Sleep and Neurocognitive aging in Population based studies

Transcription

1 Sleep and Neurocognitive aging in Population based studies Alberto Ramos, MD,MSPH, FAASM Associate Professor of Neurology University of Miami Health System Miller School of Medicine Support: R21AG056952; KL2TR (Ramos) Miami CTSI; SAC ITS Pilot study-miller School of Medicine

2 Outline Background Sleep and poor health Sleep and Aging Sleep phenotypes associated with impaired cognition/dementia Possible mechanisms

3 Why Sleep? Consolidation of memories Brain growth and development Reduce Synaptic Activity Glymphatic system

4 How much sleep are we getting? Hrs per night National Sleep Foundation. Sleep in America Poll

5 Changes in sleep with aging slow wave sleep Van Cauter E et al. JAMA. 2000;284:

6 Morbidity & Mortality Summary of sleep changes with aging Meta-analytic review of 65 sleep studies N=3557 aged years Most sleep changes occur in early and mid-years of life span In healthy older adults: Sleep architecture and efficiency changes with age Constant from age 60 to mid-90s The circadian clock naturally advances with age Sleep complaints in older adults are not due to aging Medical and psychiatric problems Medications Higher prevalence of some specific sleep disorders Sleep Duration (hrs) Ohayon et al., Sleep, 2004 Ancoli-Israel and Cooke, J Am Geriatr Soc, 2005

7 Sleep Phenotypes associated with cognitive impairment/dementia Insomnia Short and long sleep durations Sleep fragmentation Sleep disordered breathing Obstructive sleep apnea

8 From: Association of Sleep-Disordered Breathing With Cognitive Function and Risk of Cognitive ImpairmentA Systematic Review and Meta-analysis JAMA Neurol. 2017;74(10): doi: /jamaneurol Figure Legend: Forest Plot of Prospective Studies on Association Between Sleep-Disordered Breathing and Risk of Cognitive ImpairmentAll effect estimates were pooled using a weighted random-effects model. Heterogeneity: Τ 2 = 0.02; χ 2 = 11.40; df = 5; P =.04; I 2 = 56%. Test for overall effect: z = 2.51; P =.01. Error bars indicate 95% CIs. OR indicates odds ratio. Date of download: 3/15/2018 Copyright 2017 American Medical Association. All Rights Reserved.

9 Limitations to Current Knowledge Most studies used self-reported methods for sleep Sleep disturbances are prevalent in older patients In older adults, sleep disturbances can be a prodrome of dementia Most studies obtained a single sleep measure Most studies lack assessments of multiple sleep domains

10 Sleep and neurocognitive function Hispanic Community Health Study/Study of Latinos

11 Hispanic Community Health Study/ Study of Latinos Multi-center prospective population-based Examined 16,415 self-identified Hispanic/Latinos ages recruited from randomly selected households. Backgrounds: Cuban, Dominican, Mexican, Puerto Rican, and Central and South American Baseline examination: March 2008 June Annual follow-up interviews. In-person follow-up assessments from Third wave of in person follow-up expected in 2019 Sorlie, PD et al. Ann Epidem 2010: 20: 629

12 Objective Sleep Data N=14,440 sleep studies N=2,200 Actigraphy ARES Unicorder 5.2; B-Alert, Carlsbad, CA

13 Am J Respir Crit Care Med Feb 1;189(3):335-44

14 Sleep disordered breathing and Neurocognitive Function N=8,059 Mean age 56 years, 55% women The mean apnea-hypopnea index (AHI) was 8.9 ± 0.2 Gender: men was 11.5 ± 0.4 women was 6.8 ± 0.3 (p<0.001) Age: ages years was 7.4± 0.3 ages years was 9.7 ± 0.4 ages years was 11.5±0.7 (p<0.001) Adjusting for age, sex, education, ethnicity, language, income, employments status, stroke, diabetes, hypertension, depression and anxiety symptoms, smoking, BMI, Epworth sleepiness scale, sleep medications, apnea-hypopnea index and field center. Ramos et al. Neurology. 2015

15 Sleep Duration and Neurocognitive Function Adjusting for age, sex, education, ethnicity, language, income, employments status, stroke, diabetes, hypertension, depression and anxiety symptoms, smoking, BMI, Epworth sleepiness scale, sleep medications, apnea-hypopnea index and field center.

16 Exploring Sleep in Neurocognitive aging (esanar) n=3,564 Sleep at baseline ( ) and neurocognitive (NC) testing at baseline and wave 2 ( ) Exposures: moderate-severe sleep apnea, insomnia, self-reported short (<6 hours), long ( 9 hours) sleep duration Outcome: NC changes in episodic learning and memory, language, processing speed, and global cognition unpublished

17 Exploring Sleep in Neurocognitive aging (esanar) Results: 62±8 years, 55% were female with 6.4-years mean follow-up Longer sleep was associated with decline: episodic learning, β SEVLT-Sum = (se=0.08); p<0.001 memory, β SEVLT-Recall = (se=0.07); p<0.001 verbal fluency, β WF = [se=0.08]; p<0.05 Sleep apnea and insomnia phenotypes did not predict NC decline after 6 years unpublished

18 Pathways between sleep and impaired cognition Amyloid and Tau Cerebrovascular non-amyloid Kang, Lee, and Lim. Clin Psychopharmacol Neurosci 2017 Zimmerman, Aloia. 2012

19 Sleep disorders and cerebral hemodynamics during wakefulness in HCHS/SOL n=97 Basilar artery Middle cerebral artery Mean flow Pulsatility index Mean flow velocity Pulsatility index β(se) velocity AHI (3%) (0.19)** 0.01 (0.003) * 0.1 (0.17) (0.002) sleep duration, hours (1.2) (0.02) ** -0.5 (1.3) (0.01) Sleep apnea -5.1 (2.5)** 0.04 (0.04) 4.6 (2.8) 0.03 (0.03) AHI < 5 Reference Reference Reference Reference Short Sleep 0.9 (2.2) 0.04 (0.03) 0.7 (2.4) 0.05 (0.02) ** 6.8 h Reference Reference Reference Reference Models adjusted for age, sex, systolic blood pressure, diastolic blood pressure, diabetes **p<0.05 under-review JCSM

20 Summary Conclusion Poor sleep associated with vascular disease, possible mediating effects on cognition Next Steps Dr. Noam Alperin Phenotypes of sleep Apnea and neuroimaging markers of brain health Sleep apnea is the exemplar of a sleep disorder associated with dementia MRI volumes, blood flow to the brain/regional cerebral perfusion The impact of OSA more strongly linked with hypoxemia than sleep disruption Compare verbal memory, executive function, attention, and processing speed Future directions: Mechanistic studies, risk reduction for dementia Evaluate treatment of sleep apnea on MRI and cognitive measures

21 Acknowledgments The McKnight Brain Research Foundation University of Miami, Miller School of Medicine Tatjana Rundek, MD PhD Ralph Sacco, MD MS Hispanic Community Health Study/Study of Latinos Neil Schneiderman, PhD (PI-Miami) Susan Redline, MD., MPH, Brigham Women s Hospital (Sleep) Sanjay Patel, MD, MS, University of Pittsburgh (Sleep) Hector Gonzalez, PhD University of California, San Diego(PI-SOL INCA) Wassim Tarraf, PhD Wayne State University