Late-life physical activity relates to brain tissue synaptic integrity markers in older adults

Abstract

Introduction: Physical activity (PA) is widely recommended for age-related brain health, yet its neurobiology is not well understood. Animal models indicate PA is synaptogenic. We examined the relationship between PA and synaptic integrity markers in older adults.

Methods: Four hundred four decedents from the Rush Memory and Aging Project completed annual actigraphy monitoring (Mean visits = 3.5±2.4) and post mortem evaluation. Brain tissue was analyzed for presynaptic proteins (synaptophysin, synaptotagmin-1, vesicle-associated membrane proteins, syntaxin, complexin-I, and complexin-II), and neuropathology. Models examined relationships between late-life PA (averaged across visits), and timing-specific PA (time to autopsy) with synaptic proteins.

Results: Greater late-life PA associated with higher presynaptic protein levels (0.14 < β < 0.20), except complexin-II (β = 0.08). Relationships were independent of pathology but timing specific; participants who completed actigraphy within 2 years of brain tissue measurements showed largest PA-to-synaptic protein associations (0.32 < β < 0.38). Relationships between PA and presynaptic proteins were comparable across brain regions sampled.

Discussion: PA associates with synaptic integrity in a regionally global, but time-linked nature in older adults.

Keywords: actigraphy; cognitive resilience; exercise; presynaptic protein.

Figure 1.

Greater average late life physical activity relates to higher synaptic protein in brain tissue at death, with the exception of complexin-II. Note. Dashed lines represent 95%CI. Average late life physical activity represents actigraphy levels averaged across available study visits. All models adjusted for age at death, sex, education, and average late life motor10 performances. Synaptic protein levels are expressed in log10 units, standardized, and averaged across six brain regions within each participant (z-score units).

Figure 2.

The relationship between physical activity and brain tissue synaptic protein levels is stronger the more proximate the measures were taken in time (i.e., time between actigraphy monitoring and death). Note. N=150 participants 0–2 years to death and n=154 participants 3–10 years to death. Fitted regression lines adjusting for age at visit, sex, education, and motor10 performance at visit are plotted with 95% CI.