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
More filters
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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.
References
More filters
Journal ArticleDOI
Receptive prosody in nonfluent primary progressive aphasias.
TL;DR: 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).
Journal ArticleDOI
The impact of Alzheimer's disease on the functional connectivity between brain regions underlying pain perception.
Leonie J Cole,Maria Gavrilescu,Leigh A. Johnston,Leigh A. Johnston,Stephen J. Gibson,Michael Farrell,Gary F. Egan +6 more
TL;DR: The results of this study support previous research suggesting an interplay between pain and cognitive processes in patients with AD, and show inter-regional functional connectivity across most regions of the predefined pain network was shown to be greater in the patient group.
Journal ArticleDOI
Pain perception and tolerance in patients with frontotemporal dementia
Elisa Carlino,Fabrizio Benedetti,Innocenzo Rainero,G Asteggiano,Giorgia Cappa,L. Tarenzi,Sergio Vighetti,Antonella Pollo +7 more
TL;DR: The results suggest differences in pain processing changes in distinct types of dementia, while at the same time caution that pain perception assessment may depend on the criteria adopted for diagnosis.
Journal ArticleDOI
Frontotemporal dementia with amyotrophic lateral sclerosis: A clinical comparison of patients with and without repeat expansions in C9orf72
Julie S. Snowden,Jennifer M. Harris,Anna Richardson,Sara Rollinson,Jennifer C. Thompson,David Neary,David M. A. Mann,Stuart Pickering-Brown +7 more
TL;DR: Phenotypic differences exist between patients with and without C9orf72 expansions, suggesting that FTD-ALS may be underpinned by distinct neurobiological substrates, and the presence of psychiatric symptoms in the context of FTd-ALS should alert clinicians to the possibility of C9orc72 expansions.
Journal ArticleDOI
Subcortical and deep cortical atrophy in Frontotemporal Lobar Degeneration
Valentina Garibotto,Valentina Garibotto,Barbara Borroni,Chiara Agosti,Enrico Premi,Antonella Alberici,Simon B. Eickhoff,Simon B. Eickhoff,Simona Maria Brambati,Giuseppe Bellelli,Roberto Gasparotti,Daniela Perani,Alessandro Padovani +12 more
TL;DR: Correlation analyses suggested an association between GM volumes and language, psychomotor speed and behavioral disturbances and a widespread involvement of subcortical and deep cortical GM in early FTLD with patterns specific for clinical entity.
Related Papers (5)
Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.
Katya Rascovsky,John R. Hodges,David S. Knopman,Mario F. Mendez,Joel H. Kramer,John Neuhaus,John C. van Swieten,Harro Seelaar,Elise G.P. Dopper,Chiadi U. Onyike,Argye E. Hillis,Keith A. Josephs,Bradley F. Boeve,Andrew Kertesz,William W. Seeley,Katherine P. Rankin,Julene K. Johnson,Maria Luisa Gorno-Tempini,Howard J. Rosen,Caroline E. Prioleau-Latham,Albert Lee,Christopher M. Kipps,Christopher M. Kipps,Patricia Lillo,Olivier Piguet,Jonathan D. Rohrer,Martin N. Rossor,Jason D. Warren,Nick C. Fox,Douglas Galasko,David P. Salmon,Sandra E. Black,M.-Marsel Mesulam,Sandra Weintraub,Brad C. Dickerson,Janine Diehl-Schmid,Florence Pasquier,Vincent Deramecourt,Florence Lebert,Yolande A.L. Pijnenburg,Tiffany W. Chow,Facundo Manes,Jordan Grafman,Stefano F. Cappa,Morris Freedman,Murray Grossman,Bruce L. Miller +46 more
Classification of primary progressive aphasia and its variants
Maria Luisa Gorno-Tempini,Maria Luisa Gorno-Tempini,Argye E. Hillis,Sandra Weintraub,Andrew Kertesz,Mario F. Mendez,Stefano F. Cappa,J. M. Ogar,Jonathan D. Rohrer,Sandra E. Black,Bradley F. Boeve,Facundo Manes,Nina F. Dronkers,Rik Vandenberghe,Katya Rascovsky,Karalyn Patterson,Bruce L. Miller,D. S. Knopman,John R. Hodges,M.-Marsel Mesulam,Murray Grossman +20 more
Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis
Jonathan D. Rohrer,Jennifer M. Nicholas,Jennifer M. Nicholas,David M. Cash,John C. van Swieten,Elise G.P. Dopper,Lize C. Jiskoot,Rick van Minkelen,Serge A.R.B. Rombouts,M. Jorge Cardoso,Shona Clegg,Miklos Espak,Simon Mead,David L. Thomas,Enrico De Vita,Mario Masellis,Sandra E. Black,Morris Freedman,Ron Keren,Bradley J. MacIntosh,Ekaterina Rogaeva,David F. Tang-Wai,Maria Carmela Tartaglia,Robert Laforce,Fabrizio Tagliavini,Pietro Tiraboschi,Veronica Redaelli,Sara Prioni,Marina Grisoli,Barbara Borroni,Alessandro Padovani,Daniela Galimberti,Elio Scarpini,Andrea Arighi,Giorgio G. Fumagalli,James B. Rowe,Ian Coyle-Gilchrist,Caroline Graff,Caroline Graff,Marie Fallström,Vesna Jelic,Vesna Jelic,Anne Kinhult Ståhlbom,Anne Kinhult Ståhlbom,Christin Andersson,Christin Andersson,Håkan Thonberg,Håkan Thonberg,Lena Lilius,Giovanni B. Frisoni,Giuliano Binetti,Michela Pievani,Martina Bocchetta,Luisa Benussi,Roberta Ghidoni,Elizabeth Finger,Sandro Sorbi,Benedetta Nacmias,Gemma Lombardi,Cristina Polito,Jason D. Warren,Sebastien Ourselin,Nick C. Fox,Martin N. Rossor +63 more
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease
Guy M. McKhann,Guy M. McKhann,David S. Knopman,Howard Chertkow,Bradley T. Hyman,Clifford R. Jack,Claudia H. Kawas,William E. Klunk,Walter J. Koroshetz,Jennifer J. Manly,Richard Mayeux,Richard C. Mohs,John C. Morris,Martin N. Rossor,Philip Scheltens,Maria C. Carrillo,Bill Thies,Sandra Weintraub,Creighton H. Phelps +18 more