Journal
JAMA NEUROLOGY
Volume 75, Issue 6, Pages 672-680Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/jamaneurol.2018.0049
Keywords
-
Categories
Funding
- NIH [R01NS097495, U01AG006786, R01AG056366, P50AG016574, R01 AG011378, R01AG041851, U01AG045390, U54NS092089, RO1AG041797, R01-AG037551, U01-HL096917, U01-AG032438, U01-AG024904, C06RR018898, R01AG034676]
- Gerald and Henrietta Rauenhorst Foundation
- Alexander Family Alzheimer's Disease Research Professorship of theMayo Foundation
- Elsieand Marvin Dekelboum Family Foundation
- Schuler Foundation
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL096917] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS097495, U54NS092089] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P50AG016574, U01AG045390, U01AG006786, R01AG041851, R01AG056366, R01AG034676, R01AG011378, R01AG041797] Funding Source: NIH RePORTER
Ask authors/readers for more resources
IMPORTANCE Aging is associated with excessive daytime sleepiness (EDS), which has been linked to cognitive decline in the elderly. However, whether EDS is associated with the pathologic processes of Alzheimer disease remains unclear. OBJECTIVE To investigate whether EDS at baseline is associated with a longitudinal increase in regional beta-amyloid (A beta) accumulation in a cohort of elderly individuals without dementia. DESIGN, SETTING, AND PARTICIPANTS This prospective analysis included participants enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study in Olmsted County, Minnesota. Of 2900 participants, 2172 (74.9%) agreed to undergo carbon 11-labeled Pittsburgh compound B positron emission tomography (PiB-PET). We included 283 participants 70 years or older without dementia who completed surveys assessing sleepiness at baseline and had at least 2 consecutive PiB-PET scans from January 1, 2009, through July 31, 2016, after excluding 45 (13.7%) who had a comorbid neurologic disorder. MAIN OUTCOMES AND MEASURES Excessive daytime sleepinesswas defined as an Epworth Sleepiness Scale score of at least 10. The difference in A beta levels between the 2 consecutive scans (Delta PiB) in A beta-susceptible regions (prefrontal, anterior cingulate, posterior cingulate-precuneus, and parietal) was determined. Multiple linear regression models were fit to explore associations between baseline EDS and Delta PiB while adjusting for baseline age, sex, presence of the apolipoprotein E epsilon 4 allele, educational level, baseline PiB uptake, global PiB positivity (standardized uptake value ratio >= 1.4), physical activity, cardiovascular comorbidities (obesity, hypertension, hyperlipidemia, and diabetes), reduced sleep duration, respiratory symptoms during sleep, depression, and interval between scans. RESULTS Of the initial 283 participants, mean (SD) age was 77.1 (4.8) years; 204 (72.1%) were men and 79 (27.9%) were women. Sixty-three participants (22.3%) had EDS. Baseline EDS was significantly associated with increased regional A beta accumulation in the anterior cingulate (B coefficient = 0.031; 95% CI, 0.001-0.061; P = .04), posterior cingulate-precuneus (B coefficient = 0.038; 95% CI, 0.006-0.069; P = .02), and parietal (B coefficient = 0.033; 95% CI, 0.001-0.065; P = .04) regions. Association of EDS with longitudinal A beta accumulation was stronger in participants with baseline global PiB positivity in the anterior cingulate (B coefficient = 0.065; 95% CI, 0.010-0.118; P = .02) and cingulate-precuneus (B coefficient = 0.068; 95% CI, 0.009-0.126; P = .02) regions. CONCLUSIONS AND RELEVANCE Baseline EDS was associated with increased longitudinal A beta accumulation in elderly persons without dementia, suggesting that those with EDS may be more vulnerable to pathologic changes associated with Alzheimer disease. Further work is needed to elucidate whether EDS is a clinical marker of greater sleep instability, synaptic or network overload, or neurodegeneration of wakefulness-promoting centers. Early identification of patients with EDS and treatment of underlying sleep disorders could reduce A beta accumulation in this vulnerable group.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available