Accepted Manuscript Sleep quality and risk of dementia among older male veterans Kristine Yaffe, MD, Jasmine Nettiksimmons, PhD, Jerome Yesavage, MD, Amy Byers, PhD PII:

S1064-7481(15)00103-7

DOI:

10.1016/j.jagp.2015.02.008

Reference:

AMGP 474

To appear in:

The American Journal of Geriatric Psychiatry

Received Date: 3 November 2014 Revised Date:

5 February 2015

Accepted Date: 17 February 2015

Please cite this article as: K. Yaffe, J. Nettiksimmons, J. Yesavage, A. Byers, Sleep quality and risk of dementia among older male veterans, The American Journal of Geriatric Psychiatry (2015), doi: 10.1016/j.jagp.2015.02.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT 1 Abstract 146 words Manuscript 1455 words American Journal of Geriatric Psychiatry

Title: Sleep quality and risk of dementia among older male veterans

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Brief Report

Authors: Kristine Yaffe, MD; Jasmine Nettiksimmons, PhD; Jerome Yesavage, MD; Amy Byers, PhD

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Jasmine Nettiksimmons, PhD Postdoctoral researcher University of California-San Francisco

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Kristine Yaffe, MD (corresponding author) Professor of Psychiatry, Neurology, Epidemiology and Biostatistics University of California - San Francisco San Francisco Veteran Affairs Medical Center 4150 Clement Street Box 181 San Francisco, CA 94121 [email protected] Phone: 415-221-4810 x3985 Fax: 415-379-5624

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Jerome Yesavage, MD Professor of Psychiatry and Behavioral Sciences Stanford University School of Medicine Palo Alto Veteran Affairs Medical Center

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Amy Byers, PhD Associate Professor of Psychiatry University of California – San Francisco San Francisco Veteran Affairs Medical Center

ACCEPTED MANUSCRIPT 2 Support: This study was supported by The Sierra Pacific VISN Mental Illness Research, Education, and Clinical Centers (MIRECC) and by a Department of Defense grant (W81XWH-11-2-0189), which was

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administered by the Northern California Institute for Research and Education. Previous Presentation: This work was presented as a poster at the 2014 Alzheimer’s Association International Conference in Copenhagen, Denmark.

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Disclosures: Dr. Yaffe serves on data safety monitoring boards for Takeda, Inc. The other authors report

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no potential conflicts of interest.

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Keywords: sleep; dementia; veterans

ACCEPTED MANUSCRIPT 3 Abstract (146 words) Objectives: To determine whether a diagnosis of sleep disturbance is associated with dementia in older veterans.

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Design, Setting, Participants: For this retrospective cohort study, we obtained medical record data from the Department of Veterans Affairs (VA) National Patient Care Database for 200,000 randomly selected veterans aged 55 years and older. Prevalent cases of dementia from the baseline period (2000-2003) were excluded, leaving an analytic sample of N =179,738 male veterans. Follow-up took place from 2004-2011.

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Measurements: The primary outcome was all-cause dementia, ascertained using International Classification of Disease, 9th Revision (ICD9) codes. Sleep disturbance, the primary predictor, was also ascertained using ICD9 codes.

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Results: After adjusting for potential confounders, those with sleep disturbance had a 29% increased risk of dementia (hazard ratio 1.27, 95% CI: 1.20, 1.34).

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Conclusions: Sleep disturbance was associated with increased risk of dementia among a large cohort of older, primarily male veterans.

ACCEPTED MANUSCRIPT 4 Objective In the United States, almost 60% of veterans are over the age of 60 [1]. Cognitive impairment and

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dementia could have a significant impact on veterans’ healthcare costs and caregiver burden. While effective treatments for dementia remain elusive, investigating modifiable risk factors is a vital part of delaying and preventing dementia.

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Although research is limited, the literature suggests that poor sleep quality and sleep apnea are

associated with cognitive decline and dementia [2-5]. In particular, while veterans are more likely to

not been examined in older veterans [6].

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report sleep disturbances than nonveterans, the association between sleep quality and dementia has

We aimed to assess whether the diagnosis of sleep disturbance was associated with an increased risk for dementia. Further, we aimed to evaluate whether this association was modified by diagnosis of Post-

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traumatic stress disorder (PTSD) or traumatic brain injury (TBI), to which veterans may be uniquely at risk and which are associated with development of dementia [7,8]. PTSD and TBI, as they relate to dementia, will become increasingly important as the generation of veterans who fought in Iraq and

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Methods

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Afghanistan ages [9].

For this retrospective cohort study, we obtained medical record data from the Department of Veterans Affairs (VA) National Patient Care Database for 200,000 randomly selected veterans aged 55 years and older. We ascertained prevalent sleep and comorbidity diagnoses at baseline (2000-2003) and incident dementia during follow-up (2004-2011) using International Classification of Diseases, 9th Revision codes. The primary predictor was any sleep disturbance (780.5); the two main subtypes of sleep disturbance, apnea (780.51, 780.53, 780.57) and insomnia (780.52), were also examined individually. Due to the

ACCEPTED MANUSCRIPT 5 small number of females in the sample, we restricted our analysis to males. We excluded prevalent cases of dementia as well as cases with missing covariate information, resulting in an analytic sample of N=179,738. The Committee on Human Research at the University of California, San Francisco, the

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Committee for Research and Development at the San Francisco VA, and the Human Research Protection Office of the U.S. Army Medical Research and Materiel Command approved the study

We estimated hazard ratios with extended Cox regression models using age as the time scale,

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accounting for age at risk set entry and exit [10], and adjusting for baseline diabetes, hypertension, myocardial infarction, cerebrovascular disease, obesity, depression, income tertile, and education.

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Income and education were based on census data matched to the participants’ zip code. The proportional hazard assumption for primary predictors were assessed with time-varying interaction terms using time-on-study as the timescale.

In addition to all cause dementia, we examined several dementia subtypes: Alzheimer’s disease (AD;

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331.0), vascular dementia (VD; 290.4), Lewy body dementia (LBD; 331.82), Other/Not Otherwise Specified (Other; 290.0, 290.1, 290.2, 290.3, 331.1, 331.2, 331.7, 331.89, 331.9, 294.8). We also looked for effect modification of dementia risk by traumatic brain injury (TBI; 800-804, 850-854, 905.0, 907.0,

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baseline period.

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v15.52, 310.2, 873.8, 873.9, 959.01) and post-traumatic stress disorder (PTSD; 309.81), assessed during

Results

Baseline period prevalence of any type of sleep disturbance was 7.5%; prevalence of sleep-apnea and insomnia was 3.9% and 3.2%, respectively. Those with a diagnosis of sleep disturbance were slightly younger (mean age 66.9 years versus 68.5 years, F = 519.6, df =1, p

Sleep Quality and Risk of Dementia Among Older Male Veterans.

To determine whether a diagnosis of sleep disturbance is associated with dementia in older veterans...
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