Risk of Alzheimer’s Disease in Obstructive Sleep Apnea Syndrome: Amyloid-β and Tau Imaging

Abstract

Background: An association between obstructive sleep apnea (OSA) and Alzheimer's disease has been suggested but little is known about amyloid-␤ and tau deposition in this syndrome. Objective: To determine amyloid and tau burden and cognitive function in OSA in comparison with those without a diagnosis of OSA. Methods: The status of OSA was determined by asking participants about history of polysomnographic diagnosis of OSA and the use of Continuous Positive Airway Pressure (CPAP). A comprehensive neuropsychological battery measured cognitive function. Positron emission tomography (PET) was used to measure standardized uptake value ratio (SUVR) of 18 F-florbetaben and 18 F-AV1451, to quantify amyloid and tau burden. Results: 119 male Vietnam veterans completed assessment. Impairment in visual attention and processing speed and increased body mass index (BMI) were seen in subjects with OSA compared with those without a diagnosis OSA. The cortical uptake of 18 F-florbetaben was higher in the OSA group than in the control group (SUVR: 1.35 ± 0.21 versus 1.27 ± 0.16, p = 0.04). There were more apolipoprotein E 4 allele (APOE 4) carriers in the OSA group than in the control group. In multilinear regression analysis, the significance of OSA in predicting 18 F-florbetaben uptake remained independent of age and vascular risk factors but not when BMI or APOE 4 was adjusted. The reported use of CPAP (n = 14) had no effect on cognitive or amyloid PET findings. There was no significant difference in 18 F-AV1451 uptake between the two groups. Conclusions: Obstructive sleep apnea is associated with Alzheimer's disease pathology, but this relationship is moderated by APOE 4 and BMI.

Cholinergic basal forebrain degeneration due to obstructive sleep apnoea increases Alzheimer’s pathology in mice

“…Our finding that OSA exacerbates A accumulation in genetically susceptible AD mice is consistent with a previous report that exposure of mice to chronic intermittent hypoxia increases Aβ42 levels in a triple Alzheimer's disease model mouse (Shiota et al, 2013). Similarly, higher brain Aβ (Spira et al, 2014;Elias et al, 2018), or decreased Aβ and increased phosphorylated tau in the cerebrospinal fluid (Osorio et al, 2014b;Osorio et al, 2014a), has been associated with a higher oxygen desaturation in cognitively impaired OSA subjects. One explanation for these observations could be that hypoxia and HIF1α-mediated transcription can directly up-regulate the expression of β-secretase (Zhang et al, 2007), while HIF1α can operate as a regulatory subunit of γ-secretase during hypoxia (Villa et al, 2014), both of which could increase Aβ production via the amyloidogenic pathway.…”

“…Specifically our work highlights intermittent hypoxia as the decisive feature, as it induces cBF neuronal degeneration and cognitive impairment, with a coincident or subsequent increase in the levels of A when linked to a genetic risk for Aβ accumulation (potentially including an ApoE4 genotype; (Yaffe et al, 2014;Wollam et al, 2015)). Although treating the hypoxemia in our OSA model or giving CPAP in humans reduces respiratory disturbance during sleep, and improves working memory, some cognitive aspects such as complex attention and executive function remain impaired (Daulatzai, 2015), daytime sleepiness can continue, and A load can remain unchanged (Elias et al, 2018), all of which might reflect irreversible cBF neuronal loss that predates the commencement of CPAP treatment. Therefore, targeting cholinergic function (through cholinergic esterase inhibition or muscarinic agonists; ), cBF health (through p75NTR modifiers or neurotrophic mimetics; (Longo and Massa, 2013)) or specific HIF1 pathways (2ME2 is a current treatment for tumour angiogenesis) represent candidate treatments for preventing AD in the OSA 'at risk' population -those with intermittent hypoxia.…”

“…It affects more than 50% of the elderly adult population (Punjabi, 2008) and occurs due to the collapse of the upper airways, particularly during rapid eye movement (REM) sleep; this impedes airflow and requires a brief period of wakefulness in order to re-activate airway tone (Yaffe et al, 2014;Daulatzai, 2015). OSA has been associated with both an earlier age of AD onset, more rapid cognitive decline (Ancoli-Israel et al, 2008;Osorio et al, 2011;Yaffe et al, 2014) and an increased A burden as measured by PET imaging (Yun et al, 2017;Elias et al, 2018). However, OSA is not widely recognized as one of the lifestyle factors presenting increased risk of developing AD (Livingston et al, 2017).…”

Association of Late Life Depression, (Non-) Modifiable Risk and Protective Factors with Dementia and Alzheimer’s Disease: Literature Review on Current Evidences, Preventive Interventions and Possible Future Trends in Prevention and Treatment of Dementia

“…Individuals with vascular dementia, AD and other types of dementia are often diagnosed with sleeping pattern problems. Many studies, which findings are given in Table 6 , have proposed an association between sleep problems, especially, for obstructive sleep apnea patients and a higher risk of dementia [ 56 , 121 , 122 , 123 ]. Some researchers believe that obstructive sleep apnea may even start the AD neuropathological process [ 124 ].…”

Sleep characteristics and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact older adults: The CABLE study

“…In the past decade, large amounts of work have been devoted to understanding the association between various sleep disturbances (SDs) and AD pathologies. Cross‐sectional studies have suggested that greater amyloid pathology was linked with insufficient sleep duration 1,2 (including sleep deprivation 3,4 ), poor sleep quality, 1,5,6 long latency, 7,8 low efficiency, 8,9 obstructive sleep apnea (OSA), 10‐12 excessive daytime sleepiness (EDS), 2,6 and fragmentation 8 . However, the generalizability and credibility of these findings are easily compromised by small sample size and heterogeneous definition of sleep problems.…”