Noura Mohammed, Tho Alyazan Khalil Taher Al-Jabali, Nuha Yassien, Iman Osman Abufatima, Fatima Omer Ibrahim Ahmed, Soukina El Yazal, Wehiba Satti, Nadine Alalamat, Mohammed Aamer Abkar Ibrahim, Basma Tirelbar, Leepy Paudel, Islam Abdalla Abdelsadig Mahmoud, Leama Humdi, Hajer Ali, Mohammed Hammad Jaber Amin, Nadir Abdelrahman
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.
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.