MINNEAPOLIS—People who report feeling more sleepy and less rested have elevated levels of amyloid in regions of the brain that are commonly involved in Alzheimer’s disease, according to a cohort study presented at the Annual Meeting of the Associated Professional Sleep Societies.
Researchers studied 98 asymptomatic, cognitively healthy adults in late middle age from the Wisconsin Registry for Alzheimer’s Prevention program. The majority of the participants were at elevated risk for Alzheimer’s disease because of family history.
Self-reported somnolence, poorer sleep quality, and sleep problems were significantly correlated with higher levels of amyloid deposition in the cortex overall and in four subregions that are typically affected in Alzheimer’s disease.
“It does appear that there is an association between amyloid burden and sleepiness, and that relationship is present in adults who are cognitively healthy but who are at risk of developing Alzheimer’s disease in the future. They are fairly young, in terms of amyloid pathology,” said Kate Sprecher, a doctoral candidate in the neuroscience training program at the University of Wisconsin–Madison. She acknowledged that the findings may differ in a cohort not enriched for people at elevated risk for Alzheimer’s disease.
“In terms of mechanisms, we can’t say from these data whether sleep is driving amyloid deposition or whether amyloid deposition is disrupting sleep,” she added. “Nonetheless, it’s kind of tantalizing that sleep may be a tool that we can use to prevent or delay Alzheimer’s pathology. We may be able to intervene early in the disease, when people are actually able to respond to treatment, because typically, current drugs are targeting later disease, when a great deal of neurodegeneration has already taken place. So sleep may be something that we can target really early.”
The investigators plan to investigate the observed association further using objective measures of sleep and obstructive sleep apnea, according to Ms. Sprecher. “We’ll do some longitudinal follow-up as well in our cohort to see how sleep changes might relate to actual progression of the disease,” she said.
Study participants completed the Medical Outcomes Study (MOS) Sleep Scale and the Epworth Sleepiness Scale (ESS). Amyloid deposition in the brain was measured by PET performed with Pittsburgh Compound B.
The participants were age 63, on average, and two-thirds were female, reported Ms. Sprecher. Overall, 76% had a family history of Alzheimer’s disease, and 34% were positive for the APOE4 allele.
Analyses adjusted for these and other potential confounders showed a correlation between somnolence on the MOS Sleep Scale—the average of scores for drowsiness, trouble staying awake, and napping—and the burden of amyloid in the left supramarginal gyrus (correlation [r] = 0.22), the left frontal medial orbital cortex (r = 0.21), and the left frontal inferior orbital cortex (r = 0.21).
Poorer quality of sleep was correlated with amyloid burden in the cortex overall (r = 0.25) as well as in the left and right precuneus (r = 0.23 and 0.25, respectively), the right supramarginal gyrus (r = 0.23), the left and right frontal medial orbital cortex (r = 0.29 and 0.29, respectively), and the left and right frontal inferior orbital cortex (r = 0.26 and 0.25, respectively).
Scores on the Sleep Problem Index were also associated with greater burden in some of these cortical areas. Although ESS scores were significantly correlated with MOS scores, they were not directly correlated with amyloid burden in any of the regions studied.
“This [result] could be because the two questionnaires probe slightly different aspects of sleepiness,” said Ms. Sprecher. “The ESS asks how likely you are to fall asleep in several common situations such as while watching TV or driving a car. The MOS asks whether you take naps, feel sleepy during the day, or feel that you get enough sleep at night. Therefore, the MOS may be better at probing how adequate your sleep is, even if you are managing to stay awake during the day.”
—Susan London