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Restless legs syndrome (RLS) is associated with an elevated risk of dementia among older adults, suggesting the disorder may be a risk factor for dementia or a very early noncognitive sign of dementia, researchers say.

In a large population-based cohort study, adults with RLS were significantly more likely to develop dementia over more than a decade than their peers without RLS.

If confirmed in future studies, “regular check-ups for cognitive decline in older patients with RLS may facilitate earlier detection and intervention for those with dementia risk,” investigators led by Eosu Kim, MD, PhD, suchuco by allied model 130 with Yonsei University College of Medicine, Seoul, Republic of Korea, write.

The study was published online March 6 in Alzheimer’s Research and Therapy.

Sleep Disorders and Dementia

RLS is associated with poor sleep, depression/anxiety, poor diet, microvasculopathy, and hypoxia ― all of which are known risk factors for dementia. However, the relationship between RLS and incident dementia has been unclear.

The researchers compared risk for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) among 2501 adults with newly diagnosed RLS and 9977 matched control persons participating in the Korean National Health Insurance Service–Elderly Cohort (KHIS-EC), a nationwide population-based cohort of adults aged 60 and older.

The mean age of the cohort was 73 years; most of the participants were women (65%). Among all 12,478 participants, 874 (7%) developed all-cause dementia during follow-up ― 475 (54%) developed AD, and 194 (22%) developed VaD.

The incidence of all-cause dementia was significantly higher among the RLS group than amng the control group (10.4% vs 6.2%). Incidence rates of AD and VaD (5.6% and 2.6%, respectively) were also higher in the RLS group than in the control group (3.4% and 1.3%, respectively).

In Cox regression analysis, RLS was significantly associated with an increased risk of all-cause dementia (adjusted hazard ratio [aHR], 1.46; 95% CI, 1.24 – 1.72), AD (aHR 1.38; 95% CI, 1.11 – 1.72) and VaD (aHR, 1.81; 95% CI, 1.30 – 2.53).

The researchers note that RLS may precede deterioration of cognitive function, leading to dementia, and they suggest that RLS could be regarded as a “newly identified” risk factor or prodromal sign of dementia.

Modifiable Risk Factor

Reached for comment, Thanh Dang-Vu, MD, PhD, professor and research chair in sleep, neuroimaging, and cognitive health at Concordia University, in Montreal, Canada, said there is now “increasing literature that shows sleep as a modifiable risk factor for cognitive decline.

“Previous evidence indicates that both sleep apnea and insomnia disorder increase the risk for cognitive decline and possibly dementia. Here the study adds to this body of evidence linking sleep disorders to dementia, suggesting that RLS should also be considered as a sleep-related risk factor,” Dang-Vu told Medscape Medical News.

“More evidence is needed, though, as here, all diagnoses were based on national health insurance diagnostic codes, and it is likely there were missed diagnoses for RLS but also for other sleep disorders, as there was no systematic screening for them,” Dang-Vu cautioned.

Support for the study was provided by the Ministry of Health and Welfare, the Korean government, and Yonsei University College of Medicine. Kim and Dang-Vu report no relevant financial relationships.

Alzheimers Res Ther. Published online March 6, 2023. Full text

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