Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly (original) (raw)
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Evidence for brain glucose dysregulation in Alzheimer's disease
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2017
It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before...
Altered glycemia and brain—update and potential relevance to the aging brain
Hyperglycemia characterizes diabetes mellitus and is linked to its chronic and acute complications. Cognitive dysfunction in diabetes occurs especially in longstanding disease and with poor glycemic control. Recent data in humans suggests that hyperglycemia causes acute cognitive dysfunction. The underlying mechanisms are unknown but deserve further research as diabetes is becoming epidemic and will likely contribute increasingly to premature cognitive decline. The primary side effect of diabetes treatment is hypoglycemia, particularly resulting from insulin treatment. CNS adaptations to acute and chronic hypoglycemia underlie the inability of some people to promptly recognize and defend against the risk of serious hypoglycemia. Data from human and animal models may help explain how altered glycemia affects brain function both acutely and chronically. Improved mechanistic understanding of altered glycemia's effects could prevent the adverse impact of diabetes upon the CNS and give new insights into effects that may exist in normal aging.
(Pre)diabetes, brain aging, and cognition
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2009
We are glad to have our review pre-accepted for publication at BBAmolecular Basis of Disease. We have answered the points raised by the reviewers and we did the modifications suggested by them. We hope the revised paper is now in a proper form to publication at BBA -Molecular Basis of Disease. We look forward receiving your final decision. Yours sincerely, Matheus Roriz-Cruz (and coworkers) ABSTRACT Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of Diabetes Mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's Disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 Diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic Hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory
Impaired glucose tolerance in midlife and longitudinal changes in brain function during aging
Neurobiology of Aging, 2013
We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cognitively normal participants in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging underwent serial 15 O-water positron emission tomography scans (age at first scan, 69.6 AE 7.5 years) and oral glucose tolerance tests 12 years earlier (age at first oral glucose tolerance test, 57.2 AE 11.1 years). Using voxel-based analysis, we compared changes in rCBF over an 8-year period between 15 participants with IGT in midlife and 49 with NGT. Significant differences were observed in longitudinal change in rCBF between the IGT and NGT groups. The predominant pattern was greater rCBF decline in the IGT group in the frontal, parietal, and temporal cortices. Some brain regions in the frontal and temporal cortices also showed greater longitudinal increments in rCBF in the IGT group. Our findings suggest that IGT in midlife is associated with subsequent longitudinal changes in brain function during aging even in cognitively normal older individuals.
Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study
Neurology, 2012
Substantial evidence showing an association between type 2 diabetes (T2D) and cerebral atrophy, cognitive impairment, and dementia is accumulating. However, relatively little is known about the subclinical effects of high plasma glucose levels within the normal range. The aim of this study was to investigate the association between plasma glucose levels and hippocampal and amygdalar atrophy in a sample of 266 cognitively healthy individuals free of T2D, aged 60-64 years, taking part in a longitudinal study of aging. Fasting plasma glucose was assessed at wave 1. Hippocampal and amygdalar volumes were manually traced on 1.5 T MRI scans collected at wave 1 and at wave 2-4 years later. General linear model analyses were used to assess the relationship between plasma glucose and incident medial temporal lobe atrophy after controlling for a range of sociodemographic and health variables. Plasma glucose levels were found to be significantly associated with hippocampal and amygdalar atrophy and accounted for 6%-10% in volume change after controlling for age, sex, body mass index, hypertension, alcohol, and smoking. High plasma glucose levels within the normal range (<6.1 mmol/L) were associated with greater atrophy of structures relevant to aging and neurodegenerative processes, the hippocampus and amygdala. These findings suggest that even in the subclinical range and in the absence of diabetes, monitoring and management of plasma glucose levels could have an impact on cerebral health. If replicated, this finding may contribute to a reevaluation of the concept of normal blood glucose levels and the definition of diabetes.
Glycemic Status and Brain Injury in Older Individuals
Diabetes Care, 2009
OBJECTIVE To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility–Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose ≥7.0 mmol/l [11.1%]); impaired fasting glucose (IFG) (fasting blood glucose 5.6–6.9 mmol/l [36.2%]); and normoglycemic (52.7%). Outcomes were total brain volume, white and gray matter volume, white matter lesion (WML) volume, and presence of cerebral infarcts. RESULTS After adjustment for demographic and cardiovascular risk factors, participants with type 2 diabetes had significantly lower total brain volume (72.2 vs. 71.5%; P < 0.001) and lower gray and white matter volumes (45.1 vs. 44.9%, P < 0.01 a...
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identified using the scaled subprofile model/principal component analysis method, and cross-validations were conducted in both independent cohorts. A survival analysis was further conducted to calculate the predictive effect of conversion risk by using ARGMPs. The results showed that ARGMPs were characterized by hypometabolism with increasing age primarily in the bilateral medial superior frontal gyrus, anterior cingulate and paracingulate gyri, caudate nucleus, and left supplementary motor area and hypermetabolism in part of the left inferior cerebellum. The expression network scores of ARGMPs were significantly associated with chronological age (R = 0.808, p < 0.001), which was validated in both the ADNI and Xuanwu cohorts. Individuals with higher network scores exhibited a better predictive effect (HR: 0.30, 95% CI: 0.1340 ~ 0.6904, p = 0.0068). These findings indicate that ARGMPs
Magnetic Resonance Imaging, 2006
Glucose is the primary source of energy for brain cells. Because energy storage in the brain is limited, an uninterrupted supply of glucose and its rapid metabolism are essential for normal cognitive function. This study utilized an oral glucose load to examine hippocampal glucose metabolism in early Alzheimer's disease (AD)-a disease characterized by progressive deterioration of cognitive function and glucose hypometabolism. Short echo time 1 H MR spectra (20 ms) from the right hippocampus of 8 patients with probable AD, 14 healthy elderly and 14 healthy young adults were compared pre-and post-glucose loading. In contrast to the healthy adults, the AD patients exhibited significantly elevated hippocampal glucose concentrations post-glucose ingestion relative to baseline (P b.01). These results suggest that cerebral glucose hypometabolism in AD leads to an increased steady-state concentration of cerebral glucose. This research demonstrates the feasibility of studying cerebral glucose metabolism in AD with 1 H MR spectroscopy.