scholarly journals Obstructive sleep apnea and Alzheimer’s disease-related cerebrospinal fluid biomarkers in mild cognitive impairment

SLEEP ◽  
2020 ◽  
Author(s):  
Mónica Díaz-Román ◽  
Matias M Pulopulos ◽  
Miguel Baquero ◽  
Alicia Salvador ◽  
Ana Cuevas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Obstructive Sleep Apnea ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Sleep Apnea ◽  
Apnea Hypopnea Index ◽  
Obstructive Sleep ◽  
T Tau

Abstract Previous studies have demonstrated that sleep-breathing disorders, and especially obstructive sleep apnea (OSA), can be observed in patients with a higher risk of progression to Alzheimer’s disease (AD). Recent evidence indicates that cerebrospinal fluid (CSF) AD-biomarkers are associated with OSA. In this study, we investigated these associations in a sample of patients with mild cognitive impairment (MCI), a condition that is considered the first clinical phase of AD, when patients showed biomarkers consistent with AD pathology. A total of 57 patients (mean age = 66.19; SD = 7.13) with MCI were included in the study. An overnight polysomnography recording was used to assess objective sleep parameters (i.e. apnea/hypopnea index [AHI], total sleep time, sleep efficiency, sleep latency, arousal index, awakening, stage 1, 2, and slow-wave sleep and rapid eye movement sleep, periodic limb movement index, O2 saturation during sleep, and percentage of time O2 saturation <90%). Phosphorylated-tau (P-tau), total-tau (T-tau), and amyloid-beta 42 (Aβ42) were measured in CSF. Unadjusted correlation analyses showed that a higher AHI (reflecting higher OSA severity) was related to higher P-tau and T-tau (both results remained significant after Bonferroni correction, p = 0.001). Importantly, these associations were observed even after adjusting for potential confounders (i.e. age, sex, body mass index, sleep medication, smoking, hypertension, and heart disease). Although more research is needed to establish a causal link, our findings provide evidence that OSA could be related to the pathophysiological mechanisms involved in neurodegeneration in MCI patients.

scholarly journals Obstructive sleep apnea and longitudinal Alzheimer’s disease biomarker changes

SLEEP ◽  
2019 ◽  
Vol 42 (6) ◽  
Author(s):  
Omonigho M Bubu ◽  
Elizabeth Pirraglia ◽  
Andreia G Andrade ◽  
Ram A Sharma ◽  
Sandra Gimenez-Badia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Obstructive Sleep Apnea ◽  
Cognitive Impairment ◽  
Sleep Apnea ◽  
Rate Of Change ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Obstructive Sleep ◽  
T Tau

Abstract Study Objectives To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (Aβ42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) elderly. Methods Longitudinal study with mean follow-up time of 2.52 ± 0.51 years. Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF Aβ42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA. Results In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B = .06, 95% CI = .02, .11 and B = .08, 95% CI = .05, .12, respectively) and decrease in CSF Aβ42 levels (B = −2.71, 95% CI = −3.11, −2.35 and B = −2.62, 95% CI = −3.23, −2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA− participants. No significant variations in the biomarker changes over time were seen in the AD group. Conclusions In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD.

scholarly journals 0057 Actigraphy-Based Circadian Measures and Cerebrospinal Fluid Biomarkers of Neurodegeneration in Alzheimer’s Disease with Mild Cognitive Impairment

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A23-A23
Author(s):  
R Mehra ◽  
R Bhambra ◽  
J Bena ◽  
L Bekris ◽  
J Leverenz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Csf Biomarkers ◽  
Significance Level ◽  
Unit Increase ◽  
T Tau ◽  
Age And Sex

Abstract Introduction Although recent data implicates sleep and circadian disruption to neurodegeneration in Alzheimer’s Disease (AD), the association of objective circadian biomarkers and neurodegeneration remains understudied. We hypothesize that actigraphy-based circadian measures are associated with cerebrospinal fluid (CSF) biomarkers of neurodegeneration in those mild cognitive impairment due to AD (MCI-AD). Methods Eighteen patients with CSF biomarker-confirmed MCI-AD underwent actigraphy monitoring generating the following circadian measures: amplitude, F-ratio and mesor and morning collection of CSF biomarkers of neurodegeneration (Aβ42,t-tau,p-tau). Linear models were used to evaluate the association of circadian and CSF measures; logarithmic transformations were performed on neurodegenerative markers for greater normality. Analysis was performed using SAS software. A significance level of 0.05 was assumed for all tests. Results Eighteen MCI-AD patients who were 68± 6.2 years, 44% female, with median AHI=12 and underwent actigraphy monitoring for 8.2+/-3.2 days were included. There was no significant association of circadian measures and Aβ42 nor with mesor and neurodegeneration biomarkers. Amplitude was associated with both p-tau and t-tau, such that each 10 unit increase in amplitude resulted in a predicted increase in p-tau of 8% (95% CI:1%-15%, p=0.018) and an increase of 13% (3%-23%; p=0.01) in t-tau. F-ratio was positively associated with p-tau and t-tau; each 1000 unit increase in F-ratio resulted in a predicted 12% (4%-22%; p=0.007) increase in P-tau and 20%(6%-35%; p=0.005) increase in t-tau. Associations of these circadian measures and CSF levels of p-tau and t-tau remained statistically significant after adjustment for age and sex. Conclusion Among patients with symptomatic MCI stages of AD, objective measures of circadian rhythm disruption are associated with CSF-based biomarkers of neurodegeneration even after consideration of age and sex. Future investigation should clarify directionality of this association and potential utility of circadian-based interventions in the mitigation of AD progression. Support N/A

scholarly journals Anxiety is related to Alzheimer cerebrospinal fluid markers in subjects with mild cognitive impairment

2012 ◽  
Vol 43 (5) ◽  
pp. 911-920 ◽  
Author(s):  
I. H. G. B. Ramakers ◽  
F. R. J. Verhey ◽  
P. Scheltens ◽  
H. Hampel ◽  
H. Soininen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Neuropsychiatric Symptoms ◽  
Amyloid Β ◽  
Screening Guidelines ◽  
Symptoms Of Depression ◽  
T Tau

BackgroundAnxiety, apathy and depression are common in subjects with mild cognitive impairment (MCI) and may herald Alzheimer's disease (AD). We investigated whether these symptoms correlated with cerebrospinal fluid (CSF) markers for AD in subjects with MCI.MethodSubjects with MCI (n=268) were selected from the ‘Development of screening guidelines and criteria for pre-dementia Alzheimer's disease’ (DESCRIPA) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. We measured amyloid β(1-42)protein (Aβ42) and total tau (t-tau) in CSF. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory.ResultsDepressive symptoms were reported by 55 subjects (21%), anxiety by 35 subjects (13%) and apathy by 49 subjects (18%). The presence of anxiety was associated with abnormal CSF Aβ42 [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6–3.3] and t-tau (OR 2.6, 95% CI 1.9–3.6) concentrations and with the combination of abnormal concentrations of both Aβ42 and t-tau (OR 3.1, 95% CI 2.0–4.7). The presence of agitation and irritability was associated with abnormal concentrations of Aβ42 (agitation: OR 1.6, 95% CI 1.1–2.3; irritability: OR 2.2, 95% CI 1.5–3.3). Symptoms of depression and apathy were not related to any of the CSF markers.ConclusionsIn subjects with MCI, symptoms of anxiety, agitation and irritability may reflect underlying AD pathology, whereas symptoms of depression and apathy do not.

scholarly journals The Importance of Diagnosing and the Clinical Potential of Treating Obstructive Sleep Apnea to Delay Mild Cognitive Impairment and Alzheimer’s Disease: A Special Focus on Cognitive Performance

2021 ◽  
pp. 1-19
Author(s):  
Mariana Fernandes ◽  
Fabio Placidi ◽  
Nicola Biagio Mercuri ◽  
Claudio Liguori
Keyword(s):  
Alzheimer’S Disease ◽  
Obstructive Sleep Apnea ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Sleep Apnea ◽  
Cognitive Decline ◽  
Special Focus ◽  
Middle Aged ◽  
Cpap Treatment ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is a highly frequent sleep disorder in the middle-aged and older population, and it has been associated with an increased risk of developing cognitive decline and dementia, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). In more recent years, a growing number of studies have focused on: 1) the presence of OSA in patients with MCI or AD, 2) the link between OSA and markers of AD pathology, and 3) the role of OSA in accelerating cognitive deterioration in patients with MCI or AD. Moreover, some studies have also assessed the effects of continuous positive airway pressure (CPAP) treatment on the cognitive trajectory in MCI and AD patients with comorbid OSA. This narrative review summarizes the findings of studies that analyzed OSA as a risk factor for developing MCI and/or AD in the middle-aged and older populations with a special focus on cognition. In addition, it describes the results regarding the effects of CPAP treatment in hampering the progressive cognitive decline in AD and delaying the conversion to AD in MCI patients. Considering the importance of identifying and treating OSA in patients with MCI or AD in order to prevent or reduce the progression of cognitive decline, further larger and adequately powered studies are needed both to support these findings and to set programs for the early recognition of OSA in patients with cognitive impairment.

scholarly journals Obstructive sleep apnea, cognition and Alzheimer's disease: A systematic review integrating three decades of multidisciplinary research

2020 ◽  
Vol 50 ◽  
pp. 101250 ◽  
Author(s):  
Omonigho M. Bubu ◽  
Andreia G. Andrade ◽  
Ogie Q. Umasabor-Bubu ◽  
Megan M. Hogan ◽  
Arlener D. Turner ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Multidisciplinary Research ◽  
Obstructive Sleep

scholarly journals Unique Sleep and Circadian Rhythm Dysfunction Neuroinflammatory and Immune Profiles in Alzheimer’s Disease with Mild Cognitive Impairment

2021 ◽  
pp. 1-6
Author(s):  
Jagan A. Pillai ◽  
James Bena ◽  
Lynn M. Bekris ◽  
Nancy Foldvary-Schaefer ◽  
Catherine Heinzinger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Circadian Rhythm ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cerebrospinal Fluid Biomarkers ◽  
Circulating Markers

Sleep dysfunction has been identified in the pathophysiology of Alzheimer’s disease (AD); however, the role and mechanism of circadian rhythm dysfunction is less well understood. In a well-characterized cohort of patients with AD at the mild cognitive impairment stage (MCI-AD), we identify that circadian rhythm irregularities were accompanied by altered humoral immune responses detected in both the cerebrospinal fluid and plasma as well as alterations of cerebrospinal fluid biomarkers of neurodegeneration. On the other hand, sleep disruption was more so associated with abnormalities in circulating markers of immunity and inflammation and decrements in cognition.

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