death in Australia and a risk factor for cardiovascular disease.Currently, there are no disease modifying drugs available for dementia as the underlying causes are unclear.The pathogenesis of cognitive impairment in PKD is unknown, however periperial inflammation and vascular changes have been suggested to play a role.Therefore, the hypothesis of this study is to establish the first rat model of PKDinduced cognitive impairment and elucidate potential mechanisms that can contribute to the development of cognitive impairment.Methods: Male and female Lewis wild-type (WT) and Lewis polycystic kidney (LPK) rats were studied at 6, 12 and 18 weeks of age.Blood pressure was measured by tail cuff.Cognition was assessed using the novel object recognition and Y-maze tests.Aortic thickening was assessed using histology.Inflammation was measured using flow cytometry.Results: LPKs had higher blood pressure compared to WT from 6 weeks (1781 mmHg vs 1321 mmHg, n=10, P<0.05) which was maintained at 12 and 18 weeks.LPK rats had heavier kidneys (P<0.001),hearts (P<0.05) and impaired kidney function (P<0.001).The thickness of the abdominal aortic wall increased in LPKs compared to WT from 6 weeks (0.360.01 mM vs 0.320.005mM, n=9-10, P<0.05) to 18 weeks (0.640.06 mM vs 0.350.03mM, n=6-7, P<0.05).Compared to WT, kidney T cells and macrophages were increased in LPKs at 6 weeks by 1.5-fold, and 12 weeks by 2.3-and 1.9fold respectively (n=8-10, P<0.05).At 18 weeks, kidney T cells were similar between LPKs and WT while LPK kidney macrophages were reduced by 4-fold (n=8-10, P<0.05).LPK rats had intact recognition memory but spatial working memory was impaired at 12 and 18 weeks of age (n=9-10, P<0.05).Conclusion: Cognitive impairment was observed in a rat model of PKD from 12 weeks of age after the onset of hypertension, aortic thickening and kidney inflammation.Aortic thickening is a marker of aortic stiffening which can promote cognitive impairment in other disease settings.The hypertension, aortic thickening and kidney inflammation may have contributed to the development of the cognitive impairment in this rat model of PKD.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.
Koike et al. (Wed,) studied this question.