Longitudinal associations of cardiorespiratory fitness and physical activity with changes in cognitive function in breast cancer patients undergoing chemotherapy: a prospective matched-control study.

[PURPOSE] Cancer-related cognitive impairment (CRCI) is a common concern among breast cancer (BC) patients receiving chemotherapy, yet predictors of short-term cognitive change remain unclear. This study examined whether baseline cardiorespiratory fitness (CRF) and moderate-to-vigorous physical activity (MVPA) moderate changes in objectively assessed cognitive function from pre- to post-chemotherapy in BC patients, compared with age-matched healthy controls.

[METHODS] This prospective study included assessments at baseline (pre-chemotherapy) and approximately a five-month follow-up (post-chemotherapy). Participants were BC patients with stage I-III disease initiating chemotherapy and age-matched healthy controls. Cognitive function was assessed using the NIH Remote Cognition Toolbox (episodic memory, working memory, language/reading, verbal learning). CRF was measured using a remotely administered 6-min walk test, and MVPA was assessed via accelerometry. Linear mixed-effects models tested group × time × predictor (baseline CRF or MVPA) effects, adjusting for anxiety, depression, and menopausal status.

[RESULTS] Fifty-five participants were included (BC: n = 32; controls: n = 23). Episodic memory improved over time in both groups (β = 4.69, p = 0.031). Higher baseline CRF was associated with better verbal learning (β = 0.02, p = 0.023), but neither CRF nor MVPA predicted cognitive change over time (all three-way interactions p ≥ 0.05). BC patients scored lower than controls at baseline on working memory and language/reading, while verbal learning improved more in BC patients. BC patients also showed greater declines in MVPA over time.

[FINDINGS] No short-term cognitive decline was observed from pre-chemotherapy to approximately 5 months post-chemotherapy. Higher baseline fitness and physical activity were associated with better cognitive performance but did not predict cognitive change. Longer follow-up is needed to clarify treatment-related cognitive trajectories.