Chapman_2025_NPJ.Aging__

Hypertensive individuals with vascular cognitive impairment (VCI) often live alone and are less likely to adhere to prescribed medications, making the development of non-pharmacological interventions critical. How cognitive stimulation affects the vasculature of the hippocampus remains unclear but could protect against memory decline during VCI. Memory and hippocampal arteriole (HA) function were assessed in spontaneously hypertensive rats (SHR) of both sexes that either underwent cognitive stimulation or lived in isolation. Isolated SHR were treated with donepezil (acetylcholinesterase inhibitor) to compare lifestyle and pharmacological interventions and investigate the mechanisms by which the hippocampus can be protected during VCI. Cognitive stimulation selectively and persistently improved hippocampal-dependent memory and HA function that was not due to increased BDNF expression. Donepezil improved HA function and rescued memory in isolated, aged SHR. Intermittent cognitive stimulation exerted long-lasting protection on the hippocampus and its vasculature, highlighting the therapeutic potential of HAs and cognitive stimulation in VCI.