Impaired glucose tolerance in midlife and longitudinal changes in brain function during aging
Open accessAbstract
We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cognitively normal participants in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging underwent serial (15)O-water positron emission tomography scans (age at first scan, 69.6 ± 7.5 years) and oral glucose tolerance tests 12 years earlier (age at first oral glucose tolerance test, 57.2 ± 11.1 years). Using voxel-based analysis, we compared changes in rCBF over an 8-year period between 15 participants with IGT in midlife and 49 with NGT. Significant differences were observed in longitudinal change in rCBF between the IGT and NGT groups. The predominant pattern was greater rCBF decline in the IGT group in the frontal, parietal, and temporal cortices. Some brain regions in the frontal and temporal cortices also showed greater longitudinal increments in rCBF in the IGT group. Our findings suggest that IGT in midlife is associated with subsequent longitudinal changes in brain function during aging even in cognitively normal older individuals.
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APOE remains the only locus repeatedly associated with AAO, but PICALM and BIN1 have also been reported to affect AAO.
“To date, APOE remains the only locus repeatedly associated with AAO8,9, but PICALM and BIN1 have also been reported to affect AAO6,10,11.”
From A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease (2017) · cites this paper as [10]
The Discussion (page unavailable) discusses APOE ε4 in relation to cerebral blood flow and Alzheimer’s disease risk, not age at onset (AAO). Searches for PICALM, BIN1, and APOE associations with age at onset found no passage in our copy addressing the attributed claim. (LLM, conf=0.76)
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- Authors
- Thambisetty, M., Beason-Held, L. L., An, Y., Kraut, M., Metter, J., Egan, J., Ferrucci, L., O'Brien, R., & Resnick, S. M.
- Affiliations
- National Institutes of Health (US)
- National Institute on Aging (US)
- Johns Hopkins University (US)
- Corresponding author
- Thambisetty, Madhav
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 34
- Issue
- 10
- Pages
- 2271-2276
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4577027
- OpenAlex
- W2125733297
- Cited by
- 54
- References
- 26
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 8 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 1
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Intramural Research Program (N01-AG-3-2124)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- impaired glucose tolerance, midlife, regional cerebral blood flow, brain aging, longitudinal brain changes, glucose tolerance, frontal cortex, parietal cortex, temporal cortex, cognitive aging, 15O-water PET, oral glucose tolerance test, Baltimore Longitudinal Study of Aging
- MeSH terms
- Aged, Aging, Cerebral Cortex, Cerebrovascular Circulation, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Longitudinal Studies, Male, Middle Aged, Time Factors, Glucose Intolerance, Positron-Emission Tomography
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