β-Amyloid Accumulation Linked to Excessive Daytime Sleepiness

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Excessive daytime sleepiness may be a marker of brain degeneration.
Excessive daytime sleepiness may be a marker of brain degeneration.
The following article is part of live conference coverage from the 2017 American Academy of Neurology (AAN) annual meeting in Boston, Massachusetts. Neurology Advisor's staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAN 2017.

BOSTON — In a cohort of non-demented elderly patients, excessive daytime sleepiness (EDS) increased the rate of β-amyloid accumulation, according to results presented at the 2017 American Academy of Neurology Annual Meeting.

“We found that elderly subjects with [EDS] at baseline accumulated more β-amyloid in their brains, particularly in vulnerable areas,” study investigator Diego Z. Carvalho, MD, of the Mayo Clinic in Rochester, Minnesota, told Neurology Advisor. “The results confirmed our expectations, based on prior studies showing that these individuals are at increased risk for dementia. We were able to show that this risk may, at least to some extent, be secondary to more β-amyloid accumulation.”

According to Dr Carvalho, the aim of the study was to better understand the association between aging and increased daytime sleepiness, since the latter is linked to functional impairment, falls, and cognitive decline in the elderly. “We wanted to understand what is behind the cognitive decline seen in [the] elderly with [EDS] in prior studies,” Dr. Carvalho said. “Is it related to Alzheimer's disease?”

For the study, researchers enrolled 283 non-demented individuals (age ≥70) who had at least 2 serial Pittsburgh Compound-B positron emission tomography (PiB-PET) scans and had completed sleep questionnaires. Researchers defined EDS as an Epworth Sleepiness Scale score ≥10.

According to study methodology, multiple linear regression models were fit in 6 Alzheimer's disease-related regions — orbitofrontal, prefrontal, anterior cingulate, cingulate-precuneus, temporal, and parietal — to examine if baseline EDS predicted variability in amyloid accumulation between 2 serial scans.

In addition, researchers controlled for baseline age, sex, apolipoprotein E, education, regional PiB positivity (standard uptake value ratio, ≥1.4), physical activity, cardiovascular comorbidities, reduced sleep duration, respiratory symptoms during sleep, depression, and interval between scans.

Results revealed a significant association between baseline EDS and increased β-amyloid accumulation in the orbitofrontal, anterior cingulate, and cingulate/precuneus regions, although the strength of the association was greater in PiB-positive areas.

In subset analysis, EDS increased β-amyloid accumulation in the anterior cingulate (0.06; 95% CI, 0.02-0.1; P =.007), cingulate/precuneus (0.076; 95% CI, 0.03-0.12; P =.002), and parietal cortex (0.058; 95% CI, 0.01-0.11; P =.03) in patients who were amyloid positive at baseline in these regions.

“Elderly subjects with [EDS] are more vulnerable to Alzheimer's disease pathology,” Dr Carvalho concluded. “Identifying and treating sleep disorders underlying [EDS] in this population may halt or slow down the progression to dementia.”

Dr Carvalho added that it remains unclear why EDS is associated with more amyloid accumulation.

“Sleep disorders, especially [obstructive sleep apnea], may certainly play a role,” he said. “However, [EDS] may also be an early marker of degeneration of brain areas that promotes wakefulness, especially the locus coeruleus, which is involved early in Alzheimer's disease.”

Visit Neurology Advisor's conference section for continuous coverage live from AAN 2017.

Reference

Carvalho D, St. Louis E, Knopman D, et al. Excessive daytime sleepiness predicts increased β-amyloid accumulation in non-demented elderly: a longitudinal PiB-PET study. Presented at:  2017 American Academy of Neurology Annual Meeting. April 22-28, 2017; Boston, MA.

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