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Cited by 477Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeurobiology of Language and Bilingualism

Aβ amyloid and glucose metabolism in three variants of primary progressive aphasia

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Rabinovici, Gil D., Jagust, William J., Furst, Ansgar J., Ogar, Jennifer M., Racine, Caroline A., Mormino, Elizabeth C., O'Neil, James P., Lal, Rayhan A. +3 more·2008·Annals of Neurology
DOI 10.1002/ana.21451PMC PMC2648510
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Abstract

Objective: Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Aβ amyloidosis, and glucose metabolism in three PPA variants using [ 11 C]‐Pittsburgh compound B ([ 11 C]PIB) and [ 18 F]‐labeled fluorodeoxyglucose positron emission tomography ([ 18 F]FDG‐PET). Methods: Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. [ 11 C]PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). [ 18 F]FDG images were normalized to pons. Partial volume correction was applied. Results: Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) ( p < 0.02). In PIB‐positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA ( p < 0.005) but not in AD. Interpretation: LPA is associated with Aβ amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD. Ann Neurol 2008

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  • Nonamnestic clinical presentations-language, visuospatial, and executive disorders-may also be due to AD.

    “Nonamnestic clinical presentations, that is, language, visuospatial, and executive disorders, may also be due to AD [63–66].”

    From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [63]

    The Introduction states that primary progressive aphasia is a language-predominant syndrome and that some patients have AD pathology. The Results (Language and Neuropsychologic Testing; page unavailable) note relatively greater executive-test impairment in one aphasia variant, but say visuospatial function was spared in all patients. The paper therefore supports a language presentation of AD, not the full list of language, visuospatial, and executive presentations. (LLM, conf=0.87)

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Authors
Rabinovici, G. D., Jagust, W. J., Furst, A. J., Ogar, J. M., Racine, C. A., Mormino, E. C., O'Neil, J. P., Lal, R. A., Dronkers, N. F., Miller, B. L., & Gorno‐Tempini, M. L.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • University of California, San Francisco (US)
  • University of California, Berkeley (US)
  • VA Northern California Health Care System (US)
Corresponding author
Rabinovici, Gil D.
ORCID
Venue
Annals of Neurology
Publisher
Wiley
Published
2008-10
Volume
64
Issue
4
Pages
388-401
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
DOI
10.1002/ana.21451
PMC
PMC2648510
OpenAlex
W2027408391
Cited by
477
References
6
Citations by year
2026: 7 · 2025: 13 · 2024: 9 · 2023: 8 · 2022: 23 · 2021: 24 · 2020: 20 · 2019: 25 · 2018: 32 · 2017: 29 · 2016: 39 · 2015: 41 · 2014: 40 · 2013: 48 · 2012: 38
FWCI
18.97
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 37 d)
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Iris (University of Trento) (submittedVersion)
Funders
  • National Institute on Aging (P01 AG1972403, R01AG027859, AG027859, K23AG031861, P01AG019724, P50AG023501)
  • National Institute of Neurological Disorders and Stroke (R01NS050915)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neurobiology of Language and Bilingualism
Keywords
primary progressive aphasia, Alzheimer's disease, glucose metabolism, logopenic aphasia, progressive nonfluent aphasia, semantic dementia, [11C]PIB, 18F-FDG PET, brain hypometabolism, language phenotypes, temporal lobe
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Aniline Compounds, Carbon Isotopes, Dementia, Female, Glucose, Humans, Image Processing, Computer-Assisted, Language, Language Tests, Male, Middle Aged, Thiazoles, Amyloid beta-Peptides, Aphasia, Primary Progressive, Fluorodeoxyglucose F18, Positron-Emission Tomography

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