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Cited by 68Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

Tau PET imaging predicts cognition in atypical variants of Alzheimer's disease

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Phillips, Jeffrey S., Das, Sandhitsu R., McMillan, Corey T., Irwin, David J., Roll, Emily E., Da Re, Fulvio, Nasrallah, Ilya M., Wolk, David A. +1 more·2018·Human Brain Mapping
DOI 10.1002/hbm.23874PMC PMC5764792
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Abstract

Accumulation of paired helical filament tau contributes to neurodegeneration in Alzheimer's disease (AD). 18 F‐flortaucipir is a positron emission tomography (PET) radioligand sensitive to tau in AD, but its clinical utility will depend in part on its ability to predict cognitive symptoms in diverse dementia phenotypes associated with selective, regional uptake. We examined associations between 18 F‐flortaucipir and cognition in 14 mildly‐impaired patients (12 with cerebrospinal fluid analytes consistent with AD pathology) who had amnestic (n = 5) and non‐amnestic AD syndromes, including posterior cortical atrophy (PCA, n = 5) and logopenic‐variant primary progressive aphasia (lvPPA, n = 4). Amnestic AD patients had deficits in memory; lvPPA in language; and both amnestic AD and PCA patients in visuospatial function. Associations with cognition were tested using sparse regression and compared to associations in anatomical regions‐of‐interest (ROIs). 18 F‐flortaucipir uptake was expected to show regionally‐specific correlations with each domain. In multivariate analyses, uptake was elevated in neocortical areas specifically associated with amnestic and non‐amnestic syndromes. Uptake in left anterior superior temporal gyrus accounted for 67% of the variance in language performance. Uptake in right lingual gyrus predicted 85% of the variance in visuospatial performance. Memory was predicted by uptake in right fusiform gyrus and cuneus as well as a cluster comprising right anterior hippocampus and amygdala; this eigenvector explained 57% of the variance in patients' scores. These results provide converging evidence for associations between 18 F‐flortaucipir uptake, tau pathology, and patients' cognitive symptoms.

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  • Elevated tau PET binding in medial temporal lobe structures and neocortex is strongly associated with positive amyloid PET scans and with clinical impairment across the normal aging to dementia clinical spectrum.

    “Elevated tau PET binding in both medial temporal lobe structures and the neocortex is strongly associated with positive amyloid PET scans and with clinical impairment across the normal aging to dementia clinical spectrum [82,130–141].”

    From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [136]

    The Conclusions (page not provided) link neocortical tau PET uptake with cognitive performance in patients with amnestic and non-amnestic Alzheimer’s disease. But the Limitations (page not provided) state that the study did not compare tau and amyloid PET results and had no cognitively normal controls; it therefore does not support the claimed association with positive amyloid PET scans or its extension across the normal-aging-to-dementia spectrum. The Discussion also describes the medial temporal association with memory deficits as relatively modest, not strong. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Authors
Phillips, J. S., Das, S. R., McMillan, C. T., Irwin, D. J., Roll, E. E., Da Re, F., Nasrallah, I. M., Wolk, D. A., & Grossman, M.
Affiliations
  • University of Pennsylvania (US)
  • Penn Frontotemporal Degeneration Center, Department of Neurology University of Pennsylvania Philadelphia Pennsylvania 19104
Corresponding author
Phillips, Jeffrey S.
ORCID
Venue
Human Brain Mapping
Publisher
Wiley
Published
2017-11-06
Volume
39
Issue
2
Pages
691-708
ISSN
  • 1065-9471 (ISSN-L)
  • 1097-0193
DOI
10.1002/hbm.23874
PMC
PMC5764792
OpenAlex
W2767753502
Cited by
68
References
14
Citations by year
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FWCI
6.97
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Human Brain Mapping (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion)
Funders
  • National Institutes of Health (AG017586, AG010124, AG043503, NS088341)
  • Dana Foundation
  • Wyncote Foundation
  • Alzheimer's Association (AARF‐16‐443681)
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 › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
18F-flortaucipir, tau PET, Alzheimer's disease, posterior cortical atrophy, logopenic variant primary progressive aphasia, amnestic Alzheimer's disease, cognitive impairment, memory, visuospatial ability, language, anterior superior temporal gyrus, lingual gyrus, hippocampus, amygdala, mild cognitive impairment, sparse regression
MeSH terms
Aged, Alzheimer Disease, Amnesia, Atrophy, Brain, Carbolines, Cognition, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Cohort Studies, tau Proteins, Aphasia, Primary Progressive, Radiopharmaceuticals, Positron-Emission Tomography

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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