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
▪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
Mo
rbid
ity &
Mo
rta
lity
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<0.001)
Age:
▪ ages 45-54 years was 7.4± 0.3
▪ ages 55-64 years was 9.7 ± 0.4
▪ ages 65-74 years was 11.5±0.7 (p<0.001)
N=8,059
Ramos et al. Neurology. 2015
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.
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 (<6 hours), long (≥9 hours) sleep duration
▪Outcome: NC changes in episodic learning and memory, language, processing speed, and global cognition
unpublished
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<0.001
▪ memory, βSEVLT-Recall= -0.246 (se=0.07); p<0.001
▪ verbal fluency, βWF=-0.179 [se=0.08]; p<0.05
▪ Sleep apnea and insomnia phenotypes did not predict NC decline after 6 years
unpublished
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<0.05 under-review JCSM
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
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