Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly

Abstract

Poor glucose tolerance and memory deficits, short of dementia, often accompanies aging. The purpose of this study was to ascertain whether, among nondiabetic, nondemented middle-aged and elderly individuals, poorer glucose tolerance is associated with reductions in memory performance and smaller hippocampal volumes. We studied 30 subjects who were evaluated consecutively in an outpatient research setting. The composition of the participant group was 57% female and 68.6 ؎ 7.5 years of age; the participants had an average education of 16.2 ؎ 2.3 years, a score on the Mini Mental State Examination of 28.6 ؎ 1.5, a glycosylated hemoglobin (HbA1C) of 5.88 ؎ 0.74%, and a body mass index of 24.9 ؎ 4.1 kg͞m 2 . Glucose tolerance was measured by an i.v. glucose tolerance test. Memory was tested by using the Wechsler Paragraphs recall tests at the time of administering the i.v. glucose tolerance test. The hippocampus and other brain volumes were measured by using validated methods on standardized MRIs. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. These associations were independent of age and Mini Mental State Examination scores. Therefore, these data suggest that metabolic substrate delivery may influence hippocampal structure and function. This observation may bring to light a mechanism for aging brain injury that may have substantial medical impact, given the large number of elderly individuals with impaired glucose metabolism.T wenty-five percent of individuals over 65 years of age have sufficient cognitive problems, short of dementia, to affect the quality of their lives (1, 2). The ability to learn consciously and recall new information, which is known as recent or declarative memory, is one of the areas most affected during aging. However, our knowledge about the medical factors that predispose a person to age-associated cognitive problems remains undeveloped.There is a growing literature indicating that individuals with diabetes have impairments in recent memory (3-6). In addition, nondiabetic individuals with mild forms of impaired glucose tolerance (IGT) may also have cognitive impairments (7,8). The prevalence of memory problems and IGT rise with age (1, 9, 10). In addition to genetic predisposition, obesity and low levels of physical activity have been identified as risk factors for IGT in adults and children (11,12). With life expectancy and obesity on the rise, the prevalence of memory dysfunction and IGT will likely continue to climb. However, it remains to be established whether there are associations between peripheral glucose regulation and memory performance among nondemented middleaged and elderly individuals.The hippocampus, a brain structure deep in the temporal lobe, is key for recent memory formation (13-15). Hypothalamuspituitary-adrenal axis hyperactivity have been associated with hippocampal atrophy in aging (16) and in Cushing's disease (1...

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

“…Perhaps it is this key difference between type 1 and type 2 diabetes that contributes to the differential brain consequences of these two disorders. This position is, in part, supported by our prior data showing associations between insulin resistance and lower memory performance and hippocampal volumes among non-diabetic individuals [22].…”

“…For example, improvements in diabetes control have been associated with improvements in cognitive functioning [19,20]. In addition, deficits in learning and memory have also been described among non-diabetic individuals with insulin resistance (for example [21,22]), even after accounting for the possible effects of atherosclerosis [23].…”

Glucose enhancement of human memory: A comprehensive research review of the glucose memory facilitation effect

“…However, blood glucose typically remains higher for a longer period in individuals with poor glucose regulation (Donohoe and Benton, 2000). Poor glucoregulation is associated with memory impairment in both aged humans (Convit, 2005;Convit et al, 2003;Dahle et al, 2009;Kaplan et al, 2000;Lamport et al, 2009;Messier, 2005;Messier et al, 1997;Messier et al, 2003;Riby et al, 2004) and rodents (Greenwood and Winocur, 2001;Winocur, 1995). On a related note, brain glucose metabolism (including reduced and slowed capacity for facilitated glucose transport across the blood-brain barrier) is also known to become impaired as a consequence of ageing (Convit, 2005;Korol and Gold, 1998).…”

Pioglitazone does not increase cerebral glucose utilisation in a murine model of Alzheimer’s disease and decreases it in wild-type mice

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