Multicenter study on the effect of CPAP on cognitive function in patients with mild cognitive impairment and Alzheimer’s disease with OSA (DemCPAP): presentation of the protocol and preliminary data

Introduction: Obstructive sleep apnea (OSA) is associated with an increased risk of Alzheimer’s disease (AD) and its progression. Some studies suggest that continuous positive airway pressure (CPAP) therapy can delay cognitive decline and improve sleep quality in Mild Cognitive Impairment (MCI) and AD. However, large, prospective studies with long-term follow-up are needed to confirm these findings. The DemCPAP study, initiated in April 2024, is enrolling participants to address this gap. The primary objective is to assess, over a 3-year follow-up, the effects of CPAP on cognitive function in patients with amnestic MCI and mild-to-moderate AD who have moderate-to-severe OSA (Group A). These patients will be compared to two control groups: Group B, with the same pathologies where CPAP is not possible or adequate due to patient or caregiver difficulties, and Group C, consisting of patients with MCI or AD without OSA. Secondary objectives include evaluating the impact of CPAP on sleep quality, sleep quantity, and daytime sleepiness. The tertiary objective involves assessing changes in plasma AD biomarkers. Materials and methods: DemCPAP is a multicenter, prospective study conducted across eight Italian centers specializing in dementia and sleep disorders. The coordinating center is the Sleep Medicine Center, department of neurology at Villa Serena Hospital, Pescara, Italy. The study protocol has been approved by the relevant ethical committees. Patients with amnestic MCI and AD will be enrolled based on specific diagnostic criteria, with the requirement for a valid caregiver. In cases of atypical presentation, biomarker confirmation is required. OSA diagnosis will follow the third edition of the International Classification of Sleep Disorders (ICSD). CPAP titration and treatment will adhere to established guidelines .Baseline assessments include neuropsychological and somnological testing, the Psychomotor Vigilance Task (PVT), polysomnography (PSG), ApoE polymorphism analysis, AD biomarkers (Abeta 42, Abeta 42/40 ratio, TAU), and brain MRI with Scheltens’ and Fazekas scales. Participants will be categorized into "cases" (Group A) or "controls" (Groups B and C) based on PSG results and CPAP adherence, assessed three months after titration. A second PSG will evaluate OSA control during CPAP ventilation. At six months, participants will repeat a reduced set of neuropsychological and somnological tests. At 12 and 24 months, extended assessments will be performed, including PVT and reassessment of blood biomarkers at 12 months. At 36 months, extended evaluations and a new brain MRI will be done. In Group A, CPAP adherence will be monitored at each time point. Results: 28 patients have been enrolled, 27% AD and 73% MCI with OSA present in 54% of MCI and 75% of AD patients. OSA prevalence has been detected in male MCI patients, no sex prevalence in AD .Good CPAP adherence has been observed at three months post-titration in both MCI and AD patients, with no dropouts recorded. Moreover, 18 patients have already been screened for enrollment. Conclusions: CPAP treatment and good adherence in AD and MCI patients with OSA are expected to improve sleep quality, reduce daytime sleepiness, potentially reduce conversion from MCI to AD, and also improve the clinical course in AD.