Cited by 151Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

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Alzheimer's Disease Neurodegenerative Biomarkers Are Associated with Decreased Cognitive Function but Not β-Amyloid in Cognitively Normal Older Individuals

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Wirth, Miranka, Madison, Cindee M., Rabinovici, Gil D., Oh, Hwamee, Landau, Susan M., Jagust, William J.·2013·The Journal of Neuroscience

DOI 10.1523/jneurosci.4409-12.2013PMC PMC3687777

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Abstract

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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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)
ORCID: Wirth, Miranka
Rabinovici, Gil D.
Oh, Hwamee
Jagust, William J.
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
DOI: 10.1523/jneurosci.4409-12.2013
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: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
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

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Alzheimer's Disease Neurodegenerative Biomarkers Are Associated with Decreased Cognitive Function but Not β-Amyloid in Cognitively Normal Older Individuals

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