- Email: [email protected]
Cardiac Rehabilitation: Benefits to people with MCI and Alzheimer's disease
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Poster Presentations P3 POSSIBLE ROLE OF N-ACETYL CYSTEINE AGAINST ALUMINUM-INDUCED COGNITIVE DYSFUNCTION AND OXIDATIVE DAMAGE IN RATS
Anil Kumar, Panjab University, Chandigarh, India. Background: Aluminium is potent neurotoxins, involved in the initiation and progression of various cognitive disorders like Alzheimer’s disease. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. The role of oxidative stress has been well suggested in these cognitive problems. Therefore, the present study has been designed to explore the possible role N-acetyl cysteine (NAC) against aluminium mediating cognitive dysfunction and oxidative stress in rats. Methods: Aluminium chloride (100mg/kg, p.o.) was given to rats for 6 weeks daily. Rats were concomitantly treated with NAC (per se; 50 and 100 mg/kg, i.p.) daily for a period of 6 weeks. On the 3rd (21st day) and 6th week (42nd day) of the study, various behavioral test (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done to evaluate cognitive tasks. The rats were sacrificed on 43rd day following the last behavioral test and various biochemical tests were performed to assess the extent of oxidative damage. Results: Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetyl cholinesterase activity. Chronic administration of NAC significantly improved memory retention in tasks, attenuated oxidative damage and acetyl cholinesterase activity in aluminium treated rats. Conclusions: Study suggests the neuroprotective effect of NAC against aluminium-induced cognitive dysfunction and oxidative damage.
P3-306
DUAL-TASK PERFORMANCE AND NEUROCOGNITIVE FUNCTIONS IN OLDER ADULTS WITH AND WITHOUT AMNESTIC MILD COGNITIVE IMPAIRMENT
Hyuma Makizako, Hiroyuki Shimada, Takao Suzuki, Takehiko Doi, Daisuke Yoshida, Hiroshi Shimokata, Kengo Ito, Yukihiko Washimi, Hidetoshi Endo, National Center for Geriatrics and Gerontology, Aichi, Japan. Background: Poor dual-task performance with cognitive demand is an early marker of dementia. This study aims to assess attention-related performances during dual tasks and to examine the relationships between dual-task performance and multi-domain of neurocognitive functions in community-dwelling older people with no memory loss and amnestic mild cognitive impairment (aMCI) subjects. Methods: This study involved control participants without objective memory decline (n ¼ 63) and aMCI subjects (n ¼ 36). Participants were diagnosed with aMCI if they exhibited objectively determined memory impairment, as assessed via education-adjusted scores on the Wechsler Memory Scale-Revised Logical Memory II test. We measured reaction time (RT) in two conditions-low (simple-task condition) or high (dual-task condition)-cognitive demand of attentional resources. In the dual-task condition, participants were asked to perform RT responses during the dual-task with concurrent a cognitive task. Participants underwent comprehensive neurocognitive evaluation including measures of global cognitive function, memory, executive function, processing speed, and verbal fluency. The decrease of RT response under dual-task conditions (compared to simple RT), defined as dual-task cost, was calculated by the following formula: [(dual-task RT - simple RT)/simple RT 3 100]. We classified participants into three groups by tertile of dual-task cost and evaluated the association between dual-task performance and neurocognitive functions. Additionally, we compared the dual-task performance and neurocognitive functions of the aMCI group to that of the control group (participants without aMCI). Results: Across our sample of 98 older adults, poor
dual-task performance measured reaction times during concurrent cognitive tasks were significantly related with lower test scores on executive function and processing speed. Participants with aMCI demonstrated significantly poorer dual-task performance with cognitive demand than control participants did, but group differences were not observed for neurocognitive functions such as global cognitive function, executive function, processing speed and verbal fluency. Conclusions: Our results indicate that poor dual-task performance is associated with a decline in executive function and processing speed in community-dwelling older people. Additionally, poor dual-task performance with cognitive demand may be an early marker of aMCI.
P3-307
PHYSICAL ACTIVITY AND COGNITION: EFFECT AT MID-LIFE VERSUS LATE LIFE
Laura Middleton1, Susan Kirkland2, Arnold Mitnitski2, Kathleen MacPherson2, Kenneth Rockwood2, 1Sunnybrook Research Institute, Toronto, Canada; 2Dalhousie University, Halifax, Canada. Background: In most studies, people who are physically active at mid-life or late life have lower risk of late life cognitive impairment. However, research has not examined how physical activity is related to cognition at mid-life. It is possible that physical activity may augment cognition at mid-life, thus offering a cognitive reserve to protect against future cognitive decline. The objective of this study was to investigate the association between self-reported physical activity and cognitive performance at midlife (47-59 years) and late life (¼60 years) in the Healthy Heart, Healthy Brain (H3B) study. Methods: The 1205 participants in the H3B study self-reported weekly physical activity using a modified Paffenbarger questionnaire. Caloric expenditure was estimated based on duration and intensity of physical activity. Participants were dichotomized into those who met the American College of Sports Medicine guidelines (1000 kcal/week) and those who did not. Cognitive function, as assessed using the Modified Mini-Mental Examination (3MS), was normalized using the logarithmic function. The relationship between physical activity and cognitive function at mid-life and late life was assessed using linear regression models. Results: In unadjusted linear regression analyses, exercise was positively associated with cognitive performance in the H3B study (ß: 0.68, 95% CI: 0.20, 1.16). In adjusted, age-stratified analyses, high exercise was associated with better cognitive performance in late life (ß: 1.07, 95% CI: 0.24, 1.90) but not in mid-life (ß: -0.15, 95% CI: -0.55, -0.24). This was in contrast to higher vascular risk, which was associated with worse cognition at younger ages (ß: -0.50, 95% CI: -0.89, -0.11) but not older ages (ß: 0.09, 95% CI: -0.59, 0.78). Conclusions: In this study, physical activity was positively associated with cognitive performance in late life but not at mid-life. This suggests that physical activity does not protect against late life cognitive impairment by creating a cognitive reserve to draw upon during late life decline but may rather augment active processes to protect against late life neuropathology.
P3-308
CARDIAC REHABILITATION: BENEFITS TO PEOPLE WITH MCI AND ALZHEIMER’S DISEASE
Laura Middleton1, Dina Brooks2, Paul Oh3, Krista Lanct^ot4, Gary Turner1, Bradley MacIntosh1, Sandra Black4, 1Sunnybrook Research Institute, Toronto, Canada; 2University of Toronto, Toronto, Canada; 3Toronto Rehabilitation Institute, Toronto, Canada; 4Sunnybrook Health Sciences Centre, Toronto, Canada. Background: There are currently no behavioral interventions that are widely available through the medical system in Canada that are targeted to people with mild cognitive impairment (MCI) or early Alzheimer’s disease (AD). However, cardiac rehabilitation is available in all provinces in Canada and incorporates exercise, social engagement, and vascular risk
Poster Presentations P3 factor control, which are three of the most promising strategies to protect against dementia and cognitive decline. The objective of this study is to determine: (1) the feasibility for MCI and early AD patients to adhere to a cardiac rehabilitation exercise program; and (2) if there are benefits to patient physical function, cognition, and mood associated with participation in a cardiac rehabilitation exercise program. Methods: We will recruit 40 people with MCI or early AD from the 15-year ongoing Sunnybrook Dementia Study. Thus, we will leverage the longitudinal characterization of patients including extensive neuropsychological and imaging data. Participants will partake in the standard 6-month cardiac rehabilitation program at the Toronto Rehabilitation Institute, which incorporates a progressive, individualized aerobic and resistance exercise program in addition to social support and education regarding vascular risk factor control. Our comprehensive test battery will include measures of adherence (in clinic and at home), physical function, neurobehavioral function (cognition, mood, apathy), and indicators for cost-effectiveness modeling (health resource utilization, health-related quality of life). We will administer the complete battery before, in the middle of (at 3 months), and after the 6-month cardiac rehabilitation program and before and after a 6-month follow up period. Results: Preliminary pilot data indicates that 30% of cardiac rehabilitation participants have cognitive impairment. Adherence to the cardiac rehabilitation program is not significantly different between those with and without cognitive impairment (66.6% versus 73.1% respectively, p¼0.365), suggesting that cardiac rehabilitation will be feasible for people with MCI or early AD. Study enrollment will begin in mid-March. Preliminary results will be presented. Conclusions: Positive results from this trial would support expanding cardiac rehabilitation–an established, widely available program–to service people with MCI or AD, which would enable quick translation of research into clinical practice to potentially benefit this growing patient group.
P3-310
THE LIFE COGNITION STUDY: A MULTICENTER TRIAL OF PHYSICAL ACTIVITY TO PREVENT COGNITIVE DECLINE
Jeff Williamson1, Kaycee Sink2, Janine Jennings2, Mark Espeland2, Hugh Hendrie3, Joe Verghese4, Oscar Lopez5, Stephen Rapp2, Marco Pahor6, Michael Miller2, 1Wake Forest University, Winston-Salem, North Carolina, United States; 2Wake Forest University, Winston-Salem, North Carolina, United States; 3Indiana University, Indianapolis, Indiana, United States; 4Albert Einstein College of Medicine, New York, New York, United States; 5University of Pittsburgh, Pittsburgh, Pennsylvania, United States; 6University of Florida, Gainesville, Florida, United States. Background: Proven interventions for prevention of cognitive decline and dementia are lacking. Exercise may be important in preventing cognitionrelated disability in older adults but there are no large multi-center randomized trials (RCT) of long-term exercise and cognition in older adults at high risk for disability. Methods: We report the design of the Lifestyle Intervention and Independence For the Elderly (LIFE) Cognition Study, a multi-center RCT comparing impact of moderate-intensity physical activity (PA) program to a successful aging (SA) health education program on the rate of cognitive decline and incident all-cause dementia. This comparison will occur in 1,600 sedentary older persons enrolled in the overall trial which compares the incidence of major mobility disability (inability to walk 400 m) in these same groups. Eligible persons are aged 70 -89, sedentary, have functional limitations assessed by physical performance tests but are free of disability (able to walk 400 meters without sitting/ help from another person. Results: MCI prevalence estimate is 15%. PA intervention consists of 150 minutes weekly walking at moderate intensity, lower extremity resistance & balance exercises, stretching and counseling. SA intervention consists of health education seminars and upper extremity stretching. Participants will be followed a mean 2.7 years (range 1.9-3.5 years or 23-42 months). Cognition is assessed using a 30 minute screening battery with traditional interviewer administered items plus 15 minute computerized battery (baseline and 24 months). Persons scoring below
S615
specified cut offs at follow-up receive extended battery to aid in adjudicated classification (normal/MCI/dementia). LIFE study is a collaborative effort between the University of Florida, Gainesville, FL; Northwestern University, Chicago, IL; Pennington Biomedical Research Center, Baton Rouge, LA; University of Pittsburgh, Pittsburgh, PA; Stanford University, Palo Alto, CA; Tufts University, Boston, MA; Wake Forest University, Winston-Salem, NC; and Yale University, New Haven, CT. and sponsored by the National Institute on Aging (NIA). Conclusions: The LIFE Study will be the largest multi-center trial to date comparing the impact of longterm exercise versus health education on preservation of cognitive function in older persons at high risk for disability. It will also provide estimates necessary for a trial targeting exercise for preventing MCI transition to dementia.
P3-311
NATURAL FLAVONE, CALYCOPTERIN, PROTECTS DIFFERENTIATED PC12 CELLS AGAINST OXIDATIVE STRESS-INDUCED APOPTOSIS
Nazanin Namazi Sarvestani1, Niloufar Ansari2, Mohammad Ali Esmaeili3, Mehdi Moridi4, Fariba Khodagholi5, 1 Neuroscience Research Center, Tehran, Iran; 2Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3 Department of Biology, Medical Plants and Drugs Research Institute, Shahid Beheshti University, G.C, Tehran, Iran; 42Department of Biology, Medical Plants and Drugs Research Institute, Shahid Beheshti University, G.C, Tehran, Iran; 5Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Background: Neuronal cell death due to apoptosis is a common characteristic of neurodegenerative diseases. This pathway can be triggered by a variety of cytotoxic stressors, such as oxidative stress, which induce activation of executioner caspases and other signaling cascades that ultimately lead to apoptotic destruction of the cells. In the present study, we evaluated neuroprotective and anti-apoptotic effects of calycopterin against H2O2-induced apoptosis in PC12 cells. Methods: Cells were treated with 25, 50, 100 and 150 mM of calycopterin, followed by adding H2O2 (150 mM). The extent of apoptosis was assessed by MTT test, acridine orange/ethidium bromide staining, and determination of Bax/Bcl-2 and caspase-3 levels. Cellular level of catalase, SOD and GSH determined by enzymatic assays. Results: We found that calycopterin protects differentiated PC12 cells against oxidative stress-induced apoptosis. We found that this compound could decrease Bax /Bcl2 ratio, as well as caspase-3 level, compared to H2O2- treated cells. Attenuation of the extent of apoptosis was further confirmed by acridine orange/ethidium bromide staining. We found that antioxidant levels were increased significantly in the presence of calycopterin compared to H2O2- treated cells. Conclusions: We provided documentation of neuroprotective effect of a natural flavone, calycopterin, against H2O2-induced oxidative stress in PC12 cells. Neuroprotective effect of this compound could represent a promising approach for treatment of neurodegenerative diseases.
P3-312
GENE, EXERCISE AND MEMORY STUDY (GEMS): A RANDOMIZED CONTROLLED CLINICAL TRIAL TO EVALUATE THE EFFECTS OF STANDARDIZED AEROBIC EXERCISE ON NEUROCOGNITION AND NEURODEGENERATION IN AFRICAN AMERICANS WITH MILD ALZHEIMER’S DISEASE
Thomas Obisesan1, Richard Gillum2, Nisser Umar3, Vernon Bond1, Deborah Williams1, 1Howard University, Washington, District of Columbia, United States; 2Howard University Hospital, Washington, District of Columbia, United States; 3Howard University Hospital, Washington, District of Columbia, United States. Background: Physical activities and aerobic exercise are increasingly shown to slow the onset and progression of Alzheimer’s disease (AD),
Poster Presentations P3 POSSIBLE ROLE OF N-ACETYL CYSTEINE AGAINST ALUMINUM-INDUCED COGNITIVE DYSFUNCTION AND OXIDATIVE DAMAGE IN RATS
Anil Kumar, Panjab University, Chandigarh, India. Background: Aluminium is potent neurotoxins, involved in the initiation and progression of various cognitive disorders like Alzheimer’s disease. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. The role of oxidative stress has been well suggested in these cognitive problems. Therefore, the present study has been designed to explore the possible role N-acetyl cysteine (NAC) against aluminium mediating cognitive dysfunction and oxidative stress in rats. Methods: Aluminium chloride (100mg/kg, p.o.) was given to rats for 6 weeks daily. Rats were concomitantly treated with NAC (per se; 50 and 100 mg/kg, i.p.) daily for a period of 6 weeks. On the 3rd (21st day) and 6th week (42nd day) of the study, various behavioral test (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done to evaluate cognitive tasks. The rats were sacrificed on 43rd day following the last behavioral test and various biochemical tests were performed to assess the extent of oxidative damage. Results: Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetyl cholinesterase activity. Chronic administration of NAC significantly improved memory retention in tasks, attenuated oxidative damage and acetyl cholinesterase activity in aluminium treated rats. Conclusions: Study suggests the neuroprotective effect of NAC against aluminium-induced cognitive dysfunction and oxidative damage.
P3-306
DUAL-TASK PERFORMANCE AND NEUROCOGNITIVE FUNCTIONS IN OLDER ADULTS WITH AND WITHOUT AMNESTIC MILD COGNITIVE IMPAIRMENT
Hyuma Makizako, Hiroyuki Shimada, Takao Suzuki, Takehiko Doi, Daisuke Yoshida, Hiroshi Shimokata, Kengo Ito, Yukihiko Washimi, Hidetoshi Endo, National Center for Geriatrics and Gerontology, Aichi, Japan. Background: Poor dual-task performance with cognitive demand is an early marker of dementia. This study aims to assess attention-related performances during dual tasks and to examine the relationships between dual-task performance and multi-domain of neurocognitive functions in community-dwelling older people with no memory loss and amnestic mild cognitive impairment (aMCI) subjects. Methods: This study involved control participants without objective memory decline (n ¼ 63) and aMCI subjects (n ¼ 36). Participants were diagnosed with aMCI if they exhibited objectively determined memory impairment, as assessed via education-adjusted scores on the Wechsler Memory Scale-Revised Logical Memory II test. We measured reaction time (RT) in two conditions-low (simple-task condition) or high (dual-task condition)-cognitive demand of attentional resources. In the dual-task condition, participants were asked to perform RT responses during the dual-task with concurrent a cognitive task. Participants underwent comprehensive neurocognitive evaluation including measures of global cognitive function, memory, executive function, processing speed, and verbal fluency. The decrease of RT response under dual-task conditions (compared to simple RT), defined as dual-task cost, was calculated by the following formula: [(dual-task RT - simple RT)/simple RT 3 100]. We classified participants into three groups by tertile of dual-task cost and evaluated the association between dual-task performance and neurocognitive functions. Additionally, we compared the dual-task performance and neurocognitive functions of the aMCI group to that of the control group (participants without aMCI). Results: Across our sample of 98 older adults, poor
dual-task performance measured reaction times during concurrent cognitive tasks were significantly related with lower test scores on executive function and processing speed. Participants with aMCI demonstrated significantly poorer dual-task performance with cognitive demand than control participants did, but group differences were not observed for neurocognitive functions such as global cognitive function, executive function, processing speed and verbal fluency. Conclusions: Our results indicate that poor dual-task performance is associated with a decline in executive function and processing speed in community-dwelling older people. Additionally, poor dual-task performance with cognitive demand may be an early marker of aMCI.
P3-307
PHYSICAL ACTIVITY AND COGNITION: EFFECT AT MID-LIFE VERSUS LATE LIFE
Laura Middleton1, Susan Kirkland2, Arnold Mitnitski2, Kathleen MacPherson2, Kenneth Rockwood2, 1Sunnybrook Research Institute, Toronto, Canada; 2Dalhousie University, Halifax, Canada. Background: In most studies, people who are physically active at mid-life or late life have lower risk of late life cognitive impairment. However, research has not examined how physical activity is related to cognition at mid-life. It is possible that physical activity may augment cognition at mid-life, thus offering a cognitive reserve to protect against future cognitive decline. The objective of this study was to investigate the association between self-reported physical activity and cognitive performance at midlife (47-59 years) and late life (¼60 years) in the Healthy Heart, Healthy Brain (H3B) study. Methods: The 1205 participants in the H3B study self-reported weekly physical activity using a modified Paffenbarger questionnaire. Caloric expenditure was estimated based on duration and intensity of physical activity. Participants were dichotomized into those who met the American College of Sports Medicine guidelines (1000 kcal/week) and those who did not. Cognitive function, as assessed using the Modified Mini-Mental Examination (3MS), was normalized using the logarithmic function. The relationship between physical activity and cognitive function at mid-life and late life was assessed using linear regression models. Results: In unadjusted linear regression analyses, exercise was positively associated with cognitive performance in the H3B study (ß: 0.68, 95% CI: 0.20, 1.16). In adjusted, age-stratified analyses, high exercise was associated with better cognitive performance in late life (ß: 1.07, 95% CI: 0.24, 1.90) but not in mid-life (ß: -0.15, 95% CI: -0.55, -0.24). This was in contrast to higher vascular risk, which was associated with worse cognition at younger ages (ß: -0.50, 95% CI: -0.89, -0.11) but not older ages (ß: 0.09, 95% CI: -0.59, 0.78). Conclusions: In this study, physical activity was positively associated with cognitive performance in late life but not at mid-life. This suggests that physical activity does not protect against late life cognitive impairment by creating a cognitive reserve to draw upon during late life decline but may rather augment active processes to protect against late life neuropathology.
P3-308
CARDIAC REHABILITATION: BENEFITS TO PEOPLE WITH MCI AND ALZHEIMER’S DISEASE
Laura Middleton1, Dina Brooks2, Paul Oh3, Krista Lanct^ot4, Gary Turner1, Bradley MacIntosh1, Sandra Black4, 1Sunnybrook Research Institute, Toronto, Canada; 2University of Toronto, Toronto, Canada; 3Toronto Rehabilitation Institute, Toronto, Canada; 4Sunnybrook Health Sciences Centre, Toronto, Canada. Background: There are currently no behavioral interventions that are widely available through the medical system in Canada that are targeted to people with mild cognitive impairment (MCI) or early Alzheimer’s disease (AD). However, cardiac rehabilitation is available in all provinces in Canada and incorporates exercise, social engagement, and vascular risk
Poster Presentations P3 factor control, which are three of the most promising strategies to protect against dementia and cognitive decline. The objective of this study is to determine: (1) the feasibility for MCI and early AD patients to adhere to a cardiac rehabilitation exercise program; and (2) if there are benefits to patient physical function, cognition, and mood associated with participation in a cardiac rehabilitation exercise program. Methods: We will recruit 40 people with MCI or early AD from the 15-year ongoing Sunnybrook Dementia Study. Thus, we will leverage the longitudinal characterization of patients including extensive neuropsychological and imaging data. Participants will partake in the standard 6-month cardiac rehabilitation program at the Toronto Rehabilitation Institute, which incorporates a progressive, individualized aerobic and resistance exercise program in addition to social support and education regarding vascular risk factor control. Our comprehensive test battery will include measures of adherence (in clinic and at home), physical function, neurobehavioral function (cognition, mood, apathy), and indicators for cost-effectiveness modeling (health resource utilization, health-related quality of life). We will administer the complete battery before, in the middle of (at 3 months), and after the 6-month cardiac rehabilitation program and before and after a 6-month follow up period. Results: Preliminary pilot data indicates that 30% of cardiac rehabilitation participants have cognitive impairment. Adherence to the cardiac rehabilitation program is not significantly different between those with and without cognitive impairment (66.6% versus 73.1% respectively, p¼0.365), suggesting that cardiac rehabilitation will be feasible for people with MCI or early AD. Study enrollment will begin in mid-March. Preliminary results will be presented. Conclusions: Positive results from this trial would support expanding cardiac rehabilitation–an established, widely available program–to service people with MCI or AD, which would enable quick translation of research into clinical practice to potentially benefit this growing patient group.
P3-310
THE LIFE COGNITION STUDY: A MULTICENTER TRIAL OF PHYSICAL ACTIVITY TO PREVENT COGNITIVE DECLINE
Jeff Williamson1, Kaycee Sink2, Janine Jennings2, Mark Espeland2, Hugh Hendrie3, Joe Verghese4, Oscar Lopez5, Stephen Rapp2, Marco Pahor6, Michael Miller2, 1Wake Forest University, Winston-Salem, North Carolina, United States; 2Wake Forest University, Winston-Salem, North Carolina, United States; 3Indiana University, Indianapolis, Indiana, United States; 4Albert Einstein College of Medicine, New York, New York, United States; 5University of Pittsburgh, Pittsburgh, Pennsylvania, United States; 6University of Florida, Gainesville, Florida, United States. Background: Proven interventions for prevention of cognitive decline and dementia are lacking. Exercise may be important in preventing cognitionrelated disability in older adults but there are no large multi-center randomized trials (RCT) of long-term exercise and cognition in older adults at high risk for disability. Methods: We report the design of the Lifestyle Intervention and Independence For the Elderly (LIFE) Cognition Study, a multi-center RCT comparing impact of moderate-intensity physical activity (PA) program to a successful aging (SA) health education program on the rate of cognitive decline and incident all-cause dementia. This comparison will occur in 1,600 sedentary older persons enrolled in the overall trial which compares the incidence of major mobility disability (inability to walk 400 m) in these same groups. Eligible persons are aged 70 -89, sedentary, have functional limitations assessed by physical performance tests but are free of disability (able to walk 400 meters without sitting/ help from another person. Results: MCI prevalence estimate is 15%. PA intervention consists of 150 minutes weekly walking at moderate intensity, lower extremity resistance & balance exercises, stretching and counseling. SA intervention consists of health education seminars and upper extremity stretching. Participants will be followed a mean 2.7 years (range 1.9-3.5 years or 23-42 months). Cognition is assessed using a 30 minute screening battery with traditional interviewer administered items plus 15 minute computerized battery (baseline and 24 months). Persons scoring below
S615
specified cut offs at follow-up receive extended battery to aid in adjudicated classification (normal/MCI/dementia). LIFE study is a collaborative effort between the University of Florida, Gainesville, FL; Northwestern University, Chicago, IL; Pennington Biomedical Research Center, Baton Rouge, LA; University of Pittsburgh, Pittsburgh, PA; Stanford University, Palo Alto, CA; Tufts University, Boston, MA; Wake Forest University, Winston-Salem, NC; and Yale University, New Haven, CT. and sponsored by the National Institute on Aging (NIA). Conclusions: The LIFE Study will be the largest multi-center trial to date comparing the impact of longterm exercise versus health education on preservation of cognitive function in older persons at high risk for disability. It will also provide estimates necessary for a trial targeting exercise for preventing MCI transition to dementia.
P3-311
NATURAL FLAVONE, CALYCOPTERIN, PROTECTS DIFFERENTIATED PC12 CELLS AGAINST OXIDATIVE STRESS-INDUCED APOPTOSIS
Nazanin Namazi Sarvestani1, Niloufar Ansari2, Mohammad Ali Esmaeili3, Mehdi Moridi4, Fariba Khodagholi5, 1 Neuroscience Research Center, Tehran, Iran; 2Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3 Department of Biology, Medical Plants and Drugs Research Institute, Shahid Beheshti University, G.C, Tehran, Iran; 42Department of Biology, Medical Plants and Drugs Research Institute, Shahid Beheshti University, G.C, Tehran, Iran; 5Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Background: Neuronal cell death due to apoptosis is a common characteristic of neurodegenerative diseases. This pathway can be triggered by a variety of cytotoxic stressors, such as oxidative stress, which induce activation of executioner caspases and other signaling cascades that ultimately lead to apoptotic destruction of the cells. In the present study, we evaluated neuroprotective and anti-apoptotic effects of calycopterin against H2O2-induced apoptosis in PC12 cells. Methods: Cells were treated with 25, 50, 100 and 150 mM of calycopterin, followed by adding H2O2 (150 mM). The extent of apoptosis was assessed by MTT test, acridine orange/ethidium bromide staining, and determination of Bax/Bcl-2 and caspase-3 levels. Cellular level of catalase, SOD and GSH determined by enzymatic assays. Results: We found that calycopterin protects differentiated PC12 cells against oxidative stress-induced apoptosis. We found that this compound could decrease Bax /Bcl2 ratio, as well as caspase-3 level, compared to H2O2- treated cells. Attenuation of the extent of apoptosis was further confirmed by acridine orange/ethidium bromide staining. We found that antioxidant levels were increased significantly in the presence of calycopterin compared to H2O2- treated cells. Conclusions: We provided documentation of neuroprotective effect of a natural flavone, calycopterin, against H2O2-induced oxidative stress in PC12 cells. Neuroprotective effect of this compound could represent a promising approach for treatment of neurodegenerative diseases.
P3-312
GENE, EXERCISE AND MEMORY STUDY (GEMS): A RANDOMIZED CONTROLLED CLINICAL TRIAL TO EVALUATE THE EFFECTS OF STANDARDIZED AEROBIC EXERCISE ON NEUROCOGNITION AND NEURODEGENERATION IN AFRICAN AMERICANS WITH MILD ALZHEIMER’S DISEASE
Thomas Obisesan1, Richard Gillum2, Nisser Umar3, Vernon Bond1, Deborah Williams1, 1Howard University, Washington, District of Columbia, United States; 2Howard University Hospital, Washington, District of Columbia, United States; 3Howard University Hospital, Washington, District of Columbia, United States. Background: Physical activities and aerobic exercise are increasingly shown to slow the onset and progression of Alzheimer’s disease (AD),