TY - JOUR
T1 - Phenotypic subtypes of progressive dysexecutive syndrome due to Alzheimer’s disease
T2 - a series of clinical cases
AU - Corriveau-Lecavalier, Nick
AU - Machulda, Mary M.
AU - Botha, Hugo
AU - Graff-Radford, Jonathan
AU - Knopman, David S.
AU - Lowe, Val J.
AU - Fields, Julie A.
AU - Stricker, Nikki H.
AU - Boeve, Bradley F.
AU - Jack, Clifford R.
AU - Petersen, Ronald C.
AU - Jones, David T.
N1 - Funding Information:
This work was funded in part by NIH grants R01 AG011378 (C.J.), R01 AG041851 (C.J.), P50 AG016574 (R.P.), U01 AG06786 (R.P.), and by the Robert Wood Johnson Foundation, The Elsie and Marvin Dekelboum Family Foundation, The Liston Family Foundation, the Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program, The GHR Foundation, Foundation Dr. Corinne Schuler (Geneva, Switzerland), and the Mayo Foundation. Dr. Lowe consults for Bayer Schering Pharma, Piramal Life Sciences, Life Molecular Imaging, Eisai Inc., AVID Radiopharmaceuticals, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals and the NIH (NIA, NCI). Dr. Knopman serves on a Data Safety Monitoring Board for the DIAN study. He serves on a Data Safety monitoring Board for a tau therapeutic for Biogen but receives no personal compensation. He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals and the University of Southern California. He has served as a consultant for Roche, Samus Therapeutics, Third Rock and Alzeca Biosciences but receives no personal compensation. He receives funding from the NIH.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
PY - 2022/8
Y1 - 2022/8
N2 - Diagnostic criteria for a progressive dysexecutive syndrome due to Alzheimer's disease (dAD) were proposed. Clinical observations suggest substantial variability in the clinico-radiological profiles within this syndrome. We report a case series of 6 patients with dAD highlighting this heterogeneity. Average age at diagnosis was 57.3 years, and patients were followed annually with clinical, cognitive, and multimodal imaging assessments for an average of 3.7 years. Cases were divided based into three subtypes based on their pattern of FDG–PET hypometabolism: predominantly left parieto-frontal (ldAD), predominantly right parieto-frontal (rdAD), or predominantly biparietal (bpdAD) (n = 2 for each). Prominent executive dysfunction was evidenced in all patients. ldAD cases showed greater impairment on measures of verbal working memory and verbal fluency compared to other subtypes. rdAD cases showed more severe alterations in measures of visual abilities compared to language-related domains and committed more perseverative errors on a measure of cognitive flexibility. bpdAD cases presented with predominant cognitive flexibility and inhibition impairment with relative sparing of working memory and a slower rate of clinical progression. rdAD and bpdAD patients developed neuropsychiatric symptoms, whereas none of the ldAD patients did. For each subtype, patterns of tau deposition relatively corresponded to the spatial pattern of FDG hypometabolism. dAD cases could be differentiated from two clinical cases of atypical AD variants (language and visual) in terms of clinical, cognitive and neuroimaging profiles, suggesting that dAD subtypes represent clinical entities separable from other variants of the disease. The recognition of distinct dAD phenotypes has clinical relevance for diagnosis, prognosis, and symptom management.
AB - Diagnostic criteria for a progressive dysexecutive syndrome due to Alzheimer's disease (dAD) were proposed. Clinical observations suggest substantial variability in the clinico-radiological profiles within this syndrome. We report a case series of 6 patients with dAD highlighting this heterogeneity. Average age at diagnosis was 57.3 years, and patients were followed annually with clinical, cognitive, and multimodal imaging assessments for an average of 3.7 years. Cases were divided based into three subtypes based on their pattern of FDG–PET hypometabolism: predominantly left parieto-frontal (ldAD), predominantly right parieto-frontal (rdAD), or predominantly biparietal (bpdAD) (n = 2 for each). Prominent executive dysfunction was evidenced in all patients. ldAD cases showed greater impairment on measures of verbal working memory and verbal fluency compared to other subtypes. rdAD cases showed more severe alterations in measures of visual abilities compared to language-related domains and committed more perseverative errors on a measure of cognitive flexibility. bpdAD cases presented with predominant cognitive flexibility and inhibition impairment with relative sparing of working memory and a slower rate of clinical progression. rdAD and bpdAD patients developed neuropsychiatric symptoms, whereas none of the ldAD patients did. For each subtype, patterns of tau deposition relatively corresponded to the spatial pattern of FDG hypometabolism. dAD cases could be differentiated from two clinical cases of atypical AD variants (language and visual) in terms of clinical, cognitive and neuroimaging profiles, suggesting that dAD subtypes represent clinical entities separable from other variants of the disease. The recognition of distinct dAD phenotypes has clinical relevance for diagnosis, prognosis, and symptom management.
KW - Atypical Alzheimer’s disease
KW - Clinical neurology
KW - Dysexecutive syndrome
KW - FDG–PET
KW - Neuropsychology
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U2 - 10.1007/s00415-022-11025-x
DO - 10.1007/s00415-022-11025-x
M3 - Article
C2 - 35211780
AN - SCOPUS:85125133391
VL - 269
SP - 4110
EP - 4128
JO - Deutsche Zeitschrift fur Nervenheilkunde
JF - Deutsche Zeitschrift fur Nervenheilkunde
SN - 0340-5354
IS - 8
ER -