Pain and temperature processing in dementia: a clinical and neuroanatomical analysis
Phillip D. Fletcher,Laura E. Downey,Hannah L. Golden,Camilla N. Clark,Catherine F. Slattery,Ross W. Paterson,Jonathan D. Rohrer,Jonathan M. Schott,Martin N. Rossor,Jason D. Warren +9 more
TLDR
Using a semi-structured caregiver questionnaire and MRI voxel-based morphometry in patients with frontotemporal degeneration or Alzheimer’s disease, Fletcher et al. show that symptoms are underpinned by atrophy in a distributed thalamo-temporo-insular network implicated in somatosensory processing.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.read more
Citations
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Journal ArticleDOI
Interactions between decision-making and emotion in behavioral-variant frontotemporal dementia and Alzheimer’s disease
Aurélie L. Manuel,Daniel Roquet,Ramon Landin-Romero,Fiona Kumfor,Rebekah M. Ahmed,John R. Hodges,Olivier Piguet +6 more
TL;DR: It is shown that bvFTD patients were more impulsive than AD patients and CTRL and did not show any emotion-related modulation of delay discounting rate, indicating that decision-making and emotion interact at the level of the amygdala supporting findings from animal studies.
Book ChapterDOI
Hypothalamic symptoms of frontotemporal dementia disorders.
TL;DR: The physiological changes found in FTD are reviewed and the key neural networks and neuroendocrine changes mediating these changes in function discussed, including the ability to use these changes as biomarkers to aid in disease diagnosis, monitoring disease progression, and as potential treatment targets.
Journal ArticleDOI
The Seven Selves of Dementia.
TL;DR: The self is a complex and multifaceted phenomenon encompassing a variety of cognitive processes and psychosocial influences as discussed by the authors, and there is a multiplicity of self-processes, including embodied self, agentic self, implicit self, critical self, extended self, and emergent self.
Journal ArticleDOI
Thermoregulatory profile of neurodegeneration-induced dementia of the Alzheimer's type using intracerebroventricular streptozotocin in rats.
Anna Carolina Parracho Motzko-Soares,Robson Cristiano Lillo Vizin,Talita Maria Senra Martins,A. R. O. Hungaro,J. R. Sato,Maria Camila Almeida,Daniel Carneiro Carrettiero +6 more
TL;DR: This work has extensively investigated the relationship between thermoregulation and neurodegeneration‐induced dementia of the Alzheimer's type using intracerebroventricular injections of streptozotocin (icv‐STZ).
Journal ArticleDOI
Pain processing in older adults with dementia-related cognitive impairment is associated with frontal neurodegeneration
Steffie Bunk,Sytse U Zuidema,Kathrin Koch,Stefan Lautenbacher,Peter Paul De Deyn,Miriam Kunz +5 more
TL;DR: In this paper, the authors examined whether differences in pressure pain sensitivity and endogenous pain inhibition (conditioned pain modulation (CPM)) between individuals with a dementia-related cognitive impairment (N = 23) and healthy controls (N=35) are linked to dementiarelated neurodegeneration, and found that cognitively impaired individuals show decreased CPM inhibition as assessed by facial responses compared to healthy controls, which was mediated by decreased gray matter volume in the medial orbitofrontal and anterior cingulate cortex in the patient group.
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