Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study

Abstract

Rationale: Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood.

Objectives: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly.

Methods: Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device.

Measurements and main results: We found that severity of OSA indices (AHIall [F_1,88 = 4.26; P < 0.05] and AHI4% [F_1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β₄₂ using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in AD_PiB-mask (Alzheimer's disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F_1,28 = 2.96, P = 0.09; and F_1,28 = 2.32, not significant, respectively).

Conclusions: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.

Keywords: Pittsburgh compound B positron emission tomography scan; amyloid burden; cerebrospinal fluid amyloid β; cognitive impairment; obstructive sleep apnea.

Figure 1.

Relationship between longitudinal change in cerebrospinal fluid amyloid β₄₂ (Aβ42) and the natural log of apnea–hypopnea indices at baseline. AHI = apnea–hypopnea index; AHI4% = sum of all apneas and hypopneas associated with greater that 4% oxygen desaturation; AHIall = sum of all apneas, hypopneas, or arousals; CSF = cerebrospinal fluid.

Figure 2.

Relationship between longitudinal change in AD_PiB-mask and the apnea–hypopnea indices at baseline. AD_PiB-mask = Alzheimer’s disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask; AHI = apnea–hypopnea index; AHI4% = sum of all apneas and hypopneas associated with greater that 4% oxygen desaturation; AHIall = sum of all apneas, hypopneas, or arousals; PiB = Pittsburgh compound B.

Figure 3.

At cross-section, severity of obstructive sleep apnea is associated with greater brain amyloid β deposition in PiB-positive participants, whereas no such association is found in participants with PiB-negative scans. AD PiB mask = Alzheimer’s disease vulnerable regions of interest Pittsburgh compound B positron emission tomography mask; AHI4% = sum of all apneas and hypopneas associated with greater that 4% oxygen desaturation; PiB = Pittsburgh compound B.

Figure 4.

Obstructive sleep apnea–related arousals may worsen sleep quality and increase amyloid deposition in a feed-forward cycle. Aβ = amyloid β; CSF = cerebrospinal fluid; ISF = interstitial fluid; OSA = obstructive sleep apnea.

Figure 5.

Breakdown of completers and noncompleters. CSF = cerebrospinal fluid; Mod = moderate; OSA = obstructive sleep apnea; PET = positron emission tomography; PiB = Pittsburgh compound B.