Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia
Abstract
Objectives:
To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials.
Methods:
Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S).
Results:
There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere.
Conclusions:
The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects.
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Copyright © 2011 by AAN Enterprises, Inc.
Publication History
Received: December 1, 2010
Accepted: February 10, 2011
Published online: May 23, 2011
Published in print: May 24, 2011
Disclosure
Dr. Rogalski receives research support from the NIH (NIA, NIDCD). Dr. Cobia receives research support from the NIH (NIA, NIDCD). T.M. Harrison reports no disclosures. C. Wieneke receives research support from the NIH/NIDCD. Dr. Weintraub serves on the editorial boards of Alzheimer's and Dementia, the Turkish Journal of Neurology, Dementia & Neuropsychologia, and the Journal of the Brazilian Academy of Neurology; and receives research support from the NIH (NIA, NIDCD). Dr. Mesulam serves on the scientific advisory boards for the Cure Alzheimer Fund and the Association on Frontotemporal Dementia; serves on the editorial boards of Brain, Annals of Neurology, Human Brain Mapping, and Journal of Cognitive Neuroscience; receives royalties from the publication of Principles of Behavioral and Cognitive Neurology (Oxford University Press, 2000); and receives research support from the NIH (NIDCD, NIA).
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