Primary progressive aphasia and the FTD-MND spectrum disorders: clinical, pathological, and neuroimaging correlates

Abstract

Objective: Behavioral variant frontotemporal dementia (bvFTD), is commonly considered the cognitive presentation of the frontotemporal dementia-motor neuron disease (FTD-MND) spectrum disorder. We evaluated the prevalence of primary progressive aphasia in a series of pathologically confirmed cases of FTD-MND spectrum. Methods: Pathologically confirmed cases of frontotemporal lobar degeneration-motor neuron disease (FTLD-MND) were obtained from the UCSF brain bank. Cases were analyzed for presence of language impairment via retrospective chart review of research visits that include neurologic exam, in-depth cognitive testing and magnetic resonance imaging (MRI) imaging. Forty one cases were included. Thirty two were diagnosed with FTD-MND, while nine cases were diagnosed as MND-only from clinical evaluation. Results: Ten FTLD-MND cases (31%) presented with prominent or isolated language involvement consistent with a diagnosis of primary progressive aphasia (PPA), which we called progressive aphasia with motor neuron disease (PA-MND). Of these, three cases that mirrored the non-fluent variant of PPA (nfvPPA) were named nfvPA-MND. The imaging pattern of these nfvPA-MND showed atrophy strictly confined to the frontal and anterior temporal language cortical areas. Another group of seven cases that resembled patients with the semantic variant PPA (svPPA) were named svPA-MND. The group of svPPA-MND on imaging analysis showed selective atrophy of the temporal lobe and orbitofrontal cortex. Conclusions: Language impairment was a frequent phenotype of FTD-MND associated with focal atrophy patterns within the language networks. This data suggest patients with FTD-MND can present quite often with language phenotype of nfvPPA and svPPA, as opposed to exclusive bvFTD symptoms.

Keywords:

• Neuropathology
• imaging
• dementia
• primary progressive aphasia
• motor neuron disease
• frontotemporal dementia
• amyotrophic lateral sclerosis

Declaration of interest

Dr. WWS is funded by the John Douglas French Alzheimer Disease Foundation, Consortium for Frontotemporal Dementia Research, James S. McDonnell Foundation, Larry Hillblom Foundation; has received support for travel by the Alzheimer’s Association; and has received payment for lectures by the Alzheimer’s Association, American Academy of Neurology, and Novartis Korea. BLM serves as board member on the John Douglas French Alzheimer Foundation and Larry L. Hillblom Foundation; serves as a consultant for TauRx Ltd, Allon Therapeutics, Siemens, Bristol-Myers Squibb, the Tau Consortium, and the Consortium for Frontotemporal Research; has received institutional support from Novartis; and is funded by a grant from the state of California. Dr. NO is funded by the American Academy of Neurology and the ALS Association. Dr. NO has received payment for lectures by Avanir’s visiting expert program.

Additional information

Funding

The study was supported by grants from the National Institutes of Health (NINDS R01 NS050915, NIDCD K24DC015544, NIA U01AG052943, NIA P50 AG023501, NIA P01AG019724, K08 AG052648) and AAN/ALSA grant P0519279 and Foundation for the National Institutes of Health.