Increased sedentary behavior is associated with neurodegeneration and worse cognition in older adults over a 7-year period despite high levels of physical activity

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 Increased sedentary behavior is associated with neurodegeneration and worse cognition in older adults over a 7-year period despite high levels of physical activity

Marissa A. Gogniat1,2,3 Omair A. Khan4,5 Judy Li1 Chorong Park6

W. Hudson Robb1 Panpan Zhang1,4 Yunyi Sun1,4 Elizabeth E. Moore1,7

Michelle L. Houston1,8 Kimberly R. Pechman1 Niranjana Shashikumar1

L. Taylor Davis1,2,9 Dandan Liu1,4 Bennett A. Landman1,2,9,10,11 Keith R. Cole1,12

Corey J. Bolton1,13 Katherine A. Gifford1,2,14 Timothy J. Hohman1 Kelsie Full1,15

Angela L. Jefferson1,2,16

1 Vanderbilt Memory and Alzheimer’s Center, Nashville, Tennessee, USA

2 Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

3 Department of Neurology, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

4 Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA

5 Vanderbilt Brain Institute, Vanderbilt University, Medical Research Building III, Nashville, Tennessee, USA

6 College of Nursing, Seoul National University, Jongno District, Seoul, South Korea

7 Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA

8 Center for Biomedical Ethics and Society, Section of Surgical Sciences, Vanderbilt University Medical, Nashville, Tennessee, USA

9 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA

10 Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, Tennessee, USA

11 Department of Biomedical Engineering, Vanderbilt University Center, Nashville, Tennessee, USA

12 Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA

13 Division of Geriatrics, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA

14 Department of Anatomy and Neurobiology, Boston University, Boston, Massachusetts, USA

15 Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA

16 Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA

Correspondence

Angela L. Jefferson, Vanderbilt Memory and

Alzheimer’s Center, 3319 West End Avenue,

8th Floor, Nashville, TN 37203, USA.

Email: angela.jefferson@vumc.org

Statistical Analysis conducted by Omair A.

Khan, MAS, Yunyi Sun, MA, Panpan Zhang,

PhD and Dandan Liu, PhD, Department of

Abstract

INTRODUCTION: Sedentary behavior may be a modifiable risk factor for Alzheimer’s

disease (AD). We examined how sedentary behavior relates to longitudinal brain

structure and cognitive changes in older adults.

METHODS: Vanderbilt Memory and Aging Project participants (n = 404) completed

actigraphy (7 days), neuropsychological assessment, and 3T brain MRI over a 7-year

period. Cross-sectional and longitudinal linear regressions examined sedentary time

in relation to brain structure and cognition. Models were repeated testing for effect

modification by apolipoprotein E (APOE) ε4 status.

RESULTS: In cross-sectional models, greater sedentary time related to a smaller AD-

neuroimaging signature (β = -0.0001, p = 0.01) and worse episodic memory (β = -0.001,

p = 0.003). Associations differed by APOE-ε4 status. In longitudinal models, greater

sedentary time related to faster hippocampal volume reductions (β = -0.1, p = 0.008)

and declines in naming (β = -0.001, p = 0.03) and processing speed (β = -0.003, p = 0.02;

β = 0.01, p = 0.01).

DISCUSSION: Results support the importance of reducing sedentary time, particularly

among aging adults at genetic risk for AD