DEMENTIA

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, p