Donepezil Improves Obstructive Sleep Apnea in Alzheimer Disease (original) (raw)
Related papers
Sleep Medicine, 2012
Introduction/objectives: Previous publications have shown beneficial effects of cholinergic medication on obstructive sleep apnea (OSA) in Alzheimer's disease (AD) patients. We hypothesized that cholinergic medication could also improve OSA in non-AD patients. The present study evaluated the effects of donepezil on OSA in non-AD patients. Methods: A randomized, double-blind, placebo-controlled study was conducted. The final sample consisted of 21 male patients with mild to severe OSA and AHI >10 divided into two groups, a donepezil-treated group (n = 11) and a placebo-treated group (n = 10). The dosage was one tablet/day (5 mg) for the first two weeks and two tablets/day (10 mg) for the last two weeks. Polysomnography and sleepiness evaluations were performed at baseline and after one month of treatment. Groups were compared using twoway ANOVA for repeated measures with treatment-group and treatment-time as the main factors and time-treatment as an interaction effect. Results: Considering the effect of the interaction with time-treatment, there was a significant improvement in the obstructive apnea/hypopnea index, desaturation index, percentage of time with O 2 saturation 63% lower than baseline, lowest oxygen saturation, and the Epworth Sleepiness Scale (ESS) scores with donepezil treatment (p < 0.05). Sleep efficiency significantly decreased (p < 0.01). Conclusions: Donepezil treatment improved obstructive sleep apnea index, oxygen saturation, and sleepiness in parallel with a reduction in sleep efficiency. Our findings support the concept that cholinergic transmission may influence breathing regulation in OSA patients. O 2 sat 63% baseline, percentage of time spent with oxygen saturation less than or equal to 3% lower than baseline.
Laryngoscope, 2020
Background: An association between obstructive sleep apnea (OSA) and Alzheimer's disease has been suggested but little is known about amyloid- and tau deposition in this syndrome. Objective: To determine amyloid and tau burden and cognitive function in OSA in comparison to those without a diagnosis of OSA. Methods: The status of OSA was determined by asking participants about history of polysomnographic diagnosis of OSA and the use of Continuous Positive Airway Pressure (CPAP). A comprehensive neuropsychological battery measured cognitive function. Positron emission tomography (PET) was used to measure standardized uptake value ratio (SUVR) of 18 F-florbetaben and 18 F-AV1451, to quantify amyloid and tau burden. Results: 119 male Vietnam veterans completed assessment. Impairment in visual attention and processing speed and increased body mass index (BMI) were seen in subjects with OSA compared with those without a diagnosis OSA. The cortical uptake of 18 F-florbetaben was higher in the OSA group than in the control group (SUVR: 1.35 ± 0.21 versus 1.27 ± 0.16, p = 0.04). There were more apolipoprotein E 4 allele (APOE 4) carriers in the OSA group than in the control group. In multilinear regression analysis, the significance of OSA in predicting 18 F-florbetaben uptake remained independent of age and vascular risk factors but not when BMI or APOE 4 was adjusted. The reported use of CPAP (n = 14) had no effect on cognitive or amyloid PET findings. There was no significant difference in 18 F-AV1451 uptake between the two groups. Conclusions: Obstructive sleep apnea is associated with Alzheimer's disease pathology, but this relationship is moderated by APOE 4 and BMI.
Psychiatry research, 2017
We investigated whether donepezil, a cholinesterase inhibitor, can be used to treat sleep disturbances in patients with dementia with Lewy bodies (DLB). Sleep disturbances were evaluated with the sleep disturbances item of the Neuropsychiatric inventory (NPI) and an actigraph in 16 DLB patients and 24 normal elderly control (NC) subjects. The presence/absence of nine kinds of sleep symptoms, such as dream enactment, were also evaluated in the DLB patients. The DLB patients were then given 5mg/day donepezil for 14 weeks and evaluated again. Eight of the 16 DLB patients had some sleep disturbances before taking donepezil. The actigraphy data indicated that average activity count per minute in sleep (AAC), which reflects body activity at night, was significantly higher and total sleep time was significantly longer in DLB patients than in NC subjects. The NPI sleep disturbances score significantly improved and the number of DLB patients who had sleep disturbances decreased after taking ...
JAMA Neurology
Increasing evidence suggests that sleep-disordered breathing (SDB) increases the risk of developing Alzheimer clinical syndrome. However, the brain mechanisms underlying the link between SDB and Alzheimer disease are still unclear. OBJECTIVE To determine which brain changes are associated with the presence of SDB in older individuals who are cognitively unimpaired, including changes in amyloid deposition, gray matter volume, perfusion, and glucose metabolism. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study was conducted using data from the Age-Well randomized clinical trial of the Medit-Ageing European project, acquired between 2016 and 2018 at Cyceron Center in Caen, France. Community-dwelling older adults were assessed for eligibility and were enrolled in the Age-Well clinical trial if they did not meet medical or cognitive exclusion criteria and were willing to participate. Participants who completed a detailed neuropsychological assessment, polysomnography, a magnetic resonance imaging, and florbetapir and fluorodeoxyglucose positron emission tomography scans were included in the analyses. MAIN OUTCOMES AND MEASURES Based on an apnea-hypopnea index cutoff of 15 events per hour, participants were classified as having SDB or not. Voxelwise between-group comparisons were performed for each neuroimaging modality, and secondary analyses aimed at identifying which SDB parameter (sleep fragmentation, hypoxia severity, or frequency of respiratory disturbances) best explained the observed brain changes and assessing whether SDB severity and/or SDB-associated brain changes are associated with cognitive and behavioral changes. RESULTS Of 157 participants initially assessed, 137 were enrolled in the Age-Well clinical trial, and 127 were analyzed in this study. The mean (SD) age of the 127 participants was 69.1 (3.9) years, and 80 (63.0%) were women. Participants with SDB showed greater amyloid burden (t 114 = 4.51; familywise error-corrected P = .04; Cohen d, 0.83), gray matter volume (t 119 = 4.12; familywise error-corrected P = .04; Cohen d, 0.75), perfusion (t 116 = 4.62; familywise error-corrected P = .001; Cohen d, 0.86), and metabolism (t 79 = 4.63; familywise error-corrected P = .001; Cohen d, 1.04), overlapping mainly over the posterior cingulate cortex and precuneus. No association was found with cognition, self-reported cognitive and sleep difficulties, or excessive daytime sleepiness symptoms. CONCLUSIONS AND RELEVANCE The SDB-associated brain changes in older adults who are cognitively unimpaired include greater amyloid deposition and neuronal activity in Alzheimer disease-sensitive brain regions, notably the posterior cingulate cortex and precuneus. These results support the need to screen and treat for SDB, especially in asymptomatic older populations, to reduce Alzheimer disease risk.
Lancet, 2006
The cholinesterase inhibitor donepezil is used to treat mild-to-moderate Alzheimer's disease. Its efficacy in severe dementia has not been assessed and is controversial. Our aim was to ascertain the effectiveness of donepezil in patients with severe Alzheimer's disease, by focusing primarily on cognition and activities of daily living. We did a 6-month, double-blind, parallel-group, placebo-controlled study in 248 patients with severe Alzheimer's disease (mini mental state examination score 1-10) who were living in assisted care nursing homes ran by trained staff in Sweden. We assigned patients oral donepezil (5 mg per day for 30 days then up to 10 mg per day thereafter, n=128) or matched placebo (n=120). Our primary endpoints were change from baseline to month 6 in the severe impairment battery (SIB) and modified Alzheimer's Disease Cooperative Study activities of daily living inventory for severe Alzheimer's disease (ADCS-ADL-severe). We analysed outcomes for p...
Sleep, 2017
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 a...
Sleep apnea: relationship to age, sex, and Alzheimer's dementia
Sleep, 1983
The relationship of sleep apnea to age, sex, and Alzheimer's dementia was investigated in 45 elderly subjects and 10 young males, all nonobese, normotensive, nonsmoking, with no sleep complaints and no medical problems other than Alzheimer's disease. Mean apnea/hypopnea index [(AH)I] was significantly greater in elderly males than in young males or elderly females. Mean (AH)I and percentage of subjects with an (AH)I greater than 5 in the Alzheimer groups were not significantly different from age and sex-matched controls. Results were similar when the apnea index was substituted for (AH)I. The data from this preliminary study indicate that healthy, elderly males with no sleep complaints and elderly males with Alzheimer's disease experience a significant, subclinical ventilatory impairment during sleep. Data from the 10 elderly females and 10 young males indicated no such impairment. The physiological significance of this degree of sleep apnea in otherwise healthy elderly ...