A prospective analysis of elevated fasting glucose levels and cognitive function in older people: results from PROSPER and the Rotterdam Study

Abstract

Objective: To investigate the relationship between fasting glucose levels, insulin resistance, and cognitive impairment in old age. Diabetes is associated with cognitive impairment in older people. However, the link between elevated fasting glucose levels and insulin resistance in nondiabetic individuals, and the risk of cognitive impairment is unclear.

Research design and methods: We analyzed data from, in total, 8,447 participants in two independent prospective studies: the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5,019 participants, aged 69-84 years, and the Rotterdam Study, 3,428 participants, aged 61-97 years. Fasting glucose levels were assessed at baseline in both studies; fasting insulin levels were assessed in the Rotterdam Study only. Cognitive function was assessed in both studies at baseline and during follow-up.

Results: Subjects with diabetes had impaired cognitive function at baseline. In contrast, in people without a history of diabetes, there was no clear association between baseline fasting glucose levels and executive function and memory, nor was there a consistent relationship between elevated baseline fasting glucose levels and the rate of cognitive decline in either cohort. Insulin resistance (homeostasis model assessment index) was also unrelated to cognitive function and decline.

Conclusions: Elevated fasting glucose levels and insulin resistance are not associated with worse cognitive function in older people without a history of diabetes. These data suggest either that there is a threshold for effects of dysglycemia on cognitive function or that factors other than hyperglycemia contribute to cognitive impairment in individuals with frank diabetes.

FIG. 1.

A: Fasting glucose levels and cognitive function. z scores (SEM) for different cognitive test scores are plotted for study-specific quintiles of fasting glucose levels in nondiabetic participants (from lowest [quintile 1] to the highest [quintile 5] levels of fasting glucose) and for participants with a history of diabetes (DM). P values reflect the trend over the quintiles of fasting glucose levels, as well as the difference between participants without a history of diabetes (n = 7,592) and participants with a history of diabetes (n = 855). Estimates are based on the maximum number of participants available per cognitive test: global cognitive function (n = 8,447), WFT (n = 3,518), and 12-PLT (n = 5,223). B: Fasting glucose levels and change in cognitive function. z scores (SEM) represent annual change in cognitive test scores for study-specific quintiles of fasting glucose levels in nondiabetic participants (from lowest [quintile 1] to the highest [quintile 5] levels of fasting glucose) and for participants with a history of diabetes. P values reflect the trend over the quintiles of fasting glucose levels, as well as the difference between participants without a history of diabetes (n = 6,649) and participants with a history of diabetes (n = 719). Estimates are based on the maximum number of participants available per cognitive test: global cognitive function (n = 7,368), WFT (n = 2,639), and 12-PLT (n = 4,960). Linear mixed models were used, adjusted for age, sex, level of education, study (PROSPER or Rotterdam Study), BMI, HDL level, systolic blood pressure, diastolic blood pressure, country, treatment group, and test version where applicable.

FIG. 2.

A: Insulin resistance (HOMA) and cognitive function in the Rotterdam Study. z scores (SEM) for different cognitive test scores are plotted for quintiles of insulin resistance (HOMA) in nondiabetic participants (from lowest [quintile 1] to the highest [quintile 5] levels of insulin resistance [HOMA]) and for participants with a history of diabetes (DM). P values reflect the trend over the quintiles of fasting glucose levels, as well as the difference between participants without a history of diabetes (n = 3,039) and participants with a history of diabetes (n = 303). Estimates are based on the maximum number of participants available per cognitive test: global cognitive function (n = 3,342) and WFT (n = 3,424). B: Insulin resistance (HOMA) and change in cognitive function. z scores (SEM) represent annual change in cognitive test scores for quintiles of insulin resistance (HOMA) in nondiabetic participants (from lowest [quintile 1] to the highest [quintile 5] levels of insulin resistance [HOMA]) and for participants with a history of diabetes. P values reflect the trend over the quintiles of fasting glucose levels, as well as the difference between participants without a history of diabetes (n = 2,331) and participants with a history of diabetes (n = 203). Estimates are based on the maximum number of participants available per cognitive test: global cognitive function (n = 2,534) and WFT (n = 2,567). Linear mixed models were used, adjusted for age, sex, level of education, BMI, HDL level, systolic blood pressure, and diastolic blood pressure.