GHRH: COGNITION IN AGING AND MILD COGNITIVE IMPAIRMENT

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DESCRIPTION (provided by applicant): This is a revision of NIH grant application 1 R01 AG025515-01, GHRH: Cognition in Aging and Mild Cognitive Impairment. The societal burden of Alzheimer's disease (AD) and other primary neurodegenerative dementias is monumental, with total annual costs estimated at $100 billion (1996 dollars) per year in the United States. The need to identify and treat individuals as early as possible in the Alzheimer's disease process is clear, and justifies intensification of studies of individuals with Mild Cognitive Impairment (MCI) who are at risk for progression to dementia within a few years. The FDA's recent hearings on the suitability of MCI as an indication for pharmacotherapy are major indicators of its importance as a public health concern. There is considerable and compelling evidence in the literature that the actions of the somatotrophic (growth hormone releasing hormone/ growth hormone/insulin-like growth factor I) hormonal axis have significant and predictable beneficial impact on cognitive function. Supplementation of the somatotrophic axis may likely be of direct benefit to individuals such as those with MCI, who are experiencing a mild but significant cognitive impairment and who may be at particular risk for continued cognitive decline and progression into AD. We have recently shown that a five-month growth hormone releasing hormone (GHRH) treatment improves cognitive function in healthy older men and women and preliminary evidence supports the expectation of a similar effect in individuals with MCI. We believe it important to replicate and significantly extend our initial GHRH finding in healthy older adults, using a much more comprehensive cognitive assessment battery, which includes measures of memory not included in our preliminary study. We also believe it crucial to extend our examination of the cognitive function enhancing effects of GHRH to a sample of older adults with MCI. Therefore we propose to conduct a prospective, double-blind, randomized placebo-controlled study of the effects of GHRH on the cognitive function of 80 healthy normal older men and women and of 80 older men and women diagnosed with MCI.