Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults

Abstract

Midlife may be an ideal window for intervention in Alzheimer’s disease (AD). To determine whether sleep is associated with early signs of AD neuropathology (amyloid deposition) in late midlife, we imaged brain amyloid deposits using Positron Emission Tomography (PET) with [C-11]Pittsburgh Compound B (PiB), and assessed sleep with the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study (MOS) Sleep Scale in 98 cognitively healthy adults (aged 62.4 ± 5.7 years) from the Wisconsin Registry for Alzheimer’s Prevention. We used multiple regression to test the extent to which sleep scores predicted regional amyloid burden. Participants reporting less adequate sleep, more sleep problems and greater somnolence on the MOS had greater amyloid burden in AD-sensitive brain regions (angular gyrus, frontal medial orbital cortex, cingulate gyrus and precuneus). Amyloid was not associated with reported sleep amount, symptoms of sleep disordered breathing, trouble falling asleep or ESS. Poor sleep may be a risk factor for AD and a potential early marker of AD or target for preventative interventions in mid-life.

Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease?

“…The bidirectional link between sleep disturbance and Aβ pathology is observed before clinical onset of AD, and can occur independent of insomnia or apnea 12, 14, 21–23 . This indicates that the association between sleep and Aβ pathology is not just a consequence of a primary sleep disorder, or end-stage neurodegeneration.…”

“…Both subjective and objective measures of poor sleep correlate with the severity of cortical Aβ burden, CSF measures of Aβ, and phospohorylated tau in CSF 12, 14, 21–23 . Such sleep-Aβ associations have been reported in cognitively normal older adults, MCI patients, and those diagnosed with AD 12, 21–23 . Raising biomarker potential, the relationship between NREM sleep disruption and Aβ may be anatomically and neurophysiologically unique.…”

“…Thus, not only does sleep loss promote Aβ aggregation while Aβ aggregation promotes sleep loss, but sleep loss also magnifies the effect of Aβ aggregation on neuronal function. This magnification has the potential to facilitate neuronal hyperexcitability 42 , disrupt the impact of sleep on synaptic potentiation 23 , and even trigger nonlinear increases in Aβ accumulation, accelerating AD pathogenesis.…”

Do Older Adults Need Sleep? A Review of Neuroimaging, Sleep, and Aging Studies

“…Therefore, Aβ burden is often highest in the default mode network (precuneus, posterior cingulate, medial prefrontal cortex, lateral temporal cortex, hippocampal formation, angular gyrus, retrosplenial cortex)[57]. Interestingly, individuals who report more sleep disturbances also show greater Aβ burden in several default mode network regions [76]. Which sleep disturbance is most related to Aβ burden is still debated.…”

Is Sleep Disruption a Risk Factor for Alzheimer’s Disease?

“…Sprecher et al [48] demonstrated the complex relationship between Aβ burden and sleep disturbance. They found that β-amyloid deposition within medial prefrontal cortex (mPFC) was significantly correlated with the disruption degree in NREM (non-rapid eye movement) SWA (slow wave activity) generation.…”