MRI OF NEURODEGENERATIVE DISEASE AMONG AGING CHAMORROS

Oregon Health And Science University, Portland OR

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Abstract

DESCRIPTION (provided by applicant): Among the Chamorro people of Guam amyotrophic lateral sclerosis (ALS), parkinsonism-dementia complex (PDC), and Mariana Dementia (MD), represents a unique continuum of neurodegenerative disorders that are clinically heterogeneous, but share a common pathologic substrate, neurofibrillary tangles (NFTs). These NFTs although similar to Alzheimer's disease in their predilection for medial temporal lobe regions are also commonly found in precentral gyrus of the frontal cortex. Importantly, the density of pathology in these regions exists as a continuum where Chamorros affected with PDC or MD harbor significant NFT pathology in all these regions while even those clinically unaffected by neurological disease harbor tau immunoreactive neurons and a few NFT in these same areas. Recently the first MRI scanner has been sited on Guam, offering the unprecedented opportunity to determine during life in an ethnically unique, population-based sample whether brain regions are selectively vulnerable to NFT pathology. This study proposes to establish whether regional brain volume changes assessed with MRI volumetrics can distinguish among and predict the major forms of dementia likely to affect Chamorro people. The study will further examine whether rates of brain volume loss differ among cognitively intact subjects and PDC and MD patients and if the volume changes predict cognitive decline in Chamorros at high risk for dementia, those with mild cognitive impairment. By evaluating groups with high NFT burdens such as Chamorros with a family history of PDC or MD, those of Chamorro ethnicity in general (versus Caucasians) and subjects with increased oxidative stress (measured by plasma and urine F2-isoprostane concentrations) we plan to determine whether rates of regional brain loss during life result from greater susceptibility to NFT pathology.