Alzheimer disease (AD) is a neurodegenerative disorder predominantly characterized by progressive memory loss and gradual decline in global cognition.¹ Alzheimer disease is often complicated by circadian rhythm disruption and sleep disturbances, including nightly awakenings and nonrapid eye movement (non-REM)/REM sleep dysregulation, which have a major effect on the quality of life of patients and their caregivers.^2-5 Neuropathological characteristics of AD include the progressive accumulation of extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles of tau proteins, which produce the dramatic loss of neurons and synapses and derange the brain’s functional and structural physiological processes. Brain regions and networks involved in the control of the sleep-wake rhythm have been also reported to be affected in AD.⁶ At present, Aβ1-42 and total (t-tau) and phosphorylated (p-tau) tau proteins are considered the established cerebrospinal fluid (CSF) biomarkers to support a diagnosis of AD.^7-9

Obstructive sleep apnea (OSA) is a common sleep disorder. The, literature lacks studies examining sleep, cognition, and Alzheimer’s Disease (AD) cerebrospinal fluid (CSF) biomarkers in OSA patients. Therefore, we first studied cognitive performances, polysomnographic sleep, and CSF β-amyloid₄₂, tau proteins, and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea–Hypopnea Index [AHI] ≥15/hr), controls (showing an AHI < 15/hr), and patients with OSA treated by continuous positive airway pressure (CPAP). We compared results among 25 OSA, 10 OSA-CPAP, and 15 controls who underwent a protocol counting neuropsychological testing in the morning, 48-hr polysomnography followed by CSF analysis. OSA patients showed lower CSF Aβ₄₂ concentrations, higher CSF lactate levels, and higher t-tau/Aβ₄₂ ratio compared to controls and OSA-CPAP patients. OSA patients also showed reduced sleep quality and continuity and lower performances at memory, intelligence, and executive tests than controls and OSA-CPAP patients. We found significant relationships among higher CSF tau proteins levels, sleep impairment, and increased CSF lactate levels in the OSA group. Moreover, lower CSF Aβ₄₂ levels correlate with memory impairment and nocturnal oxygen saturation parameters in OSA patients. We hypothesize that OSA reducing sleep quality and producing intermittent hypoxia lowers CSF Aβ₄₂ levels, increases CSF lactate levels, and alters cognitive performances in SCI patients, thus inducing early AD clinical and neuropathological biomarkers changes. Notably, controls as well as OSA-CPAP SCI patients did not show clinical and biochemical AD markers. Therefore, OSA may induce early but possibly CPAP-modifiable AD biomarkers changes.