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Abstract
Objective To investigate evidence of the potential role of early cortical vulnerability in the development of primary progressive aphasia (PPA).
Method A 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.
Results The 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.
Conclusion This 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.
Glossary
- FD=
- frame displacement;
- FTLD=
- frontotemporal lobar degeneration;
- MINT=
- Multilingual Naming Test;
- MNI=
- Montreal Neurological Institute;
- MoCA=
- Montreal Cognitive Assessment;
- PPA=
- primary progressive aphasia;
- PRI=
- Perceptual Reasoning Index;
- PSTCR=
- perisylvian cortex;
- ROI=
- region of interest;
- ROIp=
- peak ROI;
- STG=
- superior temporal gyrus;
- VCI=
- Verbal Comprehension Index;
- WASI-II=
- Wechsler Abbreviated Scale of Intelligence, Second Edition;
- WRAT-4=
- Wide Range Achievement Test–Fourth Edition
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 281
- Received December 9, 2019.
- Accepted in final form February 27, 2020.
- © 2020 American Academy of Neurology
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