High “Normal” Blood Glucose Is Associated with Decreased Brain Volume and Cognitive Performance in the 60s: The PATH through Life Study

CONTEXT: Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes. OBJECTIVE: This study aimed to determine whether blood glucose levels in the normal range (<6.1 mmol/L) were associated with cerebral volumes in structures other than the hippocampus and amygdale, and whether these glucose-related regional volumes were associated with cognitive performance. DESIGN, SETTING AND PARTICIPANTS: 210 cognitively healthy individuals (68–73 years) without diabetes, glucose intolerance or metabolic syndrome were assessed in the large, community-based Personality and Total Health Through Life (PATH) study. MAIN OUTCOME MEASURE: Baseline blood glucose levels in the normal range (3.2–6.1 mmol/l) were used to determine regional brain volumes and associated cognitive function at wave 3. RESULTS: Higher blood glucose levels in the normal range were associated with lower grey/white matter regional volumes in the frontal cortices (middle frontal gyrus, inferior frontal gyrus precentral gyrus). Moreover, identified cerebral regions were associated with poorer cognitive performance and the structure-function associations were gender specific to men. CONCLUSION: These findings stress the need to re-evaluate what is considered as healthy blood glucose levels, and consider the role of higher normal blood glucose as a risk factor for cerebral health, cognitive function and dementia. A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia.