- Email: [email protected]
Effects of a 12-week exercise intervention on resting state brain networks in mild cognitive impairment and healthy elders
P608 P2-301
Poster Presentations: P2 COGNITIVE SUBSTUDY OF THE VITAMIN D AND OMEGA-3 TRIAL (VITAL-COG): DESIGN OF A LARGE RANDOMIZED TRIAL OF OMEGA-3 AND VITAMIN D SUPPLEMENTS IN RELATION TO COGNITIVE CHANGE
Jae Hee Kang1, Francine Grodstein1, JoAnn E. Manson1 The VITAL-Cog Research Team,1Brigham and Women’s Hospital / Harvard Medical School, Boston, MA, USA. Contact e-mail: [email protected] Background: Marine omega-3 fatty acids and vitamin D may be asso-
ciated with improved cognitive function in older persons. However, there are no large, long-term primary prevention trials, especially in African Americans. Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2 x 2 factorial trial of long-chain omega-3 fatty acid (Omacor fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) and vitamin D (in the form of vitamin D(3) [cholecalciferol], 2000 IU/day) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 healthy, U.S. men aged 50 and women aged 55, respectively. The mean treatment period will be 5 years. Baseline blood samples were collected in 16,954 participants, with follow-up blood collection in about 6000 participants. Yearly follow-up questionnaires will assess treatment compliance (plasma biomarker measures will also assess compliance in a random sample of participants), use of non-study drugs or supplements, occurrence of endpoints, and cancer and vascular risk factors. Deaths will be ascertained through national registries and other sources. VITAL-Cog is an ancillary trial, leveraging the resources of VITAL, to evaluate whether these agents influence cognitive change in a subset of older participants. Results: The primary endpoint of VITALCog is change in cognitive function as assessed by validated telephone cognitive interviews consisting of a battery of 7 tests measuring episodic memory, fluency, executive function and attention). Cognitive function will be estimated by change from baseline in the treatment versus placebo groups on a composite score derived from the cognitive battery. In VITAL-Cog, we have completed baseline cognitive assessments and have initiated the first 2-year followup assessments, among 3,500 randomized participants aged 60+ years (3000 with blood), including 600 African Americans. We will also evaluate the effects of these agents by race, APOE e4 status, and baseline plasma 25-hydroxy vitamin D (25(OH)D) and plasma EPA+DHA levels. Conclusions: The VITAL-Cog study is a highly cost-effective, ancillary study of an ongoing parent trial for the evaluation of omega-3 fatty acids and vitamin D, in delaying cognitive change, a goal of major public health importance.
P2-302
EFFECTS OF A 12-WEEK EXERCISE INTERVENTION ON RESTING STATE BRAIN NETWORKS IN MILD COGNITIVE IMPAIRMENT AND HEALTHY ELDERS
Theresa J. Smith1, Hyuk Oh1, Lauren R. Weiss1, Alfonso J. Alfini1, Katherine Reiter2, Kristy A. Nielson2,3, J. Carson Smith1, 1University of Maryland, College Park, MD, USA; 2Marquette University, Milwaukee, WI, USA; 3Medical College of Wisconsin, Milwaukee, WI, USA. Contact e-mail: [email protected] Background: It is important to identify treatments to improve brain
function in Mild Cognitive Impairment (MCI), an early stage of Alzheimer’s Disease (AD). Previous studies have shown a disruption in resting state brain networks on the AD continuum, and while physical activity appears to delay the onset of AD, it is unknown if it alters resting state brain networks in clinical populations. We inves-
tigated the effects of a 12-week treadmill walking intervention on resting state brain networks in MCI and healthy elders. Methods: Sixteen MCI and 16 healthy elders, ages 60-88, engaged in a supervised 12-week treadmill walking exercise intervention. Functional MRI (fMRI) was acquired at rest, and the voxel time courses were parceled into 90 brain regions using the AAL atlas. Correlation matrices (90x90) for each subject were entered into the NBS Connectome. Results: Using the FDR option [paired t-test; 10,000 permutations] significant connection changes (p<0.05) were found in the healthy elders but not in the MCI. Healthy elders decreased connectivity between the left thalamus and left superior orbital gyrus. Reducing permutations to 5,000 revealed decreased connectivity between the left superior orbital gyrus and the following nodes: left caudate nucleus, left pallidum, and right thalamus. Conclusions: These findings suggest 12-weeks of exercise alter functional connectivity patterns in the healthy elders, yet there is an apparent maintenance of network function in MCI. This indicates that walking may provide protective benefits to resting state networks in healthy elders while delaying the disruption of these networks in MCI. These findings continue to lend support to the use of exercise as a therapeutic intervention in MCI. It must be noted that the small number of subjects does limit the sensitivity of the analysis to detect differences.
P2-303
EFFECTS OF A COMPREHENSIVE, INDIVIDUALIZED PERSON-CENTERED MANAGEMENT PROGRAM ON PERSONS WITH MODERATELY SEVERE ALZHEIMER’S DISEASE: A RANDOMIZED CONTROLLED TRIAL— COMPREHENSIVE STUDY FINDINGS
Barry Reisberg, Isabel Monteiro, Carol Torossian, Jinfeng Xu, Khurram Janjua, Santosh Ghimire, Kathryn Sommese, Sunnie Kenowsky, New York University School of Medicine, New York, NY, USA. Contact e-mail: [email protected] Background: Persons with moderately severe AD are the most distressed AD persons (Reisberg, et al., Bull Clin Neurosci, 1989). We described some needs and potential solutions for these persons in a “science of AD management” (Reisberg, et al., Am J Alzheimers Dis Other Demen, 2002). Subsequently, memantine, the first medication for advanced AD, demonstrated efficacy. We therefore investigated a Comprehensive Individualized Person Centered Management Program (CI-PCM) in addition to memantine treatment, in moderately severe AD persons. Methods: This was a 28 week, randomized, blinded, parallel group study in which 20 probable AD subjects (MMSE range ¼ 3 - 14; Global Deterioration Scale [GDS] stage 5 or 6), with basic activity of daily living (ADL) deficits (Functional Assessment Staging [FAST] scale stages 6a), were randomly assigned to: (1) the CI-PCM program with memantine treatment or (2) memantine treatment alone. The CI-PCM program included home visits, caregiver training and support groups. Results for one primary outcome, the NYU CIBICPlus, have previously been reported. We now report outcomes for the other assessments (see Tables 1 to 3). Results: Ten subjects were randomized to each treatment condition. All completed the study. Endpoint results are reported herein (Tables 1 to 3). Both ADL assessments (the ADCS-ADLsev abr. and the FAST-DS) showed significant effects (p < 0.01) in favor of the CI-PCM subject group. Both behavioral assessments (the BEHAVE-AD-FW and the RMBPC) also showed significant disturbance reductions in the CI-PCM subjects (p ¼ 0.001 and p < 0.05, respectively). Neither cognitive assessment (the SIB or the MMSE) showed
Poster Presentations: P2 COGNITIVE SUBSTUDY OF THE VITAMIN D AND OMEGA-3 TRIAL (VITAL-COG): DESIGN OF A LARGE RANDOMIZED TRIAL OF OMEGA-3 AND VITAMIN D SUPPLEMENTS IN RELATION TO COGNITIVE CHANGE
Jae Hee Kang1, Francine Grodstein1, JoAnn E. Manson1 The VITAL-Cog Research Team,1Brigham and Women’s Hospital / Harvard Medical School, Boston, MA, USA. Contact e-mail: [email protected] Background: Marine omega-3 fatty acids and vitamin D may be asso-
ciated with improved cognitive function in older persons. However, there are no large, long-term primary prevention trials, especially in African Americans. Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2 x 2 factorial trial of long-chain omega-3 fatty acid (Omacor fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) and vitamin D (in the form of vitamin D(3) [cholecalciferol], 2000 IU/day) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 healthy, U.S. men aged 50 and women aged 55, respectively. The mean treatment period will be 5 years. Baseline blood samples were collected in 16,954 participants, with follow-up blood collection in about 6000 participants. Yearly follow-up questionnaires will assess treatment compliance (plasma biomarker measures will also assess compliance in a random sample of participants), use of non-study drugs or supplements, occurrence of endpoints, and cancer and vascular risk factors. Deaths will be ascertained through national registries and other sources. VITAL-Cog is an ancillary trial, leveraging the resources of VITAL, to evaluate whether these agents influence cognitive change in a subset of older participants. Results: The primary endpoint of VITALCog is change in cognitive function as assessed by validated telephone cognitive interviews consisting of a battery of 7 tests measuring episodic memory, fluency, executive function and attention). Cognitive function will be estimated by change from baseline in the treatment versus placebo groups on a composite score derived from the cognitive battery. In VITAL-Cog, we have completed baseline cognitive assessments and have initiated the first 2-year followup assessments, among 3,500 randomized participants aged 60+ years (3000 with blood), including 600 African Americans. We will also evaluate the effects of these agents by race, APOE e4 status, and baseline plasma 25-hydroxy vitamin D (25(OH)D) and plasma EPA+DHA levels. Conclusions: The VITAL-Cog study is a highly cost-effective, ancillary study of an ongoing parent trial for the evaluation of omega-3 fatty acids and vitamin D, in delaying cognitive change, a goal of major public health importance.
P2-302
EFFECTS OF A 12-WEEK EXERCISE INTERVENTION ON RESTING STATE BRAIN NETWORKS IN MILD COGNITIVE IMPAIRMENT AND HEALTHY ELDERS
Theresa J. Smith1, Hyuk Oh1, Lauren R. Weiss1, Alfonso J. Alfini1, Katherine Reiter2, Kristy A. Nielson2,3, J. Carson Smith1, 1University of Maryland, College Park, MD, USA; 2Marquette University, Milwaukee, WI, USA; 3Medical College of Wisconsin, Milwaukee, WI, USA. Contact e-mail: [email protected] Background: It is important to identify treatments to improve brain
function in Mild Cognitive Impairment (MCI), an early stage of Alzheimer’s Disease (AD). Previous studies have shown a disruption in resting state brain networks on the AD continuum, and while physical activity appears to delay the onset of AD, it is unknown if it alters resting state brain networks in clinical populations. We inves-
tigated the effects of a 12-week treadmill walking intervention on resting state brain networks in MCI and healthy elders. Methods: Sixteen MCI and 16 healthy elders, ages 60-88, engaged in a supervised 12-week treadmill walking exercise intervention. Functional MRI (fMRI) was acquired at rest, and the voxel time courses were parceled into 90 brain regions using the AAL atlas. Correlation matrices (90x90) for each subject were entered into the NBS Connectome. Results: Using the FDR option [paired t-test; 10,000 permutations] significant connection changes (p<0.05) were found in the healthy elders but not in the MCI. Healthy elders decreased connectivity between the left thalamus and left superior orbital gyrus. Reducing permutations to 5,000 revealed decreased connectivity between the left superior orbital gyrus and the following nodes: left caudate nucleus, left pallidum, and right thalamus. Conclusions: These findings suggest 12-weeks of exercise alter functional connectivity patterns in the healthy elders, yet there is an apparent maintenance of network function in MCI. This indicates that walking may provide protective benefits to resting state networks in healthy elders while delaying the disruption of these networks in MCI. These findings continue to lend support to the use of exercise as a therapeutic intervention in MCI. It must be noted that the small number of subjects does limit the sensitivity of the analysis to detect differences.
P2-303
EFFECTS OF A COMPREHENSIVE, INDIVIDUALIZED PERSON-CENTERED MANAGEMENT PROGRAM ON PERSONS WITH MODERATELY SEVERE ALZHEIMER’S DISEASE: A RANDOMIZED CONTROLLED TRIAL— COMPREHENSIVE STUDY FINDINGS
Barry Reisberg, Isabel Monteiro, Carol Torossian, Jinfeng Xu, Khurram Janjua, Santosh Ghimire, Kathryn Sommese, Sunnie Kenowsky, New York University School of Medicine, New York, NY, USA. Contact e-mail: [email protected] Background: Persons with moderately severe AD are the most distressed AD persons (Reisberg, et al., Bull Clin Neurosci, 1989). We described some needs and potential solutions for these persons in a “science of AD management” (Reisberg, et al., Am J Alzheimers Dis Other Demen, 2002). Subsequently, memantine, the first medication for advanced AD, demonstrated efficacy. We therefore investigated a Comprehensive Individualized Person Centered Management Program (CI-PCM) in addition to memantine treatment, in moderately severe AD persons. Methods: This was a 28 week, randomized, blinded, parallel group study in which 20 probable AD subjects (MMSE range ¼ 3 - 14; Global Deterioration Scale [GDS] stage 5 or 6), with basic activity of daily living (ADL) deficits (Functional Assessment Staging [FAST] scale stages 6a), were randomly assigned to: (1) the CI-PCM program with memantine treatment or (2) memantine treatment alone. The CI-PCM program included home visits, caregiver training and support groups. Results for one primary outcome, the NYU CIBICPlus, have previously been reported. We now report outcomes for the other assessments (see Tables 1 to 3). Results: Ten subjects were randomized to each treatment condition. All completed the study. Endpoint results are reported herein (Tables 1 to 3). Both ADL assessments (the ADCS-ADLsev abr. and the FAST-DS) showed significant effects (p < 0.01) in favor of the CI-PCM subject group. Both behavioral assessments (the BEHAVE-AD-FW and the RMBPC) also showed significant disturbance reductions in the CI-PCM subjects (p ¼ 0.001 and p < 0.05, respectively). Neither cognitive assessment (the SIB or the MMSE) showed