Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage
Objective: This study aimed to establish (1) the pattern and severity of neuropsychiatric symptoms and other non-motor symptoms of sleep and mood, across ALS phenotypes in comparison to bvFTD and (2) the contribution of non-modifiable factors including age, sex and disease state to the severity of s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.743688/full |
| _version_ | 1819039518036066304 |
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| author | Emma M. Devenney Emma M. Devenney Kate McErlean Nga Yan Tse Nga Yan Tse Jashelle Caga Jashelle Caga Thanuja Dharmadasa Thanuja Dharmadasa Thanuja Dharmadasa William Huynh William Huynh William Huynh Colin J. Mahoney Colin J. Mahoney Margaret Zoing Margaret Zoing Srestha Mazumder Srestha Mazumder Carol Dobson-Stone Carol Dobson-Stone John B. Kwok John B. Kwok Glenda M. Halliday Glenda M. Halliday John R. Hodges John R. Hodges Olivier Piguet Olivier Piguet Rebekah M. Ahmed Rebekah M. Ahmed Rebekah M. Ahmed Matthew C. Kiernan Matthew C. Kiernan Matthew C. Kiernan |
| author_facet | Emma M. Devenney Emma M. Devenney Kate McErlean Nga Yan Tse Nga Yan Tse Jashelle Caga Jashelle Caga Thanuja Dharmadasa Thanuja Dharmadasa Thanuja Dharmadasa William Huynh William Huynh William Huynh Colin J. Mahoney Colin J. Mahoney Margaret Zoing Margaret Zoing Srestha Mazumder Srestha Mazumder Carol Dobson-Stone Carol Dobson-Stone John B. Kwok John B. Kwok Glenda M. Halliday Glenda M. Halliday John R. Hodges John R. Hodges Olivier Piguet Olivier Piguet Rebekah M. Ahmed Rebekah M. Ahmed Rebekah M. Ahmed Matthew C. Kiernan Matthew C. Kiernan Matthew C. Kiernan |
| author_sort | Emma M. Devenney |
| collection | DOAJ |
| description | Objective: This study aimed to establish (1) the pattern and severity of neuropsychiatric symptoms and other non-motor symptoms of sleep and mood, across ALS phenotypes in comparison to bvFTD and (2) the contribution of non-modifiable factors including age, sex and disease state to the severity of symptoms experienced by ALS patients.Methods: Consecutive participants were recruited to the study and underwent a detailed clinical, cognitive, behavioral and neuroimaging assessment. Neuropsychiatric and other non-motor symptoms were determined using the Cambridge Behavioral Inventory, the CBI-R. The scores were converted to define impairment in terms of mild, moderate and severe symptoms for each subscale. Rate, severity and contribution of King's staging and modifiable factors were also determined and a regression model identified predictors of symptom severity.Results: In total, 250 participants (115 ALS, 98 bvFTD, and 37 ALS-FTD patients) were recruited. A similar pattern of neuropsychiatric symptom severity was identified (apathy, disinhibition and stereotypic behavior) for all behavioral phenotypes of ALS compared to bvFTD (all p > 0.05). Neuropsychiatric symptoms were also present in cases defined as ALSpure and the cognitive phenotype of ALS (ALSci) although they occurred less frequently and were at the milder end of the spectrum. Disordered sleep and disrupted mood were common across all phenotypes (all p < 0.05). The severity of sleep dysfunction was influenced by both sex and age (all p < 0.05). Neuropsychiatric symptoms, sleep and mood disorders were common early in the disease process and deteriorated in line with progression on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; all p < 0.05). Diagnostic phenotype, disease duration and global cognition scores were the strongest predictors of non-motor and neuropsychiatric impairments.Conclusion: The current findings reveal strikingly similar patterns of changes across the subgroups of ALS and bvFTD, supporting the concept of the ALS-FTD spectrum. The findings further highlight the impact of non-motor and neuropsychiatric symptoms in patients with ALS, that are often as severe as that seen in ALS-FTD and bvFTD. This study advances understanding across the ALS-FTD spectrum that may accelerate the early identification of patient needs, to ensure prompt recognition of symptoms and thereby to improve clinical awareness, patient care and management. |
| first_indexed | 2024-12-21T08:54:28Z |
| format | Article |
| id | doaj.art-699516c0614b4b02a87827e30181fbbd |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-21T08:54:28Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-699516c0614b4b02a87827e30181fbbd2022-12-21T19:09:36ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-11-011210.3389/fneur.2021.743688743688Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease StageEmma M. Devenney0Emma M. Devenney1Kate McErlean2Nga Yan Tse3Nga Yan Tse4Jashelle Caga5Jashelle Caga6Thanuja Dharmadasa7Thanuja Dharmadasa8Thanuja Dharmadasa9William Huynh10William Huynh11William Huynh12Colin J. Mahoney13Colin J. Mahoney14Margaret Zoing15Margaret Zoing16Srestha Mazumder17Srestha Mazumder18Carol Dobson-Stone19Carol Dobson-Stone20John B. Kwok21John B. Kwok22Glenda M. Halliday23Glenda M. Halliday24John R. Hodges25John R. Hodges26Olivier Piguet27Olivier Piguet28Rebekah M. Ahmed29Rebekah M. Ahmed30Rebekah M. Ahmed31Matthew C. Kiernan32Matthew C. Kiernan33Matthew C. Kiernan34Brain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaRoyal College of Surgeons in Ireland, Dublin, IrelandBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United KingdomBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaPrince of Wales Clinical School, University of New South Wales, Kensington, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaSchool of Psychology, The University of Sydney, Sydney, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaInstitute of Clinical Neurosciences, Royal Prince Alfred Hospital, Camperdown, NSW, AustraliaBrain and Mind Centre, The University of Sydney, Sydney, NSW, AustraliaFaculty of Medicine and Health, The University of Sydney, Sydney, NSW, AustraliaInstitute of Clinical Neurosciences, Royal Prince Alfred Hospital, Camperdown, NSW, AustraliaObjective: This study aimed to establish (1) the pattern and severity of neuropsychiatric symptoms and other non-motor symptoms of sleep and mood, across ALS phenotypes in comparison to bvFTD and (2) the contribution of non-modifiable factors including age, sex and disease state to the severity of symptoms experienced by ALS patients.Methods: Consecutive participants were recruited to the study and underwent a detailed clinical, cognitive, behavioral and neuroimaging assessment. Neuropsychiatric and other non-motor symptoms were determined using the Cambridge Behavioral Inventory, the CBI-R. The scores were converted to define impairment in terms of mild, moderate and severe symptoms for each subscale. Rate, severity and contribution of King's staging and modifiable factors were also determined and a regression model identified predictors of symptom severity.Results: In total, 250 participants (115 ALS, 98 bvFTD, and 37 ALS-FTD patients) were recruited. A similar pattern of neuropsychiatric symptom severity was identified (apathy, disinhibition and stereotypic behavior) for all behavioral phenotypes of ALS compared to bvFTD (all p > 0.05). Neuropsychiatric symptoms were also present in cases defined as ALSpure and the cognitive phenotype of ALS (ALSci) although they occurred less frequently and were at the milder end of the spectrum. Disordered sleep and disrupted mood were common across all phenotypes (all p < 0.05). The severity of sleep dysfunction was influenced by both sex and age (all p < 0.05). Neuropsychiatric symptoms, sleep and mood disorders were common early in the disease process and deteriorated in line with progression on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; all p < 0.05). Diagnostic phenotype, disease duration and global cognition scores were the strongest predictors of non-motor and neuropsychiatric impairments.Conclusion: The current findings reveal strikingly similar patterns of changes across the subgroups of ALS and bvFTD, supporting the concept of the ALS-FTD spectrum. The findings further highlight the impact of non-motor and neuropsychiatric symptoms in patients with ALS, that are often as severe as that seen in ALS-FTD and bvFTD. This study advances understanding across the ALS-FTD spectrum that may accelerate the early identification of patient needs, to ensure prompt recognition of symptoms and thereby to improve clinical awareness, patient care and management.https://www.frontiersin.org/articles/10.3389/fneur.2021.743688/fullALS (amyotrophic lateral sclerosis)behavioral impairmentnon-motor deficitsneuropsychiatric symptomsfrontotemporal dementia |
| spellingShingle | Emma M. Devenney Emma M. Devenney Kate McErlean Nga Yan Tse Nga Yan Tse Jashelle Caga Jashelle Caga Thanuja Dharmadasa Thanuja Dharmadasa Thanuja Dharmadasa William Huynh William Huynh William Huynh Colin J. Mahoney Colin J. Mahoney Margaret Zoing Margaret Zoing Srestha Mazumder Srestha Mazumder Carol Dobson-Stone Carol Dobson-Stone John B. Kwok John B. Kwok Glenda M. Halliday Glenda M. Halliday John R. Hodges John R. Hodges Olivier Piguet Olivier Piguet Rebekah M. Ahmed Rebekah M. Ahmed Rebekah M. Ahmed Matthew C. Kiernan Matthew C. Kiernan Matthew C. Kiernan Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage Frontiers in Neurology ALS (amyotrophic lateral sclerosis) behavioral impairment non-motor deficits neuropsychiatric symptoms frontotemporal dementia |
| title | Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage |
| title_full | Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage |
| title_fullStr | Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage |
| title_full_unstemmed | Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage |
| title_short | Factors That Influence Non-Motor Impairment Across the ALS-FTD Spectrum: Impact of Phenotype, Sex, Age, Onset and Disease Stage |
| title_sort | factors that influence non motor impairment across the als ftd spectrum impact of phenotype sex age onset and disease stage |
| topic | ALS (amyotrophic lateral sclerosis) behavioral impairment non-motor deficits neuropsychiatric symptoms frontotemporal dementia |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.743688/full |
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