0796 Restless Legs Syndrome Is Not Associated with Increased Brain Age: Insights from the Sleep Heart Health Study

Abstract Introduction Patients with restless legs syndrome (RLS) tend to have poor sleep quality. Sleep Heart Health Study (SHHS) data showed increased odds of cardiovascular disease (CVD) with RLS. However, the impact of RLS on brain aging is unknown. We hypothesized that RLS is associated with accelerated brain aging. Methods The RLS cohort was derived from a subset of the SHHS visit 2 (SHHS2) using standardized symptom-based criteria such as urge to move legs, worsening at rest, relief with movement, and evening or nighttime predominance. We used sleep EEG-based brain age index (BAI) to quantify brain aging. BAI measures the difference between an individual’s brain age and their chronological age. The BAI machine learning model was trained on a cohort of brain-healthy participants. Among 2,651 participants with available BAI, 135 had RLS. The Mann-Whitney U test was used for continuous variables and Chi-squared test was used to compare the categorical variables between the two groups (RLS vs non RLS). Results The RLS cohort had more females (68.9% vs 52.9%, p< 0.001) and a higher prevalence of hypertension (63.7% vs 53.1%, p=0.016), diabetes (4.4% vs 1.4%, p=0.015), and benzodiazepine use (9.6% vs 5.0%, p=0.042) compared to non-RLS controls. However, there was no statistically significant difference in median BAI between the RLS (BAI = 0 years) and non-RLS group (BAI = 0.12 years) after controlling for potential confounders. RLS symptom frequency (>15 days/month vs 5-15 days/month) was not associated with accelerated brain aging. BAI of high and low symptom frequency was + 0.56 and -0.54 years (p=0.781), respectively. Conclusion Using the SHHS2 dataset, RLS and its symptom frequency did not influence BAI, despite well-established negative impact of RLS on sleep quality. BAI is derived from cortical sleep EEG features, and RLS appears to have predominantly subcortical pathophysiology (striatum and thalamus). Therefore, subcortical abnormalities may not manifest as measurable cortical aging as measured by sleep EEG. Further studies are warranted to confirm these observations. Support (if any)