Phenocopy frontotemporal dementia: A case series from a national memory clinic and a review of the literature

Introduction The existence of a frontotemporal dementia phenocopy (phFTD) syndrome remains controversial. Opinions differ on whether the phenocopy presentation represents the neuropsychological manifestation of a mid-life decompensation in vulnerable pre-morbid personalities or an indolent prodrome of behavioral-variant FTD (bvFTD). Literature on this topic is sparse and clinicians and patients have little guidance around prognosis and management. Objectives To describe the demographic, neuropsychological and biomarker profiles of a case series of phFTD patients, attending the memory clinic and review relevant literature. Methods Retrospective review of all cases diagnosed with phFTD. Results Eleven cases were identified (male = 9, female = 2). Mean age 55.8 years. Subjective complaints comprised memory and language difficulties. Collateral reports described apathy, aggression, impulsivity, disinhibition, hyperorality. Function was relatively preserved though motivation or supervision for higher-level tasks was sometimes required. All had non-neurodegenerative MRI and PET scans. Neuropsychological test (NPT) findings predominantly showed executive dysfunction and fluency impairment. A total of 3/11 had non-amnestic memory impairment. Follow-up imaging and NPT were invariably unchanged; 1/11 had a pre-morbid psychiatric diagnosis; 5/11 had unusual personality traits pre-morbidly. Major psychosocial stressors were documented in 7/11. Management consisted of psychosocial interventions to support function and interpersonal relationships. Conclusions The literature describes the phFTD syndrome as predominantly affecting males though we include 2 females who meet the criteria. In keeping with our findings, personality traits and psychosocial stressors may be more common in phFTD than bvFTD. More severe symptoms, memory impairment at presentation and C9ORF72 gene mutation may predict eventual progression. Those who do not progress have minimal long-term functional impairment though behavioral symptoms persist.