Phenotypic Subtypes of Progressive Dysexecutive Syndrome Due to Alzheimer's Disease: a Series of Clinical Cases

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.