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

Fletcher, PD; Downey, LE; Golden, HL; Clark, CN; Slattery, CF; Paterson, RW; Rohrer, JD; Schott, JM; Rossor, MN; Warren, JD (2015) Pain and temperature processing in dementia: a clinical and neuroanatomical analysis. Brain, 138 (11). pp. 3360-3372. ISSN 0006-8950 https://doi.org/10.1093/brain/awv276
SGUL Authors: Clark, Camilla Neegaard

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Abstract

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.

Item Type: Article
Additional Information: © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Neurology & Neurosurgery, 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Brain
ISSN: 0006-8950
Language: en
Dates:
DateEvent
November 2015Published
12 October 2015Published Online
28 July 2015Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
091673/Z/10/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
URI: https://openaccess.sgul.ac.uk/id/eprint/112266
Publisher's version: https://doi.org/10.1093/brain/awv276

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