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The following is a summary of “Association of Initial Side of Brain Atrophy With Clinical Features and Disease Progression in Patients With GRN Frontotemporal Dementia,” published in the November 2024 issue of Neurology by Borrego-Ecija et al.   

Pathogenic variants in the granulin (GRN) gene are linked to frontotemporal dementia (FTD), presenting marked brain asymmetry. Asymmetry’s impact on symptoms and progression in GRN-associated FTD remains unclear.  

Researchers conducted a retrospective study to evaluate whether initial brain atrophy side influences FTD-GRN progression.  

They analyzed data from the Genetic Frontotemporal Initiative (GENFI), which included individuals carrying or at risk of carrying a pathogenic variant associated with FTD, GENFI participants underwent annual standardized clinical and neuropsychological assessments, MRI, and blood sampling. An asymmetry index was generated from MRI to characterize brain asymmetry in participants with or at risk of GRN-related FTD. Symptomatic patients with GRN were classified as right-GRN or left-GRN based on asymmetry, with comparisons of clinical features and progression. The asymmetry index was assessed in carriers vs. noncarriers and compared to volumetric and plasma neurofilament models. 

The results showed 399 participants (mean age 49.7 years, 59% female), consisting of 63 symptomatic carriers, 177 presymptomatic carriers, and 159 noncarriers. Symptomatic carriers exhibited higher brain asymmetry (11.6) compared to noncarriers (1.0, P<0.001) and presymptomatic carriers (1.0, P<0.001), which allowed the classification of most symptomatic carriers as either right-GRN (n = 21) or left-GRN (n = 36). Patients with right-GRN had more severe disease at baseline (β = 6.9, 95% CI 2.4–11.0, P=0.003) but showed less deterioration per year (β = −1.5, 95% CI −2.7 to −0.31, P=0.015) compared to those with left-GRN. Brain asymmetry was detectable in GRN carriers an average of 10.4 years before the onset of symptoms (SD 0.85, CI 0.01–1.68).  

They concluded that FTD-GRN presented distinct anatomical asymmetry patterns linked to initial atrophy side, symptom differences, and disease trajectory, suggesting brain asymmetry as a potential biomarker for early GRN-FTD conversion.  

Source: neurology.org/doi/10.1212/WNL.0000000000209944