Phenomenology and anatomy of abnormal behaviours in primary progressive aphasia

Abstract

Primary progressive aphasia (PPA) is a group of disorders with progressive language impairment. Abnormal behaviour may develop in PPA as the disease evolves, but the clinical features and brain basis of behavioural change in PPA have not been fully defined. 33 PPA patients (9 semantic dementia, SD, 14 progressive nonfluent aphasia, PNFA, 7 logopenic/phonological aphasia, LPA and 3 patients with a PPA syndrome in association with progranulin mutations, GRN-PPA) were assessed using the Neuropsychiatric Inventory to record behavioural changes, as well as volumetric MR imaging. The most common abnormal behaviours in SD were irritability, disinhibition, depression and abnormal appetite, in PNFA apathy, agitation and depression, in LPA anxiety, irritability, agitation and apathy, and in GRN-PPA apathy and irritability. Voxel-based morphometry analysis revealed greater atrophy of right lateral orbitofrontal cortex (OFC) in PPA patients with anxiety, apathy, irritability/lability and abnormal appetite/eating disorders, and greater atrophy of left OFC in those with disinhibition. Areas involved beyond OFC included right dorsolateral prefrontal cortex (apathy), right cingulate (irritability/lability) and left anterior superior and medial temporal lobe (disinhibition). Behavioural abnormalities may be clinically significant in PPA, and these abnormalities are underpinned by atrophy of overlapping frontotemporal networks centred on OFC.

Frontotemporal Cortical Thinning in Amyotrophic Lateral Sclerosis

“…44 Moreover, the significant thinning of the orbitofrontal and premotor areas, which we found to correlate with ALSFRS-R and disease duration, may reflect a similar cortical degeneration pattern reported in both the behavioral variant of FTD and primaryprogressive aphasia, in which atrophy of the orbitofrontal and premotor areas was found to correlate with the occurrence of severely disabling behavioral changes (ie, aberrant eating and motor behaviors). [45][46][47] It is remarkable that no correlations were found between cortical thinning of the frontotemporal areas and frontal impairment (evaluated by T-score and subscores of FrSBe scale). By contrast, previous studies have reported an association between regional volume loss in several frontotemporal areas and cognitive and behavioral symptoms in both ALS 2,14,15,20 and the behavioral variant of FTD.…”

The non-fluent/agrammatic variant of primary progressive aphasia

“…Visuospatial functioning also is relatively preserved, although there are some exceptions such as naPPA presenting in the context of CBS 58 . It is uncommon to observe a disorder of social functioning and personality early in the course ofnaPPA,although socially inappropriate behaviors seen in patients with behavioral variant FTD (bvFTD) can emerge over time, includingapathy, disinhibition or repetitive behaviors withlittle empathy and poor self-insight 59,60 . The nonlanguage spectrum of cognitive deficits in naPPA thus appears to involve limitations in working memory and executive control, but may implicate other cognitive and social domains particularly as the condition progresses.…”

Activities of Daily Living in Progressive Non-Fluent Aphasia, Logopenic Progressive Aphasia and Alzheimer’s Disease

“…Recent studies have shown that patients with PNFA are not as functionally impaired as patients with AD [9], and that cognition is more affected than ADLs [11]. Behavioural disturbances are also present in patients with PNFA [12][13][14], although ADLs in PNFA, LPA and AD they were not reported as being significantly disturbing by their carers. There have been no studies of the impact of LPA on functional ability to date.…”