Genetic susceptibility to Alzheimer's disease with concurrent sleep apnea confers greater risk for cognitive impairment

Individuals who carry the apolipoprotein ε-4 (APOE-ε4) allele, which confers a genetic susceptibility to Alzheimer’s disease, may be at greater risk of diminished cognition from sleep-disordered breathing (SDB), according to study results published ahead of print in the journal Annals of the American Thoracic Society.

“Previous studies have shown inconsistent findings between SDB and cognition, which may be due to the different tests used,” said lead author Dayna A. Johnson, PhD, MPH, MS, MSW, instructor of medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA.  

Dr. Johnson and fellow researchers, therefore, undertook this study to assess the associations between indicators of SDB and cognitive function in the Multi-Ethnic Study of Atherosclerosis, and assess effect modification by the APOE-ε4 allele.

They included a diverse population of 1,752 subjects (mean age: 68.1 years; 45.4% male), all of whom underwent Type 2 in-home polysomnography, which included measurements or percentage sleep time at less than 90% oxyhemoglobin saturation (%Sat < 90%) and apnea-hypopnea index (AHI). Researchers also analyzed Epworth Sleepiness Scale Score (ESS) and sleep apnea syndrome (SAS; AHI > 5 and ESS > 10).

Finally, they measured cognitive outcomes including the Cognitive Abilities Screening Instrument (CASI); Digit Symbol Coding Test (DSC); and Digit Span Tests (DST) Forward and Backward.

Median patient AHI was 9.0, and mean ESS was 6.0. In all, roughly 9.7% patients had SAS and 26.8% had at least one copy of the APOE-ε4 allele.

Upon adjusted analyses, Dr. Johnson and colleagues found that one standard deviation increase in %Sat < 90% and ESS score was associated with poorer attention and processing speed as measured by the DST Forward score (ß =-0.12 [standard error: 0.06] and ß =-0.13 [0.06], respectively; P < 0.05).

They also observed that SAS and higher ESS scores were associated with poorer attention and processing speed as measured by the DSC (ß =-0.69 [0.35] and ß=-1.42 [0.35], respectively; P < 0.05). The presence of APOE-ε4 allele modified the associations of %Sat < 90% with DST forward and of ESS with DSCT (P interaction < 0.05).

Therefore, they concluded that overnight hypoxemia and sleepiness were associated with cognition, with small average effect estimates similar to those estimated for several other risk factors for dementia. These associations were strongest in patients carrying the APOE-ε4 risk allele with SDB.

“Our study provides further evidence that sleep-disordered breathing negatively affects attention, processing speed, and memory, which are robust predictors of cognitive decline,” said senior author Susan Redline, MD, MPH, Peter C. Farrell Professor of Sleep Medicine, Harvard Medical School. “Given the lack of effective treatment for Alzheimer’s disease, our results support the potential for SDB screening and treatment as part of a strategy to reduce dementia risk.”

The Multi-Ethnic Study of Atherosclerosis was funded by the National Heart, Lung, and Blood Institute, which also funded various aspects of the current study.