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Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults
Open accessAbstract
OBJECTIVE: To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults. METHODS: Tau- and amyloid-PET were performed in 579 CU participants aged 50-98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A-) and normal/abnormal regional tau-PET (T+/T-). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30-49. RESULTS: scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A- and A+. CONCLUSIONS: Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.
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“it has become evident that it is the spread of NFT pathology that correlates best, and possibly causes, substantial cognitive impairment in AD”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [20]
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“The NFT tau PET signal was significantly associated with impairment of various measures of cognition, on a region-of-interest basis.When the NFT tau PET signal was stratified by amyloid status, there was no significant evidence that amyloid modified the effect of the NFT tau PET signal.”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [20]
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“In a cross-sectional study, Lowe et al. 20 studied the association of neurofibrillary (NFT) tau PET and Aβ PET on cognition in 579 cognitively unimpaired adults.The participants' median age was 70 and abnormal NFT tau PET, defined as a signal in the entorhinal region, was seen in 20%, while abnormal Aβ was seen in 34% of the cohort.”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [20]
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Self-citationNeuropathological stageing of Alzheimer-related changes.
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“The gold standard of AD diagnosis relies on autopsy data quantifying Aβ and NFT load throughout the brain.(3) The relationship of cognitive decline to these pathologies as seen at autopsy is well-described(4,5); however, the relationship of cognitive decline and these 2 pathologies early in the disease process is not…”
MethodResultInfluentialAlbert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152 · cited 1×
“Amyloid-PET can identify Aβ plaques and is an important tool for understanding AD pathogenisis.(11,12) Tau-PET using AV-1451 identifies AD NFT burden throughout disease progression.”
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Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
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Primary age-related tauopathy (PART): a common pathology associated with human aging
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The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Karran, E., & De Strooper, B. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00391-w · Cited by 742
Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease
Vogel, J. W., Iturria‐Medina, Y., Strandberg, O. T., Smith, R. A., Levitis, E., Evans, A. C., Hansson, O., Initiative, A. D. N., Weiner, M. W., Aisen, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15701-2 · Cited by 537
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Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age
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Metadata
- Authors
- Lowe, V. J., Bruinsma, T. J., Wiste, H. J., Min, H.-K., Weigand, S. D., Fang, P., Senjem, M. L., Therneau, T. M., Boeve, B. F., Josephs, K. A., Pandey, M. K., Murray, M. E., Kantarci, K., Jones, D. T., Vemuri, P., Graff-Radford, J., Schwarz, C. G., Machulda, M. M., Mielke, M. M., Roberts, R. O., Knopman, D. S., Petersen, R. C., & Jack, C. R.
- Affiliations
- From the Departments of Radiology (V.J.L., T.J.B., H.-K.M., P.F., M.L.S., M.K.P., K.K., D.T.J., P.V., C.G.S., C.R.J.), Health Sciences Research (H.J.W., S.D.W., T.M.T., M.M. Mielke, R.O.R.), Information Technology (M.L.S.), Neurology (B.F.B., K.A.J., D.T.J., J.G.-R., M.M. Mielke, D.S.K., R.C.P.), Neuroscience (M.E.M.), and Psychiatry and Psychology (M.M. Machulda), Mayo Clinic, Rochester, MN.
- ORCID
- Lowe, Val J.
- Bruinsma, Tyler J.
- Wiste, Heather J.
- Min, Hoon-Ki
- Weigand, Stephen D.
- Fang, Ping
- Senjem, Matthew L.
- Therneau, Terry M.
- Boeve, Bradley F.
- Josephs, Keith A.
- Pandey, Mukesh K.
- Murray, Melissa E.
- Kantarci, Kejal
- Jones, David T.
- Vemuri, Prashanthi
- Schwarz, Christopher G.
- Machulda, Mary M.
- Mielke, Michelle M.
- Knopman, David S.
- Petersen, Ronald C.
- Jack, Clifford R.
- Venue
- Neurology
- Published
- 2019-07-02
- Volume
- 93
- Issue
- 1
- Pages
- e29-e39
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC6659005
- OpenAlex
- W2947200125
- Cited by
- 107
- References
- 50
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 13 · 2023: 15 · 2022: 23 · 2021: 19 · 2020: 11 · 2019: 4
- FWCI
- 11.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- Pfizer
- Biogen
- Mayo Foundation for Medical Education and Research
- National Institutes of Health
- Genentech
- Avid Radiopharmaceuticals
- National Institute on Aging (U01AG006786, R01AG011378, RF1AG057547, R01AG041851, R37AG011378, P50AG016574)
- National Institute on Deafness and Other Communication Disorders (R01DC010367)
- National Institute of Neurological Disorders and Stroke (R01NS089544, R21NS094489, R01NS089757, R01NS097495)
- 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
- tau PET, neurofibrillary tangles, cognitive performance, memory performance, entorhinal cortex, medial temporal lobe, amyloid PET, standardized uptake value ratio, language performance, Mayo Clinic Study of Aging
- MeSH terms
- Aged, Aged, 80 and over, Amyloid, Brain, Cognition, Cross-Sectional Studies, Female, Humans, Male, Memory, Middle Aged, Cohort Studies, tau Proteins, Positron-Emission Tomography
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