Microvascular damage in diabetic nephropathy and the subsequent risk of Alzheimer’s disease: a systematic review

Abstract

Introduction: Diabetic nephropathy (DN), a major microvascular complication of diabetes, is increasingly implicated in systemic vascular dysfunction and may contribute to the pathogenesis of Alzheimer’s disease (AD). Microvascular injury is a recognized mechanism in AD, and DN-related damage may raise the risk of cognitive decline. Methods: Following the PRISMA 2020 guidelines, we searched PubMed, Scopus, and the Cochrane Library (2000–2025) for studies on DN-related vascular damage and cognitive outcomes. Quality was assessed using the Newcastle–Ottawa Scale and the AXIS tool. Results: Of 275 records, nine studies were included (cross-sectional and longitudinal, with up to 37.5 years of follow-up). DN was measured via eGFR, albuminuria, the fibrinogen-to-albumin ratio, or ICD codes; cognition via assessed using amyloid PET, neurocognitive tests, or registry data. All studies found that impaired kidney function was associated with a greater risk of AD or cognitive decline. Conclusion: Available evidence links DN-related microvascular damage to a higher risk of AD, suggesting a kidney–brain axis. However, causality remains uncertain and requires longitudinal and mechanistic studies to clarify these pathways.