Longitudinal Progression of Cognitive Decline Correlates with Changes in the Spatial Pattern of Brain 18 F-FDG PET
Open accessAbstract
UNLABELLED: Evaluating the symptomatic progression of mild cognitive impairment (MCI) caused by Alzheimer disease (AD) is practically accomplished by tracking performance on cognitive tasks, such as the Alzheimer Disease Assessment Scale's cognitive subscale (ADAS_cog), the Mini-Mental Status Examination (MMSE), and the Functional Activities Questionnaire (FAQ). The longitudinal relationships between cognitive decline and metabolic function as assessed using (18)F-FDG PET are needed to address both the cognitive and the biologic progression of disease state in individual subjects. We conducted an exploratory investigation to evaluate longitudinal changes in brain glucose metabolism of individual subjects and their relationship to the subject's changes of cognitive status. METHODS: We describe a method to determine correlations in (18)F-FDG spatial distribution over time. This parameter is termed the regional (18)F-FDG time correlation coefficient (rFTC). By using linear mixed-effects models, we determined the difference in the rFTC decline rate between controls and subjects at high risk of developing AD, such as individuals with MCI or the presence of apolipoprotein E (APOE)-ε4 allele. The association between each subject's rFTC and performance on cognitive tests (ADAS_cog, MMSE, and FAQ) was determined with 2 different correlation methods. All subject data were downloaded from the Alzheimer Disease Neuroimaging Initiative. RESULTS: The rFTC values of controls remained fairly constant over time (-0.003 annual change; 95% confidence interval, -0.010-0.004). In MCI patients, the rFTC declined faster than in controls by an additional annual change of -0.02 (95% confidence interval, -0.030 to -0.010). In MCI patients, the decline in rFTC was associated with cognitive decline (ADAS_cog, P = 0.011; FAQ, P = 0.0016; MMSE, P = 0.004). After a linear effect of time was accounted for, visit-to-visit changes in rFTC correlated with visit-to-visit changes in all 3 cognitive tests. CONCLUSION: Longitudinal changes in rFTC detect subtle metabolic changes in individuals associated with variations in their cognition. This analytic tool may be useful for a patient-based monitoring of cognitive decline.
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Reduction in glucose metabolism in the brain is common in Alzheimer's patients.
“it is well documented that a reduction in glucose metabolism in the brain is common in Alzheimer’s patients.36, 37, 38”
From Bacopa monnieri (L.) wettst. Extract protects against glutamate toxicity and increases the longevity of Caenorhabditis elegans (2020) · cites this paper as [36]
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- Authors
- Shokouhi, S., Claassen, D., Kang, H., Ding, Z., Rogers, B., Mishra, A., Riddle, W. R., & Initiative, F. T. A. D. N.
- Affiliations
- Vanderbilt University (US)
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2013-07-17
- Volume
- 54
- Issue
- 9
- Pages
- 1564-1569
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC4134885
- OpenAlex
- W2138923981
- Cited by
- 54
- References
- 32
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 7 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 2 · 2013: 2
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Alzheimer's Association
- Vanderbilt University
- National Institutes of Health (5u01ag024904-10)
- Canadian Institutes of Health Research
- National Institute on Aging (U01-AG-024904, P30AG010129, K01AG030514)
- National Cancer Institute (R01CA109106, K25CA168936)
- National Institute of Neurological Disorders and Stroke (K23NS080988)
- National Institute of Biomedical Imaging and Bioengineering (K99EB009106, R01EB000461, R00EB009106)
- 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
- mild cognitive impairment, Alzheimer's disease, cognitive decline, 18F-FDG PET, brain glucose metabolism, longitudinal metabolic changes, APOE ε4, functional activity, ADAS-Cog, patient monitoring
- MeSH terms
- Aged, Aged, 80 and over, Aging, Brain, Female, Humans, Longitudinal Studies, Male, Middle Aged, Sensitivity and Specificity, Reproducibility of Results, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography, Cognitive Dysfunction, Spatio-Temporal Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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