Thursday, October 25, 2012

Brain Imaging Surrogate Markers for Detection and Prevention of Cognitive Aging and Alzheimer's Disease

       With increasing knowledge of the neuropathological and cognitive changes preceding Alzheimer's disease (AD), clinical trials have begun to focus on preventive treatments aimed at slowing age-related cognitive decline and delaying onset of AD.

      Studying participants with minimal deficits leads to diagnostic heterogeneity and a need for larger samples in order to detect active drug effects. This chapter summarizes results of several studies designed to address such issues. Middle-aged and older adults with mild memory complaints were studied using brain imaging and measures of the major known genetic risk for AD, the apolipoprotein E-4 (apo E-e4) allele.

      In a study of positron emission tomography during mental rest, glucose metabolic rates were significantly lower in apo E-e4 carriers in brain regions affected by AD. Another study using functional magnetic resonance imaging showed increased brain activation during memory tasks in apo E-e4 carriers in similar brain regions. Longitudinal follow-up after 2 years indicated the potential utility of such brain-imaging measures, combined with genetic-risk information, as surrogate markers in prevention-treatment trials for cognitive aging and AD.

      Additional development of novel approaches using positron emission tomography to directly measure the neuritic plaques and neurofibrillary tangles of AD offers promise of more specific measures of disease progression in future clinical trials.

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