Clinical Significance of Sleep-Disordered Breathing in Alzheimer's Disease

AbstractAlzheimer’s disease (AD) and sleep-disordered breathing (SDB) are prevalent conditions with rising burden. It is suggested that SDB may contribute to cognitive decline and advanced aging. Here, we assessed the link between self-reported SDB and gray matter volume in patients with AD, mild cognitive impairment (MCI) and healthy controls (HC). We further investigated whether SDB was associated with advanced brain aging. We included a total of 330 participants, divided based on self-reported history of SDB, and matched across diagnoses for age, sex and presence of the ApoE4 allele, from the Alzheimer’s Disease Neuroimaging Initiative. Gray-matter volume was measured using voxel-wise morphometry and differences reflecting SDB, cognitive status, and their interaction were evaluated. Further, using an age-prediction model fitted on gray-matter data of external datasets, we predicted study participants’ age from their structural scans. Cognitive decline (MCI/AD diagnosis) and advanced age were associated with lower gray matter volume in various regions, particularly in the bilateral temporal lobes. BrainAGE was well predicted from the morphological data in HC and, as expected, elevated in MCI and particularly in AD. However, there was neither a significant difference between regional gray matter volume in any diagnostic group related to the SDB status nor an SDB-by-cognitive status interaction. Also, we found neither a significant difference in BrainAGE gap (estimated - chronological age) related to SDB nor an SDB-by-cognitive status interaction. In summary, contrary to our expectations, we were not able to find a general nor a diagnostic specific effect on either gray-matter volumetric or brain aging.Statement of significanceDementia syndromes including Alzheimer’s disease (AD), are a major global concern, and unraveling modifiable predisposing risk factors is indispensable. Sleep-disordered breathing (SDB) and its most prevalent form, obstructive sleep apnea, are suggested as modifiable risk factors of AD, but their contribution to AD hallmarks, like brain atrophy and advanced brain aging, is not clear to this day. While self-reported SDB is suggested to propagate aging process and cognitive decline to AD in clinical studies, here, we demonstrated that, SDB might not necessarily associate to brain atrophy and the advanced brain aging assessed by morphological data, in AD progession. However, multimodal longitudinal studies with polysomnographic assessment of SDB are needed to confirm such fundings.

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Alzheimer’s Disease, Sleep Disordered Breathing, and Microglia: Puzzling out a Common Link

Cells ◽

10.3390/cells10112907 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2907

Author(s):

Tyler K. Ulland ◽

Andrea C. Ewald ◽

Andrew O. Knutson ◽

Kaitlyn M. Marino ◽

Stephanie M. C. Smith ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Models ◽

Human Disease ◽

Intermittent Hypoxia ◽

Sleep Disordered Breathing ◽

Molecular Responses ◽

Neuroimmune System ◽

Disordered Breathing

Sleep Disordered Breathing (SDB) and Alzheimer’s Disease (AD) are strongly associated clinically, but it is unknown if they are mechanistically associated. Here, we review data covering both the cellular and molecular responses in SDB and AD with an emphasis on the overlapping neuroimmune responses in both diseases. We extensively discuss the use of animal models of both diseases and their relative utilities in modeling human disease. Data presented here from mice exposed to intermittent hypoxia indicate that microglia become more activated following exposure to hypoxia. This also supports the idea that intermittent hypoxia can activate the neuroimmune system in a manner like that seen in AD. Finally, we highlight similarities in the cellular and neuroimmune responses between SDB and AD and propose that these similarities may lead to a pathological synergy between SDB and AD.

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Sleep-disordered breathing and Alzheimer's disease: A nationwide cohort study

Psychiatry Research ◽

10.1016/j.psychres.2019.01.086 ◽

2019 ◽

Vol 273 ◽

pp. 624-630 ◽

Cited By ~ 7

Author(s):

Joo Eun Lee ◽

Seong Wu Yang ◽

Yeong Jun Ju ◽

Seung Kuk Ki ◽

Ki Hong Chun

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Study ◽

Sleep Disordered Breathing ◽

Disordered Breathing

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Sleep Quality Improvement Enhances Neuropsychological Recovery and Reduces Blood Aβ42/40 Ratio in Patients with Mild–Moderate Cognitive Impairment

Medicina ◽

10.3390/medicina57121366 ◽

2021 ◽

Vol 57 (12) ◽

pp. 1366

Author(s):

Haihua Huang ◽

Mingqiu Li ◽

Menglin Zhang ◽

Jiang Qiu ◽

Haiyan Cheng ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Quality Improvement ◽

Sleep Quality ◽

Sleep Disorder ◽

Sleep Disordered Breathing ◽

Rating Scale ◽

Control Group ◽

Neuropsychological Assessments ◽

Disordered Breathing

Background and objectives: Alzheimer’s disease is a progressive brain degeneration and is associated with a high prevalence of sleep disorders. Amyloid β peptide-42/40 (Aβ42/40) and Tau-pT181 are the core biomarkers in cerebrospinal fluid and blood. Accumulated data from studies in mouse models and humans demonstrated an aberrant elevation of these biomarkers due to sleep disturbance, especially sleep-disordered breathing (SDB). However, it is not clear if sleep quality improvement reduces the blood levels of Ab42/40 ratio and Tau-pT181 in Alzheimer’s disease patients. Materials and Methods: In this prospective study, a longitudinal analysis was conducted on 64 patients with mild–moderate cognition impairment (MCI) due to Alzheimer’s disease accompanied by SDB. Another 33 MCI cases without sleep-disordered breathing were included as the control group. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) score system. Neuropsychological assessments were conducted using the Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Clinical Dementia Rating (CDR), 24-h Hamilton Rating Scale for Depression (HRSD-24), and Hamilton Anxiety Rating Scale (HAMA) scoring systems. Aβ42, Aβ40, and Tau-pT181 protein levels in blood specimens were measured using ELISA assays. All patients received donepezil treatment for Alzheimer’s disease. SDB was managed with continuous pressure ventilation. Results: A significant correlation was found among PSQI, HRSD-24, HAMA, Aβ42/40 ratio, and Tau-pT181 level in all cases. In addition, a very strong and negative correlation was discovered between education level and dementia onset age. Compared to patients without SDB (33 non-SD cases), patients with SDB (64 SD cases) showed a significantly lower HRSD-24 score and a higher Aβ42/40 ratio Tau-pT181 level. Sleep treatment for patients with SDB significantly improved all neuropsychological scores, Aβ42/40 ratio, and Tau-pT181 levels. However, 11 patients did not completely recover from a sleep disorder (PSQI > 5 post-treatment). In this subgroup of patients, although HAMA score and Tau-pT181 levels were significantly reduced, MoCA and HRSD-24 scores, as well as Aβ42/40 ratio, were not significantly improved. ROC analysis found that the blood Aβ42/40 ratio held the highest significance in predicting sleep disorder occurrence. Conclusions: This is the first clinical study on sleep quality improvement in Alzheimer’s disease patients. Sleep quality score was associated with patient depression and anxiety scores, as well as Aβ42/40 ratio and Tau-pT181 levels. A complete recovery is critical for fully improving all neuropsychological assessments, Aβ42/40 ratio, and Tau-pT181 levels. Blood Aβ42/40 ratio is a feasible prognostic factor for predicting sleep quality.

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