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Cited by 222Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

Brain imaging evidence of preclinical Alzheimer's disease in normal aging

Open access
Jagust, William, Gitcho, Amy, Sun, Felice, Kuczynski, Beth, Mungas, Dan, Haan, Mary·2006·Annals of Neurology
DOI 10.1002/ana.20799
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Abstract

Objective: This study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people. Methods: We performed positron emission tomography using [18 F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community‐dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.8 years, with approximately annual evaluation of global cognition (the Modified Mini‐Mental State Examination) and episodic memory (delayed recall). Baseline brain volumes and glucose metabolism were evaluated in relation to the rate of change in cognitive test scores. Results: Six subjects developed incident dementia or cognitive impairment (converters). Baseline positron emission tomography scans showed regions in left and right angular gyrus, left mid‐temporal gyrus, and left middle frontal gyrus that predicted the rate of change on the Modified Mini‐Mental State Examination (p < 0.001). The left hemisphere temporal and parietal regions remained significant when converters were excluded. Both hippocampal (p = 0.03) and entorhinal cortical volumes (p = 0.01) predicted decline on delayed recall over time, and entorhinal cortical volumes remained significant when converters were excluded (p = 0.02). These brain volumes did not predict Modified Mini‐Mental State Examination decline. Interpretation: These results indicate that temporal and parietal glucose metabolism predict decline in global cognitive function, and medial temporal brain volumes predict memory decline in normal older people. The anatomical location of these findings suggests detection of preclinical Alzheimer's disease pathology. Ann Neurol 2006

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  • Patients with mild cognitive impairment and Alzheimer's disease exhibit deficits in brain energy metabolism years before symptom onset.

    “Numerous studies show that patients with mild cognitive impairment (MCI) and AD exhibit deficits in brain energy metabolism years before disease symptom onset [8][9][10][11] .”

    From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [8]

    The Results and Discussion (page unavailable) link lower baseline glucose metabolism in cognitively normal older adults to later cognitive decline over approximately four years, suggesting presymptomatic AD. The paper also reports lower metabolism in people with MCI who later develop dementia, but explicitly says MCI patients are not presymptomatic; it does not establish that patients with MCI and AD had metabolic deficits years before symptom onset. (LLM, conf=0.87)

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Cited by

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Authors
Jagust, W., Gitcho, A., Sun, F., Kuczynski, B., Mungas, D., & Haan, M.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • University of California, Berkeley (US)
  • University of California, Davis (US)
  • University of Michigan (US)
Corresponding author
Jagust, William
ORCID
Venue
Annals of Neurology
Publisher
Wiley
Published
2006-02-08
Volume
59
Issue
4
Pages
673-681
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.20799
OpenAlex
W2032157350
Cited by
222
References
7
Citations by year
2026: 6 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 4 · 2021: 12 · 2020: 5 · 2019: 6 · 2018: 9 · 2017: 11 · 2016: 9 · 2015: 14 · 2014: 15 · 2013: 13 · 2012: 12
FWCI
9.55
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Deep Blue (University of Michigan) (submittedVersion)
Funders
  • National Institute on Aging (AG 10220, AG-12975, R01AG012975, R01AG010220, R03AG033751)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-60753, R01DK060753)
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
preclinical Alzheimer's disease, normal aging, cognitive decline, glucose metabolism, medial temporal lobe, hippocampus, entorhinal cortex, brain volume, episodic memory, angular gyrus, 18F-FDG PET, structural MRI
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Brain Mapping, Female, Glucose, Hispanic or Latino, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Mental Recall, Case-Control Studies, Fluorodeoxyglucose F18, Positron-Emission Tomography

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