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

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