Sleep Disorders an Early Dementia 'Warning Sign'?

Pauline Anderson

August 03, 2022

Sleep disorders are associated with a 17% increased risk for dementia, results from a large registry-based study show.

Dr Gunhild Waldemar

"From our research, we can't exclude a diagnosis of a sleep disorder in many cases being a warning sign for dementia," study investigator Gunhild Waldemar, MD, professor of clinical neurology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, told Medscape Medical News.

She added that the results should be a reminder to clinicians about the importance of early diagnosis and treatment of a sleep disorder to reduce the patient's future risk for dementia.

The findings were presented at the Alzheimer's Association International Conference (AAIC) 2022.

Growing Evidence Base

Previous research has revealed a wide range of modifiable risk factors for dementia, and growing evidence suggests sleep disorders are among them.

However, studies examining associations between poor sleep and dementia often relied on relatively small cohorts, short time intervals, retrospective surveys, or self-reported exposure data, Waldemar noted.

"Our study is based on a nationwide cohort of people, and it includes everyone, because we have full healthcare coverage in Denmark. So, there are no missing people and no dropouts," she said.

The study data were derived from large, comprehensive Danish health registries and included individuals born from 1928 to 1953 who were followed for 40 years after turning 50, from January 1, 1978, to December 31, 2018.

Researchers linked population data with information on hospital-based sleep disorder diagnoses and hospital-based late-onset dementia in persons older than 65. They calculated incidence rate ratios (IRRs) and adjusted for sex, age, calendar year, highest education level at age 50, and somatic and psychiatric morbidities.

The study included about 1.49 million individuals. Of these, 41,704 were diagnosed with a sleep disorder. The percentage was higher in men (69.1%) than in women (30.9%).

During the follow-up period, 1235 participants (3%) were diagnosed with dementia. The mean age of the first dementia diagnosis was 75.6 years.

Results showed a significant 17% increased risk for dementia with any sleep disorder (adjusted IRR, 1.17; 95% CI, 1.11 – 1.24). The risk was mainly among men, although there was a weaker, nonsignificant risk among women.

Among 28,327 participants with sleep apnea, there was a 13% increased risk for dementia, but this was also significant only for men. Waldemar noted that sleep apnea is much more common in men than women, possibly because they are more likely to be overweight and have pulmonary disease.

Two Possible Interpretations

The category of "other specific sleep disorders" included insomnia, hypersomnia, nonorganic sleep disorders, sleep-related movement disorders, and parasomnia. For men with "other specific sleep disorders," the IRR was 2.0 (95% CI, 1.71 – 2.32).

Because parasomnia is a known early symptom of certain dementias, including Parkinson's disease and Lewy body dementia, the researchers excluded these from the analysis. After exclusion, the IRR for dementia for those with "other sleep disorders" was 1.4 (95% CI, 1.21 – 1.62).

With regard to age groups, the investigators found that the risk was greatest for those older than 65. Assessing dementia risk within 5 years and after 5 years of a sleep disorder diagnosis showed that the risk was increased by 35% during the first 5 years (IRR, 1.35; 95% CI, 1.21 – 1.62).

"So, it was mainly in the first 5 years after a sleep disorder diagnosis that we saw the increased risk," Waldemar noted.

She said there are two possible interpretations of the results ― either sleep disorders are a risk factor for future dementia, or they are a very early symptom of dementia.

Determining which interpretation is more accurate "is not black and white," she said. In some cases, receiving a sleep disorder diagnosis could also mean receiving a dementia diagnosis within the next 5 years, while in other cases, the sleep disorder diagnosis may indicate a long-term risk factor, Waldemar said.

A possible mechanism involves the lymphatic system, which clears toxic compounds, including amyloid beta, from the brain during sleep.

While the study was based on strong and reliable data from nationwide registries and had a long follow-up, it does have some limitations, Waldemar noted. For example, the data are only from inpatient and outpatient hospital contacts, not from primary care.

In addition, the study did not include detailed information on how long people slept, the quality of their sleep, or different dementia types, Waldemar added.

Nothing New?

Commenting on the study, Kristian Steen Frederiksen, MD, PhD, director of the Clinical Trial Unit at the Danish Dementia Research Center, Copenhagen, Denmark, told Medscape Medical News the findings are quite "robust" and are based on "a very large sample" of the Danish population.

"Physicians should be vigilant in elderly patients developing sleep disorders, as it may be a harbinger of dementia," said Frederiksen, who presented dementia research highlights at a meeting of the European Academy of Neurology.

However, Frederiksen noted that the registry-based study was subject to possible bias, owing, for example, to underreporting of certain sleep disorders.

Also weighing in for Medscape Medical News, clinical neurologist David Knopman, MD, Mayo Clinic, Rochester, Minnesota, said a stronger short-term risk for dementia following a sleep disorder diagnosis but weaker evidence of a long-term risk is a "key" finding.

"This could potentially point towards sleep disorders as an early symptom of dementia," said Knopman, whose research focuses on late-life cognitive disorders.

However, beyond disrupted nighttime sleep being a "plausible" early symptom of dementia, "I would not read more into it," he said.

"The study says nothing about disease mechanisms. In particular, this work is not informative about amyloid clearance," he added.

Knopman also noted that he does not consider the study as particularly newsworthy. "Sleep disruption is quite well known as an early symptom of dementia," he said.

Waldemar has served as consultant/speaker for Roche, Biogen, and Novo Nordisk. Knopman has disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2022: Abstract 63813. Presented August 2, 2022.

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