Ryan P. Coburn, H. Botha, J. Graff‐Radford, R. Reichard, David T. Jones, V. Ramanan
{"title":"Dysexecutive Alzheimer's Disease with Lewy Body Disease Co-Pathology.","authors":"Ryan P. Coburn, H. Botha, J. Graff‐Radford, R. Reichard, David T. Jones, V. Ramanan","doi":"10.2174/1567205019666220308152219","DOIUrl":null,"url":null,"abstract":"BACKGROUND\nAlzheimer's disease can present atypically as a progressive dysexecutive syndrome (dAD), an entity which preferentially affects younger individuals and is frequently misdiagnosed, highlighting the imperative for additional research.\n\n\nOBJECTIVE\nTo 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.\n\n\nMETHODS\nClinical 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.\n\n\nDISCUSSION\nAlthough 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.\n\n\nCONCLUSION\nA 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.","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Alzheimer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1567205019666220308152219","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
BACKGROUND
Alzheimer's disease can present atypically as a progressive dysexecutive syndrome (dAD), an entity which preferentially affects younger individuals and is frequently misdiagnosed, highlighting the imperative for additional research.
OBJECTIVE
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.
期刊介绍:
Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer''s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ''bird''s-eye view'' of the current state of Alzheimer''s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.