In a recent study published in the journal JAMA Network Open, researchers evaluated the association between sleep patterns and age-associated cognitive alterations among older adults.
Study: Longitudinal Sleep Patterns and Cognitive Impairment in Older Adults. Image Credit: Tero Vesalainen / Shutterstock
Background
Amyloid deposition, which appears ≥15 years before cognitive impairment, precedes cognitive decline. The most effective treatment strategy may be to target pathogenic mechanisms early in the disease's progression. Identifying the factors that precede cognitive and functional decline can lead to therapy and prevention decades before the development of dementia.
Sleep disturbance has been associated with dementia; however, it is unknown how longitudinal variations in sleep affect the occurrence of cognitive impairments. Short sleep duration and poor sleep quality are associated with a higher pathological load of Alzheimer's disease. Simple sleep metrics restrict studies that demonstrate a relationship between chronic sleep disturbance and dementia diagnosis.
About the study
In the present study, researchers investigated whether longitudinal patterns of self-documented sleep duration were associated with cognitive impairment among older adults.
The team longitudinally analyzed the Seattle Longitudinal Study (SLS) data; the study assessed cognitive function (between 1997 and 2020) and self-documented sleep durations (between 1993 and 2012) among older adults. The team enrolled SLS participants from the Health Maintenance Organization (HMO) of Washington and the Group Health Cooperative (GHC) of Puget Sound from 1956 to 2020. The researchers included only individuals who provided complete demographic data and those who were administered the neuropsychologic battery and filled out the Health Behavior Questionnaire (HBQ).
Self-reported demographic data included sex (male or female), ethnicity, race, apolipoprotein E ε4 (APOE*E4) allele carrier status, and educational attainment. The participants filled out the HBQ every three to five years, five times from 1993 to 2012, and underwent neuropsychological assessments every five to seven years from 1997 to 2019. Cognitive impairment was the study outcome, as described by performances below thresholds on the Mattis Dementia Rating Scale (DRS, scores below 129) and the Mini-Mental State Examination (MMSE, scores below 26). In addition, the SLS neuropsychological battery included the Center for Epidemiologic Studies-Depression Scale (CES-D).
Sleep duration was self-reported as the median of night sleep over the previous week and evaluated longitudinally at several time points. The researchers evaluated sleep phenotypes [short sleep (less than seven hours), medium sleep (seven hours), long sleep (more than seven hours)], median duration of sleep, sleep duration alterations, and sleep variability. They performed Cox proportional-type hazard regression modeling to determine the hazard ratios (HRs) and data analysis between September 2020 and May 2023.
Results
Among the SLS participants enrolled initially, only 1,104 who completed neuropsychological assessments and the HBQ were included in the study after excluding 278 individuals lacking demographic information, especially the APOE genotype. As a result, 826 individuals [with a mean age of 76 years; 57% (n=468) women; 26% (n=217) APOE*E4 carriers] comprised the study population.
Cox proportional regression modeling (concordance, 0.8) showed that higher variability in sleep patterns (HR, 3.1) and short sleeper status (HR, 3.7) were significantly related to cognitive impairment. The team observed higher cognitive decline with advancing age. Of 614 individuals, 44 (seven percent) showed a cognitive decline at the final assessment, with a higher cognitive decline among older individuals.
Educational attainment (HR, 1.2) and possessing ≥1.0 APOE*E4 copies (HR, 2.1) were significantly related to cognitive impairment. Modeling considering the influence of depression showed that APOE*E4 carrier status (HR, 2.1) and educational attainment (HR, 1.1) were significantly related to cognitive decline risk. Short sleepers (HR, 2.8) and increasing variability in sleep patterns (HR, 2.2) were significantly related to age-associated cognitive decay.
Incorporating longitudinal sleep assessment parameters in the models showed that several factors were significantly related to cognitive impairment risk, including educational attainment (HR, 1.3), APOE*E4 carrier status (HR, 2.7), short-sleep phenotypes (HR, 3.7), and higher variability in sleep patterns (HR, 3.1). The study found a significant correlation between age and educational attainment, with older individuals being less educated.
However, the team found no significant differences in APOE*E4 allele status by age. Global CES-D scores showed that individuals aged 65 to 84 years reported lower depression compared to those aged <56 and ≥85 years. Age also significantly influenced sleep duration, with older individuals experiencing longer sleep durations and fewer short- and medium-sleepers. Age was associated with lower sleep variability across longitudinal sleep duration assessments.
Overall, the study findings showed that short sleep duration and significant sleep variability were associated with poor cognitive function. Chronic sleep disturbance may raise cardiovascular disease, metabolic syndrome, stroke, depression, and diabetes risks, which increase cognitive decay risk. Sleep deprivation is associated with increased amyloid plaque load as well as faster ventricular enlargement, aggravating Alzheimer's disease-associated neurodegeneration. Sleep-active-type glymphatic activity aids amyloid, α-synuclein, and tau clearance, whereas acute sleep deprivation decreases it.
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