Dysexecutive Alzheimer’s Disease with Lewy Body Disease Co-Pathology

Ryan P. Coburn, Hugo Botha, Jonathan Graff-Radford, R. Ross Reichard, David T. Jones, Vijay K. Ramanan

Research output: Contribution to journalArticlepeer-review


Background: Alzheimer’s disease can present atypically as a progressive dysexecutive syndrome (dAD), an entity that preferentially affects younger individuals and is frequently misdiagnosed, highlighting the imperative for additional research. Objective: The objective of this study is to characterize the clinical, antemortem neuroimaging, and postmortem neuropathologic features of two cases of young-onset dAD who displayed evidence of Lewy body disease (LBD) co-pathology at autopsy. Methods: Clinical histories, antemortem MRI and PET imaging, and postmortem neuropathologic data were reviewed for each patient. Case Descriptions/Results: Canonical features of dAD were observed in both cases, including progressive and predominant impairment in tasks related to working memory and cognitive flexibility, a lack of major behavioral/personality changes, and evidence of abnormal amyloid and tau deposition by antemortem amyloid and tau PET and postmortem neuropathology. Relative sparing of hippocampal involvement was observed in both individuals, in keeping with many cases of clinically atypical AD. One of the patients developed subtle parkinsonian signs as well as paranoia and irritability in the years prior to passing. In both cases, transitional (brainstem and limbic) LBD co-pathology was observed at autopsy. Discussion: Although LBD co-pathology is not uncommon in AD overall, the presence of LBD pathology in these young-onset cases of dAD (including a case with apparent symptomatic correlate) warrants further investigation for broader frequency and underlying pathophysiology. Conclusion: A better understanding of which specific young-onset AD phenotypes are associated with LBD co-pathology would have important implications for counseling, treatment, clinical trial enrollment, and knowledge on disease mechanisms.

Original languageEnglish (US)
Pages (from-to)330-333
Number of pages4
JournalCurrent Alzheimer research
Issue number4
StatePublished - Apr 2022


  • Alzheimer’s disease
  • Lewy body disease
  • MRI
  • PET
  • atypical AD
  • case report
  • neuropathology

ASJC Scopus subject areas

  • General Medicine


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