Association of Excessive Daytime Sleepiness With Longitudinal β-Amyloid Accumulation in Elderly Persons Without Dementia

Abstract

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 β-amyloid (Aβ) accumulation in a cohort of elderly individuals without dementia. DESIGN, SETTING, AND PARTICIPANTSThis 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 MEASURESExcessive daytime sleepiness was defined as an Epworth Sleepiness Scale score of at least 10. The difference in Aβ levels between the 2 consecutive scans (ΔPiB) in Aβ-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 ΔPiB while adjusting for baseline age, sex, presence of the apolipoprotein E ε4 allele, educational level, baseline PiB uptake, global PiB positivity (standardized uptake value ratio Ն1.4), physical activity, cardiovascular comorbidities (obesity, hypertension, hyperlipidemia, and diabetes), reduced sleep duration, respiratory symptoms during sleep, depression, and interval between scans. RESULTSOf 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 Aβ accumulation in the anterior cingulate

Sleep as a Potential Biomarker of Tau and β-Amyloid Burden in the Human Brain

“…For example, sleep quality and sleep-EEG alterations are recognized to co-occur with the transition into mild cognitive impairment and AD (Prinz et al, 1982;Hita-Yañez et al, 2013). In addition, subjective impairments in sleep (Spira et al, 2013(Spira et al, , 2018Sprecher et al, 2015;Carvalho et al, 2018) and the loss of Ͻ1 Hz non-rapid eye movement (NREM) slow-wave activity (SWA) (Mander et al, 2015) predict levels of A␤ aggregation as measured by PET.…”

Los trastornos del sueño y su compleja relación con las funciones cognitivas.

“…Los trastornos de sueño en adultos mayores sin demencia, pero que ya tienen acumulación de beta amiloide incluyen trastornos del sueño NREM, con un aumento en el número de interrupciones del sueño NREM, peor calidad objetiva y subjetiva de sueño NREM y disminución de la actividad de ondas lentas < 1Hz (58), así como excesiva somnolencia diurna (59).…”

Transient arousal modulations contribute to resting-state functional connectivity changes associated with head motion parameters

“…They thus can provide a flexible and convenient estimate of the brain arousal to any data sets with rsfMRI data, including recent large-scale imaging initiatives collected from healthy subjects and patients, e.g., the UK Biobank (Miller et al 2016) and Alzheimer's Disease Neuroimaging Initiative (ADNI) (Jack et al 2008). Together with other modalities of data, this may create new opportunities for understanding the mechanisms of arousal regulation as well as its role in the development of many neurological diseases of arousal relevance, e.g., Alzheimer's disease (Erik S. Musiek et al 2018;Carvalho et al 2018).…”