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

Alzheimers Dement. 2022 Nov;18(11):2023-2035. doi: 10.1002/alz.12530. Epub 2022 Jan 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actigraphy
  • Aging / pathology
  • Animals
  • Brain*
  • Exercise*