Ogie Queen Umasabor-Bubu

EFFECT OF OBSTRUCTIVE SLEEP APNEA (OSA) ON RATE OF CHANGE OF AD BIOMARKERS IN COGNITIVELY NORMAL, MCI AND AD ELDERLY: FINDINGS FROM THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE (ADNI) COHORT

Background: Evidence from numerous research implicates disturbed sleep or lack of sleep as one of the risk factors for Alzheimer’s disease (AD) and in a recent meta-analysis, we confirmed the association providing an “average” magnitude of effect. However, the extent of the risk of the association of disturbed sleep with AD biomarkers remains uncertain. We conducted further subgroup meta-analyses to quantify the effect of disturbed sleep on cognitive impairment; preclinical AD and symptomatic AD respectively. Methods:PubMed, Embase, Web of Science, and the Cochrane library were used to identify original published literature for this review. Sleep problems and/or disorders were the risk factor of interest in this meta-analysis, and grouped as sleep quality, sleep duration, circadian rhythm abnormalities, insomnia, and obstructive sleep apnea (OSA) for sub-group analyses. Our target variables included the use of cognitive tests assessing cognitive impairment; the use of AD biomarkers or abnormal proteins assessing preclinical AD; and the use of ICD9/DSMIV diagnoses of symptomatic AD. Effect estimates of individual studies were pooled and relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. Meta-regression analyses examining the effect of potential influencing factors was also conducted. Results:Twentyseven observational studies (n 1⁄4 69,216 participants) that provided 52 RR estimates were included in the meta-analysis. Subgroup meta-analytic findings showed a RR increase inverse to diagnostic confidence (e.g., 1.60, 1.70 and 3.80 for AD, Cognitive Impairment and preclinical AD, P-value <.001 for all). Relative risk for AD and/or cognitive decline was (RR: 2.37, 1.86, 1.62, 1.38 and 1.38, p<.001 for all) for OSA, sleep quantity, sleep quality, insomnia, and circadian rhythm abnormalities respectively. Meta-regression results suggested that sample size might have significantly influenced the effect size such that larger sample size studies tended to result in smaller risk and vice versa. Conclusions:Our findings suggest that disturbed sleep had a four-fold association with AD biomarkers. OSA also appeared to be a strong risk factor for AD. Since changes in AD biomarkers are predictive of persons that ultimately develop AD, these results highlight potential mechanistic relationships that are vital for potential prevention of AD.

SLEEP DISORDERED BREATHING AND BRAIN BETA-AMYLOID BOTH PREDICT TIME-TO-PROGRESSION FROM COGNITIVE NORMAL TO MILD COGNITIVE IMPAIRMENT WITH BRAIN BETA-AMYLOID MODIFYING THE PROGRESSION RISK

and maximally for protocol-3 at 17446687 mm. The linearregression between protocol-2-3 showed the strongest relationship (p< 0.001; r 1⁄4 0.92), while the relationship between “penumbra” volumes for Protocol-1-2 (p1⁄4 0.003; r1⁄4 0.68) and Protocol-1-3 (p 1⁄4 0.013; r 1⁄4 0.56) were less robust. In addition, protocol-3 appeared optimal for co-registration of diffusion tensor and arterial spin labeling imaging for the detection of pre-WMH pathologic changes within the “penumbra“. Conclusions: Reliable volumetric quantification methodologies are essential for the determination of longitudinal WMH change over a one-year period, amenable to use in future clinical trials of small vessel ischemic disease. Future work, validating our optimal WMH “penumbra” quantification protocol amenable to multi-site studies is underway currently.

OBSTRUCTIVE SLEEP APNEA, BRAIN BETA-AMYLOID MEASURES AND TIME-TO-PROGRESSION FROM MILD COGNITIVE IMPAIRMENT TO ALZHEIMER’S DISEASE

Age, years, mean (SD) 76.7 (8.16) Female, n (%) 82 (51.9%) White, n (%) 124 (78.5%) Education, years, mean (SD) 17.2 (2.29) APOE e4+, n (%) 35 (27.1%) PiB+, n (%) 48 (30.4%) Clinical diagnosis, n (%) Cognitively normal 153 (96.8%) Mild cognitive impairment 3 (1.90%) Dementia 2 (1.27%) Follow-up duration, years, mean (SD) 2.50 (3.15) Individuals with: 1 visit, n (%) 71 (44.9%) 2 visits 35 (22.2%) 3 visits 20 (12.7%) 4 visits 11 (6.96%) 5 visits 10 (6.33%) 6-8 visits 11 (6.96%)

OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH LONGITUDINAL INCREASES IN AMYLOID BURDEN IN ELDERLY MILD COGNITIVE IMPAIRMENT INDIVIDUALS

Cross sectional analysis has shown an association between Obstructive Sleep Apnea (OSA) severity and A burden using amyloidPET among Mild Cognitive Impairment (MCI) patients. However, whether OSA accelerates longitudinal increases in amyloid beta (A ) burden in MCI patients is presently unclear. Study participants included a total of 798 subjects with a diagnosis of MCI and were a subset of the ADNI cohort (adni.loni.usc.edu). OSA was self-reported and participants were labeled either as OSA+ or OSA . A burden was determined by florbetapir SUVRs. To test whether OSA is associated with the rate of change in A data longitudinally, multilevel mixed effects linear regression was used to fit the models with randomly varying intercepts and slopes allowing dependence on OSA status. The final model was adjusted for age, sex, body mass index, education, CPAP use status, history of respiratory disease, hypertension, diabetes, and history of cardiovascular disease. A significant variation in the change (slope) in A volumes over time was seen (p<.0001). The covariance between the baseline A level and A volume change over time indicated that OSA subjects experienced greater mean change differences in brain A volumes over time (p < .0001). The rate of change in A deposition also varied significantly across OSA groups over the follow-up period. Obstructive Sleep Apnea possibly facilitates longitudinal increases in amyloid burden in elderly Mild Cognitive Impairment individuals. Further research examining mechanisms underlying effects of OSA on the longitudinal increases in A burden is needed.