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Progressive dysexecutive syndrome due to Alzheimer’s disease: A description of 55 cases and comparisons to other clinical AD phenotypes
Author(s) -
Townley Ryan A,
GraffRadford Jonathan,
Mantyh William G.,
Botha Hugo,
Polsinelli Angelina J.,
Przybelski Scott A.,
Machulda Mary M.,
Senjem Matthew L.,
Murray Melissa E.,
Reichard Ross R.,
Savica Rodolfo,
Boeve Bradley F.,
Drubach Daniel A.,
Josephs Keith A.,
Knopman David S.,
Lowe Val J.,
Jack Clifford R.,
Petersen Ronald C.,
Jones David T.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.040622
Subject(s) - executive dysfunction , neuropsychology , dementia , neuroimaging , pathophysiology , positron emission tomography , medicine , psychology , dysexecutive syndrome , pathology , disease , neuroscience , cognition
Background We report a group of individuals presenting with a progressive dementia syndrome characterized by predominant dysfunction in core executive functions and positive biomarkers for Alzheimer’s pathophysiology. Method In this retrospective review, we report on 55 participants with a clinically defined progressive dysexecutive syndrome with 18 F‐fluorodeoxyglucose‐positron emission tomography (FDG) and AD biomarker positivity. A subset of these individuals enrolled in our ADRC were compared to other phenotypic variants of AD. Result Sixty‐two percent were female with a mean of 15.2 years of education. Mean age of symptom onset was 53.8 while mean age at diagnosis was 57.2 years. Multi‐domain cognitive impairment was evident in neuropsychological testing with executive dysfunction most consistently and severely affected. The frontal and/or parietal regions demonstrate clear hypometabolism on positron emission tomography in all cases. Genetic testing for autosomal dominant genes was negative in all 8 participants tested and at least one APOE ε 4 allele was present in 14/26. EEG was abnormal in 14/17 cases. CSF and neuroimaging biomarkers (PIB‐PET and Tau‐PET) were consistent with Alzheimer’s disease pathophysiology, although CSF p‐tau was normal in 24% of cases. In two participants that came to autopsy, the hippocampus was relatively spared compared to frontal and parietal cortex. Participants presenting with a progressive dysexecutive syndrome and evidence of AD pathology are labeled dAD. Comparing FDG in dAD relative to other AD phenotypes revealed unique areas of relatively greater hypometabolism in parieto‐frontal cortex and relative sparing of medial temporal (vs typical AD), visual (vs PCA), and left temporal (vs lvPPA) (Figure 1). Controlling for age did not alter patterns of regional differences. This demonstrates regional variability related to clinical phenotype not accountable by variation in age, duration, stage, or severity (Figure 2). Conclusion A progressive dysexecutive syndrome should be recognized as a distinct clinical phenotype. This clinical presentation can be due to Alzheimer’s disease but is not specific for any single etiology (non‐AD cases of progressive dysexecutive syndrome will be discussed). Prominent impairment of executive task performance, young‐age of onset, normal CSF p‐tau, and relative preservation of the hippocampus were commonly encountered in this case series of dAD.