Modifiers of cognitive function and brain structure in middle-aged and elderly individuals with type 2 diabetes mellitus

Abstract

Cognitive deficits and hippocampal atrophy, features that are shared with aging and dementia, have been described in type 2 diabetes mellitus (T2DM). T2DM is associated with obesity, hypertension, dyslipidemia, hypothalamic pituitary adrenocortical (HPA) axis abnormalities and inflammation, all of which have been shown to negatively impact the brain. However, since most reports in T2DM focused on glycemic control, the relative contribution of these modifying factors to the impairments observed in T2DM remains unclear. We contrasted 41 middle-aged dementia-free volunteers with T2DM (on average 7 years since diagnosis) with 47 age-, education-, and gender-matched non-insulin resistant controls on cognition and brain volumes. HPA axis activity and other modifiers that accompany T2DM were assessed to determine their impact on brain and cognition. Individuals with T2DM had specific verbal declarative memory deficits, reduced hippocampal and prefrontal volumes, and impaired HPA axis feedback control. Diminished cortisol suppression after dexamethasone and dyslipidemia were associated with decreased cognitive performance, whereas obesity was negatively related to hippocampal volume. Moreover, prefrontal volume was influenced by worse glycemic control. Thus, obesity and altered cortisol levels may contribute to the impact of T2DM on the hippocampal formation, resulting in decreased verbal declarative memory performance.

Association Between Diabetes and Hippocampal Atrophy in Elderly Japanese: The Hisayama Study

“…For the other potential mechanisms, diabetes may cause brain atrophy as a result of microvascular ischemic disease (2) or elevated cortisol levels by the impaired feedback mechanism in the hypothalamicpituitary-adrenal axis (23). Since it is reported that the hippocampus is more vulnerable to hypoglycemia, hypoxia (24,25), and elevated cortisol levels (23) than other brain regions, atrophy may occur more predominantly in the hippocampus compared with other brain regions.…”

Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation

“…Cognitive dysfunction due to diabetes have been reported previously [11,12]. A recent study revealed that the increased oxidative stress in diabetes produces oxidative damage in many regions of rat brain including the hippocampus [13].…”

Central lipid detection and the regulation of feeding behavior

“…We can suppose that nutritional lipids present in HF, HFHS and cafeteria diet could directly modulate mesolimbic system and may contribute to a further attenuation of mesolimbic responsivity to food, as it is suspected in other brain areas. In fact, there is increasing evidence that obesity is associated with impairment on certain cognitive function, such as executive function, attention and memory (Gunstad et al, 2007;Bruce-Keller et al, 2009;Bruehl et al, 2009). Although co-morbid medical conditions (cerebrovascular pathology, hypertension and diabetes) are known to affect cognition adversely, there is also evidence that high BMI, by itself, might impair various cognitive domains particularly executive function (Gunstad et al, 2007) which could be explain by a lower baseline prefrontal (OFC included) metabolism (Volkow et al, 2009).…”