Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [ 11 C]PiB
Open accessAbstract
OBJECTIVE: To investigate whether longitudinal declines in cognition are associated with higher fibrillar amyloid-beta (Abeta) deposition in vivo in individuals without dementia. METHOD: [(11)C]PiB images were obtained to measure fibrillar Abeta burden in 57 participants without dementia from the Baltimore Longitudinal Study of Aging. Participants (33 men, 24 women) had a mean (SD) age of 78.7 (6.2) years. Six participants (4 men, 2 women) had mild cognitive impairment defined as Clinical Dementia Rating = 0.5. To measure [(11)C]PiB retention, distribution volume ratios (DVR) for 15 regions of interest were estimated by fitting a simplified reference tissue model to the measured time activity curves. Mixed effects regression was used to predict cognitive trajectories over time using data before and including time of PiB (mean follow-up 10.8 years), with mean cortical DVR, age at baseline, sex, and education as independent predictors. Voxel-based analysis identified local associations. RESULTS: [(11)C]PiB retention was higher in older individuals. Greater declines over time in mental status and verbal learning and memory, but not visual memory, were associated significantly with higher PiB retention. Voxel-based analysis showed significant associations in frontal and lateral temporal regions. CONCLUSIONS: Higher Abeta deposition is associated with greater longitudinal decline in mental status and verbal memory in the preceding years. The differential association for verbal but not visual memory may reflect the greater reliance of verbal word list learning on prefrontal regions, which show early Abeta deposition. Prospective imaging may help distinguish between individuals with evolving neuropathology who develop accelerated cognitive decline vs those with normal aging.
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Since the publication of the 2011 NIA-AA guidelines, data have accumulated indicating that cognitive decline in Alzheimer's disease occurs continuously over a long period.
“Since the publication of the 2011 guidelines, data have continued to accumulate indicating that the cognitive decline in AD occurs continuously over a long period [6–8]”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [6]
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- Authors
- Resnick, S. M., Sojkova, J., Zhou, Y., An, Y., Ye, W., Holt, D. P., Dannals, R. F., Mathis, C. A., Klunk, W. E., Ferrucci, L., Kraut, M. A., & Wong, D. F.
- Affiliations
- Johns Hopkins University (US)
- National Institutes of Health (US)
- Corresponding author
- An, Y.
- ORCID
- Venue
- Neurology
- Published
- 2010-03-09
- Volume
- 74
- Issue
- 10
- Pages
- 807-815
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2839197
- OpenAlex
- W1999367055
- Cited by
- 288
- References
- 4
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 11 · 2020: 41 · 2019: 16 · 2018: 20 · 2017: 17 · 2016: 18 · 2015: 19 · 2014: 24 · 2013: 34 · 2012: 25
- FWCI
- 20.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Energy
- Dana Foundation (U01 AG024904)
- Amgen
- Bristol-Myers Squibb (U01 AG024904, AG024904)
- Eli Lilly and Company (U01 AG024904, AG024904)
- AstraZeneca
- Sanofi
- Johns Hopkins University
- University of Pittsburgh (P50 AG005133)
- Orexigen Therapeutics
- University of Cambridge
- Elan (U01 AG024904)
- Otsuka Pharmaceutical
- National Institutes of Health (and K24, N01-AG-3-2124, U01-AG024904, AG005133, AG024904, MH079017, AG025204, AG025516)
- Avid Radiopharmaceuticals
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Aging (U01-AG-024904, N01-AG-32124, R01AG018402, P01AG025204, AG-005133, RF1AG025516, P50AG005133, AG 024904, R01AG031110, AG025204, R37AG025516, ZIAAG000191)
- National Institute of Mental Health (U01 AG024904, R01MH077852, R01MH078175, MH 077852, R01MH085328, MH085328)
- National Institute on Drug Abuse (K24 DA00412, K24DA000412)
- National Institute of Biomedical Imaging and Bioengineering (U01 AG024904, AG024904)
- 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
- fibrillar amyloid-beta, cognitive decline, [11C]PIB, amyloid PET, mild cognitive impairment, verbal memory, visual memory, normal aging, prefrontal cortex, lateral temporal cortex, distribution volume ratio, longitudinal cognitive trajectories, Alzheimer's disease risk
- MeSH terms
- Aged, Aged, 80 and over, Amyloid, Aniline Compounds, Brain Mapping, Carbon Radioisotopes, Cognition Disorders, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Neuropsychological Tests, Retrospective Studies, Thiazoles, Positron-Emission Tomography
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