Insulin resistance and risk of dementia and cognitive impairment in older Mexican Americans.

摘要

Type 2 diabetes is implicated as a risk factor for cognitive impairment in older ages, but the mechanisms for this association are uncertain. The role of diabetes, hyperinsulinemia, body fat distribution, and a polymorphism in the peroxisome proliferator-activated receptor-gamma gene, Pro 12Ala, in relation to incidence of cognitive impairment were examined in a cohort of 1,789 Mexican Americans. Participants were aged 60-101 at baseline in 1998-99 and residents of the Sacramento, California area. Dementia and 'cognitive impairment but not demented' (CIND) status were determined annually by a multi-stage assessment protocol. Incident cases of dementia and CIND were combined. Analyses were conducted using Cox proportional hazards regression. The hazard ratio (HR) relating diabetes to dementia/CIND after 4 years of follow-up was 2.7 (1.6, 4.8). In non-diabetic participants age 60-80 years at baseline, an increase of 10 muIU/mL of insulin was associated with an HR of 1.8 (1.2, 2.7) for dementia/CIND. A weak inverse relationship was observed between insulin and rate of dementia/CIND among non-diabetic participants older than age 80 at baseline (HR = 0.56; 0.16, 2.0). There was an increased rate of dementia/CIND among diabetic individuals for carriers of the Ala variant of the Pro12Ala polymorphism after 5 years of follow-up (HR = 2.1; 1.0, 4.4) and an increased rate for male carriers of an Ala allele (HR = 2.5; 1.2, 5.2) but not for females (HR = 0.74; 0.37, 1.5). Compared to those with body mass index 25.0 kg/m2, participants with a body mass index of 25.0-29.9 kg/m2 had a 48% decrease in rate of dementia/CIND (HR = 0.52; 0.30 to 0.91), while participants with body mass index ≥30 kg/m2 had a 61% decreased rate of dementia/CIND (HR = 0.39; 0.20, 0.78). There was a moderate positive association between waist circumference and dementia/CIND for the middle tertile of waist circumference compared to the lowest textile (HR = 1.8; 1.1, 3.1) and for those in the highest tertile compared to the lowest (HR = 1.9; 0.91, 3.8). The improvement of insulin sensitivity in older ages may have beneficial effects on cognitive health.