DPP-4 inhibitors for preventing post-stroke cognitive impairment in diabetic patients with acute ischemic stroke: a retrospective cohort study.

OBJECTIVE

To evaluate the preventive effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) on post-stroke cognitive impairment (PSCI) in patients with type 2 diabetes mellitus (T2DM) and concurrent acute ischemic stroke (AIS).

METHODS

A retrospective cohort study was conducted on 236 patients with T2DM+AIS recruited from April 2021 to October 2024. Patients were grouped based on DPP-4i use: an observation group (107 cases) with DPP-4i therapy and a control group (129 cases) without. Patients' baseline demographics, clinical features, laboratory indices, and follow-up data were extracted from the electronic medical record system. The primary outcome measure was the incidence of PSCI, defined as a Montreal Cognitive Assessment Scale (MoCA) score <26 at six months after AIS. Secondary outcomes included inflammatory cytokines, oxidative stress markers, neuroprotective factors (BDNF), glycemic metabolism indicators, and life quality [Barthel Index (BI), Functional Independence Measure (FIM), and Instrumental Activities of Daily Living (IADL)].

RESULTS

At 6 months after AIS, the incidence of PSCI was significantly lower in the observation group than in the control group (P<0.05). Furthermore, inflammatory and oxidative stress marker levels were decreased whereas BDNF level was significantly elevated in the observation group compared to the control group (all P<0.05). According to the quality-of-life assessment, patients receiving DPP-4i had higher BI, FIM, and IADL scores (P<0.05), along with a lower all-cause readmission rate (P<0.05). Subgroup analysis indicated that different DPP-4i types (e.g., sitagliptin, saxagliptin) had consistent cognitive protective effects (P>0.05).

CONCLUSION

DPP-4i can lower PSCI risk in T2DM+AIS patients. Its mechanism involves multi-dimensional effects like anti-inflammation, anti-oxidation, insulin sensitivity enhancement, and neuroprotection.