Implications of Obstructive Sleep Apnea on the Cognitive Evolution of Alzheimer's Disease Patients

Background: Sleep-disordered breathing encompasses a group of diseases, of which obstructive sleep apnea (OSA) is most frequent. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease; it is manifested as an initial deficit of episodic memory that evolves into global cognitive and psychosocial dysfunction, and its prevalence is increasing around the world. OSA has been described as a risk factor for AD, and its prevalence is higher in AD patients. However, little is known about the influence of OSA on cognition in the AD population.The aim of this study was to evaluate the impact of nontreated OSA on the cognitive evolution of patients with mild-moderate AD, to investigate whether the magnitude of the cognitive decline is associated with the severity of OSA and to evaluate the influence of OSA on several cognitive subdomains in AD patients. Methods: In this single-center study, patients with mild-moderate AD were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography. OSA was defined as an apnea-hypopnea index (AHI) >15/h. AD severity was assessed using the Mini-Mental State Examination (MMSE). The primary outcome was to measure the change in cognitive score on the Alzheimer’s Disease Assessment Scale-cognitive scale (ADAS-cog) from baseline to 12 months in patients with mild AD with and without OSA. An extensive battery of neuropsychological tests, including the Epworth Sleepiness Scale (ESS), were performed and APOE status was measured. Findings: The cohort included 144 patients with a mean (SD) age of 75.19 (5.30) years; 72 (57.6%) were women, and the mean MMSE score was 23.5 (2.24) points at baseline. The mean (SD) change in the ADAS-cog score at 12 months was 3.19 (5.61) in the non-OSA group and 0.08 (5.62) in the OSA group, with a difference between the groups of -3.36 (95%CI 0.19 to 0.16; p=0.002). Regarding the changes in the ADAS-cog subitems at 12 months, ideational praxis, remembering test instructions and commands showed a significant difference between the groups (p<0.05). We did not observe significant differences in cognitive subdomains, such as memory or executive functioning, or for caregiver overload, on the extensive battery of neuropsychological assessments at 12 months. No significant differences were found according to OSA severity group by ADAS-cog or MMSE at 12 months neither at 36 months by MMSE.According to the MMSE score at 36 months, the mean change was similar between the groups, with a difference of 1.69 (95%CI -1.26 to 4.64; p = 0.445). Interpretation: In this large cohort of patients with AD, we demonstrated that that OSA did not worsen cognitive evolution after 1 year of follow-up, either in global cognition or in the different cognitive subdomains, or global cognition after 3 years of follow-up. Based on these findings, OSA does not modify the cognitive evolution of patients in mild or moderate stages of Alzheimer’s disease. Trial Registration: This study was registered with ClinicalTrials.gov (number NCT02814045). Funding Statement: This work was supported by “Fundacio La Marato TV3” (Gerard Pinol), the Spanish Respiratory Society (SEPAR), PERIS SLT008/18/00050, the Health Department of Generalitat de Catalunya and ALLER. This work was supported by the IRBLleida Biobank (B.0000682) and PLATAFORMA BIOBANCOS PT17/0015/0027/. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: This study was conducted in accordance with the Declaration of Helsinki, and it was approved by the care ethics committee of Hospital Arnau de Vilanova de Lleida (CE-1218). All patients signed informed consent.