BACKGROUND: This study aimed to elucidate the impact of exercise timing on inflammatory markers and cognitive function in elderly women with type 2 diabetes mellitus (T2DM), with a particular focus on the expression of proteins implicated in Alzheimer's disease (AD) pathogenesis, including TYRO protein tyrosine kinase-binding protein (TYROBP), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), transforming growth factor beta (TGF-beta), apolipoprotein E (APOE), and Osteopontin (SPP1). OBJECTIVES: This research aimed to address: Which exercise time- morning or evening- provides greater health benefits for elderly women with T2DM, particularly regarding key health indicators? METHODS: This study was a randomized controlled trial. A total of 45 women, aged 55 to 65 years, diagnosed with T2DM, were randomly assigned to morning exercise, evening exercise, or control groups using a computer-generated random number sequence. The tool used in this study is the Montreal Cognitive Function Questionnaire. The intervention consisted of a 12-week aerobic exercise (TPMP) regimen, calibrated to 60 to 70% of the participants' maximum heart rate reserve. Protein expression levels were quantified pre-and post-intervention using enzyme-linked immunosorbent assay (ELISA). To mitigate bias, outcome assessors were blinded to participant group allocation via a data coding protocol. RESULTS: The results of MANCOVA and ANCOVA showed that aerobic activities in the morning and evening have a significant effect on cognitive performance in older adults (F 14.17, p < 0.05); and the effects of exercise training in the evening hours are greater. Also, morning exercise was associated with a statistically significant reduction in TGF-beta and SPP1 levels (p < 0.05), whereas evening exercise significantly decreased TYROBP and sTREM2 levels (p < 0.01). Notably, APOE levels were markedly elevated in the evening exercise group, with a significant increase compared to the control group (p < 0.05) and the morning exercise group (p < 0.01). CONCLUSIONS: The findings suggest that a structured TPMP program, regardless of timing, can beneficially modulate key inflammatory markers associated with AD in women with T2DM. These results highlight the potential for exercise as a non-pharmacological intervention to mitigate AD risk in this vulnerable population.

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