This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary objective of this neuroimaging (NI) project is to identify brain correlates of memory decline and predictors of future decline using high field MR imaging and spectroscopy. Study participants were recruited from the Einstein Aging Study (EAS). Specific neuroimaging data included measurement of brain volume (estimates of gray-matter, white-matter, and ventricular system volumes) and volumetric measurements of the hippocampus, a region known to be involved in memory (0.75x1.0x1.5mm = 1.125mm3 pixel resolution). In addition, MR spectroscopy is used to measure the metabolic activity of nerve cells within the hippocampus. We hypothesized that during mild memory decline and during the preclinical onset of dementia nerve cell metabolism changes before nerve cells are lost; if this is correct, we predicted that nerve metabolism (as measured by hippocampal N-acetylaspartate (NAA) concentration ratio would change before volumetric measures decline. These measurements of NAA and the NAA /Creatine (NAA/CR) ratio have been applied in epilepsy, multiple sclerosis, stroke, amyotrophic lateral sclerosis and Alzheimer disease to localize disease and to provide an index of disease severity and volume. In this study we use volumetric and metabolic imaging to assess brain structure and function in individuals with an intermediate state of cognitive impairment that predicts AD and mixed dementia - Amnestic Cognitive Impairment (ACI) as well as matched controls. We did image individuals with Non-Amnestic Cognitive (NonACI) Impairment as proposed to focus resources on the more promising high risk group. Imaging measures will be used to predict the development of these intermediate states in cognitively normal individuals as well as to predict the development of AD and mixed dementia in normal subjects. We have completed 4 kinds of preliminary studies: 1. Hippocampal MRS data from 6 elderly Einstein Aging Study subjects with ACI, 4 elderly control subjects without ACI and 10 young adults. Although there is not sufficient power in the aged group to demonstrate a hemispheric difference between young and aged groups, combining the left and right hippocampal data is sufficient in this group to detect a significant difference between the aged and younger adult controls. 2. Correlations between spectroscopic and cognitive measures among elderly EAS subjects. We found in that spectral data from the left hippocampus was correlated with verbal memory (R=0.75, p0.015). As predicted, assessment of the right hippocampus found no significant relationship with category fluency. Right hippocampal spectral data correlated with the Blessed score (R=0.70, p0.025). With this small group of subject volunteers, no significant relationship was detected between performance and hippocampal volumetry. 3. Data on 17 control subjects demonstrating whole brain tissue segmentation. Both the total brain volume and the fractional gray matter volumes (GM/(CSF+GM+WM)) are in agreement with published values (Ge et al 2002, combined genders, under 50 years of age, 52.5% fraction gray). For women (n=7) the total brain volume was 1.27'b10.14, for men (n=10) this was 1.41'b10.15 liters. The fraction gray matter volume was 1.27'b10.14, for men (n=10) this was 1.41'b10.15 liters. The fraction of gray matter volume linearly decreases with age (R=0.51, p.04). 4. Data reproducibility of our spectroscopic data. Reproducibility is an important concern of any MR imaging and spectroscopic study. The hippocampus, in particular, is a region of significant structural variability. To assess the reproducibility of the spectroscopic study, we acquired repeated datasets (all acquired on separate days, up to 5 months apart) from four volunteers through the hippocampus and whole brain. Data were analyzed in terms of stability of the NAA/Cr measurement, hippocampal and whole brain volumetry. The reproducibility of the present data is approximately 10%. This compares well to other studies of reproducibility, which have found values of 10 to 22% (Maton et al, Chard et al). Nonetheless, given the importance of such measurements in the hippocampus, we will be improving the acquisition and analysis through implementation of voxel shifting methods. During the studies there were no adverse reactions. Three subjects were scheduled for imaging but did not participate because of claustrophobia (n= 2) or other reasons (n= 1).
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