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Alzheimer's Disease Neurodegenerative Biomarkers Are Associated with Decreased Cognitive Function but Not β-Amyloid in Cognitively Normal Older Individuals
Open accessAbstract
β-Amyloid (Aβ) plaque deposition and neurodegeneration within temporoparietal and hippocampal regions may indicate increased risk of Alzheimer's disease (AD). This study examined relationships between AD biomarkers of Aβ and neurodegeneration as well as cognitive performance in cognitively normal older individuals. Aβ burden was quantified in 72 normal older human subjects from the Berkeley Aging Cohort (BAC) using [11 C] Pittsburgh compound B (PIB) positron emission tomography. In the same individuals, we measured hippocampal volume, as well as glucose metabolism and cortical thickness, which were extracted from a template of cortical AD-affected regions. The three functional and structural biomarkers were merged into a highly AD-sensitive multimodality biomarker reflecting neural integrity. In the normal older individuals, there was no association between elevated PIB uptake and either the single-modality or the multimodality neurodegenerative biomarkers. Lower neural integrity within the AD-affected regions and a control area (the visual cortex) was related to lower scores on memory and executive function tests; the same association was not found with PIB retention. The relationship between cognition and the multimodality AD biomarker was stronger in individuals with the highest PIB uptake. The findings indicate that neurodegeneration occurs within AD regions regardless of Aβ deposition and accounts for worse cognition in cognitively normal older people. The impact of neural integrity on cognitive functions is, however, enhanced in the presence of high Aβ burden for brain regions that are most affected in AD.
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“By contrast, additional research has highlighted the fact that measures of neurodegeneration or neuronal injury that are commonly used in AD research—magnetic resonance imaging (MRI), fluoro-deoxyglucose (FDG) PET, and CSF total tau (T-tau)—are not specific for AD but rather are nonspecific indicators of damage that may derive from a variety of etiologies, for example, cerebrovascular injury [29].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [29]
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“Our hypothesis, therefore, can accommodate a growing realization that for many subjects with suspected AD, or who have an increased risk of developing AD, what are currently considered downstream biomarker changes potentially precede upstream biomarker changes [206-213].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [211]
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Metadata
- Authors
- Wirth, M., Madison, C. M., Rabinovici, G. D., Oh, H., Landau, S. M., & Jagust, W. J.
- Affiliations
- University of California, Berkeley (US)
- Lawrence Berkeley National Laboratory (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-03-27
- Volume
- 33
- Issue
- 13
- Pages
- 5553-5563
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3687777
- OpenAlex
- W2039421157
- Cited by
- 151
- References
- 75
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 1 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 15 · 2018: 8 · 2017: 12 · 2016: 19 · 2015: 17 · 2014: 20 · 2013: 15
- FWCI
- 16.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- National Science Foundation (U01 AG024904)
- Foundation for the National Institutes of Health (U01AG024904, Grant U01 AG024904, AG024904)
- Alzheimer's Association (K23-AG031861, P50 AG023501, AG010129, NIRG-07-59422, U01 AG024904, P01-AG1972403)
- Bristol-Myers Squibb (U01 AG024904, AG024904)
- AstraZeneca
- Biogen (U01 AG024904, AG024904)
- Alzheimer's Disease Neuroimaging Initiative (U01AG024904, AG024904)
- Amorfix Life Sciences
- BioClinica (U01 AG024904, AG024904)
- Northern California Institute for Research and Education (U01 AG024904)
- John Douglas French Alzheimer's Foundation
- Bayer HealthCare
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (131515)
- Eisai (U01 AG024904, AG024904)
- National Institutes of Health (3u01ag024904-10s2, AG023501, U01-AG024904, Grant U01 AG024904, AG010129, AG024904, AG034570)
- University of California, Los Angeles
- University of California, San Diego
- University of California, San Francisco
- Canadian Institutes of Health Research (U01 AG024904)
- National Institute on Aging (U01-AG-024904, P30AG010129, AG1972403, P01 AG1972403, AG 024904, K01AG030514, AG010129, AG034570, AG023501, K23AG031861, R01AG034570, P50AG023501)
- National Institute of Biomedical Imaging and Bioengineering (U01 AG024904, AG024904)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, neurodegeneration, amyloid-beta, Pittsburgh compound B, cognitively normal older adults, hippocampal volume, cortical glucose metabolism, cortical thickness, neural integrity, memory, executive function, amyloid plaques
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Amyloid, Analysis of Variance, Aniline Compounds, Brain Mapping, Cognition Disorders, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Radioisotopes, Thiazoles, Reproducibility of Results, Biomarkers, Linear Models, Fluorodeoxyglucose F18, Positron-Emission Tomography
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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