Sleep-disordered breathing advances cognitive decline in the elderly

Abstract

Objective: To examine whether the presence of sleep-disordered breathing (SDB) is associated with an earlier age at mild cognitive impairment (MCI) or Alzheimer disease (AD)-dementia onset in participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We also examined whether continuous positive airway pressure (CPAP) use is associated with delayed onset of cognitive decline.

Methods: From the ADNI cohort, 3 subsets with progressively stringent criteria were created in a step-wise manner. Age at MCI or AD-dementia onset was the main outcome variable. Analyses were performed separately for each subset in untreated SDB+ vs SDB- and untreated SDB+ vs CPAP+ groups. Chi-square and t tests were performed to examine between-group differences. Survival analyses were performed using the Kaplan-Meier method, compared by the log-rank test, and assessed by multivariate Cox regression adjusting for potential confounders.

Results: SDB+ patients had a younger age at MCI onset in all subsets (MC1: 72.63 vs 83.67; MC2: 72.15 vs 83.45; MC3: 77.40 vs 89.89; p < 0.01). SDB+ patients had a younger age at AD-dementia onset only in our most conservative subset (AC3: 83.46 vs 88.13; p < 0.05). In a combined outcome analysis, SDB+ patients had a younger age at onset to MCI or AD-dementia in all subsets. In subsets 1 and 2, CPAP use delayed the age at MCI onset (CMC1: 72.63 vs 82.10; CMC2: 72.11 vs 82.10; p < 0.01).

Conclusions: Consistent with our hypothesis, the presence of SDB was associated with an earlier age at cognitive decline. Our findings in CPAP+ participants suggest that CPAP treatment of SDB may delay progression of cognitive impairment.

Figure 1. Stepwise exclusion process for MCI and AD subsets

Survival analysis on age at MCI/AD onset was performed on 3 subsets defined by progressively stringent criteria for inclusion: the first subset (C1) excluded participants with missing data; the second subset (C2) excluded participants with ambiguous group allocation; and the third subset only contained participants with incident MCI or AD (C3). AD = Alzheimer disease; ADNI = Alzheimer's Disease Neuroimaging Initiative; BMI = body mass index; MCI = mild cognitive impairment; OSA = obstructive sleep apnea.

Figure 2. Survival analysis comparing patients who were SDB− and SDB+ for all MCI and AD subsets

Survival curves of age at MCI or AD-dementia onset using the Kaplan–Meier method showing patients who were SDB+ to have a significantly younger age at MCI onset than SDB− in all subsets and to have a significantly younger age at AD-dementia onset than SDB− in our most conservative subset. AD = Alzheimer disease; MCI = mild cognitive impairment; SDB = sleep-disordered breathing.