Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis

Abstract

Introduction: Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear.

Development: Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and β-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations.

Conclusions: Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment.

Keywords: Alzheimer's disease; Cerebral glucose metabolism; Diabetes mellitus de tipo 2; Diabetes mellitus type 2; Enfermedad de Alzheimer; Estrés oxidativo; Fármacos hipoglucémicos; Hypoglycaemic drugs; Insulin resistance; Metabolismo cerebral de la glucosa; Oxidative stress; Resistencia a la insulina.