Loss of Insight in Syndromes Associated with Frontotemporal Lobar Degeneration: Clinical and Imaging Features.

Objectives: The present study aims to assess the prevalence, associated clinical symptoms, longitudinal changes, and imaging correlates of Loss of Insight (LOI), which is still unexplored in syndromes associated with Frontotemporal Lobar Degeneration (FTLD).

Design: Retrospective longitudinal cohort study, from Oct 2009 to Feb 2023.

Setting: Tertiary Frontotemporal Dementia research clinic.

Participants: A sample of 712 FTLD patients, 331 of whom had follow-up evaluation.

Measurements: LOI was assessed by interview with the primary caregiver. Univariate and multiple logistic regression and linear mixed models were used to estimate predictors and longitudinal changes over time associated with LOI. Voxel-based morphometry and structural covariance analyses of brain structural MRI images were implemented in Statistical Parametric Mapping.

Results: LOI was reported in 45% of patients (321/712, 95%CI = 41-49), with progressively increased prevalence from prodromal to severe dementia stages. LOI was more prevalent in the behavioural variant FTD, in the semantic variant of Primary Progressive Aphasia (svPPA) and FTD with Amyotrophic Lateral Sclerosis than in other phenotypes (all p-values<0.001). LOI severity increased over time only in patients with svPPA (β = +0.59, p <0.001) and clustered with other behavioral symptoms (all p-values <0.05). Finally, LOI was significantly associated with greater atrophy in the right medial orbital gyrus (p <0.001 uncorrected). Structural covariance analysis demonstrated loss of negative correlation between right medial orbital gyrus and regions belonging to the Default Mode Network (DMN), such as the left precuneus and the left angular gyrus (p ≤0.05 family-wise error-corrected) in FTLD patients with LOI.

Conclusions: A better comprehension of LOI mechanisms could lead to more effective interventions and healthcare policies.