Thursday, 21 August 2003
This presentation is part of : Translational Research in Alzheimer Disease: From the Lab to the Clinic

S089-005 Differentiating Brain Glucose Metabolism in Normal Aging and AD

Vicente Ibanez, HUG, Geneva, Switzerland

Objective: The relationship of Alzheimer's disease (AD) and aging has been always of interest, since anatomopathological and metabolic alterations have been observed in both normal aging and AD. Decreases in volumes of neocortical gray matter and subcortical structures have been described in normal aging and AD. Correspondingly, increased cerebrospinal fluid (CSF) spaces also have been reported as evidence of cortical atrophy. The increase of the CSF space due to brain atrophy leads to an underestimation of glucose metabolism in PET studies. This study wishes to determine if regional glucose metabolism is reduced during aging and if the hypometabolism has the same cortical distribution than that in Alzheimer's disease when controlling for brain atrophy.

Design/Materials and Methods: We studied brain glucose metabolism using PET in 30 normotensive healthy adult volunteers and 15 AD patients. Normal volunteers were screened for neurological or psychiatric disorders or for other diseases that might contribute to brain dysfunction. For normals, two groups were considered on the basis of age, a young group (11 subjects, aged 22-34 years) and an old group (19 subjects, aged 55-84 years). All AD patients fulfilled the criteria for probable AD using the NINCDS-ADRDA guidelines. We excluded patients with possible cerebrovascular disease using the Hachinski ischemic scale.

Results: In the absence of the brain atrophy correction, the anterior insula, the lateral prefrontal cortex, the supratemporal gyrus, and the anterior cingulate cortex have significantly reduced regional glucose metabolism in the elderly. After correcting the metabolic values for the presence of atrophy, a statistically significant reduction in glucose metabolism remained only in the cingulate cortex. In AD patients, before correcting for the brain atrophy, regional glucose metabolism values were reduced in the inferior parietal cortex and the lateral temporal cortex. The posterior cingulate and the precuneus also had reduced glucose metabolism. Following correction, regional glucose metabolism remained significantly reduced in AD patients.

Conclusion: These analyses suggest that previously reported age declines in glucose metabolism in healthy subjects, if uncorrected for the atrophy, do not reflect intrinsic reductions in glucose metabolism, but only the effect of tissue loss. Conversely, in AD, the glucose hypometabolism is real and not an artifact due to atrophy. These results are consistent with the hypothesis that the hypometabolism observed in AD represents synaptic dysfunction in the affected regions. The few and small metabolic changes that are found in the elderly do not represent a prologue to metabolic changes observed in AD since the regional pattern of decreased glucose metabolism before correction for the atrophy in the elderly is very different from the pattern observed in Alzheimer's disease. In vivo imaging tools like magnetic resonance imaging (MRI) and positron emission tomography (PET) provide an opportunity to examine human brain structure and function in relation to age and dementia. Future research studies will benefit from the development of new imaging techniques for small animals, by allowing to in-vivo study the metabolic changes observed under different neuropharmacological experimental conditions.

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