Sex differences in Spinocerebellar ataxia type 1: clinical presentation and progression

Sex differences in Spinocerebellar ataxia type 1: clinical presentation and progression | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Sex differences in Spinocerebellar ataxia type 1: clinical presentation and progression Fabiana Colucci, Sara Stefanelli, Elena Contaldi, Andrea Gozzi, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6236602/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Jul, 2025 Read the published version in The Cerebellum → Version 1 posted 11 You are reading this latest preprint version Abstract Background Spinocerebellar ataxia type 1 (SCA1) is characterised by motor and cognitive symptoms. Sex-specific differences in disease presentation and progression remain poorly understood. This study investigates the role of sex in clinical-demographic and motor/cognitive outcomes in SCA1. Methods This single-centre, longitudinal observational cohort study was conducted at the University Hospital of Ferrara between 2021 and 2024. Consecutively, genetically confirmed SCA1 patients were evaluated at baseline and after 24±6 months. Assessments included comprehensive neuropsychological testing and auditory event-related potentials (aERPs). Motor function was evaluated using the Scale for Assessment and Rating of Ataxia (SARA). Results Sixteen SCA1 patients (9 males, seven females) were evaluated at baseline, with 10 patients (5 males, five females) completing follow-up. Even if most cognitive functions were preserved in both sexes at baseline, males showed significantly worse performance in emotion attribution tasks than females (42.8 ± 8.5 vs 53.1 ± 5.7, p = 0.029). Over time, both sexes showed slightly worsening cognitive performance, with males demonstrating deficits in verbal fluency, visual memory recall, and emotion attribution (p < 0.05). In the same group, motor impairment worsened at follow-up, though not significantly. aERPs revealed no differences between sexes at follow-up. Conclusion Sex may influence cognitive outcomes in SCA1, with male patients showing greater vulnerability to cognitive decline. aERPs did not show significant modifications. These findings highlight the importance of considering sex-specific approaches in the clinical management of SCA1 patients and the higher values of a comprehensive neuropsychological assessment compared to the neurophysiological approach with aERPs to reach these slight changes over time. Spinocerebellar ataxia SCA1 Sex Cognition Cognitive decline aERPs Figures Figure 1 Introduction Patients with cerebellar ataxia experience not only motor but also non-motor symptoms. There is growing evidence that cognitive impairment occurs during disease progression in Spinocerebellar Ataxia (SCA) patients [1–5]. Several groups have conducted specific analyses of cerebellar disease’s demographic and cognitive characteristics, with clear results for a direct association of cognitive impairment to disease duration [6]. Prediction of cognitive progression in SCA according to sex difference is more uncertain. The sex-related cognitive decline for SCA type 1, one of the more common SCAs in Italy [7], is poorly defined and has not yet been specifically addressed in any available clinical study, notwithstanding the emerging importance of this biological variable in clinical and research studies, including ataxia. Globally, limited documentation considering the sex-related differences in SCA epidemiology, phenomenology, progression, therapy responses and complications is available [8–11]. We analyzed patients with SCA1 to account for the possible role of sex as a major variable in clinic-demographic features and motor and cognitive presentation and progression. Second, we used auditory event-related potentials (aERPs) to study cognitive processes. Studies on endogenous event-related potentials (ERPs) in spinocerebellar ataxias (SCAs) are restricted [4]. aERPs provide information about attention and memory: in the "oddball" paradigm, subjects respond only to specific target stimuli randomly presented among non-target stimuli. ERPs reflect cognitive processing: early components (N100, N200) represent sensory and perceptual processes, reflecting the automatic attention abilities in identification and response to stimuli, while the later component, P300, requires conscious attention. P300 is considered an index of active cognitive processing involving various brain areas, reflecting attention, discrimination and working memory. Indeed, P300 amplitude is directly related to the performance in memory, attention, and executive functions, while the latency to the neuronal speed to generate a response. This approach has been applied to study cognitive changes, not only in ageing and neurodegenerative disorders [12–16] but also in cerebellar ataxias, including SCA1 and SCA2 [4, 17, 18]. However, no data are available on sex-related differences. Materials and Methods This single-center, longitudinal observational cohort study was conducted at the University Hospital of Ferrara between August 2021 and July 2024. 2.1. Participants Between July 2021 and April 2022, patients genetically diagnosed with spinocerebellar ataxia type 1 (SCA1) and referred to the Movement Disorders Centre at Ferrara Hospital were consecutively evaluated for eligibility criteria. Exclusion criteria were i) a score > 24 on the Motor Scale for Assessment and Rating of Ataxia (SARA), and/or ii) a lower score at Mini-Mental State Examination score (MMSE < 24), and/or hearing loss. All enrolled participants were native Italian speakers and capable of providing informed consent. Participants were evaluated longitudinally: at baseline (T0) and after 24±6 months (T1). The study protocol received approval from the local institutional review board (CE 453/2021), and all participants provided informed written consent. The study adhered to the ethical principles outlined in the 1964 Declaration of Helsinki and its subsequent amendments. 2.2. Data Collection We gathered information at baseline on the age of first motor cerebellar symptoms onset, the disease duration at the time of assessment, years of education, the number of CAG repeat expansions, and whether the inheritance was paternal or maternal. Additionally, at T0 and T1, information on the severity of motor symptoms was evaluated using the SARA scale [19]. The data at baseline have already been published in previous work by our group [4]. 2.3. Neuropsychological Testing Neuropsychological assessments were administered at T0 and T1 by the same neuropsychologist (SS). The raw scores of each test were adjusted to Italian normative data for sex, age and education. To define abnormal results, the available cut-off scores were used. The assessment included: Mini-mental State Examination (MMSE) to briefly screen the cognitive status [20] Frontal Assessment Battery (FAB) to assess executive functions: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy [21]; Verbal fluency test (F-A-S letters) to evaluate lexical retrieval. It requires processing speed [22]; Trail Making Test (TMT) A-B, to measure executive functions: the TMT-A assesses selective attention and motor speed, while in TMT-B, the attentional shifting [23]; Raven Colored Progressive Matrices (RCPM) to assess non-verbal reasoning ability and visuospatial processing skills [24]; Stroop Test, evaluating many executive functions: selective attention, sensitivity to interference and inhibitory control [25]; Rey-Osterrieth Complex Figure (ROCF) to investigate by copying the ability of construction practice and visuospatial planning, and by recalling the visual memory [26]; Prose memory test (Babcock’s short tale-BST) to measure the verbal-episodic memory [27]; Emotion Attribution Task (EAT) to explore part of social cognition: emotion attribution. By 58 short stories, happiness, sadness, anger, fear, envy, embarrassment or disgust could be elicited [28]; 2.4. Electrophysiological Assessment Auditory event-related potential (a-ERP) was performed at T0 and T1. The software used for delivering a-ERPs was KeypointTM (Natus Neurology Incorporated, Middleton, WI, USA). The assessment was conducted according to the oddball paradigm: participants wearing earphones, pseudo-randomly received at least 100 auditory stimuli (inter-stimulus interval 1200 ms), "standard" or "target". Stimuli had the same mean sound level of 74.97 ± 3.15 dB and duration of 200 ms, but different sound frequencies, being 2000-Hz for standard stimuli and 1500-Hz for target ones. In addition, standard stimuli had a presentation probability of 80%, while target stimuli of 20% [29]. Participants should be focused on the target stimuli and this response was recorded from scalp electrodes, placed on Cz (international 10/20 system). In the assembly of the electroencephalogram, electrodes were placed at Fz, Cz and Pz, while the electrode reference was on the earlobe. We obtained values on the Peak latency and amplitude of the N100, N200, and P300 components [30]. 2.5. Statistical Analysis Counts or percentages are used for categorical variables and mean ± standard deviation (SD) or median and interquartile range (IQR) for continuous variables. The chi-square test or Fisher’s exact test was used to compare binary variables, while the T-test or the Mann-Whitney was applied for continuous variables according to their distribution. Differences between groups were explored by analysis of variance (ANOVA) and covariance (ANCOVA). SPSS software support (IBM, v20) was used for all the statistical analyses, considering statistical significance if the results of p were < 0.05. Results The study involved 16 SCA1 participants at baseline (T0), consisting of 9 men and 7 women. The mean (SD) age at clinical onset for males was 41.8 (7) years, and their mean (SD) age at the time of the study was 47.8 (6.9) years. Females showed a mean (SD) age at the onset of 40.7 (9.8) years and a mean (SD) age at the time of enrollment of 48.1 (10.2) years. At baseline, women had a longer disease duration than men, in the absence of significance [7.4 (4.0) years vs. 6 (3.9) years, p = ns ]. There were neither statistically significant differences between sex and age at onset nor between sex and age at the time of enrollment. The mean (SD) years of education were 10.6 (2.5) and 12.0 (3.5) in men and women, respectively ( p = ns ). The number of triplets carrying the ataxin-1 gene was greater in males 49.8 (7.9) than in females 45.3 (3.4), without statistical significance. Overall, participants have mild-to-moderate motor deficits, assessed by the SARA scale: 12.2 (4.2) in males and 10.7 (6.4) in female patients ( p = ns ). Table 1 . Table 1 Clinical-demographic characteristics of participants at the baseline (T0) Males Females p N (%) 9 (56.3) 7 (43.8) - Onset age, mean (SD) 41.8 (7.0) 40.7 (9.8) ns Age at enroll, mean (SD) 47.8 (6.9) 48.1 (10.2) ns Education, mean (SD) 10.6 (2.5) 12.0 (3.5) ns Disease Duration, mean (SD) 6.0 (3.9) 7.4 (4.0) ns CAG expansion, mean (SD) 49.8 (7.9) 45.3 (3.4) ns SARA scale 12.2 (4.2) 10.7 (6.4) ns Table 2 reports data on neuropsychological assessment at T0 according to sex. Overall, both males and females showed scores in normal ranges, except in emotion attribution tasks, where male patients showed pathological cut-off and a worse performance compared to females [mean (SD) EAT: 42.8 (8.5) males vs 53.1 (5.7) females, p = 0.029]. Table 2 Mean (SD) obtained at each neuropsychological assessment test at baseline (T0), reported according to sex and adjusted for age. Test (pathological cut-off) Males N = 9 Females N = 7 p MMSE (< 24) 29.1 (1.0) 29.6 (0.5) ns FAB (< 13.4) 15.9 (1.3) 15.8 (1.8) ns Verbal fluency (< 17.35) 24.4 (9.7) 24.6 (1.0) ns RCPM ( 4.24) 0.36 (0.9) 0.42 (0.9) ns Test Stroop (time) (> 36.92) 22.9 (10.0) 21.9 (8.0) ns TMT A (> 94) 80.0 (24.5) 57.8 (15.1) ns TMT B (> 187) 135.7 (36.1) 108.6 (35.4) ns TMT B-A (> 187) 40.7 (32.9) 51.1 (31.0) ns ROCF (< 28.53) 33.5 (3.2) 34.1 (1.3) ns ROCF – recall (< 9.46) 11.2 (5.4) 15.5 (5.0) ns BST (< 8.2) 7.7 (2.6) 10.3 (3.8) ns EAT (< 44.19) 42.8 (8.5) 53.1 (5.7) 0.029 Table 3 Clinical-demographic characteristics of participants at follow-up (T1) Males Females p N (%) 5 (50.0) 5 (50.0) - Time of follow-up, mean (SD) -months 21 (4) 20 (6) ns Onset age, mean (SD) -years 39.6 (4.6) 43.4 (7.3) ns Education, mean (SD) -years 11.0 (2.7) 10.6 (2.5) ns Disease Duration, mean (SD) -years 10.2 (3.8) 10.8 (3.9) ns CAG expansion, mean (SD) 51.8 (9.1) 45.2 (3.3) ns SARA scale, mean (SD) 18.8 (6.8) 14.0 (6.5) ns At T1, six patients dropped out: two due to difficulties in reaching the center with caregivers, and four refused to undergo further neuropsychological and neurophysiological assessments, which they considered lengthy and tiring. Data were collected from the remaining 10 patients, evenly divided between both sexes (Table 3 ). The male patients (n = 5) who continued in the follow-up had a mean (SD) age at clinical onset of 39.6 (4.6) years and disease duration of 10.2 (3.8) years. Female patients showed similar results, with a mean (SD) age at clinical onset of 43.4 (7.3) years and disease duration of 10.8 (3.9) years. The mean (SD) years of education were 11.0 (2.7) for men and 10.6 (2.5) for women (p = ns). The number of triplets repeats in the ataxin-1 gene was higher in males [mean (SD): 51.8 (9.1)] compared to females [45.2 (3.3)], though this difference was not statistically significant. Table 4 Mean (SD) obtained at each neuropsychological assessment test at T1, reported according to sex and adjusted for age. SARA score for motor assessment. Test (pathological cut-off) Males N = 5 Females N = 5 p MMSE (< 24) 29.0 (1.2) 29.6 (0.5) ns FAB (< 13.4) 15.2 (1.7) 16.6 (1.5) ns Verbal fluency (< 17.35) 16.6 (4.8) 27.3 (6.1) < 0.05 RCPM ( 4.24) 0.75 (1.3) 0.60 (1.0) ns Test Stroop (time) (> 36.92) 32.4 (6.8) 18.0 (5.2) 94) 75.7 (25.7) 49.8 (6.6) ns TMT B (> 187) 139.7 (36.1) 101.8 (39.1) ns TMT B-A (> 187) 48.0 (43.2) 52.6 (36.8) ns ROCF (< 28.53) 32.3 (3.3) 34.2 (1.5) ns ROCF – recall (< 9.46) 7.0 (6.2) 13.7 (2.9) < 0.05 BST (< 8.2) 9.7 (1.9) 10.5 (4.3) ns EAT (< 44.19) 44.0 (4.3) 55.8 (1.5) < 0.05 SARA scale 18.8 (6.8) 14.0 (6.5) ns Table 4 shows data on motor (SARA scale) and neuropsychological assessment at T1 in the 10 patients who performed follow-up. At follow-up, males continued to display moderate motor impairment, which was greater than in females, albeit without statistical significance [mean (SD) SARA scale: males 18.8 (6.8) vs. females 14.0 (6.5)]. Regarding neuropsychological tests, all resulted in normal ranges in females, while males showed deficits in verbal fluency test [mean (SD), 16.6 (4.8)], recall of Copy Rey Figure [mean (SD), 7.0 (6.2)], and, still, in emotional attribution tasks [mean (SD), 44.0 (4.3)]. Comparing each test between sexes, females performed better on the verbal fluency test [mean (SD), males 16.6 (4.8) vs females 27.3 (6.1), p < 0.05], Stroop test in terms of time [mean (SD) males 32.4 (6.8) vs females 18.0 (5.2), p < 0.05], recall of Copy Rey Figure [mean (SD) males 7.0 (6.2) vs females 13.7 (2.9), p < 0.05], and emotion attribution tasks [mean (SD) males 44.0 (4.3) vs females 55.8 (1.5), p < 0.05]. Table 5 shows the differences observed between T1 and T0 at neuropsychological assessment according to sex. A slight worsening can be observed in all performances in both sexes, without statistical significance. Table 5 Mean difference (SD) of scores obtained at each neuropsychological assessment test at T1 vs. T0, reported according to sex and adjusted for age. Test Male Famale p MMSE -1.3 (2.3) -0.2 (0.8) ns FAB -0.6 (0.9) 0.2 (1.5) ns Verbal fluency -3.6 (2.6) 5.0 (7.5) ns RCPM -2.5 (5.3) 2.2 (5.0) ns Test Stroop (errors) 0.8 (2.1) 0.6 (1.0) ns Test Stroop (time) 2.7 (13.4) -2.4 (8.1) ns TMT A 7 (6.2) 9 (8.1) ns TMT B 17 (12.6) 18 (13) ns TMT B-A 16 (13.7) 18.6 (15.3) ns ROCF 0.2 (1.2) -0.3 (2.0) ns ROCF – recall -1.9 (4.7) 1.2 (5.8) ns BST -1.1 (5.1) -2.1 (2.9) ns EAT (< 44.19) -2.1 (3.4) -2.2 (3.1) ns Analysis of ERPS, Fig. 1 shows the latencies (A) and amplitudes (B) data of aERPs in the 10 patients who underwent both neuropsychological examinations (T0 and T1). No differences were detected in the two timelines in each sex group. The differences between sex at baseline and follow-up of aERP are described in Table 6 and revealed only a higher N100 amplitude in females compared to males at baseline; no further differences were detected at follow-up (Table 6 ). Table 6 Event-related potentials: principal components at T0 and T1 [of which latency (lat) and amplitude (amp) were measured], and mean difference (SD) by sex. M F p diff (M vs F) P300lat (T0) 375.3 (53.0) 409.3 (63.3) ns P300lat (T1) 374.0 (43.6) 385.8 (25.2) ns P300lat (T1-T0) 1.2 (83.1) -15.3 (27.8) ns P300amp (T0) 3.4 (3.1) 4.8 (5.8) ns P300amp (T1) 4.5 (5.7) 2.2 (1.5) ns P300amp (T1-T0) 0.7 (7.8) -4.9 (7.4) ns N100lat (T0) 104.3 (5.9) 97.5 (4.8) ns N100lat (T1) 117.4 (39.4) 101.0 (2.9) ns N100lat (T1-T0) 13.3 (42.8) 4.1 (5.4) ns N100amp (T0) 5.6 (2.1) 6.6 (3.0) 0.03 N100amp (T1) 6.7 (4.2) 4.4 (3.4) ns N100amp (T1-T0) 1.3 (2.6) -3.6 (6.6) ns N200lat (T0) 249.7 (36.7) 273.9 (45.7) ns N200lat (T1) 263.3 (39.2) 254.5 (29.9) ns N200lat (T1-T0) 26.2 (61.0) 14.5 (47.6) ns N200amp (T0) 3.5 (1.6) 3.7 (2.4) ns N200amp (T1) 3.1 (2.0) 1.9 (0.5) ns N200amp (T1-T0) -0.6 (3.2) -1.6 (3.3) ns Discussion Clinical progression Of the 16 patients (nine male) initially enrolled in the study at baseline, 10 (five male) were included in the follow-up assessment at 24±6 months. In terms of age of onset (approximately 41 years), SCA1 affects both males and females similarly, consistent with previous studies [9, 10]. Interestingly, although not statistically significant, a tendency for earlier disease onset in males compared to females was noted, with males typically presenting symptoms towards the end of the fourth decade of life, while females tend to experience onset at the beginning of the fifth decade. This is in line with Du Montcel and colleagues, who demonstrated a 5-year earlier presentation of ataxia symptoms in males compared to females [9]. However, the literature does not consistently report clear sex-based differences in the age of onset or disease complexity, though it is well-established that these factors are correlated with the size of the expanded alleles [10]. Each additional repeat caused the largest reduction in age at the onset of 0.049 years [10]. Indeed, men in the present cohort exhibited a higher average number of CAG triplet expansions compared to women (51.8 vs. 45.2), and this might explain the earlier age at presentation of symptoms. However, the gender effects on the age of onset and mean CAG repeats were not so clear and not confirmed in other studies [31]. Indeed, Riess et al., in a cohort of SCA1 and SCA3 patients, noted gender effects in SCA patients on transmission rather than clinical expression [31]. Regarding motor impairment and disease progression, in the present study, both sexes presented with mild-to-moderate motor deficits at baseline as measured by the SARA scale. According to SCA type, sex differences in disease motor progression should be carefully considered. In SCA6, previous research by Jacobi et al. found that the female sex is associated with faster progression, with a hazard ratio of 1.7 (95% CI: 1.1–2.6) for progression to more advanced disability stages [10]. Conversely, our data suggests a potential opposite trend in SCA1, with males potentially experiencing faster motor deterioration. Although this difference didn't reach statistical significance in our small cohort, males showed a more pronounced increase in SARA scores over follow-up (from 12.2 to 18.8) compared to females (from 10.7 to 14.0). This contrasting pattern suggests that the influence of sex on disease progression may vary according to SCA subtype, potentially reflecting differences in underlying pathophysiological mechanisms or sex-specific modifiers of disease expression. Beyond the specific differences among the various SCA subtypes, our findings confirm the well-documented clinical progression of cerebellar motor dysfunction in patients with SCA, representing a fundamental characteristic of the pathology, regardless of potential variables that might modulate its rate or expression [10, 32]. The clinical progression in patients with SCA was globally analysed by Weber and colleagues, who combined data from two major European cohorts with a three-year follow-up focused on health-related quality of life progression [11]. The research revealed that quality of life decline was particularly pronounced in males with younger disease onset (before age 40) and with a BMI between 30 and 35 [11]. Generally, with disease progression, quality of life is influenced by increasingly severe cerebellar problems (i.e. dysarthria, dysphagia) and mild cognitive problems [8]. However, the progression of cognition according to sex has been less analysed. Indeed, the present study focused mainly on this aspect, showing that affected patients, even 10 years after disease onset, presented neuropsychological test scores within normal limits at baseline. However, a deterioration in scores was observed across all tests during follow-up, indicating a decrease (albeit within normal limits) in cognitive performances. These findings support the notion that progressive cerebellar and neuronal degeneration in SCA1 affects not only motor functions but also cognitive domains [4, 33–38]. When considering cognitive and emotional processing differences between males and females with SCA1, this study showed that males consistently performed worse than females in emotion attribution tasks, with statistically significant differences at both baseline (p = 0.029) and follow-up (p < 0.05). This suggests a specific deficit in social cognition affecting male SCA1 patients more severely. In addition, at follow-up, females outperformed men on both the verbal fluency test and the Stroop test time. It is important to note that the verbal fluency test assesses not only language and executive functions but also cognitive flexibility, specifically evaluating the patient’s ability to access their lexical knowledge [22]. Literature indicates that patients with higher SARA scores often show an inverse correlation with verbal fluency test scores [4]. This suggests that motor involvement, particularly dysarthria, may influence verbal fluency as measured by this test. In our cohort, men demonstrated a more severe clinical presentation, which could partly explain this result. Similarly, differences in Stroop test time performance may be attributed to the higher disease severity in males. Additionally, the role of saccadic movements in test execution should not be underestimated. Studies have shown that increased latency in saccadic movements correlates with executive dysfunction in frontal regions [39–40]. While ocular movements were not assessed in terms of speed in this study, the greater severity of the disease in men, coupled with a higher number of CAG triplet expansions, may suggest a more pronounced slowing of extrinsic ocular motility. These findings support the notion that cerebellar disorders like SCA1 affect cognitive domains beyond motor control [41], with a particular impact on executive functions and emotional processing. The cerebellum's role in cognition and emotion is increasingly recognized, and our data suggests these networks may be differently affected in males versus females with SCA1. Neurophysiological progression In our analysis, event-related potentials were recorded in response to auditory stimuli (aERPs). After processing, we examined various ERP components (P300, N100, N200) in terms of latency and amplitude. No significant differences were observed in the aERPs between T0 and T1 for the entire sample. However, when comparing the sexes, N100 amplitude was higher in females at baseline. This component is associated with early sensory processing and attention allocation. The lack of significant neurophysiological differences at follow-up, despite clear cognitive differences, suggests that functional compensation mechanisms might be at play, particularly in female patients. To our knowledge, no studies in the literature have investigated neurophysiological follow-up via ERPs in a homogeneous population of SCA1 patients and the correlation with sex. Longitudinal studies often involve heterogeneous populations across various SCA genotypes [10]. The main limitations of the study are: i) the small sample size, particularly at follow-up (n = 10), limits statistical power and generalizability, and ii) the high dropout rate (37.5%) might introduce selection bias, as patients with more severe symptoms might have been more likely to discontinue. Future studies should aim to recruit larger cohorts with balanced sex representation and investigate potential protective factors that might explain the relative preservation of cognitive functions in female SCA1 patients. The relationship between CAG repeat length and cognitive outcomes also warrants further investigation. In addition, a longer follow-up period (> 24 months) may likely be needed to predict progression toward a dementia-like state Conclusion This study provides preliminary evidence for sex-based differences in cognitive and emotional processing in SCA1 patients, with males showing greater vulnerability. While motor progression appears to affect both sexes, the pattern of cognitive decline may be influenced by sex-specific factors that deserve further investigation. Regarding the neurophysiological findings studied through the use of event-related auditory potentials, no sex differences were found between T0 and T1, indicating that neurophysiological examination does not represent a reliable test for assessing the evolution of cognitive impairment in this patient group in all populations, in each sex and between sexes. The documented gender differences highlight the importance of considering gender as a significant factor in clinical assessment and the need for gender-specific therapeutic approaches, with potentially greater attention to interventions targeting motor and cognitive symptoms in males. However, it's important to note that these are general trends, and individual patient care should always be tailored to specific needs regardless of gender. Declarations Ethical Approval: The study protocol received approval from the local institutional review board (CE 453/2021), and all participants provided informed written consent. The study adhered to the ethical principles outlined in the 1964 Declaration of Helsinki and its subsequent amendments. All participants gave written consent before participating in the study. Clinical trial number not applicable Conflicts of interest: The authors declare no conflict of interest. Funding: No funding supported this research. Data availability : The data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions. Author Contribution Authors’ contributions: FC contributed to the conception of the work, acquisition and interpretation of data, and drafted the work; SS contributed to acquisition and interpretation of data, and drafted the work; EA contributed to the conception and design of the work, acquisition and interpretation of data; AG contributed to acquisition of data; MP contributed to analysis and interpretation of data; PA contributed to acquisition and analysis of data; JGG contributed to acquisition and interpretation of data; DG contributed to acquisition of data; MS contributed to the conception of the work and revised it critically for important intellectual content. All authors approved the final manuscript. Data Availability The data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions. References Sokolovsky N, Cook A, Hunt H, Giunti P, Cipolotti L. 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Epub 2022 Feb 21. PMID: 35188716; PMCID: PMC8935317. Weber N, Buchholz M, Rädke A, Faber J, Schmitz-Hübsch T, Jacobi H, Klockgether T, Hoffmann W, Michalowsky B; EUROSCA study group; ESMI study group. Factors Influencing Health-Related Quality of Life of Patients with Spinocerebellar Ataxia. Cerebellum. 2024 Aug;23(4):1466-1477. doi: 10.1007/s12311-024-01657-2. Epub 2024 Jan 27. PMID: 38279001; PMCID: PMC11269494. van Dinteren R, Arns M, Jongsma ML, Kessels RP. P300 development across the lifespan: a systematic review and meta-analysis. PLoS One. 2014 Feb 13;9(2):e87347. Murphy C, Solomon ES, Haase L, Wang M, Morgan CD. Olfaction in aging and Alzheimer's disease: event-related potentials to a cross-modal odor-recognition memory task discriminate ApoE epsilon4+ and ApoE epsilon 4- individuals. Ann N Y Acad Sci. 2009 Jul;1170:647-57. Gilbert PE, Murphy C. The effect of the ApoE epsilon4 allele on recognition memory for olfactory and visual stimuli in patients with pathologically confirmed Alzheimer's disease, probable Alzheimer's disease, and healthy elderly controls. J Clin Exp Neuropsychol. 2004 Sep;26(6):779-94. Polich J. Clinical application of the P300 event-related brain potential. Phys Med Rehabil Clin N Am. 2004 Feb;15(1):133-61. Golob EJ, Ringman JM, Irimajiri R, Bright S, Schaffer B, Medina LD, Starr A. Cortical event-related potentials in preclinical familial Alzheimer disease. Neurology. 2009 Nov 17;73(20):1649-55. Rodríguez-Labrada R, Velázquez-Pérez L, Ortega-Sánchez R, Peña-Acosta A, Vázquez-Mojena Y, Canales-Ochoa N, Medrano-Montero J, Torres-Vega R, González-Zaldivar Y. Insights into cognitive decline in spinocerebellar Ataxia type 2: a P300 event-related brain potential study. Cerebellum Ataxias. 2019 Mar 4;6:3. J, Valis M, Masopust J, Urban A, Zumrova A, Talab R, Kuba M, Kubova Z, Langrova J. An electrophysiological study of visual processing in spinocerebellar ataxia type 2 (SCA2). Cerebellum. 2011 Mar;10(1):32-42. Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Schöls L, Szymanski S, van de Warrenburg BP, Dürr A, Klockgether T, Fancellu R. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006 Jun 13;66(11):1717-20. Magni E, Binetti G, Bianchetti A, Rozzini R, Trabucchi M. Mini-Mental State Examination: a normative study in Italian elderly population. Eur J Neurol. 1996 May;3(3):198-202. Appollonio I, Leone M, Isella V, Piamarta F, Consoli T, Villa ML, Forapani E, Russo A, Nichelli P. The Frontal Assessment Battery (FAB): normative values in an Italian population sample. Neurol Sci. 2005 Jun;26(2):108-16. Carlesimo GA, Caltagirone C, Gainotti G. The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the Mental Deterioration Battery. Eur Neurol. 1996;36(6):378-84. Giovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, Capitani E. Trail making test: normative values from 287 normal adult controls. Ital J Neurol Sci. 1996 Aug;17(4):305-9. Basso A, Capitani E, Laiacona M. Raven's coloured progressive matrices: normative values on 305 adult normal controls. Funct Neurol. 1987 Apr-Jun;2(2):189-94. PMID: 3666548. Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A. A short version of the Stroop test: Normative data in an Italian population sample Nuova Riv Neurol. 2002. 12:111–115 Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A. Rey-Osterrieth complex figure: normative values in an Italian population sample. Neurol Sci. 2002 Mar;22(6):443-7.. Standardizzazione e taratura italiana di test neuropsicologici. Gruppo Italiano per lo Studio Neuropsicologico dell'Invecchiamento [Italian standardization and classification of Neuropsychological tests. The Italian Group on the Neuropsychological Study of Aging]. Ital J Neurol Sci. 1987 Dec;Suppl 8:1-120. Italian. Prior M., Marchi S., Sartori G. Cognizione sociale e comportamento, Volume 1. Uno strumento per la misurazione. Padova: Upsel Domeneghini Editore. 2003. Remijn GB, Hasuo E, Fujihira H, Morimoto S. An intro- duction to the measurement of auditory event-related potentials (ERPs). Acoust Sc Tech. 2014; 35:229–242 Patel SH, Azzam PN. Characterization of N200 and P300: selected studies of the Event-Related Potential. Int J Med Sci. 2005;2(4):147-54. doi: 10.7150/ijms.2.147. Epub 2005 Oct 1. Riess O, Epplen JT, Amoiridis G, Przuntek H, Schöls L. Transmission distortion of the mutant alleles in spinocerebellar ataxia. Hum Genet. 1997 Feb;99(2):282-4. doi: 10.1007/s004390050355. PMID: 9048937. Luo L, Wang J, Lo RY, Figueroa KP, Pulst SM, Kuo PH, Perlman S, Wilmot G, Gomez CM, Schmahmann J, Paulson H, Shakkottai VG, Ying SH, Zesiewicz T, Bushara K, Geschwind M, Xia G, Subramony SH, Ashizawa T, Kuo SH. The Initial Symptom and Motor Progression in Spinocerebellar Ataxias. Cerebellum. 2017 Jun;16(3):615-622. doi: 10.1007/s12311-016-0836-3. PMID: 27848087; PMCID: PMC5429172. Silveri M. C. Contribution of the cerebellum and the basal ganglia to language production: speech, word fluency, and sentence construction evidence from pathology. Cerebellum. 2020; 20, 282–294. doi: 10.1007/s12311-020- 01207-6. Bürk K, Bösch S, Globas C, Zühlke C, Daum I, Klockgether T, Dichgans J. Executive dysfunction in spinocerebellar ataxia type 1. Eur Neurol. 2001; 46(1):43-8. doi: 10.1159/000050755. PMID: 11455183 Klinke I, Minnerop M, Schmitz-Hübsch T, Hendriks M, Klockgether T, Wüllner U, et al. Neuropsychological features of patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. Cerebellum Lond Engl. 2010 settembre; 9(3):433–42. Sokolovsky N, Cook A, Hunt H, Giunti P, Cipolotti L. A preliminary characterisation of cognition and social cognition in spinocerebellar ataxia types 2, 1, and 7. Behav Neurol. 2010; 23(1–2):17–29. Ma J, Wu C, Lei J, Zhang X. 2014. Vol. Cognitive impairments in patients with spinocerebellar ataxia types 1, 2 and 3 are positively correlated to the clinical severity of ataxia symptoms. Int J Clin Exp Med. 2014; 7:5765–71. Fancellu R, Paridi D, Tomasello C, Panzeri M, Castaldo A, Genitrini S, Soliveri P, Girotti F. Longitudinal study of cognitive and psychiatric functions in spinocerebellar ataxia types 1 and 2. J Neurol. 2013; 260:3134–43. Pandolfo M, Manto M. Cerebellar and Afferent Ataxias. Contin Lifelong Learn Neurol. 2013 ottobre; 19:1312–43. Rodríguez-Labrada R, Velázquez-Pérez L, Seigfried C et al. Saccadic latency is prolonged in in Spinocerebellar Ataxia type 2 and correlates with the frontal-executive dysfunctions. J Neurol Sci. 2011 Jul 15; 306(1-2):103-7. Hoche F, Guell X, Vangel MG et al. The cerebellar cognitive affective/Schmahmann syndrome scale. Brain. 2018 Jan 1;141(1):248-270. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6236602","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":441433905,"identity":"69e4a502-252e-43b6-8461-9e55800391bc","order_by":0,"name":"Fabiana Colucci","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIiWNgGAWjYBAC+wM8DAcgTOYGICEhxw9iJxTg1mLAANfCCNZiLAmiEgzwa2FA0sKQuOEARBy3FvazBw/83GHHwN/e2Cbxo8YicfP51YkfHhgwyPOLHcDuF568hIO9Z5IZJM4cbJPsOSZhvO3G280SQIcZzpydgMNhOQYHeNuYGQwkEtukGRskZLfdOLsBpCXB4DYOLfxvDA7+bauHa2HcPOPs5h94tUjkGBzmbTsM16K4gb93G35bJN4lHJZtO84D9EuzJcgvEjd4t1kkGEjg9gt/7uGPb9uq5fjbmw/e+FFTJ8fff3bzzR8VNvL80ti1wAAPgikBVimBVzka4D9AiupRMApGwSgYAQAArtZfLUYsZo4AAAAASUVORK5CYII=","orcid":"","institution":"University of Ferrara","correspondingAuthor":true,"prefix":"","firstName":"Fabiana","middleName":"","lastName":"Colucci","suffix":""},{"id":441433906,"identity":"aa784053-22ff-47b6-9d2b-5cf73e960237","order_by":1,"name":"Sara Stefanelli","email":"","orcid":"","institution":"Azienda Ospedaliero-Universitaria S. Anna","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Stefanelli","suffix":""},{"id":441433907,"identity":"95ef8db9-4b0f-459d-aae7-76743afd03fc","order_by":2,"name":"Elena Contaldi","email":"","orcid":"","institution":"Istituto Ortopedico Gaetano Pini","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Contaldi","suffix":""},{"id":441433908,"identity":"f37783c5-1aeb-48f5-8b10-ba6ef6cc0976","order_by":3,"name":"Andrea Gozzi","email":"","orcid":"","institution":"Azienda Ospedaliero-Universitaria S. Anna","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Gozzi","suffix":""},{"id":441433909,"identity":"9ef8ce41-7ab4-431b-831e-106d9d6c0899","order_by":4,"name":"Maura Pugliatti","email":"","orcid":"","institution":"University of Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Maura","middleName":"","lastName":"Pugliatti","suffix":""},{"id":441433910,"identity":"753b81e4-7c80-44f7-9237-d3c741636cce","order_by":5,"name":"Pietro Antenucci","email":"","orcid":"","institution":"University of Ferrara","correspondingAuthor":false,"prefix":"","firstName":"Pietro","middleName":"","lastName":"Antenucci","suffix":""},{"id":441433911,"identity":"a78fa855-1319-42e3-af75-edba5fa6c8d2","order_by":6,"name":"Jay Guido Capone","email":"","orcid":"","institution":"Azienda Ospedaliero-Universitaria S. Anna","correspondingAuthor":false,"prefix":"","firstName":"Jay","middleName":"Guido","lastName":"Capone","suffix":""},{"id":441433912,"identity":"aa991369-c752-44f2-91df-f757bd4038d6","order_by":7,"name":"Daniela Gragnaniello","email":"","orcid":"","institution":"Azienda Ospedaliero-Universitaria S. Anna","correspondingAuthor":false,"prefix":"","firstName":"Daniela","middleName":"","lastName":"Gragnaniello","suffix":""},{"id":441433913,"identity":"81f6c2fc-310b-4d38-ab6e-5b795c39073b","order_by":8,"name":"Mariachiara Sensi","email":"","orcid":"","institution":"Azienda Ospedaliero-Universitaria S. Anna","correspondingAuthor":false,"prefix":"","firstName":"Mariachiara","middleName":"","lastName":"Sensi","suffix":""}],"badges":[],"createdAt":"2025-03-16 08:53:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6236602/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6236602/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12311-025-01881-4","type":"published","date":"2025-07-10T15:57:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80710304,"identity":"6a84a337-16ff-40f6-b663-aa3b3c23bb62","added_by":"auto","created_at":"2025-04-16 08:59:41","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":52812,"visible":true,"origin":"","legend":"\u003cp\u003eEvent-related potentials: principal components at T0 and T1 [of which latency (lat) amplitude (amp) were measured], and mean difference (SD) by sex.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6236602/v1/f17d5ff8a5da7f6a13d6a7e8.jpg"},{"id":86700137,"identity":"aa8160c5-8031-46d9-8e2f-b00b35cfa0c4","added_by":"auto","created_at":"2025-07-14 16:11:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1227825,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6236602/v1/5fbd2ca7-7095-4c6a-96bd-25aa0624c280.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sex differences in Spinocerebellar ataxia type 1: clinical presentation and progression","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePatients with cerebellar ataxia experience not only motor but also non-motor symptoms. There is growing evidence that cognitive impairment occurs during disease progression in Spinocerebellar Ataxia (SCA) patients [1\u0026ndash;5]. Several groups have conducted specific analyses of cerebellar disease\u0026rsquo;s demographic and cognitive characteristics, with clear results for a direct association of cognitive impairment to disease duration [6]. Prediction of cognitive progression in SCA according to sex difference is more uncertain.\u003c/p\u003e \u003cp\u003eThe sex-related cognitive decline for SCA type 1, one of the more common SCAs in Italy [7], is poorly defined and has not yet been specifically addressed in any available clinical study, notwithstanding the emerging importance of this biological variable in clinical and research studies, including ataxia. Globally, limited documentation considering the sex-related differences in SCA epidemiology, phenomenology, progression, therapy responses and complications is available [8\u0026ndash;11].\u003c/p\u003e \u003cp\u003eWe analyzed patients with SCA1 to account for the possible role of sex as a major variable in clinic-demographic features and motor and cognitive presentation and progression.\u003c/p\u003e \u003cp\u003eSecond, we used auditory event-related potentials (aERPs) to study cognitive processes. Studies on endogenous event-related potentials (ERPs) in spinocerebellar ataxias (SCAs) are restricted [4]. aERPs provide information about attention and memory: in the \"oddball\" paradigm, subjects respond only to specific target stimuli randomly presented among non-target stimuli. ERPs reflect cognitive processing: early components (N100, N200) represent sensory and perceptual processes, reflecting the automatic attention abilities in identification and response to stimuli, while the later component, P300, requires conscious attention. P300 is considered an index of active cognitive processing involving various brain areas, reflecting attention, discrimination and working memory. Indeed, P300 amplitude is directly related to the performance in memory, attention, and executive functions, while the latency to the neuronal speed to generate a response.\u003c/p\u003e \u003cp\u003eThis approach has been applied to study cognitive changes, not only in ageing and neurodegenerative disorders [12\u0026ndash;16] but also in cerebellar ataxias, including SCA1 and SCA2 [4, 17, 18]. However, no data are available on sex-related differences.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis single-center, longitudinal observational cohort study was conducted at the University Hospital of Ferrara between August 2021 and July 2024.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Participants\u003c/h2\u003e \u003cp\u003eBetween July 2021 and April 2022, patients genetically diagnosed with spinocerebellar ataxia type 1 (SCA1) and referred to the Movement Disorders Centre at Ferrara Hospital were consecutively evaluated for eligibility criteria. Exclusion criteria were i) a score\u0026thinsp;\u0026gt;\u0026thinsp;24 on the Motor Scale for Assessment and Rating of Ataxia (SARA), and/or ii) a lower score at Mini-Mental State Examination score (MMSE\u0026thinsp;\u0026lt;\u0026thinsp;24), and/or hearing loss.\u003c/p\u003e \u003cp\u003e All enrolled participants were native Italian speakers and capable of providing informed consent. Participants were evaluated longitudinally: at baseline (T0) and after 24\u0026plusmn;6 months (T1).\u003c/p\u003e \u003cp\u003e The study protocol received approval from the local institutional review board (CE 453/2021), and all participants provided informed written consent. The study adhered to the ethical principles outlined in the 1964 Declaration of Helsinki and its subsequent amendments.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e2.2. Data Collection\u003c/h3\u003e\n\u003cp\u003eWe gathered information at baseline on the age of first motor cerebellar symptoms onset, the disease duration at the time of assessment, years of education, the number of CAG repeat expansions, and whether the inheritance was paternal or maternal. Additionally, at T0 and T1, information on the severity of motor symptoms was evaluated using the SARA scale [19]. The data at baseline have already been published in previous work by our group [4].\u003c/p\u003e\n\u003ch3\u003e2.3. Neuropsychological Testing\u003c/h3\u003e\n\u003cp\u003eNeuropsychological assessments were administered at T0 and T1 by the same neuropsychologist (SS). The raw scores of each test were adjusted to Italian normative data for sex, age and education. To define abnormal results, the available cut-off scores were used. The assessment included:\u003c/p\u003e \u003cp\u003e\u003col style=\"list-style-type:lower-alpha;\"\u003e\u003cli\u003e\u003cp\u003eMini-mental State Examination (MMSE) to briefly screen the cognitive status [20]\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eFrontal Assessment Battery (FAB) to assess executive functions: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy [21];\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e Verbal fluency test (F-A-S letters) to evaluate lexical retrieval. It requires processing speed [22];\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eTrail Making Test (TMT) A-B, to measure executive functions: the TMT-A assesses selective attention and motor speed, while in TMT-B, the attentional shifting [23];\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eRaven Colored Progressive Matrices (RCPM) to assess non-verbal reasoning ability and visuospatial processing skills [24];\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eStroop Test, evaluating many executive functions: selective attention, sensitivity to interference and inhibitory control [25];\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eRey-Osterrieth Complex Figure (ROCF) to investigate by copying the ability of construction practice and visuospatial planning, and by recalling the visual memory [26];\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eProse memory test (Babcock\u0026rsquo;s short tale-BST) to measure the verbal-episodic memory [27];\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eEmotion Attribution Task (EAT) to explore part of social cognition: emotion attribution. By 58 short stories, happiness, sadness, anger, fear, envy, embarrassment or disgust could be elicited [28];\u003c/p\u003e\u003c/li\u003e\u003c/ol\u003e\u003c/p\u003e\n\u003ch3\u003e2.4. Electrophysiological Assessment\u003c/h3\u003e\n\u003cp\u003eAuditory event-related potential (a-ERP) was performed at T0 and T1. The software used for delivering a-ERPs was KeypointTM (Natus Neurology Incorporated, Middleton, WI, USA). The assessment was conducted according to the oddball paradigm: participants wearing earphones, pseudo-randomly received at least 100 auditory stimuli (inter-stimulus interval 1200 ms), \"standard\" or \"target\". Stimuli had the same mean sound level of 74.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15 dB and duration of 200 ms, but different sound frequencies, being 2000-Hz for standard stimuli and 1500-Hz for target ones. In addition, standard stimuli had a presentation probability of 80%, while target stimuli of 20% [29].\u003c/p\u003e \u003cp\u003eParticipants should be focused on the target stimuli and this response was recorded from scalp electrodes, placed on Cz (international 10/20 system). In the assembly of the electroencephalogram, electrodes were placed at Fz, Cz and Pz, while the electrode reference was on the earlobe. We obtained values on the Peak latency and amplitude of the N100, N200, and P300 components [30].\u003c/p\u003e\n\u003ch3\u003e2.5. Statistical Analysis\u003c/h3\u003e\n\u003cp\u003eCounts or percentages are used for categorical variables and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median and interquartile range (IQR) for continuous variables. The chi-square test or Fisher\u0026rsquo;s exact test was used to compare binary variables, while the T-test or the Mann-Whitney was applied for continuous variables according to their distribution. Differences between groups were explored by analysis of variance (ANOVA) and covariance (ANCOVA). SPSS software support (IBM, v20) was used for all the statistical analyses, considering statistical significance if the results of \u003cem\u003ep\u003c/em\u003e were \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study involved 16 SCA1 participants at baseline (T0), consisting of 9 men and 7 women. The mean (SD) age at clinical onset for males was 41.8 (7) years, and their mean (SD) age at the time of the study was 47.8 (6.9) years. Females showed a mean (SD) age at the onset of 40.7 (9.8) years and a mean (SD) age at the time of enrollment of 48.1 (10.2) years. At baseline, women had a longer disease duration than men, in the absence of significance [7.4 (4.0) years vs. 6 (3.9) years, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;ns\u003c/em\u003e]. There were neither statistically significant differences between sex and age at onset nor between sex and age at the time of enrollment. The mean (SD) years of education were 10.6 (2.5) and 12.0 (3.5) in men and women, respectively (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;ns\u003c/em\u003e). The number of triplets carrying the ataxin-1 gene was greater in males 49.8 (7.9) than in females 45.3 (3.4), without statistical significance. Overall, participants have mild-to-moderate motor deficits, assessed by the SARA scale: 12.2 (4.2) in males and 10.7 (6.4) in female patients (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;ns\u003c/em\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical-demographic characteristics of participants at the baseline (T0)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMales\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemales\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (56.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOnset age, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41.8 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.7 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge at enroll, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47.8 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e48.1 (10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEducation, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.6 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.0 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisease Duration, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.0 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.4 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCAG expansion, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e49.8 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45.3 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSARA scale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.2 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.7 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e reports data on neuropsychological assessment at T0 according to sex. Overall, both males and females showed scores in normal ranges, except in emotion attribution tasks, where male patients showed pathological cut-off and a worse performance compared to females [mean (SD) EAT: 42.8 (8.5) males vs 53.1 (5.7) females, p\u0026thinsp;=\u0026thinsp;0.029].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean (SD) obtained at each neuropsychological assessment test at baseline (T0), reported according to sex and adjusted for age.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest (pathological cut-off)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMales\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;9\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemales\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMMSE (\u0026lt;\u0026thinsp;24)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29.1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29.6 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFAB (\u0026lt;\u0026thinsp;13.4)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15.9 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15.8 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVerbal fluency (\u0026lt;\u0026thinsp;17.35)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24.4 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24.6 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRCPM (\u0026lt;\u0026thinsp;18.96)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31.0 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.4 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest Stroop (errors) (\u0026gt;\u0026thinsp;4.24)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.36 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.42 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest Stroop (time) (\u0026gt;\u0026thinsp;36.92)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22.9 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21.9 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT A (\u0026gt;\u0026thinsp;94)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80.0 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e57.8 (15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT B (\u0026gt;\u0026thinsp;187)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e135.7 (36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e108.6 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT B-A (\u0026gt;\u0026thinsp;187)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40.7 (32.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51.1 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF (\u0026lt;\u0026thinsp;28.53)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33.5 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34.1 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF \u0026ndash; recall (\u0026lt;\u0026thinsp;9.46)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.2 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15.5 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBST (\u0026lt;\u0026thinsp;8.2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.7 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.3 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEAT (\u0026lt;\u0026thinsp;44.19)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e42.8 (8.5)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53.1 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.029\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical-demographic characteristics of participants at follow-up (T1)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMales\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemales\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime of follow-up, mean (SD) -months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOnset age, mean (SD) -years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.6 (4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.4 (7.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEducation, mean (SD) -years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.0 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.6 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisease Duration, mean (SD) -years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.2 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.8 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCAG expansion, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.8 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.2 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSARA scale, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.8 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.0 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAt T1, six patients dropped out: two due to difficulties in reaching the center with caregivers, and four refused to undergo further neuropsychological and neurophysiological assessments, which they considered lengthy and tiring. Data were collected from the remaining 10 patients, evenly divided between both sexes (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The male patients (n\u0026thinsp;=\u0026thinsp;5) who continued in the follow-up had a mean (SD) age at clinical onset of 39.6 (4.6) years and disease duration of 10.2 (3.8) years. Female patients showed similar results, with a mean (SD) age at clinical onset of 43.4 (7.3) years and disease duration of 10.8 (3.9) years. The mean (SD) years of education were 11.0 (2.7) for men and 10.6 (2.5) for women (p\u0026thinsp;=\u0026thinsp;ns).\u003c/p\u003e \u003cp\u003eThe number of triplets repeats in the ataxin-1 gene was higher in males [mean (SD): 51.8 (9.1)] compared to females [45.2 (3.3)], though this difference was not statistically significant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean (SD) obtained at each neuropsychological assessment test at T1, reported according to sex and adjusted for age. SARA score for motor assessment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest (pathological cut-off)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMales\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFemales\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMMSE (\u0026lt;\u0026thinsp;24)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29.0 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29.6 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFAB (\u0026lt;\u0026thinsp;13.4)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15.2 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.6 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVerbal fluency (\u0026lt;\u0026thinsp;17.35)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16.6 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27.3 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRCPM (\u0026lt;\u0026thinsp;18.96)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31.5 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31.5 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest Stroop (errors) (\u0026gt;\u0026thinsp;4.24)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.75 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.60 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest Stroop (time) (\u0026gt;\u0026thinsp;36.92)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.4 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18.0 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT A (\u0026gt;\u0026thinsp;94)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75.7 (25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49.8 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT B (\u0026gt;\u0026thinsp;187)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e139.7 (36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e101.8 (39.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT B-A (\u0026gt;\u0026thinsp;187)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48.0 (43.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52.6 (36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF (\u0026lt;\u0026thinsp;28.53)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.3 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34.2 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF \u0026ndash; recall (\u0026lt;\u0026thinsp;9.46)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.0 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13.7 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBST (\u0026lt;\u0026thinsp;8.2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.7 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.5 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEAT (\u0026lt;\u0026thinsp;44.19)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44.0 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55.8 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSARA scale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18.8 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.0 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows data on motor (SARA scale) and neuropsychological assessment at T1 in the 10 patients who performed follow-up. At follow-up, males continued to display moderate motor impairment, which was greater than in females, albeit without statistical significance [mean (SD) SARA scale: males 18.8 (6.8) vs. females 14.0 (6.5)].\u003c/p\u003e \u003cp\u003eRegarding neuropsychological tests, all resulted in normal ranges in females, while males showed deficits in verbal fluency test [mean (SD), 16.6 (4.8)], recall of Copy Rey Figure [mean (SD), 7.0 (6.2)], and, still, in emotional attribution tasks [mean (SD), 44.0 (4.3)]. Comparing each test between sexes, females performed better on the verbal fluency test [mean (SD), males 16.6 (4.8) vs females 27.3 (6.1), p\u0026thinsp;\u0026lt;\u0026thinsp;0.05], Stroop test in terms of time [mean (SD) males 32.4 (6.8) vs females 18.0 (5.2), p\u0026thinsp;\u0026lt;\u0026thinsp;0.05], recall of Copy Rey Figure [mean (SD) males 7.0 (6.2) vs females 13.7 (2.9), p\u0026thinsp;\u0026lt;\u0026thinsp;0.05], and emotion attribution tasks [mean (SD) males 44.0 (4.3) vs females 55.8 (1.5), p\u0026thinsp;\u0026lt;\u0026thinsp;0.05].\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows the differences observed between T1 and T0 at neuropsychological assessment according to sex. A slight worsening can be observed in all performances in both sexes, without statistical significance.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean difference (SD) of scores obtained at each neuropsychological assessment test at T1 vs. T0, reported according to sex and adjusted for age.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFamale\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMMSE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.3 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFAB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.6 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVerbal fluency\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-3.6 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.0 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRCPM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-2.5 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest Stroop (errors)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.8 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest Stroop (time)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.7 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.4 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT B-A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.6 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.2 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.3 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF \u0026ndash; recall\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.9 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBST\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.1 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEAT (\u0026lt;\u0026thinsp;44.19)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-2.1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.2 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAnalysis of ERPS, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the latencies (A) and amplitudes (B) data of aERPs in the 10 patients who underwent both neuropsychological examinations (T0 and T1). No differences were detected in the two timelines in each sex group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe differences between sex at baseline and follow-up of aERP are described in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e and revealed only a higher N100 amplitude in females compared to males at baseline; no further differences were detected at follow-up (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEvent-related potentials: principal components at T0 and T1 [of which latency (lat) and amplitude (amp) were measured], and mean difference (SD) by sex.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eM\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eF\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003csub\u003e\u003cem\u003ediff (M vs F)\u003c/em\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP300lat (T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e375.3 (53.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e409.3 (63.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP300lat (T1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e374.0 (43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e385.8 (25.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP300lat (T1-T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.2 (83.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-15.3 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP300amp (T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.4 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.8 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP300amp (T1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.5 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.2 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP300amp (T1-T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.7 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-4.9 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN100lat (T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e104.3 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e97.5 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN100lat (T1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e117.4 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e101.0 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN100lat (T1-T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.3 (42.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.1 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN100amp (T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.6 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.6 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN100amp (T1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.7 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.4 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN100amp (T1-T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.3 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-3.6 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN200lat (T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e249.7 (36.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e273.9 (45.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN200lat (T1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e263.3 (39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e254.5 (29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN200lat (T1-T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26.2 (61.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.5 (47.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN200amp (T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.5 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.7 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN200amp (T1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.1 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.9 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eN200amp (T1-T0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.6 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-1.6 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ens\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eClinical progression\u003c/h2\u003e \u003cp\u003eOf the 16 patients (nine male) initially enrolled in the study at baseline, 10 (five male) were included in the follow-up assessment at 24\u0026plusmn;6 months. In terms of age of onset (approximately 41 years), SCA1 affects both males and females similarly, consistent with previous studies [9, 10]. Interestingly, although not statistically significant, a tendency for earlier disease onset in males compared to females was noted, with males typically presenting symptoms towards the end of the fourth decade of life, while females tend to experience onset at the beginning of the fifth decade. This is in line with Du Montcel and colleagues, who demonstrated a 5-year earlier presentation of ataxia symptoms in males compared to females [9]. However, the literature does not consistently report clear sex-based differences in the age of onset or disease complexity, though it is well-established that these factors are correlated with the size of the expanded alleles [10]. Each additional repeat caused the largest reduction in age at the onset of 0.049 years [10]. Indeed, men in the present cohort exhibited a higher average number of CAG triplet expansions compared to women (51.8 vs. 45.2), and this might explain the earlier age at presentation of symptoms. However, the gender effects on the age of onset and mean CAG repeats were not so clear and not confirmed in other studies [31]. Indeed, Riess et al., in a cohort of SCA1 and SCA3 patients, noted gender effects in SCA patients on transmission rather than clinical expression [31].\u003c/p\u003e \u003cp\u003eRegarding motor impairment and disease progression, in the present study, both sexes presented with mild-to-moderate motor deficits at baseline as measured by the SARA scale. According to SCA type, sex differences in disease motor progression should be carefully considered. In SCA6, previous research by Jacobi et al. found that the female sex is associated with faster progression, with a hazard ratio of 1.7 (95% CI: 1.1\u0026ndash;2.6) for progression to more advanced disability stages [10]. Conversely, our data suggests a potential opposite trend in SCA1, with males potentially experiencing faster motor deterioration. Although this difference didn't reach statistical significance in our small cohort, males showed a more pronounced increase in SARA scores over follow-up (from 12.2 to 18.8) compared to females (from 10.7 to 14.0). This contrasting pattern suggests that the influence of sex on disease progression may vary according to SCA subtype, potentially reflecting differences in underlying pathophysiological mechanisms or sex-specific modifiers of disease expression. Beyond the specific differences among the various SCA subtypes, our findings confirm the well-documented clinical progression of cerebellar motor dysfunction in patients with SCA, representing a fundamental characteristic of the pathology, regardless of potential variables that might modulate its rate or expression [10, 32].\u003c/p\u003e \u003cp\u003eThe clinical progression in patients with SCA was globally analysed by Weber and colleagues, who combined data from two major European cohorts with a three-year follow-up focused on health-related quality of life progression [11]. The research revealed that quality of life decline was particularly pronounced in males with younger disease onset (before age 40) and with a BMI between 30 and 35 [11]. Generally, with disease progression, quality of life is influenced by increasingly severe cerebellar problems (i.e. dysarthria, dysphagia) and mild cognitive problems [8]. However, the progression of cognition according to sex has been less analysed. Indeed, the present study focused mainly on this aspect, showing that affected patients, even 10 years after disease onset, presented neuropsychological test scores within normal limits at baseline. However, a deterioration in scores was observed across all tests during follow-up, indicating a decrease (albeit within normal limits) in cognitive performances. These findings support the notion that progressive cerebellar and neuronal degeneration in SCA1 affects not only motor functions but also cognitive domains [4, 33\u0026ndash;38]. When considering cognitive and emotional processing differences between males and females with SCA1, this study showed that males consistently performed worse than females in emotion attribution tasks, with statistically significant differences at both baseline (p\u0026thinsp;=\u0026thinsp;0.029) and follow-up (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This suggests a specific deficit in social cognition affecting male SCA1 patients more severely.\u003c/p\u003e \u003cp\u003e In addition, at follow-up, females outperformed men on both the verbal fluency test and the Stroop test time. It is important to note that the verbal fluency test assesses not only language and executive functions but also cognitive flexibility, specifically evaluating the patient\u0026rsquo;s ability to access their lexical knowledge [22]. Literature indicates that patients with higher SARA scores often show an inverse correlation with verbal fluency test scores [4]. This suggests that motor involvement, particularly dysarthria, may influence verbal fluency as measured by this test. In our cohort, men demonstrated a more severe clinical presentation, which could partly explain this result. Similarly, differences in Stroop test time performance may be attributed to the higher disease severity in males. Additionally, the role of saccadic movements in test execution should not be underestimated. Studies have shown that increased latency in saccadic movements correlates with executive dysfunction in frontal regions [39\u0026ndash;40]. While ocular movements were not assessed in terms of speed in this study, the greater severity of the disease in men, coupled with a higher number of CAG triplet expansions, may suggest a more pronounced slowing of extrinsic ocular motility.\u003c/p\u003e \u003cp\u003eThese findings support the notion that cerebellar disorders like SCA1 affect cognitive domains beyond motor control [41], with a particular impact on executive functions and emotional processing. The cerebellum's role in cognition and emotion is increasingly recognized, and our data suggests these networks may be differently affected in males versus females with SCA1.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eNeurophysiological progression\u003c/h2\u003e \u003cp\u003eIn our analysis, event-related potentials were recorded in response to auditory stimuli (aERPs). After processing, we examined various ERP components (P300, N100, N200) in terms of latency and amplitude. No significant differences were observed in the aERPs between T0 and T1 for the entire sample. However, when comparing the sexes, N100 amplitude was higher in females at baseline. This component is associated with early sensory processing and attention allocation. The lack of significant neurophysiological differences at follow-up, despite clear cognitive differences, suggests that functional compensation mechanisms might be at play, particularly in female patients.\u003c/p\u003e \u003cp\u003eTo our knowledge, no studies in the literature have investigated neurophysiological follow-up via ERPs in a homogeneous population of SCA1 patients and the correlation with sex. Longitudinal studies often involve heterogeneous populations across various SCA genotypes [10].\u003c/p\u003e \u003cp\u003eThe main limitations of the study are: i) the small sample size, particularly at follow-up (n\u0026thinsp;=\u0026thinsp;10), limits statistical power and generalizability, and ii) the high dropout rate (37.5%) might introduce selection bias, as patients with more severe symptoms might have been more likely to discontinue. Future studies should aim to recruit larger cohorts with balanced sex representation and investigate potential protective factors that might explain the relative preservation of cognitive functions in female SCA1 patients. The relationship between CAG repeat length and cognitive outcomes also warrants further investigation. In addition, a longer follow-up period (\u0026gt;\u0026thinsp;24 months) may likely be needed to predict progression toward a dementia-like state\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study provides preliminary evidence for sex-based differences in cognitive and emotional processing in SCA1 patients, with males showing greater vulnerability. While motor progression appears to affect both sexes, the pattern of cognitive decline may be influenced by sex-specific factors that deserve further investigation. Regarding the neurophysiological findings studied through the use of event-related auditory potentials, no sex differences were found between T0 and T1, indicating that neurophysiological examination does not represent a reliable test for assessing the evolution of cognitive impairment in this patient group in all populations, in each sex and between sexes.\u003c/p\u003e \u003cp\u003eThe documented gender differences highlight the importance of considering gender as a significant factor in clinical assessment and the need for gender-specific therapeutic approaches, with potentially greater attention to interventions targeting motor and cognitive symptoms in males. However, it's important to note that these are general trends, and individual patient care should always be tailored to specific needs regardless of gender.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthical Approval:\u003c/strong\u003e \u003cp\u003eThe study protocol received approval from the local institutional review board (CE 453/2021), and all participants provided informed written consent. The study adhered to the ethical principles outlined in the 1964 Declaration of Helsinki and its subsequent amendments. All participants gave written consent before participating in the study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eClinical trial number\u003c/strong\u003e \u003cp\u003enot applicable\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflicts of interest:\u003c/strong\u003e \u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNo funding supported this research.\u003c/p\u003e \u003cp\u003e \u003cb\u003eData availability\u003c/b\u003e: The data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthors\u0026rsquo; contributions: FC contributed to the conception of the work, acquisition and interpretation of data, and drafted the work; SS contributed to acquisition and interpretation of data, and drafted the work; EA contributed to the conception and design of the work, acquisition and interpretation of data; AG contributed to acquisition of data; MP contributed to analysis and interpretation of data; PA contributed to acquisition and analysis of data; JGG contributed to acquisition and interpretation of data; DG contributed to acquisition of data; MS contributed to the conception of the work and revised it critically for important intellectual content. All authors approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSokolovsky N, Cook A, Hunt H, Giunti P, Cipolotti L. A preliminary characterisation of cognition and social cognition in spinocerebellar ataxia types 2, 1, and 7. Behav Neurol. 2010;23(1-2):17-29. \u003c/li\u003e\n\u003cli\u003eB\u0026uuml;rk K, Globas C, B\u0026ouml;sch S, Klockgether T, Z\u0026uuml;hlke C, Daum I, Dichgans J. Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J Neurol. 2003 Feb;250(2):207-11. \u003c/li\u003e\n\u003cli\u003eMoriarty A, Cook A, Hunt H, Adams ME, Cipolotti L, Giunti P. 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Neurology. 2009 Nov 17;73(20):1649-55. \u003c/li\u003e\n\u003cli\u003eRodr\u0026iacute;guez-Labrada R, Vel\u0026aacute;zquez-P\u0026eacute;rez L, Ortega-S\u0026aacute;nchez R, Pe\u0026ntilde;a-Acosta A, V\u0026aacute;zquez-Mojena Y, Canales-Ochoa N, Medrano-Montero J, Torres-Vega R, Gonz\u0026aacute;lez-Zaldivar Y. Insights into cognitive decline in spinocerebellar Ataxia type 2: a P300 event-related brain potential study. Cerebellum Ataxias. 2019 Mar 4;6:3. \u003c/li\u003e\n\u003cli\u003eJ, Valis M, Masopust J, Urban A, Zumrova A, Talab R, Kuba M, Kubova Z, Langrova J. An electrophysiological study of visual processing in spinocerebellar ataxia type 2 (SCA2). Cerebellum. 2011 Mar;10(1):32-42.\u003c/li\u003e\n\u003cli\u003eSchmitz-H\u0026uuml;bsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Sch\u0026ouml;ls L, Szymanski S, van de Warrenburg BP, D\u0026uuml;rr A, Klockgether T, Fancellu R. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006 Jun 13;66(11):1717-20. \u003c/li\u003e\n\u003cli\u003eMagni E, Binetti G, Bianchetti A, Rozzini R, Trabucchi M. Mini-Mental State Examination: a normative study in Italian elderly population. Eur J Neurol. 1996 May;3(3):198-202. \u003c/li\u003e\n\u003cli\u003eAppollonio I, Leone M, Isella V, Piamarta F, Consoli T, Villa ML, Forapani E, Russo A, Nichelli P. The Frontal Assessment Battery (FAB): normative values in an Italian population sample. Neurol Sci. 2005 Jun;26(2):108-16. \u003c/li\u003e\n\u003cli\u003eCarlesimo GA, Caltagirone C, Gainotti G. The Mental Deterioration Battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The Group for the Standardization of the Mental Deterioration Battery. Eur Neurol. 1996;36(6):378-84. \u003c/li\u003e\n\u003cli\u003eGiovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, Capitani E. Trail making test: normative values from 287 normal adult controls. Ital J Neurol Sci. 1996 Aug;17(4):305-9. \u003c/li\u003e\n\u003cli\u003eBasso A, Capitani E, Laiacona M. Raven\u0026apos;s coloured progressive matrices: normative values on 305 adult normal controls. Funct Neurol. 1987 Apr-Jun;2(2):189-94. PMID: 3666548.\u003c/li\u003e\n\u003cli\u003eCaffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A. A short version of the Stroop test: Normative data in an Italian population sample Nuova Riv Neurol. 2002. 12:111\u0026ndash;115\u003c/li\u003e\n\u003cli\u003eCaffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A. Rey-Osterrieth complex figure: normative values in an Italian population sample. Neurol Sci. 2002 Mar;22(6):443-7..\u003c/li\u003e\n\u003cli\u003eStandardizzazione e taratura italiana di test neuropsicologici. Gruppo Italiano per lo Studio Neuropsicologico dell\u0026apos;Invecchiamento [Italian standardization and classification of Neuropsychological tests. The Italian Group on the Neuropsychological Study of Aging]. Ital J Neurol Sci. 1987 Dec;Suppl 8:1-120. Italian. \u003c/li\u003e\n\u003cli\u003ePrior M., Marchi S., Sartori G. Cognizione sociale e comportamento, Volume 1. Uno strumento per la misurazione. Padova: Upsel Domeneghini Editore. 2003.\u003c/li\u003e\n\u003cli\u003eRemijn GB, Hasuo E, Fujihira H, Morimoto S. 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Brain. 2018 Jan 1;141(1):248-270. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Spinocerebellar ataxia, SCA1, Sex, Cognition, Cognitive decline, aERPs","lastPublishedDoi":"10.21203/rs.3.rs-6236602/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6236602/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSpinocerebellar ataxia type 1 (SCA1) is characterised by motor and cognitive symptoms. Sex-specific differences in disease presentation and progression remain poorly understood. This study investigates the role of sex in clinical-demographic and motor/cognitive outcomes in SCA1.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis single-centre, longitudinal observational cohort study was conducted at the University Hospital of Ferrara between 2021 and 2024. Consecutively, genetically confirmed SCA1 patients were evaluated at baseline and after 24\u0026plusmn;6 months. Assessments included comprehensive neuropsychological testing and auditory event-related potentials (aERPs). Motor function was evaluated using the Scale for Assessment and Rating of Ataxia (SARA).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSixteen SCA1 patients (9 males, seven females) were evaluated at baseline, with 10 patients (5 males, five females) completing follow-up. Even if most cognitive functions were preserved in both sexes at baseline, males showed significantly worse performance in emotion attribution tasks than females (42.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5 vs 53.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7, p\u0026thinsp;=\u0026thinsp;0.029). Over time, both sexes showed slightly worsening cognitive performance, with males demonstrating deficits in verbal fluency, visual memory recall, and emotion attribution (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the same group, motor impairment worsened at follow-up, though not significantly. aERPs revealed no differences between sexes at follow-up.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSex may influence cognitive outcomes in SCA1, with male patients showing greater vulnerability to cognitive decline. aERPs did not show significant modifications. These findings highlight the importance of considering sex-specific approaches in the clinical management of SCA1 patients and the higher values of a comprehensive neuropsychological assessment compared to the neurophysiological approach with aERPs to reach these slight changes over time.\u003c/p\u003e","manuscriptTitle":"Sex differences in Spinocerebellar ataxia type 1: clinical presentation and progression","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-16 08:59:36","doi":"10.21203/rs.3.rs-6236602/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-27T09:08:46+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-19T22:20:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-11T03:06:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-08T19:48:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329498343650765946660993466611196636392","date":"2025-03-29T02:07:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"277128237701940993798693424314973185583","date":"2025-03-27T22:32:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325487982907479604216144168214632238735","date":"2025-03-27T20:36:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-27T12:56:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-19T03:46:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-19T03:44:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Cerebellum","date":"2025-03-16T08:44:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b5517f5e-1066-4722-970c-3708325ed615","owner":[],"postedDate":"April 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-14T16:10:33+00:00","versionOfRecord":{"articleIdentity":"rs-6236602","link":"https://doi.org/10.1007/s12311-025-01881-4","journal":{"identity":"the-cerebellum","isVorOnly":false,"title":"The Cerebellum"},"publishedOn":"2025-07-10 15:57:45","publishedOnDateReadable":"July 10th, 2025"},"versionCreatedAt":"2025-04-16 08:59:36","video":"","vorDoi":"10.1007/s12311-025-01881-4","vorDoiUrl":"https://doi.org/10.1007/s12311-025-01881-4","workflowStages":[]},"version":"v1","identity":"rs-6236602","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6236602","identity":"rs-6236602","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}