Longitudinal PET evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer’s disease treatment studies
Abstract
OBJECTIVE: It is well established that regional cerebral metabolic rates for glucose assessed by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with Alzheimer's disease in the mental resting state (eyes and ears covered) provide a sensitive, in vivo metabolic index of Alzheimer's disease dementia. Few studies, however, have evaluated longitudinal declines in regional cerebral glucose metabolism in patients with dementia caused by Alzheimer's disease. In addition, the available studies have not used recently developed brain mapping algorithms to characterize the progression of Alzheimer's disease throughout the brain, and none considered the statistical power of regional cerebral glucose metabolism in testing the ability of treatments to attenuate the progression of dementia. METHOD: The authors used FDG PET and a brain mapping algorithm to investigate cross-sectional reductions in regional cerebral glucose metabolism, longitudinal decline in regional cerebral glucose metabolism after a 1-year follow-up, and the power of this method to evaluate treatments for Alzheimer's disease in patients with mild to moderate dementia. PET scans were initially acquired in 14 patients with Alzheimer's disease and 34 healthy comparison subjects of similar age and sex. Repeat scans were obtained in the patients 1 year later. Power analyses for voxels showing maximal decline over the 1-year period in regional cerebral glucose metabolism (mg/100 g per minute) were computed to estimate the sample sizes needed to detect a significant treatment response in a 1-year, double-blind, placebo-controlled treatment study. RESULTS: The patients with Alzheimer's disease had significantly lower glucose metabolism than healthy comparison subjects in parietal, temporal, occipital, frontal, and posterior cingulate cortices. One year later, the patients with Alzheimer's disease had significant declines in glucose metabolism in parietal, temporal, frontal, and posterior cingulate cortices. Using maximal glucose metabolism reductions in the left frontal cortex, we estimated that as few as 36 patients per group would be needed to detect a 33% treatment response with one-tailed significance of p</=0.005 and 80% power in a 1-year, double-blind, placebo-controlled treatment study. CONCLUSIONS: These findings indicate that brain metabolism as assessed by FDG PET during mental rest is a sensitive marker of disease progression in Alzheimer's disease over a 1-year period. These findings also support the feasibility of using FDG PET as an outcome measure to test the ability of treatments to attenuate the progression of Alzheimer's disease.
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PET studies have shown that AD brains exhibit decreased glucose metabolism in distinct regions.
“Positron emission tomography (PET) studies have shown that AD brains exhibit decreased glucose metabolism in distinct regions (Alexander et al., 2002; Minoshima et al., 1995).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Alexander et al., 2002
B-M3, enriched with mitochondrial proteins, was decreased across AD cases.
“Module B-M3, enriched with mitochondrial proteins, was also decreased across AD cases, consistent with a loss of mitochondrial function and hypometabolic phenotype observed in patients with AD (Alexander et al., 2002).”
From A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer’s Disease (2017) · cites this paper as Alexander et al., 2002
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- Authors
- Alexander, G. E., Chen, K., Pietrini, P., Rapoport, S. I., & Reiman, E. M.
- Affiliations
- Arizona State University (US)
- Venue
- American Journal of Psychiatry
- Published
- 2002-05-01
- Volume
- 159
- Issue
- 5
- Pages
- 738-745
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2152060070
- Cited by
- 532
- References
- 32
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 15 · 2023: 9 · 2022: 14 · 2021: 18 · 2020: 14 · 2019: 14 · 2018: 13 · 2017: 17 · 2016: 20 · 2015: 16 · 2014: 24 · 2013: 21 · 2012: 32
- FWCI
- 9.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- 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, dementia, regional cerebral glucose metabolism, FDG-PET, statistical power analysis, treatment outcome measures, disease progression, frontal cortex, posterior cingulate cortex, sample size determination
- MeSH terms
- Aged, Alzheimer Disease, Brain, Cerebral Cortex, Clinical Trials as Topic, Female, Follow-Up Studies, Glucose, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Placebos, Psychiatric Status Rating Scales, Research Design, Severity of Illness Index, Tomography, Emission-Computed, Treatment Outcome, Outcome Assessment, Health Care, Disease Progression, Fluorodeoxyglucose F18
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