Lower Cerebral Metabolic Rate Of Glucose Research Articles

Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures.

Brain and systemic glucose metabolism in the healthy elderly following fish oil supplementation

Cerebral metabolic rate of glucose (CMRg) is lower in individuals affected by cognitive decline and dementia, especially in Alzheimer's disease. However, as yet there is no consensus as to whether CMRg decreases during healthy aging. Epidemiological studies show that weekly consumption of fish abundant in ω3 fatty acids has a protective effect on cognition during aging. Thus, the primary objective of this human study was to use positron emission tomography analysis with 18F-fluorodeoxyglucose to evaluate whether supplementation with a fish oil rich in ω3 fatty acids increases cerebral glucose metabolism in young or elderly adults. Healthy young (23±5y old; n=5) and elderly (76±3y old; n=6) women and men were included in the study. Semi-quantitative expression of the data as ‘standardized uptake values’ showed that elderly participants had significantly lower cerebral glucose metabolism compared with the young group. However, when expressed quantitatively a CMRg, there was no effect of age or ω3 supplementation on glucose metabolism in any of the brains regions studied. Higher plasma triglyceride levels and higher plasma insulin levels were associated with lower CMRg in several regions, suggesting that a trend towards the metabolic syndrome may be associated with cerebral hypometabolism. We conclude that under these experimental conditions, ω3 supplementation did not affect brain glucose metabolism in the healthy elderly. Future studies in this area should address whether glucose intolerance or other conditions linked to the metabolic syndrome impact negatively on brain glucose metabolism and cognition.

Hypometabolism in Alzheimer-Affected Brain Regions in Cognitively Healthy Latino Individuals Carrying the Apolipoprotein E ε4 Allele

To investigate with fluorodeoxyglucose positron emission tomography whether regional reductions in the cerebral metabolic rate for glucose (CMRgl) previously found in cognitively healthy late-middle-aged apolipoprotein E (APOE) epsilon4 carriers extend to members of the Latino Mexican American community. Prospective cohort study. Banner Alzheimer's Institute, Phoenix, Arizona. Eleven APOE epsilon4 carriers and 16 noncarriers from Arizona's Latino community (mean [SD] age, 54.6 [6.4] years) matched for sex, mean age, and educational level and who were predominantly of self-designated Mexican origin. A brain mapping algorithm was used to compare cross-sectional regional CMRgl in Latino APOE epsilon4 carriers vs noncarriers. Participant groups had similar distributions for age, sex, education, family history of dementia, clinical ratings, and neuropsychological test scores. Latino APOE epsilon4 carriers had lower CMRgl than the noncarriers in the posterior cingulate, precuneus, and parietal regions previously found to be preferentially affected in patients with Alzheimer disease (AD) and cognitively healthy non-Latino APOE epsilon4 carriers. Additionally, the Latino APOE epsilon4 carriers had lower CMRgl in the middle and anterior cingulate cortex, hippocampus, and thalamus. This study provides support for the relationship between APOE epsilon4 and risk of AD in Latino individuals. It illustrates the role of positron emission tomography as a presymptomatic endophenotype for the assessment of AD risk factors and supports the inclusion of Latino APOE epsilon4 carriers in proof-of-concept studies using fluorodeoxyglucose PET to evaluate promising presymptomatic treatments in cognitively healthy carriers of this common AD susceptibility gene.

P2-037: Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer's disease neuroimaging initiative

Alzheimer's disease (AD) is characterized by regional reductions in fluorodeoxyglucose positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl), which are correlated with clinical severity, progressive and apparent before the onset of dementia or mild cognitive impairment (MCI). We have been using statistical parametric mapping (SPM) to analyze PET data from probable AD patients, amnestic MCI (aMCI) patients and normal controls (NC) from the AD Neuroimaging Initiative (ADNI). Our objective was to characterize patterns of cerebral hypometabolism in probable AD and aMCI, and correlate lower Mini-Mental State Examination (MMSE) scores with lower regional CMRgl in both the overall cohort of probable AD, aMCI and NC subjects and the probable AD group. Baseline PET images from 298 subjects, including 74 probable AD (age 70±10, MMSE 23.5±2.2), 142 aMCI (age 67±12, MMSE 27.1±1.7) and 82 NC (69±10 years old, MMSE 28.9±1.1), were analyzed on a voxel-by-voxel basis using SPM5. ANOVA with pair-wise comparisons contrasted regional CMRgl in the three subject groups. Linear regression correlated lower MMSE scores with lower CMRgl in the overall cohort and probable AD group. Compared to NC, the probable AD and aMCI groups each had lower CMRgl bilaterally in previously characterized posterior cingulate, precuneus, and parietotemporal regions (P<0.05 corrected for multiple comparisons), and occipital cortex, hippocampus, parahippocampal gyrus and fusiform gyrus (uncorrected P<0.005). Compared to NC, the probable AD group had lower CMRgl in frontal regions (corrected P<0.05). In the overall cohort, lower MMSE scores were correlated with lower CMRgl in the posterior cingulate, precuneus, parietotemporal and frontal regions (P<0.05, corrected for multiple comparisons). In the probable AD group, lower MMSE scores were correlated with lower CMRgl in left frontal and temporal regions (uncorrected P<0.001). Findings from this large multi-center study confirm the previously characterized pattern of regional hypometabolism in AD and aMCI and implicate additional brain regions. Furthermore, they confirm the previously characterized correlation between severity of clinical impairment in a combined group of patients and controls, but suggest strongest correlations between clinical severity of frontal and temporal regions by the time AD patients satisfy criteria for dementia.

Correlations between apolipoprotein E ε4 gene dose and brain-imaging measurements of regional hypometabolism

Patients with Alzheimer's disease (AD) have abnormally low positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) in regions of the precuneus and the posterior cingulate, parietotemporal, and frontal cortex. Apolipoprotein E (APOE) epsilon4 gene dose (i.e., the number of epsilon4 alleles in a person's APOE genotype) is associated with a higher risk of AD and a younger age at dementia onset. We previously found that cognitively normal late-middle-aged APOE epsilon4 carriers have abnormally low CMRgl in the same brain regions as patients with probable Alzheimer's dementia. In a PET study of 160 cognitively normal subjects 47-68 years of age, including 36 epsilon4 homozygotes, 46 heterozygotes, and 78 epsilon4 noncarriers who were individually matched for their gender, age, and educational level, we now find that epsilon4 gene dose is correlated with lower CMRgl in each of these brain regions. This study raises the possibility of using PET as a quantitative presymptomatic endophenotype to help evaluate the individual and aggregate effects of putative genetic and nongenetic modifiers of AD risk.