Neuropsychological features of progranulin-associated frontotemporal dementia: a nested case-control study

The distinction between sporadic and genetic behavioural-variant frontotemporal dementia (bvFTD) regarding some neuropsychological (NP) features remains challenging. Specifically, progranulin (GRN)-associated bvFTD frequently presents with early episodic memory impairment and some degree of parietal dysfunction which are supporters of Alzheimer's disease (AD) diagnosis. In this context, we aimed to characterize the NP profile of GRN-bvFTD as compared to sporadic-bvFTD and AD in patients with mild dementia (Mini-Mental State Examination score ≥ 17 and Clinical Dementia Rating Scale score ≤ 1. We identified 21 patients at Centro Hospitalar e Universitário de Coimbra, Portugal with GRN mutations belonging to fifteen different families. As our focus was bvFTD variants, FTD-related aphasic forms (3 patients) were excluded. The remaining 18 GRN-bvFTD were further matched with 18 sporadic-bvFTD and 18 AD patients according to disease staging, age and education. All patients completed the Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA) and a comprehensive NP assessment battery. Results were converted into z-scores. Differences between groups in individual NP measures and NP domains were assessed through non-parametric tests (Kruskal-Wallis test analysis) and eta squared (ŋ²) was calculated as a measure of effect size. Group comparisons show that GRN patients have worse performances on verbal retrieval processes (P = 0.039, ŋ²= 0.110) and visuoconstructive abilities (P = 0.039, ŋ²= 0.190) than sporadic bvFTD forms. When compared to AD, GRN patients present a higher impairment in frontal (P = 0.001, ŋ²= 0.211) and parietal (P = 0.041, ŋ²= 0.129) measures and a better performance in memory tasks (P = 0.020, ŋ²= 0.120). Sporadic-bvFTD forms are worse than AD in frontal measures (P = 0.032, ŋ²= 0.200), being better in both memory (P = 0.010, ŋ²= 0.131) and visuospatial skills (P = 0.023, ŋ²= 0.231). Considering these results, we conclude that GRN-bvFTD patients present a NP profile that associates the typical patterns of FTD and AD deficits. This is particularly expressive in visuoconstructive abilities, which was the more discriminative feature between groups, followed by episodic verbal memory. This study was approved by the Institutional Ethics Committee of Centro Hospitalar e Universitário de Coimbra, Portugal (CE-029/2019) on June 24, 2019.