title: Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Departamento de Neurología, Hospital Sirio Libanés, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: dominguezraulo@yahoo.com.ar.
authors.forename: R O
authors.initials: RO
authors.lastname: Domínguez
authors.affiliation: Departamento de Neurología, Hospital Juan A. Fernández, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: M A
authors.initials: MA
authors.lastname: Pagano
authors.affiliation: Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: E R
authors.initials: ER
authors.lastname: Marschoff
authors.affiliation: Departamento de Neurología, Hospital Sirio Libanés, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: S E
authors.initials: SE
authors.lastname: González
authors.affiliation: Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: M G
authors.initials: MG
authors.lastname: Repetto
authors.affiliation: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Bioquímica y Medicina Molecular (IBIMOL, UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: J A
authors.initials: JA
authors.lastname: Serra
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology*; D003072:Cognition Disorders / Q000209:etiology; D003704:Dementia / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D018384:Oxidative Stress
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