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 - 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
SN - 0340-5354
VL - 269
SP - 4110
EP - 4128
JO - Journal of Neurology
JF - Journal of Neurology
IS - 8
ER -