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

Abstract

ContextType 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.ObjectiveThis 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 Participants210 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 MeasureBaseline 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.ResultsHigher 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.ConclusionThese 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.

Glycated haemoglobin (HbA1c), diabetes and trajectories of change in episodic memory performance

“…However, several studies have suggested that higher glucose levels may contribute to cognitive deficits or decline among those without diabetes,4 6 10 a finding we could not confirm. Methodological variations may be at play.…”

“…High glucose levels among individuals with type 2 diabetes have been linked to poorer global cognition, verbal memory, and executive function2 and declines in global cognition and processing speed 3. Furthermore, elevated but clinically normal glucose levels have been linked to cognitive status in studies including individuals without diabetes4 10 and in studies that did not use diabetes classification 11 12. Among individuals without diabetes, it appears that this effect may be stronger in women than men, specifically in relation to memory performance 5 6…”

Clinical Characteristics for the Relationship between Type-2 Diabetes Mellitus and Cognitive Impairment: A Cross-Sectional Study

“…The mechanism of this phenomenon revealed that hyperglycemia might cause an increasing risk of microvascular disease and structural changes in the hippocampus [30]. Besides, Morby [31] pointed out that even among the elderly population with higher-blood glucose levels in the normal range, the frontal cortex could be impacted to result in impairment in working memory, executive function, information processing speed and language. Another research focusing on the relationship between MCI and diabetes suggested an association of MCI with diabetes mellitus in the aspects of onset, duration and severity [32].…”

Long-Term Subclinical Hyperglycemia and Hypoglycemia as Independent Risk Factors for Mild Cognitive Impairment in Elderly People

“…One study has even suggested that elderly people with relative high blood glucose level in normal range also suffer from cognitive impairment (Mortby et al 2013). Moreover, some studies have reported possible therapeutic effect of hypoglycemic measures on cognitive impairment (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group et al 2007;Luchsinger et al 2011), and repeated hypoglycemic episodes caused by inappropriate treatment may still cause the progression of dementia (Whitmer et al 2009).…”