An estimated 65% of individuals demonstrate multi-domain cognitive impairment post-stroke, although little is known about the varying role of cognitive risk and protective factors in pre-, peri-, and post-ischemic stroke phases. Longitudinal changes in global cognitive function after ischemic stroke are not well characterized, especially in older adults over age 80. We examined global cognitive function trajectories in these three phases across a mean follow-up of 8.12 (2.30) years in 159 female stroke survivors aged 65–79 at baseline using linear mixed models with change points. In separate models controlling for demographic variables, we tested the interaction of baseline risk and protective factors with stroke phase on global cognitive function. None of the pre-stroke global cognitive function means or trajectories differed significantly. At the time of ischemic stroke, higher body mass index, the presence of hypertension, low optimism, and higher physical function were all associated with significantly greater mean decreases in global cognition (all p’s <.0.0001), but were not significantly different from the contrasting level (all p’s > 0.05). Higher body mass index, the presence of hypertension, low optimism, and higher physical function were in turn protective of global cognitive decline post- ischemic stroke (all contrasting p values <.01). Baseline factors may play either a risk or a protective role in global cognitive function depending on the phase of ischemic stroke.