From diabetic foot to dementia: A neurovascular continuum linking systemic diabetic vasculopathy, cerebral small vessel disease, and glymphatic dysfunction - 19/07/26
Abstract |
Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is increasingly recognized as a major risk factor for cognitive decline and dementia. Epidemiological studies consistently demonstrate that individuals with diabetes exhibit a significantly elevated risk of both vascular cognitive impairment and Alzheimer’s disease [1,2]. Beyond hyperglycemia, systemic vascular dysfunction has emerged as a central mechanism underlying diabetes-related brain injury. Diabetes induces widespread vascular alterations, including endothelial dysfunction, arterial stiffening, oxidative stress, and chronic low-grade inflammation [3,4]. These processes affect both peripheral and cerebral circulation and may contribute to the development of cerebral small vessel disease (CSVD), a major substrate of cognitive decline [10–12]. Increased arterial stiffness may impair the Windkessel effect and facilitate the transmission of excessive pulsatile energy into fragile cerebral perforating arteries, thereby promoting microvascular injury and white matter damage [13–17]. In addition, diabetes-associated disruption of the neurovascular unit (NVU) may lead to blood–brain barrier dysfunction, neuroinflammation, and neuronal injury [20–30]. Impairment of the glymphatic system responsible for the clearance of metabolic waste products such as amyloid-β and tau may further contribute to neurodegenerative processes [31–41]. In this review, we propose a “systemic vascular continuum” linking peripheral diabetic vasculopathy, cerebral small vessel disease, neurovascular unit dysfunction, and glymphatic impairment. Within this framework, diabetic foot ulcer (DFU) is presented as a clinically visible peripheral phenotype and surrogate marker of advanced systemic vascular injury rather than a direct causal factor [5–9]. This integrative model provides a conceptual framework for understanding diabetes-associated cognitive impairment and highlights vascular-targeted preventive and therapeutic strategies as promising approaches for risk stratification and intervention.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Systemic vascular injury links diabetic complications to dementia. |
• | Arterial stiffness is associated with cerebral microvascular injury in diabetes. |
• | NVU disruption and glymphatic failure may promote Aβ accumulation. |
• | Diabetic foot ulcer reflects advanced neurovascular vulnerability. |
• | Targeting vascular pathways may prevent diabetes-related dementia. |
Plan
Vol 201
Article 119681- août 2026 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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