Is sleep apnea the missing link between high blood pressure and Alzheimer's?

By Neha MathurReviewed by Benedette Cuffari, M.Sc.Oct 29 2023

In a recent review article published in the journal Hypertension Research, researchers evaluate the relationship between the 'non-dipper' pattern of hypertension and obstructive sleep apnea (OSA) and its involvement in the development of Alzheimer’s disease (AD).

Study: Obstructive sleep apnea and non-dipper: Epiphenomena or risks of Alzheimer’s disease?: A review from the HOPE Asia Network. Image Credit: Independence_Project / Shutterstock.com

Non-dipper hypertension and OSA

Under normal conditions, blood pressure (BP) at night will often decrease by about 10% as compared to normal day-time levels, which is a phenomenon known as ‘dipper’ hypertension. Comparatively, non-dipper hypertension refers to nocturnal BP levels that decline by less than 10% of day-time BP levels. Importantly, individuals with non-dipper hypertension are at an increased risk of various health conditions, including end-organ damage, as well as cardiovascular morbidity and mortality.

OSA, even in its mild forms, can increase nocturnal BP through various mechanisms, thus indicating that this condition can directly contribute to non-dipper hypertension and its associated cardiovascular risks. In one recent review, researchers found that OSA significantly increases the risk of non-dipper hypertension; however, nasal continuous positive airway pressure (CPAP) treatments of six hours or less have been shown to reduce the risk of non-dipper hypertension in about 70% of OSA patients.

Non-dipper hypertension and AD

As compared to healthy individuals, AD patients often have significantly higher mean 24-hour BP, 24-hour systolic BP (SBP), and nocturnal SBP. Likewise, several studies have reported that nocturnal BP did not decrease in AD patients.

Various mechanisms have been proposed to potentially contribute to non-dipper hypertension in AD patients, including smaller brain volume, white matter hyperintensity, microbleeds, and cerebral atrophy. Increased sympathetic nervous system activity, particularly within the hypothalamic-pituitary-adrenal axis, may also contribute to the non-dipper phenotype in AD. Reduced baroreceptor sensitivity (BRS) has also been frequently observed in AD, which may also contribute to altered BP levels in this patient population.

The higher BP levels observed in AD patients may also lead to arterial remodelling that exacerbates the production of amyloid b (Ab) plaques. Likewise, arterial stiffening and microvascular dysfunction can limit Ab clearance, thereby further increasing Ab levels within the brain.

Role of the insular cortex in AD pathology

The insular cortex (Ic), located in a region of the brain where middle cerebral arteries reside, is a crucial component of a complex cortical network that regulates the central autonomic nervous system in response to emotional stress. Damage to the Ic has been associated with sleep apnea, myocardial injury, altered BP levels, and higher plasma levels of brain natriuretic peptide and catecholamine.

Ischemia affecting the Ic has been correlated with higher nocturnal BP and norepinephrine levels as compared to patients without Ic involvement. Patients who have experienced left Ic-involved stroke often exhibit lower BRS than those with right IC involvement. Sleep apnea has also been observed in left IC-involved stroke.

Previous studies have demonstrated that early AD may affect the Ic before clinical symptoms have developed and can be accompanied by altered nocturnal BP levels and sleep apnea in elderly patients.  

Understanding the relationship between OSA and AD

Despite the vast amount of research that has been dedicated to understanding the causes and pathophysiology of both OSA and AD, the relationship between these two conditions remains poorly understood.

Nevertheless, one previous meta-analysis found that AD patients have a five-fold greater prevalence of OSA than patients without cognitive impairment. In fact, several AD-related biomarkers, including Ab40 and AB42 and several tau proteins, have been observed in both blood and cerebrospinal fluid (CSF) samples obtained from OSA patients. Hypoxia, which is a hallmark of OSA, also triggers tau phosphorylation, neuronal degeneration, axonal dysfunction, and amyloid plaque formation, all of which are key features of AD.  

Several studies have reported that CPAP treatment can have a protective effect on cognitive function, particularly on the incidence of mild cognitive impairment (MCI) and AD. Likewise, the cognitive functions in OSA patients with MCI and AD have been significantly improved with long-term CPAP treatment. These beneficial effects may be attributed to the anti-hypertensive effects of CPAP treatment, including reduced nocturnal BP.

Conclusions

The current study findings indicate that OSA may lead to non-dipper hypertension, which subsequently contributes to AD pathology. However, future studies are needed to elucidate the precise pathophysiological mechanisms that contribute to the complex relationship between non-dipper hypertension, OSA, and AD.