Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia
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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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svPPA is commonly associated with striking asymmetric atrophy of the dominant hemisphere temporal pole.
“svPPA is commonly associated with striking asymmetric atrophy of the dominant hemisphere temporal pole (Rogalski et al., 2011).”
From Differential diagnosis of frontotemporal dementia subtypes with explainable deep learning on structural MRI (2024) · cites this paper as Rogalski et al., 2011
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- Authors
- Rogalski, E., Cobia, D., Harrison, T. M., Wieneke, C., Weintraub, S., & Mesulam, M.-M.
- Affiliations
- Northwestern University (US)
- From the Cognitive Neurology and Alzheimer's Disease Center (E.R., T.M.H., C.W., S.W., M.-M.M.), Department of Psychiatry and Behavioral Sciences (D.C., S.W.), and Department of Neurology (M.-M.M.), Northwestern University Feinberg School of Medicine, Chicago, IL.
- Venue
- Neurology
- Published
- 2011-05-24
- Volume
- 76
- Issue
- 21
- Pages
- 1804-1810
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3100122
- OpenAlex
- W2130888418
- Cited by
- 252
- References
- 23
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 14 · 2023: 10 · 2022: 21 · 2021: 27 · 2020: 21 · 2019: 24 · 2018: 14 · 2017: 15 · 2016: 18 · 2015: 14 · 2014: 18 · 2013: 23 · 2012: 8
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Northwestern University (AG13854)
- University of Oxford
- National Institutes of Health (5kl2rr025740-02, DC008552, AG13854)
- National Institute on Aging (AG13854, 5KL2RR025740, P30AG013854)
- National Institute on Deafness and Other Communication Disorders (AG13854, 5KL2RR025740, R01DC008552, DC008552)
- National Center for Research Resources (5KL2RR025740, AG13854, UL1RR025741)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neurobiology of Language and Bilingualism
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- primary progressive aphasia, logopenic variant, semantic variant, cortical atrophy, cortical thickness, language loss, longitudinal disease progression, word comprehension, grammatical processing, language network, inferior frontal gyrus, temporoparietal junction, lateral temporal cortex, left hemisphere lateralization, clinical trial design
- MeSH terms
- Aged, Clinical Trials as Topic, Humans, Language Disorders, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Psychomotor Performance, Disease Progression, Aphasia, Primary Progressive
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