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Qualitative variables at baseline were compared by chi-squared test.

Characteristics of those with and without observed apnea at baseline were compared by t or χ tests, stratified by sex.

Clinical features at baseline were compared by IDE with ANCOVA for continuous variables or Mantel-Haenszel χ for categorical variables stratified by sex.

Treatments and changes between follow-up and baseline were compared by analysis of variance (ANOVA), t test and Chi-square test.

Changes of mRS, BI, CDR, and MMSE from the baseline were compared by mixed-effects model with repeated measurements (MMRM) with visits defined as fixed effect and baseline values as covariates.

Changes in outcome from baseline were compared between groups by mean differences and their 95% confidence intervals using independent t-test (P = 0.05).

Subject characteristics at baseline were compared among groups stratified by the presence or absence of OSA and obesity by Student t test for continuous variables and χ test for categorical variables.

Gene and protein expression changes over baseline were compared between study arms by two-tailed Mann–Whitney test.

Changes in all parameters from baseline were compared between the two groups by Mann–Whitney U-tests.

Second, RLSQoL overall life impact scores at baseline were compared between severity subgroups defined by dividing the patients into three groups on the basis of their CGI-S scores.

Baseline characteristics were compared by gender, and the lost to follow-up group was compared with the cohort baseline group using Pearson χ or Fisher's exact test for categorical data, whereas continuous data were tested with Student t test or Wilcoxon Mann–Whitney U test.