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

Neurocase. Feb-Apr 2019;25(1-2):39-47. doi: 10.1080/13554794.2019.1609522. Epub 2019 Apr 29.


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

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / complications*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Basal Ganglia Diseases / complications*
  • Basal Ganglia Diseases / pathology
  • Basal Ganglia Diseases / physiopathology
  • Female
  • Frontotemporal Dementia / complications*
  • Frontotemporal Dementia / pathology
  • Frontotemporal Dementia / physiopathology
  • Humans
  • Neuroimaging
  • Primary Progressive Nonfluent Aphasia / etiology*
  • Primary Progressive Nonfluent Aphasia / pathology
  • Primary Progressive Nonfluent Aphasia / physiopathology