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
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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
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Journal ArticleDOI
Primary progressive aphasia: a clinical approach.
Charles R. Marshall,Chris J.D. Hardy,Anna Volkmer,Lucy L. Russell,Rebecca L. Bond,Phillip D. Fletcher,Camilla N. Clark,Catherine J. Mummery,Jonathan M. Schott,Martin N. Rossor,Nick C. Fox,Sebastian J. Crutch,Jonathan D. Rohrer,Jason D. Warren +13 more
TL;DR: A clinical approach to the progressive aphasias is presented, based on the experience of these disorders and directed at non-specialists, and a prospect for future progress is concluded, emphasising generic information processing deficits and novel pathophysiological biomarkers.
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The clinical spectrum of sporadic and familial forms of frontotemporal dementia.
TL;DR: This review aims to clarify the often confusing terminology of FTD, and outline the various clinical features and diagnostic criteria of sporadic and familial FTD syndromes.
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Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype
TL;DR: It is possible therefore that FTLD is a reflection of dysfunction within lysosomal/proteasomal systems resulting in failure to remove potentially neurotoxic aggregates, which ultimately overwhelm capacity to function.
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Pain in amyotrophic lateral sclerosis
TL;DR: Given the multifactorial nature of pain in patients with ALS, different treatments have been suggested, ranging from non-steroidal anti-inflammatory drugs, drugs for neuropathic pain, opioids, and cannabinoids, to physical therapy strategies and preventive assistive devices.
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Psychological and Cognitive Markers of Behavioral Variant Frontotemporal Dementia-A Clinical Neuropsychologist's View on Diagnostic Criteria and Beyond.
Andreas Johnen,Maxime Bertoux +1 more
TL;DR: A critical appraisal of common methods to access the behavioral and psychological symptoms as well as the cognitive alterations presented in the diagnostic criteria for Behavioral variant frontotemporal dementia is aimed at.
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TL;DR: 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, which could help to define biomarkers that can stage presymPTomatic disease and track disease progression.
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