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The prevalence of dementia will double in the next three decades in the U.S.; effective treatment or prevention for dementia is urgently needed. The current exploratory project aims to evaluate and understand how the brain and cognition may improve after a 12-week intervention that combines brain training and aerobic exercise training to improve brain function, both in those with mild cognitive impairment (some with possible prodromal Alzheimer's disease) and with healthy aging. Findings from this pilot project will guide and refine the development of a future larger clinical trial that aligns with the goals of the National Alzheimer's Plan of Action (NAPA), especially regarding "Prevent and Effectively Treat Alzheimer's Disease (AD) by 2025.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aerobic Exercise | Experimental | Progressive aerobic exercise 3x/week for 12 weeks. |
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| Cognitive Training | Experimental | Adaptive cognitive training on Cogmed 5x/week for a total of 25 sessions in 5-8 weeks. |
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| Combined Cognitive and Aerobic Exercise | Experimental | Combined progressive aerobic exercise 3x/week for 12 weeks and adaptive cognitive training on Cogmed 5x/week for a total of 25 sessions in 5-8 weeks simultaneously. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Progressive aerobic exercise | Behavioral | Progressive aerobic exercise |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Brain structure measures | Changes in brain volume measures from T1-weighted images (volumes in mm3) | At baseline and at 4 weeks after the corresponding training program. |
| Changes in brain cortical thickness measures | Changes in brain cortical thickness measures from T1-weighted images (thickness measures in mm) | At baseline and at 4 weeks after the corresponding training program. |
| Changes in Brain microstructure measures | Changes in brain measures of diffused tensor imaging (diffusion coefficient in mm²/s) | At baseline and at 4 weeks after the corresponding training program. |
| Changes in Brain blood flow from Arterial spin labeling magnetic resonance imaging (ASL-MRI) in milliliters/100 g/minutes | Changes in Brain blood flow from Arterial spin labeling magnetic resonance imaging (ASL-MRI) in milliliters/ 100 g/ minutes | At baseline and at 4 weeks after the corresponding training program. |
| Changes in Brain Activation on functional MRI | Changes in functional MRI from blood oxygen level dependence (BOLD) contrast on fMRI (in percentage change) | At baseline and at 4 weeks after the corresponding training program. |
| Changes in cognitive performance, emotions, and motor function based on NIH toolbox | Changes in cognitive performance, emotions, and motor function in raw scores measured by the NIH Toolbox® (reports will be generated as T scores, with higher T scores indicating better outcomes) |
| Measure | Description | Time Frame |
|---|---|---|
| VO2peak | VO2peak will be used as the primary measure of aerobic capacity. Subjects will be asked to exercise to voluntary exhaustion during a treadmill test using a modified Bruce protocol. Oxygen (O2) consumption, carbon dioxide (CO2) production, and minute ventilation will be measured breath-by-breath using a metabolic cart and the average of the final two 20 second values of O2 consumption are VO2peak. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Linda Chang, M.D., M.S. | Contact | 410 706 1036 | LChang@som.umaryland.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland Baltimore | Recruiting | Baltimore | Maryland | 21201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24895057 | Background | Chacko BK, Kramer PA, Ravi S, Benavides GA, Mitchell T, Dranka BP, Ferrick D, Singal AK, Ballinger SW, Bailey SM, Hardy RW, Zhang J, Zhi D, Darley-Usmar VM. The Bioenergetic Health Index: a new concept in mitochondrial translational research. Clin Sci (Lond). 2014 Sep;127(6):367-73. doi: 10.1042/CS20140101. | |
| 28837640 | Background |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| Adaptive cognitive training |
| Behavioral |
Adaptive cognitive training |
|
| Combined | Behavioral | Combine adaptive cognitive and progressive aerobic exercise training |
|
| At baseline and at 4 weeks after the corresponding training program. |
| Changes in executive function using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | Changes in executive function using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) (reports will be generated as T scores, with lower T scores indicating better outcomes and T scores higher than 65 indicating significant impairments in the executive function) | At baseline and at 4 weeks after the corresponding training program. |
| Changes in Blood Bioenergetic Markers | Platelet mitochondrial respiration (OCR) and extracellular acidification rates (ECAR) will be evaluated to assess bioenergetic profiles in platelets isolated from whole blood of fasted participants. OCR will be measured using a Seahorse model XFe96 machine as the high throughput platform. Measurements of OCR/ECAR will be performed with the following modifications. Platelets will be isolated from whole blood with a Beckman Allegra model X-30R centrifuge. Platelets will be counted using a Nexcelom Bioscience Cellometer (Lawrence, MA) using Calcein acetoxymethyl (AM) ester dye to enable the seeding of 10,000,000 platelets per well. | At baseline and at 4 weeks after the corresponding training program. |
| At baseline and within one week after the corresponding training program. |
| Vidorreta M, Wang Z, Chang YV, Wolk DA, Fernandez-Seara MA, Detre JA. Whole-brain background-suppressed pCASL MRI with 1D-accelerated 3D RARE Stack-Of-Spirals readout. PLoS One. 2017 Aug 24;12(8):e0183762. doi: 10.1371/journal.pone.0183762. eCollection 2017. |
| 28737289 | Background | Dolui S, Vidorreta M, Wang Z, Nasrallah IM, Alavi A, Wolk DA, Detre JA. Comparison of PASL, PCASL, and background-suppressed 3D PCASL in mild cognitive impairment. Hum Brain Mapp. 2017 Oct;38(10):5260-5273. doi: 10.1002/hbm.23732. Epub 2017 Jul 24. |
| 35444526 | Background | Hol HR, Flak MM, Chang L, Lohaugen GCC, Bjuland KJ, Rimol LM, Engvig A, Skranes J, Ernst T, Madsen BO, Hernes SS. Cortical Thickness Changes After Computerized Working Memory Training in Patients With Mild Cognitive Impairment. Front Aging Neurosci. 2022 Apr 4;14:796110. doi: 10.3389/fnagi.2022.796110. eCollection 2022. |
| 29101632 | Background | Panee J, Gerschenson M, Chang L. Associations Between Microbiota, Mitochondrial Function, and Cognition in Chronic Marijuana Users. J Neuroimmune Pharmacol. 2018 Mar;13(1):113-122. doi: 10.1007/s11481-017-9767-0. Epub 2017 Nov 4. |
| 29098063 | Background | Tyrrell DJ, Bharadwaj MS, Jorgensen MJ, Register TC, Shively C, Andrews RN, Neth B, Keene CD, Mintz A, Craft S, Molina AJA. Blood-Based Bioenergetic Profiling Reflects Differences in Brain Bioenergetics and Metabolism. Oxid Med Cell Longev. 2017;2017:7317251. doi: 10.1155/2017/7317251. Epub 2017 Oct 2. |
| 23158761 | Background | Chang L, Holt JL, Yakupov R, Jiang CS, Ernst T. Lower cognitive reserve in the aging human immunodeficiency virus-infected brain. Neurobiol Aging. 2013 Apr;34(4):1240-53. doi: 10.1016/j.neurobiolaging.2012.10.012. Epub 2012 Nov 15. |
| 16585053 | Background | Chang L, Yakupov R, Cloak C, Ernst T. Marijuana use is associated with a reorganized visual-attention network and cerebellar hypoactivation. Brain. 2006 May;129(Pt 5):1096-112. doi: 10.1093/brain/awl064. Epub 2006 Apr 3. |
| 15893942 | Background | Tomasi D, Caparelli EC, Chang L, Ernst T. fMRI-acoustic noise alters brain activation during working memory tasks. Neuroimage. 2005 Aug 15;27(2):377-86. doi: 10.1016/j.neuroimage.2005.04.010. |
| 15589105 | Background | Tomasi D, Ernst T, Caparelli EC, Chang L. Practice-induced changes of brain function during visual attention: a parametric fMRI study at 4 Tesla. Neuroimage. 2004 Dec;23(4):1414-21. doi: 10.1016/j.neuroimage.2004.07.065. |
| 12948723 | Background | Ernst T, Chang L, Arnold S. Increased glial metabolites predict increased working memory network activation in HIV brain injury. Neuroimage. 2003 Aug;19(4):1686-93. doi: 10.1016/s1053-8119(03)00232-5. |
| 12427881 | Background | Ernst T, Chang L, Jovicich J, Ames N, Arnold S. Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology. 2002 Nov 12;59(9):1343-9. doi: 10.1212/01.wnl.0000031811.45569.b0. |
| 26833223 | Background | Chang L, Lohaugen GC, Douet V, Miller EN, Skranes J, Ernst T. Neural correlates of working memory training in HIV patients: study protocol for a randomized controlled trial. Trials. 2016 Feb 2;17:62. doi: 10.1186/s13063-016-1160-4. |
| 24886034 | Background | Flak MM, Hernes SS, Chang L, Ernst T, Douet V, Skranes J, Lohaugen GC. The Memory Aid study: protocol for a randomized controlled clinical trial evaluating the effect of computer-based working memory training in elderly patients with mild cognitive impairment (MCI). Trials. 2014 May 3;15:156. doi: 10.1186/1745-6215-15-156. |
| 27761943 | Background | Chang L, Lohaugen GC, Andres T, Jiang CS, Douet V, Tanizaki N, Walker C, Castillo D, Lim A, Skranes J, Otoshi C, Miller EN, Ernst TM. Adaptive working memory training improved brain function in human immunodeficiency virus-seropositive patients. Ann Neurol. 2017 Jan;81(1):17-34. doi: 10.1002/ana.24805. Epub 2016 Dec 28. |
| 22470330 | Background | Brehmer Y, Westerberg H, Backman L. Working-memory training in younger and older adults: training gains, transfer, and maintenance. Front Hum Neurosci. 2012 Mar 27;6:63. doi: 10.3389/fnhum.2012.00063. eCollection 2012. |
| 29592650 | Background | Kramer AF, Colcombe S. Fitness Effects on the Cognitive Function of Older Adults: A Meta-Analytic Study-Revisited. Perspect Psychol Sci. 2018 Mar;13(2):213-217. doi: 10.1177/1745691617707316. |
| 17629545 | Background | Kramer AF, Erickson KI. Capitalizing on cortical plasticity: influence of physical activity on cognition and brain function. Trends Cogn Sci. 2007 Aug;11(8):342-8. doi: 10.1016/j.tics.2007.06.009. Epub 2007 Jul 12. |