Independent associations of sleep and physical activity with cognition are mediated by hippocampal microstructure in middle-aged and older adults

Daniel D Callow; Adam P Spira; Vadim Zipunnikov; Corinne Pettigrew; Andreia Faria; Sarah K Wanigatunga; Marilyn Albert; Arnold Bakker; Anja Soldan; BIOCARD Research Team

doi:10.1016/j.neurobiolaging.2024.11.011

Independent associations of sleep and physical activity with cognition are mediated by hippocampal microstructure in middle-aged and older adults

Neurobiol Aging. 2024 Dec 5:147:22-31. doi: 10.1016/j.neurobiolaging.2024.11.011. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: dcallow3@jh.edu.
² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Johns Hopkins Center on Aging and Health, Baltimore, MD, USA.
³ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁵ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Johns Hopkins Center on Aging and Health, Baltimore, MD, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

PMID: 39647405
DOI: 10.1016/j.neurobiolaging.2024.11.011

Abstract

Sleep and physical activity levels are both associated with cognitive performance among older adults; however, the brain mechanisms underlying these beneficial relationships remain poorly understood. This study investigated cross-sectional associations of actigraphic estimates of physical activity and sleep with cognition and diffusion imaging-based measures of medial temporal lobe (MTL) gray matter microstructural integrity in adults free of dementia. Participants were 132 older adults from the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) cohort study (119 cognitively unimpaired and 13 with mild cognitive impairment; mean age=70.8 years). Multiple linear regression analyses assessed the relationships between total volume of physical activity (TVPA), total sleep time (TST), and sleep efficiency (SE) with cognitive performance and MTL microstructural integrity. Results indicated that greater TVPA and SE were both independently associated with higher hippocampal and parahippocampal microstructure integrity (indicated by lower mean diffusivity) and better visuospatial processing abilities, independent of the volume of these structures and of amyloid burden, measured by positron emission tomography. Additionally, higher hippocampal microstructure statistically mediated the independent associations of physical activity and sleep with visuospatial abilities, independent of MTL volume and Aβ load. These findings suggest that physical activity and sleep are independently associated with cognitive performance, and that hippocampal microstructural integrity may be an underlying mechanism supporting these associations.

Keywords: Alzheimer's Disease; Diffusion Weighted Imaging; Exercise; Medial Temporal Lobe; Modifiable Lifestyle Factors; Sleep; Visuospatial Abilities.