Increased Glucose Levels Are Associated With Episodic Memory in Women
Objective. Patients with type 2 diabetes have an increased risk of a reduction in cognitive function. We investigated the hypothesis that plasma glucose is associated with a reduction in episodic and/or semantic memory already in nondiabetic subjects.
Research Design and Methods. We linked two large population-based datasets in Sweden: the Betula study, in which a random sample from the population aged 35–85 years was investigated for cognitive function, including episodic and semantic memory; and the Västerbotten Intervention Program, a health survey with subjects aged 40, 50, and 60 years, that includes measuring of fasting and 2-h plasma glucose, along with other risk factors for diabetes and cardiovascular disease. We identified 411 (179 men and 232 women, mean age 50.6 ± 8.0 years) nondiabetic subjects, free from dementia, who had participated in the two surveys within 6 months.
Results. Women had better episodic (score 7.37 ± 1.42) and semantic memory (score 16.05 ± 2.76) than men (score 6.59 ± 1.29 and 15.15 ± 2.92, respectively, P < 0.001 for both). In an adjusted multivariate model, fasting plasma glucose (fPG) and 2-h plasma glucose (2hPG) were significantly negatively associated with episodic memory (fPG: B –0.198, SE 0.068, β –0.209, P = 0.004; and 2hPG: B –0.061, SE 0.031, β –0.148, P = 0.048, respectively) in women but not in men. The association was not found in relation to semantic memory.
Conclusions. We conclude that an increase in plasma glucose is associated with impairment in episodic memory in women. This could be explained by a negative effect on the hippocampus caused by raised plasma glucose levels.

The association between type 2 diabetes and different forms of cognitive impairment is well established. The mechanism behind the association is, however, still unrevealed. There are at least two alternative ethiopathogenic mechanisms linking diabetes to cognitive dysfunction. The first is the atherosclerotic mechanism , leading to an increased risk of vascular dementia and Alzheimer's disease. The second mechanism is the effect of metabolic disturbances per se on brain function. Experimental studies in animals and humans have shown that poor glucose regulation is associated with poorer performance in cognitive tests. Also, recent studies on subjects with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) have reported a more profound cognitive decline than in subjects without IFG or IGT.

In contrast to previous studies that often used general cognitive processing as a dependent measure, we wanted to focus on a domain of cognition that is theoretically much developed, namely declarative memory as being composed of episodic and semantic memory. Episodic memory is more vulnerable to disturbances occurring in relation to diseases, including various metabolic conditions (rev. in ). To propose a theoretically tenable explanation of the effect of a disease or some medical/biological condition, it is often necessary to demonstrate dissociation between memory systems that are based on different neural correlates. It has often been the case that episodic and semantic memories reveal such dissociations (rev. in ). The basic reason for this variability in vulnerability is assumed to be the degree to which the hippocampus is involved in each task.

Thus, longstanding high glucose levels, defined as either IFG, IGT, or diabetes, have an impact on cognitive function. However, since the cutoffs for IFG, IGT, and diabetes are arbitrary, the aim was to use glucose level as a continuous variable in order to examine whether hyperglycemia in nondiabetic adults affects cognitive function when confounding factors are taken into account.