Associations of brain lesions at autopsy with polysomnography features before death

Abstract

Objective: To determine how sleep-disordered breathing, nocturnal hypoxia, and changes in sleep architecture in the elderly may be related to the development of the neuropathologic correlates of dementia.Methods: The Honolulu-Asia Aging Study is a prospective cohort study of Japanese American men in Honolulu, HI. We examined brain lesions at autopsy (Braak stage, neurofibrillary tangle and neuritic plaque counts, microinfarcts, generalized brain atrophy, lacunar infarcts, Lewy bodies [LBs], neuronal loss and gliosis in the locus ceruleus) in 167 participants who underwent polysomnography in 1999-2000 (mean age, 84 years) and died through 2010 (mean 6.4 years to death). Polysomnography measures included the apnea-hypopnea index, duration of apnea or hypopnea, duration of hypoxemia, minimum oxygen saturation (SpO 2 ), duration of slow-wave sleep (SWS, non-REM stage N3), and arousals.Results: Sleep duration with SpO 2 ,95% was associated with higher levels of microinfarcts (adjusted odds ratio [OR] 3.88, 95% confidence interval [CI] 1.10-13.76, comparing the highest to lowest quartiles of %sleep with SpO 2 ,95%). Greater SWS duration was associated with less generalized atrophy (adjusted OR 0.32, 95% CI 0.10-1.03, comparing highest to lowest quartiles of %sleep in SWS). LBs were less common with greater %sleep with SpO 2 ,95% (adjusted OR 0.17, 95% CI 0.04-0.78, comparing highest to lowest quartiles). Higher minimum SpO 2 during REM sleep was associated with less gliosis and neuronal loss in the locus ceruleus. Cognitive scores declined less among men with greater SWS duration. LRT 5 likelihood ratio test; NFT 5 neurofibrillary tangle; NP 5 neuritic plaque; OR 5 odds ratio; OSA 5 obstructive sleep apnea; PSG 5 polysomnography; SBP 5 systolic blood pressure; SDB 5 sleep-disordered breathing; SpO 2 5 oxygen saturation as measured by pulse oximetry; SWS 5 slow-wave sleep. Conclusions:Sleep-disordered breathing (SDB), 1 nocturnal hypoxia, 1 and changes in sleep architecture 2,3 may lead to dementia in the elderly. A causal association is supported by the finding that continuous positive airway pressure treatment in patients with obstructive sleep apnea (OSA) may improve cognition, even after dementia has developed. 4 It remains unclear how SDB, nocturnal hypoxia, and sleep architecture may be related to the development of brain lesions associated with dementia. Hypoxia and altered brain perfusion during sleep may cause neuronal injury, leading to impaired cognitive functioning. Alternatively, abnormalities in regions such as the locus ceruleus may alter sleep architecture or control

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

“…However, oxygen desaturations (number of drops by ≥3% per minute) correlated strongly with smaller hippocampal and parietal white matter estimates. Consistent with these desaturation findings, in the Honolulu-Asia Aging Study, lower oxygen saturation levels predicted post-mortem autopsy findings of microinfarcts, Lewy bodies, and gliosis and neuronal loss by approximately 6 years [101]. These results converge with Yaffe et al’s [102] finding that oxygen desaturations were predictive of developing mild cognitive impairment or dementia whereas arousals and other measures of sleep fragmentation were not predictive.…”

Sleep apnoea and the brain: a complex relationship

“…Of note, in a prospective study higher nocturnal oxygenation during REM sleep was associated with less gliosis and neuronal loss in the locus coeruleus 65 . Major depression, on the other hand, is associated with exaggerated REM sleep qualities and deficiency in monoamine activity .…”

“…An independent association between excessive daytime somnolence and cognitive impairment has been demonstrated and several prospective studies have shown that excessive daytime somnolence is associated with an increased risk of cognitive decline and dementia 14 . In a prospective cohort study (The Honolulu-Asia Aging Study), lower nocturnal oxygenation and reduction in SWS nREM sleep were associated with the development of microinfarcts and brain atrophy 65 . Conversely, men with longer SWA sleep showed slower cognitive decline 65 .…”

“…In a prospective cohort study (The Honolulu-Asia Aging Study), lower nocturnal oxygenation and reduction in SWS nREM sleep were associated with the development of microinfarcts and brain atrophy 65 . Conversely, men with longer SWA sleep showed slower cognitive decline 65 .…”

The Clinical Evaluation and Use of Sleep Studies in Neurological Practice

“…In the Apnea Positive Pressure Long-term Efficacy Study (APPLES), middle age patients, with an average age of 52 years, showed a mild increase in cognitive function with continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea [31••]. Recent studies have identified nocturnal hypoxia and decreased slow-wave sleep as risk factors for gray matter changes, but not for Alzheimer's disease or Lewy body dementia [32]. To date, evidence regarding the impact of obstructive sleep apnea treatment on cognitive function in the elderly is inconclusive.…”