Phenomenology and anatomy of abnormal behaviours in primary progressive aphasia

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.