Abstract
ObjectiveTo investigate evidence of the potential role of early cortical vulnerability in the development of primary progressive aphasia (PPA).MethodA woman with a diagnosis of PPA and her 9 adult siblings, 7 with developmental language disabilities, underwent neuropsychological testing, structural MRI, and resting-state fMRI. Whole-exome sequencing was conducted for genes associated with dyslexia or with neurodegenerative dementia.ResultsThe siblings demonstrated lower verbal than nonverbal cognitive test scores in a developmental dyslexia pattern. On structural MRI, although the siblings did not differ from controls in total brain volume, the left hemisphere language area volume was significantly smaller than the right. Furthermore, cortical connectivity between the left superior temporal area, previously identified as the region of peak atrophy in the proband early in the course of illness, and adjacent language network components, including the planum temporale, was decreased in the siblings. No distinctive genetic signatures were identified.ConclusionThis report further supports the hypothesis that at least some cases of PPA may be based on a familial language network vulnerability that interferes with the acquisition of language in some members and that makes the language network a locus of least resistance to the effects of an independently late-Arising neurodegenerative disease in others. This association offers a conceptual model to explain why identical neurodegenerative diseases may selectively target the language network in some individuals while targeting networks that regulate memory or behavior in others. The genetic basis for this vulnerability remains to be determined.
Original language | English (US) |
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Pages (from-to) | E847-E855 |
Journal | Neurology |
Volume | 95 |
Issue number | 7 |
DOIs | |
State | Published - Aug 18 2020 |
Funding
This work was supported in part by the following grants from the UN NIH: National Institute of Deafness and Communication Disorders DC008552 (M. Mesulam, principal investigator [PI]); National Institute on Aging AG056258 (E. Rogalski, PI); National Institute of Neurological Disorders and Stroke R01 NS075075 (E. Rogalski, PI); National Institute of Deafness and Communication Disorders K23 DC014303-01A1 (B. Bonakdarpour, PI); The John Douglas French Alzheimer's Foundation, the Tau Consortium, the Eleanor Leslie Chair in Innovative Brain Research from the Brain Research Institute, and the Semel Institute for Neuroscience and Human Behavior at the University of California Los Angeles (G. Coppola, PI); and AG013854, Core Center grant to Northwestern University, National Institute on Aging (R. Vassar, PI).
ASJC Scopus subject areas
- Clinical Neurology