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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

    Support: R21AG056952; KL2TR000461 (Ramos) Miami CTSI;

    SAC ITS Pilot study-Miller School of Medicine

  • Outline


    ▪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?















    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


    ▪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



    Basilar artery Middle cerebral artery

    Mean flow


    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


  • Summary


    ▪ 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