Plasma sDPP4 (Soluble Dipeptidyl Peptidase-4) and Cognitive Impairment After Noncardioembolic Acute Ischemic Stroke

Abstract

Background: DPP4 (dipeptidyl peptidase-4) inhibitors have been proven to promote neuronal regeneration, reverse the development of cognitive deficits. However, the association of circulating soluble form (sDPP4 [soluble DPP4]) with poststroke cognitive impairment (PSCI) is unclear. We aimed to investigate the association between plasma sDPP4 levels and PSCI in patients with ischemic stroke. Methods: A total of 600 noncardioembolic stroke patients were included based on a preplanned ancillary study from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used the Montreal Cognitive Assessment to evaluate cognitive function at 3 months follow-up after ischemic stroke. Binary logistic regression analyses were performed to investigate the association of plasma sDPP4 levels with subsequent PSCI. We further calculated integrated discrimination improvement and category-free net reclassification improvement to investigate the incremental prognostic effect of plasma sDPP4 beyond the basic model with conventional risk factors. Results: Plasma sDPP4 was inversely associated with PSCI after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartile of sDPP4 was 0.49 (0.29–0.81; P for trend=0.011). Each 1-SD increase of logarithm-transformed plasma sDPP4 concentration was associated with 17% (odds ratio, 0.83 [95% CI, 0.70–0.99]) lower risk of PSCI. Adding plasma sDPP4 to the basic model notably improved risk reclassification for PSCI, as shown by a category-free net reclassification improvement of 19.10% (95% CI, 2.52%–35.68%; P =0.03) and integrated discrimination improvement of 0.79% (95% CI, 0.13%–1.46%; P =0.02). Conclusions: Higher plasma sDPP4 levels were associated with decreased risk of cognitive impairment after noncardioembolic ischemic stroke.

Plasma Soluble Dipeptidyl Peptidase-4: A Possible Mechanism for Identifying and Managing Poststroke Cognitive Impairment

“…In those with preexisting dementia pathology, stroke may accelerate existing neurodegeneration. The association between sDPP4 and PSCI observed by You et al 4 was hypothesized to be related to the observed relationship between inhibition of DPP4 and low amyloid burden. The hypothesized pathway between higher sDPP4 and reduced PSCI was based on human cohort studies and animal studies suggesting an inverse relationship between DPP4 activity and concentrations of sDPP4.…”

“…DPP4 inhibitors have also recently emerged as a therapeutic agent of interest for trials of dementia prevention, possibly by reducing amyloid β peptide burden and tau phosphorylation. 3 In a recent study by You et al, 4 the authors demonstrated an association between high levels of the circulating sDPP4 and lower risk of PSCI in patients with a first ever noncardioembolic acute ischemic stroke. The results indicate a dual potential: the identification of a novel molecular biomarker to identify those at risk of PSCI, and a future mechanism for developing therapeutic treatments through an enhanced understanding of the pathogenesis of PSCI.…”