| Background:Spinocerebellar ataxia type 3(Spinocerebellar ataxia type 3,SCA3),also known as Machado-Joseph disease(MJD),is the most common autosomal dominant genetic nervous system in my country One of the degenerative diseases,ATXN3 is its pathogenic gene.Studies have shown that DNA damage is closely related to aging,and SCA3 has significant DNA damage.Therefore,we speculate that SCA3 patients have significant aging.However,so far,there are no research reports on the degree of aging of SCA3 patients,its influencing factors and the effect of aging on common clinical phenotypes of SCA3.Therefore,this study intends to recruit SCA3 patients and gender-and age-matched normal controls to detect the telomere length,skin aging degree and cortical thickness of the study subjects,evaluate the aging degree of SCA3 patients from three dimensions,and further analyze the aging indicators.The influencing factors and whether they affect the clinical phenotypes such as age of onset and severity of the disease will ultimately explore the aging of SCA3 patients more comprehensively.Methods:In the present study,142 molecular-confirmed SCA3 patients were recruited from Department of Neurology,the First Affiliated Hospital of Fujian Medical University from September 2020 to January 2021.The self-designed follow-up registration form was used to collect and record detailed medical history and physical examination of the nervous system.The Scale for the Assessment and Rating of Ataxia(SARA)and the International Cooperative Ataxia Rating Scale(ICARS)were used to assess the severity of ataxia in SCA3 patients.A total of 104 SCA3 patients were selected and 83 healthy controls matched for gender,age and life background were recruited,and the telomere length of DNA was detected by quantitative PCR in peripheral blood.At the same time,138 SCA3 patients were selected,and 80 healthy controls with matching gender,age and life background were included.A set of three photographs(one front full face and two others from 45° left and right sides with respect to the nose axis)were taken in the same environment and All pictures were blind-coded and evaluated by 5 trained experts,using the specific scales of severity provided by the Asian Skin Aging Atlas.In addition,48 adult patients with SCA3 and 52 healthy controls with matching gender,age,and life background were selected.After the enrollees were scanned by MRI,Freesurfer was used to measure the cortical thickness.Multivariable linear regression model was used to analyze the effects of telomere length,skin aging and cortical thickness on the age of onset of patients and the severity of ataxia,and to explore the potential factors affecting the aging of SCA3 patients.Results:1.A total of 104 SCA3 patients and 83 age-and gender-matched healthy controls were included in this study.Among 104 SCA3 patients,63 were males(58.24%)and41 were females(41.76%),with an average age of onset It was 35.91 ± 11.67 years,the average course of disease was 10.34 ± 6.09 years,the average number of CAG repeats in normal and amplified alleles were 21.10 ± 7.09 and 74.41 ± 3.71,respectively.The severity of ataxia: SARA scale score was 13.68 ± 7.25 points,ICARS scale score is 35.25 ± 16.53.There was no significant difference in gender and age distribution between the SCA3 patient group and the healthy control group(gender p = 0.165;age p = 0.140).The relative telomere length of 104 SCA3 patients was significantly lower than that of the healthy control group(0.58 ± 0.18 vs.0.66± 0.24,p = 0.011).Follow-up age(β =-0.499,p = 0.000)and CAG amplified fragments(β =-1.607,p = 0.000)had a negative effect on telomere length.Telomere length was positively correlated with age of onset(β = 0.121,p = 0.001).However,there was no significant correlation between telomere length and the severity of ataxia(β =-0.045,p = 0.277).2.This study included 138 SCA3 patients and 80 age and gender matched healthy controls for comparison and analysis.Among the 138 SCA3 patients,72 were males(52.17%)and 66 females(47.83%).The average age of onset was 34.35 ± 13.68 years,and the average course of disease was 8.20 ± 5.09 years.Among normal and amplified alleles The average number of CAG repeats were 20.53 ± 8.46 and 70.68 ±16.76,respectively,the SARA scale score was 13.06 ± 7.59 points,and the ICARS scale score was 35.77 ± 17.94.There was no significant difference in gender and age distribution between SCA3 patients and the control group(sex p = 0.786;age p = 0.115).The statistical results showed that the skin aging score of the SCA3 group was significantly higher than that of the healthy control group(2.36 ± 0.86 vs.2.04 ± 0.97,p = 0.010).It was found that the follow-up age(β = 0.727,p = 0.000)had a positive effect on the skin aging score.However,there was no significant correlation between the skin aging score and the severity of the disease(β = 0.052,p= 0.596).3.This study included 48 adult SCA3 patients and 52 age-and gender-matched healthy controls for comparison and analysis of cerebral cortex thickness by cranial magnetic resonance.Among 48 SCA3 patients,22 were males(45.83%)and 26 were females(54.17 %).There was no significant difference in gender and age distribution between SCA3 patients and the control group(sex p = 0.689;age p =0.630).The statistical results showed that the thickness of the left cortex of the SCA3 group was significantly lower than that of the healthy control group(2.40 ± 0.71 vs.2.45 ± 0.62,p = 0.001),and the thickness of the right cortex of the adult SCA3 group was significantly lower than that of the healthy control group(2.40 ± 0.70 vs.2.45 ±0.71,p = 0.001).The duration of SCA3 was negatively correlated with the thickness of the left and right cortical layers(β = 0.401,p = 0.006;β = 0.393,p = 0.008).It was found that there was no correlation between the thickness of the cortex and the age of onset(β =-0.063,p = 0.501;β =-0.004,p = 0.966)and there was no correlation between the thickness of the cortex and the severity of the disease(β =-0.252,p = 0.100;β =-0.229,p = 0123).Conclusions:1.Compared with healthy controls,the relative telomere length of SCA3 patients is shorter,and the telomere length is positively correlated with the age of onset,and the follow-up age and CAG amplified fragments are negatively correlated with the telomere length.2.Compared with healthy controls,the skin aging of SCA3 patients is more serious,and skin aging is positively correlated with the follow-up age.However,there is no significant correlation between the skin aging score and the severity of the disease.3.Compared with healthy controls,the atrophy of the left and right cerebral cortex of adult SCA3 patients is more severe. |
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