Topography of Cross-sectional and Longitudinal Glucose Metabolic Deficits in Alzheimer's Disease: Pathophysiologic Implications
Abstract
Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non-contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD.
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PET reveals abnormally low prefrontal and whole-brain glucose metabolism in more severely affected Alzheimer's disease patients.
“abnormally low prefrontal and whole-brain levels in more severely affected patients”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [10]
PET reveals characteristic abnormalities in patients with probable and definite Alzheimer's disease, including abnormally low parietal, temporal, and posterior cingulate glucose metabolism.
“When used to measure cerebral glucose metabolism, PET reveals characteristic abnormalities in patients with probable and definite Alzheimer's disease, including abnormally low parietal, temporal, and posterior cingulate levels”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [10]
PET reveals a progressive decline in glucose metabolism levels over time in Alzheimer's disease.
“and a progressive decline in these levels over time.”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [10]
The observation of metabolic reductions is consistent with reports that reductions in regional glucose metabolism increase as Alzheimer's disease progresses from a presymptomatic stage to mild symptoms and then to increasingly severe stages.
“This observation is consistent with reports that reductions in regional glucose metabolism increase as Alzheimer's disease progresses from a presymptomatic stage to one characterized by mild symptoms, and ultimately to increasingly severe stages.[9][10][11][12][13]”
From Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E (1996) · cites this paper as [10]
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- Authors
- Smith, G. S.
- Corresponding author
- Smith, Gwenn S.
- ORCID
- Smith, Gwenn S.
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 1992-11-01
- Volume
- 49
- Issue
- 11
- Pages
- 1142
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2113406852
- Cited by
- 178
- References
- 67
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 4 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 7 · 2014: 6 · 2013: 2 · 2012: 8
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (1P30-AG08051, P30AG008051)
- National Institute of Mental Health (1 ROI MH 43965-04)
- 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 › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- Alzheimer's disease, brain glucose metabolism, longitudinal metabolic changes, temporal lobe, parietal association areas, subcortical gray matter, brain atrophy, disease stage, neuropathology, neurotransmitter deficits, dementia diagnosis
- MeSH terms
- Aged, Alzheimer Disease, Analysis of Variance, Cerebral Cortex, Cross-Sectional Studies, Female, Glucose, Humans, Longitudinal Studies, Male, Middle Aged, Tomography, Emission-Computed, Tomography, X-Ray Computed
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