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The impact of amyloid‐beta and tau on prospective cognitive decline in older individuals
Open accessAbstract
Objectives: Amyloid‐beta (Aβ) and tau pathologies are commonly observed among clinically normal older individuals at postmortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer's disease (AD) remains to be fully elucidated. Methods: One hundred thirty‐seven older individuals (age = 76.3 ± 6.22 years) participating in the Harvard Aging Brain Study underwent Aβ ( 11 C‐Pittsburgh compound B) and tau ( 18 F‐flortaucipir) positron emission tomography (PET) with prospective neuropsychological assessments following PET imaging (mean number of cognitive visits = 2.8 ± 1.1). Tau and Aβ PET measures were assessed in regions of interest (ROIs) as well as vertex‐wise map analyses. Cognitive change was evaluated with Memory and Executive Function composites. Results: Higher levels of Aβ and tau were both associated with greater memory decline, but not with change in executive function. Higher cortical Aβ was associated with higher tau levels in all ROIs, independent of age, and very elevated levels of tau were observed primarily in clinically normal with elevated Aβ. A significant interaction between tau and Aβ was observed in both ROI and map‐level analyses, such that rapid prospective memory decline was observed in participants who had high levels of both pathologies. Interpretation: Our results are consistent with the supposition that both Aβ and tau are necessary for memory decline in the preclinical stages of AD. These findings may be relevant for disambiguating aging and early cognitive manifestations of AD, and to inform secondary prevention trials in preclinical AD. Ann Neurol 2019;00:1–3 ANN NEUROL 2019;85:181–193.
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“The regional specificity of these findings aligns with evidence that entorhinal cortex is a site of preclinical neuropathological tau deposition that is elevated for APOE4 carriers [37] and predicts cognitive decline [38], and which undergoes accelerated atrophy in preclinical AD [39].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [38]
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Metadata
- Authors
- Sperling, R. A., Mormino, E. C., Schultz, A. P., Betensky, R. A., Papp, K. V., Amariglio, R. E., Hanseeuw, B. J., Buckley, R., Chhatwal, J., Hedden, T., Marshall, G. A., Quiroz, Y. T., Donovan, N. J., Jackson, J., Gatchel, J. R., Rabin, J. S., Jacobs, H., Yang, H., Properzi, M., Kirn, D. R., Rentz, D. M., & Johnson, K. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Sperling, Reisa A.
- ORCID
- Sperling, Reisa A.
- Mormino, Elizabeth C.
- Schultz, Aaron P.
- Betensky, Rebecca A.
- Papp, Kathryn V.
- Amariglio, Rebecca E.
- Hanseeuw, Bernard J.
- Buckley, Rachel
- Chhatwal, Jasmeer
- Hedden, Trey
- Marshall, Gad A.
- Quiroz, Yakeel T.
- Donovan, Nancy J.
- Jackson, Jonathan
- Gatchel, Jennifer R.
- Rabin, Jennifer S.
- Jacobs, Heidi
- Yang, Hyun‐Sik
- Properzi, Michael
- Rentz, Dorene M.
- Johnson, Keith A.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2019-01-21
- Volume
- 85
- Issue
- 2
- Pages
- 181-193
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC6402593
- OpenAlex
- W2905538154
- Cited by
- 286
- References
- 52
- Citations by year
- 2026: 22 · 2025: 57 · 2024: 42 · 2023: 29 · 2022: 29 · 2021: 52 · 2020: 38 · 2019: 17
- FWCI
- 20.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- National Institute on Aging (K24 AG035007, P01AG036694)
- 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
- amyloid-beta, tau protein, preclinical Alzheimer's disease, cognitive decline, memory decline, executive function, tau PET, normal aging, older adults, secondary prevention
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Longitudinal Studies, Male, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Cognitive Dysfunction, Memory, Episodic
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