The following is a summary of “Frequency and Longitudinal Course of Behavioral and Neuropsychiatric Symptoms in Participants With Genetic Frontotemporal Dementia,” published in the September 2024 issue of Neurology by Schönecker et al.

Patients with genetic frontotemporal dementia (FTD) typically experience behavioral and neuropsychiatric symptoms.

Researchers conducted a retrospective study to define, quantify, and investigate the temporal and regional link between behavioral and neuropsychiatric phenotypes and brain atrophy in genetic FTD.

They analyzed data from the Genetic Frontotemporal Dementia Initiative cohort study of pathogenic variant carriers in c9orf72, progranulin (GRN), or microtubule-associated protein tau (MAPT) genes. The principal component analysis determined behavioral and neuropsychiatric clusters, which were compared between groups. Relationships between neuropsychiatric clusters and MRI-assessed atrophy were specified by voxel-based morphometry. Linear and generalized linear mixed effects models estimated the longitudinal course of symptoms.

The results showed 522 participants: 221 c9orf72 (138 presymptomatic), 213 GRN (157 presymptomatic), and 88 MAPT (62 presymptomatic) pathogenic variant carriers. Principal component analysis showed 5 phenotypic clusters (67.6% of variance), labeled diverse behavioral, affective, psychotic, euphoric/hypersexual, and tactile hallucinations phenotypes. For participants with behavioral or neuropsychiatric symptoms, affective symptoms were more regular across groups (83.6% — 88.1%), followed by diverse behavioral symptoms (68.4% — 77.9%). In c9orf72 and GRN pathogenic variant carriers, psychotic symptoms (32.0% and 19.4%, respectively) were more frequent than euphoric/hypersexual symptoms (28.7% and 14.2%, respectively), which was the other way around in MAPT pathogenic variant carriers (28.6% and 23.8%). Although diverse behavioral symptoms were associated with gray and white matter frontotemporal atrophy, only a tiny atrophy cluster in the right thalamus was associated with psychotic symptoms. Euphoric/hypersexual symptoms were associated with atrophy in mesial temporal lobes, basal forebrain structures, and the striatum (P<0.05), and estimated time to symptom onset, genetic group, education, and sex-influenced behavioral and neuropsychiatric symptoms (P<0.05). Notably, in c9orf72 pathogenic variant carriers, psychotic symptoms may start decades before recognition of the onset of illness.

They concluded that multiple behavioral and neuropsychiatric symptom clusters in genetic FTD relate to distinct cerebral atrophy patterns influenced by time, gene, sex, and education, guiding diagnostic evaluations and clinical trial design.

Source: neurology.org/doi/10.1212/WNL.0000000000209569