Pain and temperature processing in dementia: a clinical and neuroanatomical analysis.

Symptoms suggesting altered processing of pain and temperature have been described in dementia diseases and may contribute importantly to clinical phenotypes, particularly in the frontotemporal lobar degeneration spectrum, but the basis for these symptoms has not been characterized in detail. Here we analysed pain and temperature symptoms using a semi-structured caregiver questionnaire recording altered behavioural responsiveness to pain or temperature for a cohort of patients with frontotemporal lobar degeneration (n = 58, 25 female, aged 52-84 years, representing the major clinical syndromes and representative pathogenic mutations in the C9orf72 and MAPT genes) and a comparison cohort of patients with amnestic Alzheimer's disease (n = 20, eight female, aged 53-74 years). Neuroanatomical associations were assessed using blinded visual rating and voxel-based morphometry of patients' brain magnetic resonance images. Certain syndromic signatures were identified: pain and temperature symptoms were particularly prevalent in behavioural variant frontotemporal dementia (71% of cases) and semantic dementia (65% of cases) and in association with C9orf72 mutations (6/6 cases), but also developed in Alzheimer's disease (45% of cases) and progressive non-fluent aphasia (25% of cases). While altered temperature responsiveness was more common than altered pain responsiveness across syndromes, blunted responsiveness to pain and temperature was particularly associated with behavioural variant frontotemporal dementia (40% of symptomatic cases) and heightened responsiveness with semantic dementia (73% of symptomatic cases) and Alzheimer's disease (78% of symptomatic cases). In the voxel-based morphometry analysis of the frontotemporal lobar degeneration cohort, pain and temperature symptoms were associated with grey matter loss in a right-lateralized network including insula (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest) and anterior temporal cortex (P < 0.001 uncorrected over whole brain) previously implicated in processing homeostatic signals. Pain and temperature symptoms accompanying C9orf72 mutations were specifically associated with posterior thalamic atrophy (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest). Together the findings suggest candidate cognitive and neuroanatomical bases for these salient but under-appreciated phenotypic features of the dementias, with wider implications for the homeostatic pathophysiology and clinical management of neurodegenerative diseases.

Receptive prosody in nonfluent primary progressive aphasias.

INTRODUCTION: Prosody has been little studied in the primary progressive aphasias (PPAs), a group of neurodegenerative disorders presenting with progressive language impairment. METHODS: Here we conducted a systematic investigation of different dimensions of prosody processing (acoustic, linguistic and emotional) in a cohort of 19 patients with nonfluent PPA syndromes (11 with progressive nonfluent aphasia, PNFA; five with progressive logopenic/phonological aphasia, LPA; three with progranulin-associated aphasia, GRN-PPA) compared with a group of healthy older controls. Voxel-based morphometry (VBM) was used to identify neuroanatomical associations of prosodic functions. RESULTS: Broadly comparable receptive prosodic deficits were exhibited by the PNFA, LPA and GRN-PPA subgroups, for acoustic, linguistic and affective dimensions of prosodic analysis. Discrimination of prosodic contours was significantly more impaired than discrimination of simple acoustic cues, and discrimination of intonation was significantly more impaired than discrimination of stress at phrasal level. Recognition of vocal emotions was more impaired than recognition of facial expressions for the PPA cohort, and recognition of certain emotions (in particular, disgust and fear) was relatively more impaired than others (sadness, surprise). VBM revealed atrophy associated with acoustic and linguistic prosody impairments in a distributed cortical network including areas likely to be involved in perceptual analysis of vocalisations (posterior temporal and inferior parietal cortices) and working memory (fronto-parietal circuitry). Grey matter associations of emotional prosody processing were identified for negative emotions (disgust, fear, sadness) in a broadly overlapping network of frontal, temporal, limbic and parietal areas. CONCLUSIONS: Taken together, the findings show that receptive prosody is impaired in nonfluent PPA syndromes, and suggest a generic early perceptual deficit of prosodic signal analysis with additional relatively specific deficits (recognition of particular vocal emotions).