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Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease
Open accessAbstract
OBJECTIVE: To examine the independent and interactive influences of neuroimaging biomarkers on retrospective cognitive decline. METHODS: F-AV-45) amyloid PET scan, and a structural MRI scan were recruited from the Knight Alzheimer Disease Research Center at Washington University in St. Louis. Cognition was assessed with standard measures reflecting episodic memory, executive functioning, semantic fluency, and processing speed. RESULTS: Results from retrospective longitudinal analyses showed that each biomarker had a univariate association with the global cognitive composite; however, when each marker was analyzed in a single statistical model, only tau was a significant predictor of global cognitive decline. There was an interaction between tau and amyloid such that tau-related cognitive decline was worse in individuals with high amyloid. There was also an interaction with hippocampal volume indicating that individuals with high levels of all 3 pathologies exhibited the greatest declines in cognition. Additional analyses within each cognitive domain indicated that tau had the largest negative influence on tests of episodic memory and executive functioning. CONCLUSIONS: Together, these results suggest that increasing levels of tau most consistently relate to declines in cognition preceding biomarker collection. These findings support models of Alzheimer disease (AD) staging that suggest that elevated β-amyloid alone may be insufficient to produce cognitive change in individuals at risk for AD and support the use of multiple biomarkers to stage AD progression.
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“In contrast, cross-sectional and longitudinal human cohort studies of biomarkers support a scenario in which amyloid pathology (Aβ42 lowering in CSF, positive amyloid PET imaging) precedes tau pathology (tau-PET and phospho-Tau elevation in CSF) and then neurodegeneration 126-128 .”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [128]
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Metadata
- Authors
- Aschenbrenner, A. J., Gordon, B. A., Benzinger, T. L. S., Morris, J. C., & Hassenstab, J. J.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- Venue
- Neurology
- Published
- 2018-08-28
- Volume
- 91
- Issue
- 9
- Pages
- e859-e866
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC6133625
- OpenAlex
- W2887375324
- Cited by
- 290
- References
- 19
- Citations by year
- 2026: 25 · 2025: 45 · 2024: 27 · 2023: 31 · 2022: 48 · 2021: 46 · 2020: 33 · 2019: 29 · 2018: 6
- FWCI
- 22.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P50AG005681, P01AG003991, U01AG032438, P01AG026276, K01AG053474)
- 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, tau PET, amyloid PET, hippocampal volume, cognitive decline, neuroimaging biomarkers, episodic memory, executive function, processing speed, semantic fluency
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Cognition Disorders, Female, Hippocampus, Humans, Male, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Cohort Studies, tau Proteins, Positron-Emission Tomography
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- CoChat. (2026). Citation check: Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease. https://app.cochat.ai/papers/10.1212/wnl.0000000000006075
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- Aschenbrenner, A. J., Gordon, B. A., Benzinger, T. L. S., Morris, J. C., & Hassenstab, J. J. (2018). Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000006075
