Abstract
IMPORTANCE The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. OBJECTIVE To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). DESIGN, SETTING, AND PARTICIPANTS This prospective clinical-pathologic case serieswas conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA. MAIN OUTCOMES AND MEASURES Clinical, cognitive, neuroimaging, and pathology results. RESULTS Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy. CONCLUSIONS AND RELEVANCE Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95%of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.
Original language | English |
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Pages (from-to) | 342-352 |
Number of pages | 11 |
Journal | JAMA Neurology |
Volume | 75 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2018 |
Bibliographical note
Funding Information:Funding/Support: The study was supported by grants from the Alfonso Martin Escudero Foundation, National Institutes of Health (National Institute of Neurological Disorders and Stroke grant R01 NS050915 and National Institute on Aging grants P50 AG03006, P50 AG023501, P01 AG019724, R01 AG045611, R01 AG027859, and K24 DC015544-01), grant DHS04-35516 from the State of California, grant 03–75271 DHS/ADP/ARCC from the Alzheimer’s Disease Research Centre of California; Alzheimer’s Association, Larry L. Hillblom Foundation, John Douglas French Alzheimer's Foundation, Koret Family Foundation, Consortium for Frontotemporal Dementia Research, Tau Consortium, McBean Family Foundation, Career Scientist Award from the US Department of Veterans Affairs Clinical Sciences R&D Program, and Avid Radiopharmaceuticals.
Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
ASJC Scopus subject areas
- Clinical Neurology