Qualitative Assessment of Longitudinal Changes in Phenocopy Frontotemporal Dementia

Abstract

Phenocopy frontotemporal dementia (phFTD) shares core characteristics with behavioral variant frontotemporal dementia (bvFTD), yet without associated cognitive deficits and brain abnormalities on conventional magnetic resonance imaging (MRI), and without progression. Using advanced MRI techniques, we previously observed subtle structural and functional brain changes in phFTD similar to bvFTD. The aim of the current study was to follow these as well as cognition in phFTD over time, by means of a descriptive case series. Cognition, gray matter (GM) volume and white matter (WM) microstructure, and perfusion of 6 phFTD patients were qualitatively compared longitudinally (3-years follow-up), and cross-sectionally with baseline data from 9 bvFTD patients and 17 controls. For functional brain changes, arterial spin labeling (ASL) was performed to assess GM perfusion. For structural brain changes, diffusion tensor imaging was performed to assess WM microstructure and T1w imaging to assess GM volume. MRI acquisition was performed at 3T (General Electric, US). Clinical profiles of phFTD cases at follow-up are described. At follow-up phFTD patients showed clinical symptomatology similar to bvFTD, but had a relatively stable clinical profile. Longitudinal qualitative comparisons in phFTD showed some deterioration of language and memory function, a stable pattern of structural brain abnormalities and increased perfusion over time. Additionally, both baseline and follow-up cognitive scores and structural values in phFTD were generally in between those of controls and bvFTD. Although a descriptive case series does not allow for strong conclusions, these observations in a unique longitudinal phFTD patient cohort are suggestive of the notion that phFTD and bvFTD may belong to the same disease spectrum. They may also provide a basis for further longitudinal studies in phFTD, specifically exploring the structural vs. functional brain changes. Such studies are essential for improved insight, accurate diagnosis, and appropriate treatment of phFTD.

The Behavioral Variant Frontotemporal Dementia Phenocopy Syndrome: A Review

“…Their 2019 case series attempts to address this with the description of 6 genetically screened patients with phenocopy whose gray matter volumes were noted to be in between those of the comparator bvFTD and healthy control groups and unchanged at repeat assessment close to 3 years later. 47 Although these studies are limited by the small sample sizes, the rigorous selection criteria, which included genetic testing, enhance the validity of the results. The findings are the first to provide evidence of underlying neuropathological changes that may account for the phenocopy presentation.…”

“…Their 2019 case series attempts to address this with the description of 6 genetically screened patients with phenocopy whose gray matter volumes were noted to be in between those of the comparator bvFTD and healthy control groups and unchanged at repeat assessment close to 3 years later. 47…”

Premorbid de novo artistic creativity in frontotemporal dementia (FTD) syndromes

“…Occasionally, patients with bvFTD phenocopy syndromes and slowly progressive bvFTD, respectively, may show a C9ORF72 hexanucleotide expansion (Khan et al 2012;Devenney et al 2018). Given the comparatively subtle, slow, or non-progressive clinical, neuropsychological, and neuroimaging changes in FTD phenocopy syndrome, a common disease spectrum for the bvFTD phenocopy syndrome and the bvFTD has been proposed (Meijboom et al 2019).…”