Sleep and Neurocognitive aging in Population based studies Sleep and Neurocognitive aging in...

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  • 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

    aramos@med.miami.edu

    Support: R21AG056952; KL2TR000461 (Ramos) Miami CTSI;

    SAC ITS Pilot study-Miller School of Medicine

    mailto:aramos@med.miami.edu

  • Outline

    ▪Background

    ▪Sleep and poor health

    ▪Sleep and Aging

    ▪Sleep phenotypes associated with impaired cognition/dementia

    ▪Possible mechanisms

  • Why Sleep?

    ▪Consolidation of memories

    ▪Brain growth and development

    ▪Reduce Synaptic Activity

    ▪Glymphatic system

  • How much sleep are we getting?

    9.0

    7.5

    6.8

    0.0

    1.0

    2.0

    3.0

    4.0

    5.0

    6.0

    7.0

    8.0

    9.0

    10.0

    1910 1975 2005

    Hrs per night

    National Sleep Foundation. Sleep in America Poll

  • Changes in sleep with aging

    Van Cauter E et al. JAMA. 2000;284:861-868

    slow wave sleep

  • Summary of sleep changes with aging

    ▪ Meta-analytic review of 65 sleep studies N=3557 aged 5-102 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

    4 5 6 7 8 9 10

    M o

    rb id

    it y &

    M o

    rt a

    li ty

    Sleep Duration (hrs)

    Ohayon et al., Sleep, 2004

    Ancoli-Israel and Cooke, J Am Geriatr Soc, 2005

  • Sleep Phenotypes associated with cognitive impairment/dementia

    ▪ Insomnia

    ▪Short and long sleep durations

    ▪Sleep fragmentation

    ▪Sleep disordered breathing

    •Obstructive sleep apnea

  • Date of download: 3/15/2018 Copyright 2017 American Medical Association.

    All Rights Reserved.

    From: Association of Sleep-Disordered Breathing With Cognitive Function and Risk of Cognitive ImpairmentA Systematic

    Review and Meta-analysis

    JAMA Neurol. 2017;74(10):1237-1245. doi:10.1001/jamaneurol.2017.2180

    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: Τ2 = 0.02; χ2 = 11.40; df = 5; P = .04; I2 = 56%. Test for overall effect:

    z = 2.51; P = .01. Error bars indicate 95% CIs. OR indicates odds ratio.

    Figure Legend:

  • 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

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

  • Hispanic Community Health Study/ Study of Latinos

    • Multi-center prospective population-based

    • Examined 16,415 self-identified Hispanic/Latinos ages 18-74 recruited from randomly selected households.

    • Backgrounds: Cuban, Dominican, Mexican, Puerto Rican, and Central and South American

    • Baseline examination: March 2008 – June 2011.

    • Annual follow-up interviews.

    • In-person follow-up assessments from 2014-2017

    • Third wave of in person follow-up expected in 2019

    Sorlie, PD et al. Ann Epidem 2010: 20: 629

  • Objective Sleep Data

    • N=14,440 sleep studies

    • 2008-2012

    ARES Unicorder 5.2; B-Alert,

    Carlsbad, CA

    • N=2,200 Actigraphy

    • 2009-2013

  • Am J Respir Crit Care Med. 2014 Feb 1;189(3):335-44

  • Sleep disordered breathing and Neurocognitive Function

    ▪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

  • 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.

  • Exploring Sleep in Neurocognitive aging (eSANAR) n=3,564

    ▪Sleep at baseline (2008-2011) and neurocognitive (NC) testing at baseline and wave 2 (2016-2017)

    ▪Exposures: moderate-severe sleep apnea, insomnia, self-reported short (

  • 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, βSEVLT-Sum= -0.327 (se=0.08); p

  • Kang, Lee, and Lim. Clin Psychopharmacol Neurosci 2017

    Pathways between sleep and impaired cognition

    Amyloid and Tau Cerebrovascular non-amyloid

    Zimmerman, Aloia. 2012

  • Sleep disorders and cerebral hemodynamics during wakefulness in HCHS/SOL

    n=97

    β(SE)

    Basilar artery Middle cerebral artery

    Mean flow

    velocity

    Pulsatility index Mean flow velocity Pulsatility index

    AHI (3%) -0.38 (0.19)** 0.01 (0.003) * 0.1 (0.17) 0.001 (0.002)

    sleep duration, hours -0.28 (1.2) -0.04 (0.02) ** -0.5 (1.3) -0.002 (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

  • Summary

    Conclusion

    ▪ Poor sleep associated with vascular disease, possible mediating effects on cognition

    ▪ Sleep apnea is the exemplar of a sleep disorder associated with dementia

    ▪ The impact of OSA more strongly linked with hypoxemia than sleep disruption

    ▪ Future directions: Mechanistic studies, risk reduction for dementia

    Next Steps Dr. Noam Alperin

    ▪ Phenotypes of sleep Apnea and neuroimaging markers of brain health

    ▪ MRI volumes, blood flow to the brain/regional cerebral perfusion

    ▪ Compare verbal memory, executive function, attention, and processing speed

    ▪ Evaluate treatment of sleep apnea on MRI and cognitive measures

  • 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