Dataset Information

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

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.

SUBMITTER: Fletcher PD

PROVIDER: S-EPMC4620514 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Fletcher Phillip D PD Downey Laura E LE Golden Hannah L HL Clark Camilla N CN Slattery Catherine F CF Paterson Ross W RW Rohrer Jonathan D JD Schott Jonathan M JM Rossor Martin N MN Warren Jason D JD

Brain : a journal of neurology 20151012 Pt 11

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 frontotempora ...[more]

PMID: 26463677

Similar Datasets

Project description:Voice processing in neurodegenerative disease is poorly understood. Here we undertook a systematic investigation of voice processing in a cohort of patients with clinical diagnoses representing two canonical dementia syndromes: temporal variant frontotemporal lobar degeneration (n = 14) and Alzheimer's disease (n = 22). Patient performance was compared with a healthy matched control group (n = 35). All subjects had a comprehensive neuropsychological assessment including measures of voice perception (vocal size, gender, speaker discrimination) and voice recognition (familiarity, identification, naming and cross-modal matching) and equivalent measures of face and name processing. Neuroanatomical associations of voice processing performance were assessed using voxel-based morphometry. Both disease groups showed deficits on all aspects of voice recognition and impairment was more severe in the temporal variant frontotemporal lobar degeneration group than the Alzheimer's disease group. Face and name recognition were also impaired in both disease groups and name recognition was significantly more impaired than other modalities in the temporal variant frontotemporal lobar degeneration group. The Alzheimer's disease group showed additional deficits of vocal gender perception and voice discrimination. The neuroanatomical analysis across both disease groups revealed common grey matter associations of familiarity, identification and cross-modal recognition in all modalities in the right temporal pole and anterior fusiform gyrus; while in the Alzheimer's disease group, voice discrimination was associated with grey matter in the right inferior parietal lobe. The findings suggest that impairments of voice recognition are significant in both these canonical dementia syndromes but particularly severe in temporal variant frontotemporal lobar degeneration, whereas impairments of voice perception may show relative specificity for Alzheimer's disease. The right anterior temporal lobe is likely to have a critical role in the recognition of voices and other modalities of person knowledge.

Project description:Humour is a complex cognitive and emotional construct that is vulnerable in neurodegenerative diseases, notably the frontotemporal lobar degenerations. However, humour processing in these diseases has been little studied. Here we assessed humour processing in patients with behavioural variant frontotemporal dementia (n = 22, mean age 67 years, four female) and semantic dementia (n = 11, mean age 67 years, five female) relative to healthy individuals (n = 21, mean age 66 years, 11 female), using a joint cognitive and neuroanatomical approach. We created a novel neuropsychological test requiring a decision about the humorous intent of nonverbal cartoons, in which we manipulated orthogonally humour content and familiarity of depicted scenarios. Structural neuroanatomical correlates of humour detection were assessed using voxel-based morphometry. Assessing performance in a signal detection framework and after adjusting for standard measures of cognitive function, both patient groups showed impaired accuracy of humour detection in familiar and novel scenarios relative to healthy older controls (p < .001). Patient groups showed similar overall performance profiles; however the behavioural variant frontotemporal dementia group alone showed a significant advantage for detection of humour in familiar relative to novel scenarios (p = .045), suggesting that the behavioural variant syndrome may lead to particular difficulty decoding novel situations for humour, while semantic dementia produces a more general deficit of humour detection that extends to stock comedic situations. Humour detection accuracy was associated with grey matter volume in a distributed network including temporo-parietal junctional and anterior superior temporal cortices, with predominantly left-sided correlates of processing humour in familiar scenarios and right-sided correlates of processing novel humour. The findings quantify deficits of core cognitive operations underpinning humour processing in frontotemporal lobar degenerations and suggest a candidate brain substrate in cortical hub regions processing incongruity and semantic associations. Humour is a promising candidate tool with which to assess complex social signal processing in neurodegenerative disease.

Project description:BACKGROUND:Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin (GRN), microtubule-associated protein tau (MAPT), or chromosome 9 open reading frame 72 (C9orf72). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia. METHODS:We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT, or C9orf72, or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers. FINDINGS:Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test -0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all -0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference -0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference -0·2, SE 0·1). INTERPRETATION:Structural imaging and cognitive changes can be identified 5-10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials. FUNDING:Centres of Excellence in Neurodegeneration.

Project description:Relating clinical symptoms to neuroanatomical profiles of brain damage and ultimately to tissue pathology is a key challenge in the field of neurodegenerative disease and particularly relevant to the heterogeneous disorders that comprise the frontotemporal lobar degeneration spectrum. Here we present a retrospective analysis of clinical, neuropsychological and neuroimaging (volumetric and voxel-based morphometric) features in a pathologically ascertained cohort of 95 cases of frontotemporal lobar degeneration classified according to contemporary neuropathological criteria. Forty-eight cases (51%) had TDP-43 pathology, 42 (44%) had tau pathology and five (5%) had fused-in-sarcoma pathology. Certain relatively specific clinicopathological associations were identified. Semantic dementia was predominantly associated with TDP-43 type C pathology; frontotemporal dementia and motoneuron disease with TDP-43 type B pathology; young-onset behavioural variant frontotemporal dementia with FUS pathology; and the progressive supranuclear palsy syndrome with progressive supranuclear palsy pathology. Progressive non-fluent aphasia was most commonly associated with tau pathology. However, the most common clinical syndrome (behavioural variant frontotemporal dementia) was pathologically heterogeneous; while pathologically proven Pick's disease and corticobasal degeneration were clinically heterogeneous, and TDP-43 type A pathology was associated with similar clinical features in cases with and without progranulin mutations. Volumetric magnetic resonance imaging, voxel-based morphometry and cluster analyses of the pathological groups here suggested a neuroanatomical framework underpinning this clinical and pathological diversity. Frontotemporal lobar degeneration-associated pathologies segregated based on their cerebral atrophy profiles, according to the following scheme: asymmetric, relatively localized (predominantly temporal lobe) atrophy (TDP-43 type C); relatively symmetric, relatively localized (predominantly temporal lobe) atrophy (microtubule-associated protein tau mutations); strongly asymmetric, distributed atrophy (Pick's disease); relatively symmetric, predominantly extratemporal atrophy (corticobasal degeneration, fused-in-sarcoma pathology). TDP-43 type A pathology was associated with substantial individual variation; however, within this group progranulin mutations were associated with strongly asymmetric, distributed hemispheric atrophy. We interpret the findings in terms of emerging network models of neurodegenerative disease: the neuroanatomical specificity of particular frontotemporal lobar degeneration pathologies may depend on an interaction of disease-specific and network-specific factors.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets