with amyloid pathology [51] among APOE4 carriers.”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [49]
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“…thalamic structure and function in AD appears complex and perhaps nonlinear, as thalamic atrophy in MCI [48] and hypometabolism in APOE4 carriers [49] have been observed, whereas others have reported increased thalamic volume [50] and hypermetabolism with amyloid pathology [51] among APOE4…”
BackgroundAPOE-ε4-related differences in left thalamic microstructure in cognitively healthy adults
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- Authors
- Langbaum, J. B. S., Chen, K., Caselli, R. J., Lee, W., Reschke, C., Bandy, D., Alexander, G. E., Burns, C. M., Kaszniak, A. W., Reeder, S. A., Corneveaux, J. J., Allen, A. N., Pruzin, J., Huentelman, M. J., Fleisher, A. S., & Reiman, E. M.
- Affiliations
- Banner Sun Health Research Institute (US)
- Banner Alzheimer’s Institute (US)
- Mayo Clinic in Arizona (US)
- University of Arizona (US)
- Translational Genomics Research Institute (US)
- University of California San Diego (US)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2010-04-01
- Volume
- 67
- Issue
- 4
- Pages
- 462-8
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC2943432
- OpenAlex
- W2094768089
- Cited by
- 100
- References
- 59
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 4 · 2017: 6 · 2016: 11 · 2015: 7 · 2014: 10 · 2013: 4 · 2012: 8
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- McKnight Foundation
- National Institute on Aging (P30-AG-19610, R01AG031581, P30AG019610)
- National Institute of Mental Health (R01-MH57899, R01MH057899)
- National Institute of Neurological Disorders and Stroke (R01NS059873)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- APOE ε4, Alzheimer's disease risk, hypometabolism, brain glucose metabolism, posterior cingulate cortex, precuneus, hippocampus, thalamus, cingulate cortex, FDG-PET
- MeSH terms
- Aged, Alzheimer Disease, Brain, Brain Diseases, Metabolic, Brain Mapping, Cross-Sectional Studies, DNA Mutational Analysis, Female, Gene Frequency, Genetic Markers, Genetic Testing, Genotype, Heterozygote, Genetic Carrier Screening, Hispanic or Latino, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Cohort Studies, Fluorodeoxyglucose F18, Genetic Predisposition to Disease, Positron-Emission Tomography, Apolipoprotein E4
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