The relation of familial longevity and progression of disability in multiple sclerosis

Gao, Xin (2019) The relation of familial longevity and progression of disability in multiple sclerosis. MSc(Res) thesis, University of Nottingham.

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Background: Multiple sclerosis (MS) is an immune-mediated demyelinating disease with immune system attacking the protective myelin sheath that covers nerve fibres and causes neurological deficits. Ageing is a factor that is related to the progression of disease disability. Previous studies have shown an inheritance of longevity. The genetic or familial effect on disability progression in MS has not been studied in detail previously.

Aims: This study aims to explore the association between familial longevity and Multiple sclerosis severity score (MSSS), which is a measurement of the rate of disability progression in MS. Another aim of this study is to evaluate the frailty index (FI) of patients and family members, and its relationship with the MSSS.

Methods: A self-reported questionnaire was designed based on the literature review. The MSSS was measured by disease duration and Expanded Disability Status Scale (EDSS). In total, 323 patients were recruited from the Nottingham cohort of the MS Registry and responded to the questionnaire in the MS clinic or by post. The relation of familial longevity and individual frailty was assessed by multiple linear regression. The effect of familial longevity, frailty and neurological degenerative disease history was extracted by principal component analysis (PCA).

Results: Multiple regression showed that while adjusted for significant covariates, the relation between MSSS and interaction of ‘parental age, neurological degenerative disease history, and frailty’ was significant but relatively weak (β = -0.304, p<0.000). We also showed that the association between MSSS and current patients’ frailty was significant but relatively weak (β= 0.169, p<0.000). Cox regression showed a significant association between risk of reaching EDSS 6.5 (adjusted HR=1.119, p<0.000) / transition to the secondary progressive stage (adjusted HR=1.123, p<0.000) and current patients’ frailty index, but not for the extracted interaction of ‘parental age, neurological disease history and frailty’.

Conclusion: We found that familial longevity alone may not be associated with any change in the progression rate of MS disability when controlled by other covariates in this exploratory study. Nevertheless, the parental ageing (defined as the interaction of ‘parental age, neurological disease history and frailty’ in the current study) may weakly relate to MSSS. Patients’ frailty, but not that of parents or grandparents correlated with faster progression of MS disability. Further study may provide more definitive results on the familial influences on MS progression rate.

Item Type: Thesis (University of Nottingham only) (MSc(Res))
Supervisors: Evangelou, Nikos
Constantinescu, Cris
Keywords: Multiple sclerosis severity score; Disability progression; Frailty index; Familial longevity
Subjects: W Medicine and related subjects (NLM Classification) > WL Nervous system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 55800
Depositing User: GAO, Xin
Date Deposited: 08 Apr 2019 13:51
Last Modified: 07 May 2020 13:46

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