Phenotypic subtypes of progressive dysexecutive syndrome due to Alzheimer’s disease: a series of clinical cases

• Published in: Journal of neurology 2022-08, Vol.269 (8), p.4110-4128
• Main Authors: Corriveau-Lecavalier, Nick, Machulda, Mary M., Botha, Hugo, Graff-Radford, Jonathan, Knopman, David S., Lowe, Val J., Fields, Julie A., Stricker, Nikki H., Boeve, Bradley F., Jack, Clifford R., Petersen, Ronald C., Jones, David T.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - complications; Alzheimer Disease - diagnostic imaging; Alzheimer's disease; Brain - diagnostic imaging; Brain damage; Case reports; Cognitive ability; Diagnosis; Executive function; Fluorodeoxyglucose F18; Humans; Language; Medicine; Medicine & Public Health; Memory; Memory, Short-Term; Neurodegenerative diseases; Neuroimaging; Neurology; Neuropsychological Tests; Neuroradiology; Neurosciences; Original Communication; Patients; Phenotype; Phenotypes; Positron emission tomography; Positron-Emission Tomography - methods; Short term memory; Symptom management; Tau protein
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-022-11025-x

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.