Robert Krikorian - US grants

DESCRIPTION (provided by applicant): Estrogens produce a multitude of complex effects in the brain by means of a variety of mechanisms. Accumulating data has indicated that these actions mediate enhancing effects on cognition and mood as well as perhaps prophylaxis against age-and disease-related cognitive-cerebral decline. Phytoestrogens have demonstrated estrogenic activity. They have been studied with respect to benefits for cardiovascular function, preservation of bone, and reduction of risk for cancer, but there is little prospective research regarding effects on mental function. In addition, phytoestrogens generally are not prescribed by practitioners for mental health effects. However, many women experiencing peri-and post-menopausal symptoms consume marketed phytoestrogens, in particular soy-derived isoflavone products, under the perception of general health benefits, including presumably enhanced mental function. The goal of this exploratory research is to develop preliminary data regarding the efficacy of isoflavone phytoestrogens in producing improvement in cognitive function in late middle-aged and elderly postmenopausal women with symptoms of memory impairment and, therefore, increased risk for development of progressive dementia such as Alzheimer?s Disease. A secondary goal will be to examine changes in basal cortisol levels, as a means of assessing the effect of the intervention on an endocrine parameter that has significance for hippocampal function, particularly in the aged. We will administer a 16-week protocol of isoflavone supplementation in a randomized, double-blind, placebo-controlled study to menopausal women aged 55 to 75 years with forgetfulness and other symptoms of cognitive decline, but who do not meet criteria for probable dementia. We will assess changes in neuropsychological measures of executive function ability and episodic memory, in basal cortisol levels, and in mood. It is our expectation that the demonstration of positive responses to this intervention in this at-risk population will establish the basis for future, more comprehensive studies of dosage, mechanisms, and duration of effect. Ultimately, such research may establish the basis for the use of isoflavones as an alternative treatment that would provide mental and general health benefits without the risks associated with traditional hormone replacement therapies.

[unreadable] DESCRIPTION (provided by applicant): This grant application seeks support to develop preliminary data concerning a behavioral intervention aimed at ameliorating age-associated cognitive decline. It will investigate the effect of an aerobic fitness intervention on cognitive function in elderly individuals with Mild Cognitive Impairment (MCI). MCI has been recognized as a transitional condition in the development of Alzheimer's Disease (AD). Recent studies have shown that aerobic exercise potentiates neurogenesis in the hippocampus and neocortex and enhances cognitive abilities mediated by these brain structures in elderly adults. Exercise also has been shown to increase neurotrophic factors. Furthermore, inverse relationships have been observed in the aged between glucocorticoid levels and hippocampal and neocortical integrity, and elevations of cortisol have been implicated in AD. We propose an exploratory study evaluating the efficacy of an aerobic exercise intervention in enhancing cognitive function in MCI. A secondary goal is assessment of the effect of the intervention on modulation of basal cortisol level, an indirect index of hippocampal and neocortical integrity. In a randomized, controlled study, we will conduct a 12-week aerobic conditioning program with previously sedentary men and women with Mild Cognitive Impairment. We will investigate changes in executive function ability, episodic memory function, and basal cortisol. Changes in mood, cardiac function, and aerobic capacity also will be assessed as possible mediating factors. The findings of this study would represent an initial but essential step in evaluating the efficacy of aerobic exercise as a behavioral factor that ultimately might be found to delay, arrest, or conceivably reverse progression of age-related cognitive decline. It also would yield data indicating the effectiveness of the intervention in modulating cortisol, elevation of which is associated with substantial risk for cerebral deterioration in the elderly. The demonstration of an ameliorating effect would provide the basis for future investigations examining the specific nature of the cognitive-cerebral adaptations to exercise, the relative benefits of different forms of exercise, and issues of dosage and duration of effect. [unreadable] [unreadable]

The Power Up!: Creating Leaders for Community College & High School Technology/Engineering project is a professional development program for high school and community college educators.

Intellectual Merit: The project meets five critical needs:
1) The need to engage college students just starting engineering/technology programs with creative and realistic problem-solving activities;
2) The need for instructional programs at the high school level that lead students to consider pursuing technical studies at college; and
3) The need for high school and college faculties to work together to smooth the transition from high school to college.
In order to bring the benefits of the proposed program to a wider audience, 4) a cadre of teacher leaders is being developed and 5) the program is increasing awareness among high school guidance counselors, college faculty advisors, and parents about the importance of technology and engineering programs that are open and accessible to all students at the high school and college levels.

This project focuses on one area of engineering/technology education: energy and power technologies. At a national level, energy and power technologies are becoming increasingly important for society's continued development and growth. Engineers and technicians are needed to manage and maintain the current sources and grids while simultaneously alternative sources need to be explored for the future.

Power Up! is a collaboration between the Museum of Science, Boston; four community colleges in Massachusetts: Bunker Hill Community College, North Shore Community College, Quinsigamond Community College, and Springfield Technical College; three industry partners: Keyspan Energy, Northern Power, and The Engineering Center; eight school districts; and the Department of Education Tech Prep Network.

Broader Impacts: The project is developing, pilot-testing, and refining a systemic model for how high schools, community college, and industry partners can collaborate to develop new technology/engineering programs and pathways for students that can be disseminated nationwide. The project also fosters the creation of articulated pathways to enhance curriculum for sequences through high school, community colleges, and beyond in the field of engineering and technology. Finally the Power Up! content courses for high school and community colleges and instructional units that revolve around energy, power engineering and technology and the active, project-based learning and materials for counselor and public workshops are available for use across the state and nation.

DESCRIPTION (provided by applicant): Older adults with age-related cognitive decline experience at least modest inefficiency in everyday functioning and have increased risk of developing dementia, in particular Alzheimer's disease (AD). With the expansion of the elderly population there is concern that the prevalence of AD may increase substantially beyond previous projections that ranged from 11 to 16 million affected individuals by the year 2050. Current pharmaceutical therapies provide only partial and transient symptomatic improvement and produce adverse responses in some individuals. At this time, early intervention represents the optimal approach for slowing or preventing further cognitive decline. Omega-3 fatty acid deficiency represents a plausible pathoetiological mechanism for neuropathology associated with cognitive aging and dementia, and omega-3 fatty acid treatment has positive effects on a number of putative mechanisms of age-related decline. In addition, basic animal research during the last decade and very recent human preliminary data indicate that blueberry supplementation produces substantial neurobiological benefit and has the potential to ameliorate age-related cognitive decline. Further, there are indications that the combined effects of these nutraceutical approaches may offer more potent additive as well as complementary benefits aimed specifically at neurodegenerative mechanisms. Our long-term objective is to develop a nutraceutical intervention strategy that can be effective when applied with older adults experiencing age-related decline. In this investigation, we will evaluate the efficacy of combined omega-3 fatty acid and blueberry supplementation in improving memory function in elderly individuals with early memory changes. We propose a 6-month randomized, double-blind, placebo-controlled trial involving daily supplementation with these nutraceutical products and longitudinal assessment up to one year after baseline. Our primary outcomes will be assessment of change in aspects of memory function and daily functioning in response to the intervention. We plan to use the findings of this study to support future, more comprehensive research examining mechanisms of action, dosage, and duration of effects in older adults. This proposal was generated in response to the NIA request for proposals to investigate novel, combined non-pharmaceutical interventions designed to improve cognitive function in older adults. PUBLIC HEALTH RELEVANCE: Evidence-based treatments are urgently needed for elderly individuals with or at risk for age-related cognitive decline. As an initial step to establish early intervention and prevention strategies, this application proposes a double-bind placebo-controlled treatment trial to evaluate the neurocognitive benefits of combined omega-3 fatty acid and blueberries in elderly subjects at risk for age-related cognitive decline.