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

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 kg/m(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.