Atypical clinical features associated with mixed pathology in a case of non-fluent variant primary progressive aphasia

ABSTRACT

A 66-year-old woman presented with agrammatism and apraxia of speech, meeting criteria for non-fluent/agrammatic variant primary progressive aphasia (nfvPPA). However, three years later, she developed frontal/executive, short-term phonological memory, visuospatial, and visual memory deficits suggesting involvement of multiple brain networks. Multimodal neuroimaging showed damage of both fronto-striatal and posterior brain regions. She was found to have multiple pathological processes: corticobasal degeneration (CBD), Alzheimer’s disease (AD), and TAR DNA-binding protein (TDP)-43 type A. We hypothesize that cognitive and neuroimaging findings consistent with damage to multiple brain networks, each associated with vulnerability to certain molecular disease subtypes, could indicate mixed pathology.

KEYWORDS:

• Non-fluent agrammatic primary progressive aphasia
• syntax network
• corticobasal degeneration
• Alzheimer’s disease neuropathology
• TDP-43 type A neuropathology

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by the National Institutes of Health (MLGT, NINDS R01 NS050915), (MLGT, NIDCD K24 DC015544), (BM, NIA P50 AG023501), (BM, NIA P01 AG019724), (BM, Alzheimer’s Disease Center of California (03-75271 DHS/ADP/ARCC));Alzheimer’s Disease Research Center of California [03-75271];National Institute of Neurological Disorders and Stroke [R01 NS050915];National Institute on Deafness and Other Communication Disorders [K24 DC015544,R01 DC016291-01];National Institute on Aging [P01 AG019724,P50 AG023501].