Phenocopy syndrome of behavioral variant frontotemporal dementia: a systematic review

Abstract

Background The phenocopy syndrome of behavioral variant of frontotemporal dementia (phFTD) refers to patients presenting with neuropsychiatric symptoms mimicking the behavioral variant frontotemporal dementia (bvFTD), but lacking frontotemporal atrophy/hypometabolism on neuroimaging and not evolving to dementia during the follow-up. It is important to recognize phFTD for clinical and research purposes. Objective The aim of this study was to perform a systematic review of the available literature on phFTD taking into account its clinical, cognitive, imaging, genetic, and pathological features. Methods and results We searched for the following terms in two electronic databases (PubMed and Scopus): “frontotemporal dementia and slowly progressive,” “frontotemporal dementia and phenocopy,” “frontotemporal dementia and non-progressive,” “frontotemporal dementia and benign progression,” and “frontotemporal dementia and benign.” We did not include review articles. Papers had to be written in English, French, Portuguese, or Spanish. Overall, 235 studies were retrieved in the initial search. A total of 31 studies composed the final selection, comprising 292 patients. Patients with phFTD are predominantly male and have no major cognitive deficits, with globally preserved executive functions and episodic memory. Some cases ( n = 7) of slowly progressive FTD have been associated with C9orf72 genetic expansion. There are only four reports of phFTD neuropathological data, with two patients with no neurodegenerative findings and two with frontotemporal lobar degeneration with ubiquitin-positive inclusions. Conclusion The neurobiological underpinnings of phFTD remain unknown. It is controversial whether phFTD belongs to the FTD spectrum. Studies with biomarkers and pathological data are needed to solve the phFTD conundrum.

The bvFTD phenocopy syndrome: a case study supported by repeated MRI, [18F]FDG-PET and pathological assessment

“…Neuropathological assessed phFTD cases are scarce yet important for further understanding of the etiology and in this manner complementary to clinical assessment (Valente et al, 2019). The following case description confirms the absence of postmortem neurodegeneration fitting FTD in a patient that for over 9 years fulfilled the criteria for (possible) bvFTD with slowly progressive behavioral disturbances and language difficulties reported by the spouse.…”

“…Also, this case concerned a male patient. Interestingly, there is an impressive imbalance toward male patients in the phFTD compared to bvFTD, which is yet unexplained (Valente et al, 2019).…”

“…Also, in phFTD various cognitive deficits are reported, such as source memory deficits and lower Mini Mental State Exam (MMSE) scores compared to healthy controls. These deficits might be attributable to attention deficits and work pace, influencing other test scores (Irish et al, 2012;Valente et al, 2019).…”

Psychological and Cognitive Markers of Behavioral Variant Frontotemporal Dementia–A Clinical Neuropsychologist's View on Diagnostic Criteria and Beyond

“…These shared symptoms may explain why bvFTD patients are frequently misdiagnosed with psychiatric disorders as outlined before (9, 12), but they also explain why, on the basis of the FTDC criteria, a significant proportion of psychiatric patients could be misdiagnosed as possible bvFTD (10, 11, 38, 39). Related to the issue of clinical misdiagnoses based on the FTDC criteria and further complicating the picture, a condition mimicking bvFTD has been been described and labeled “bvFTD phenocopy syndrome,” implying that patients may display the typical behavioral symptoms of bvFTD but show no progression and no evidence of atrophy or hypometabolism [for a recent systematic review on features of individuals with phenocopy bvFTD, see (40)].…”

Qualitative Assessment of Longitudinal Changes in Phenocopy Frontotemporal Dementia

“…Phenocopy frontotemporal dementia (phFTD) is a clinical syndrome predominantly affecting men (1), that is much debated, as it shares core features with behavioral variant frontotemporal dementia (bvFTD) but does not follow its disease course. These core features are behavioral changes, such as apathy, behavioral disinhibition, and loss of insight (2).…”