Disentangling Clinical Profiles of Apathy in Behavioral Variant Frontotemporal Dementia

Abstract

Background: Apathy is highly frequent in behavioral variant frontotemporal dementia (bvFTD). It is presumed to involve different pathophysiological mechanisms and neuroanatomical regions. Objective: We explored the hypothesis that subgroups showing distinct profiles of apathy and distinct patterns of atrophy within frontal lobes could be disentangled in bvFTD. Methods: Using data-driven clustering applied to 20 bvFTD patients, we isolated subgroups according to their profiles on the three subscales of the Dimensional Apathy Scale (DAS). We explored their apathy profiles and atrophy patterns. Apathy profiles were characterized through both subjective measures of apathy by questionnaires and measures including objective behavioral metrics. Atrophy patterns were obtained by voxel-based morphometry, contrasting each bvFTD subgroup with healthy controls (N = 16). Results: By clustering based on DAS dimensions, we disentangled three subgroups of bvFTD patients, with distinct apathy profiles and atrophy patterns. One subgroup, which presented the smallest pattern of atrophy (including orbitofrontal cortex) with a right asymmetry, was characterized by high self-reported emotional and initiation apathy and by a self-initiation deficit reversible by external guidance. In other subgroups showing more diffuse bilateral atrophies extending to lateral prefrontal cortex, apathy was not reversible by external guidance and more difficulty to focus on goal-management was observed, especially in the subgroup with the largest atrophy and highest levels of executive apathy. Conclusion: Distinct clinical profiles of apathy, corresponding to distinct anatomical subtypes of bvFTD, were identified. These findings have implications for clinicians in a perspective of precision medicine as they could contribute to personalize treatments of apathy.

High delay discounting relates to core symptoms and to pulvinar atrophy in frontotemporal dementia

“…This study was part of a larger-scale protocol that also collected other data that are reported elsewhere. 21,[23][24][25] Participants were recruited in the context of a clinical study at the Paris Brain Institute in France (Clinicaltrials.gov: NCT03272230). 21,[23][24][25] This clinical study aimed at assessing several behavioural symptoms (disinhibition and apathy) and investigating their neural correlates in behavioural variant frontotemporal dementia.…”

“…21,[23][24][25] Participants were recruited in the context of a clinical study at the Paris Brain Institute in France (Clinicaltrials.gov: NCT03272230). 21,[23][24][25] This clinical study aimed at assessing several behavioural symptoms (disinhibition and apathy) and investigating their neural correlates in behavioural variant frontotemporal dementia. BvFTD patients were recruited in two tertiary referral centres in Paris: the Pitié-Salpêtrière Hospital and the Lariboisière Fernand-Widal Hospital.…”

Rehabilitation Services for Young-Onset Dementia: Examples from High- and Low–Middle-Income Countries

“…Behaviour modification strategies can be developed based on contingency management, where a person with bvFTD is rewarded with something they value after they have completed a certain activity of daily living (see a full description with examples in O’Connor et al 2016 [ 45 ]). When setting up interventions for bvFTD, understanding each individual’s cognitive and behavioural profile (e.g., apathy subtype) is pivotal to effective personalised care [ 46 , 47 ].…”