mSIM: Mobile Simultaneous Aerobic Exercise and Memory Training Intervention for Amnestic Mild Cognitive Impairment

NCT04185298 | Terminated Results DMC

• 2 other identifiers: 20191298R21AG061494
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The mSIM study involves developing and conducting feasibility testing of a web-based application that will deliver mobile-based simultaneous exercise and memory skills training program (mSIM) for amnesic Mild Cognitive Impairment (aMCI) patients. The randomized control trial (RCT) will evaluate the efficacy of mSIM on memory performance and everyday functioning using 2 study arms (Group 1 activity monitoring control (via Fitbit) (CON) vs Group 2 mSIM intervention plus activity monitoring via Fitbit). mSIM treatment response will be evaluated using neuropsychological and functional evaluation. Concentration levels of peripheral biomarkers Brain-derived neurotrophic factor (BDNF) and norepinephrine (NE) also be assessed.

Conditions

Amnestic Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (2)

• Memory Function Composite Score

  Global Z-Score including results from RAVLT (Rey's Auditory Verbal Learning Test), Wechsler Memory Scale Fourth Edition (WMS-IV) Logical Memory and Visual Reproduction tests. The global z score was constructed by: First z-transforming all raw test scores (RAVLT, Logical Memory (LM) I Total, LM II Total, Visual Reproduction (VR) I and VR II) Averaging over RAVLT Z, LM Z, and VR Z to obtain a global Z 0=sample mean; higher scores indicate better outcomes.

  Baseline, approximately 3 months and approximately 6 months

• Functional Abilities

  Assessed using the Multifactorial Memory Questionnaire (MMQ) Satisfaction Sub-scale (0-72 points). Higher scores indicate better outcomes.

  Baseline, approximately 3 months and approximately 6 months

Secondary Outcomes (2)

• Resting Brain-derived Neurotrophic Factor (BDNF)

  Baseline and approximately 6 months

• Resting Norepinephrine (NE)

  Baseline and approximately 6 months

Study Arms (2)

Group 1 (No treatment)

ACTIVE COMPARATOR

Group 1: Participants will have continuous activity monitoring (via Fitbit)

Behavioral: mSIM intervention plus activity monitoring

Group 2 (Experimental)

EXPERIMENTAL

Group 2: Participants will receive the mSIM treatment and have their activity monitored continuously (via Fitbit)

Behavioral: Activity monitoring

Interventions

mSIM intervention plus activity monitoring BEHAVIORAL

Participants will receive the full mSIM intervention and be monitored (via Fitbit)

Group 1 (No treatment)

Activity monitoring BEHAVIORAL

Participants will have activity monitored (via Fitbit)

Group 2 (Experimental)

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be age 50 to 80 at time of informed consent.
• Subjects must confirm an aMCI diagnosis either by providing records from a clinical assessment within 6 months of enrollment in this study or through a brief memory assessment by study staff at screening.
• Subjects must be proficient in spoken and written English for consenting as well as for study participation since the intervention in this study is currently only available in English.
• Subjects with medical conditions must be stable for these conditions. Stable control on medication is acceptable.
• Subjects, with or without assistance, must be able to use a computer and web interface. If assistance is needed, it must be readily available to them.
• Subjects are required to have internet with Wi-Fi at the location of their mSIM training.
• Subject must have normal visual acuity (or corrected to normal) and normal color vision as indicated by self-report.
• Subject must have adequate hearing acuity as indicated by self-report.
• Subject must have adequate motor capacity to use a mobile phone/iPad/computer as indicated by self-report.
• Subjects must be able to provide medical clearance to participate in an unsupervised, moderate intensity exercise program from a physician.

You may not qualify if:

• Subjects must not have an existing diagnosis of a neurodegenerative disorder (e.g., Alzheimer's Disease, Lewy Body Dementia, Frontal-Temporal Dementia).
• Subjects must not have a prior diagnosis that might impact cognition and movement abilities including: significant cardiovascular disease, significant respiratory disease, illness or injury, substance abuse, schizophrenia, bipolar disorder, or other neurological diseases.
• Subjects must not have a previous Mini Mental State Exam (MMSE) score below 19.
• Subjects must not have a previous Clinical Dementia Rating (CDR) global score of ≥2.
• Subjects must not have a Montreal Cognitive Assessment (MoCA)43 score of below 18 previously or during their screening evaluation.
• Subjects must not demonstrate a progression of aMCI to dementia at screening based on the best judgement of a study Clinical Neuropsychologist.
• Subjects must not currently participate in a high level of physical activity prior to study start as assessed by the International Physical Activity Questionnaire (IPAQ) at screening.
• Subjects must not endorse that they are unable to participate in moderate intensity aerobic activities, such as fast walking or passing/kicking a ball to a partner at screening.

Sponsors & Collaborators

• Jennifer Bramen: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Pacific Brain Health Center

Santa Monica, California, 90404, United States

Location

Related Publications (48)

• Rozzini L, Chilovi BV, Conti M, Bertoletti E, Delrio I, Trabucchi M, Padovani A. Conversion of amnestic Mild Cognitive Impairment to dementia of Alzheimer type is independent to memory deterioration. Int J Geriatr Psychiatry. 2007 Dec;22(12):1217-22. doi: 10.1002/gps.1816.

  PMID: 17562522 BACKGROUND

• Naismith SL, Glozier N, Burke D, Carter PE, Scott E, Hickie IB. Early intervention for cognitive decline: is there a role for multiple medical or behavioural interventions? Early Interv Psychiatry. 2009 Feb;3(1):19-27. doi: 10.1111/j.1751-7893.2008.00102.x.

  PMID: 21352171 BACKGROUND

• Merrill DA, Small GW. Prevention in psychiatry: effects of healthy lifestyle on cognition. Psychiatr Clin North Am. 2011 Mar;34(1):249-61. doi: 10.1016/j.psc.2010.11.009. Epub 2010 Dec 16.

  PMID: 21333851 BACKGROUND

• Rodakowski J, Saghafi E, Butters MA, Skidmore ER. Non-pharmacological interventions for adults with mild cognitive impairment and early stage dementia: An updated scoping review. Mol Aspects Med. 2015 Jun-Oct;43-44:38-53. doi: 10.1016/j.mam.2015.06.003. Epub 2015 Jun 10.

  PMID: 26070444 BACKGROUND

• Smith PJ, Blumenthal JA, Hoffman BM, Cooper H, Strauman TA, Welsh-Bohmer K, Browndyke JN, Sherwood A. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med. 2010 Apr;72(3):239-52. doi: 10.1097/PSY.0b013e3181d14633. Epub 2010 Mar 11.

  PMID: 20223924 BACKGROUND

• Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, Macchi C. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med. 2011 Jan;269(1):107-17. doi: 10.1111/j.1365-2796.2010.02281.x. Epub 2010 Sep 10.

  PMID: 20831630 BACKGROUND

• Huckans M, Hutson L, Twamley E, Jak A, Kaye J, Storzbach D. Efficacy of cognitive rehabilitation therapies for mild cognitive impairment (MCI) in older adults: working toward a theoretical model and evidence-based interventions. Neuropsychol Rev. 2013 Mar;23(1):63-80. doi: 10.1007/s11065-013-9230-9. Epub 2013 Mar 8.

  PMID: 23471631 BACKGROUND

• Snowden M, Steinman L, Mochan K, Grodstein F, Prohaska TR, Thurman DJ, Brown DR, Laditka JN, Soares J, Zweiback DJ, Little D, Anderson LA. Effect of exercise on cognitive performance in community-dwelling older adults: review of intervention trials and recommendations for public health practice and research. J Am Geriatr Soc. 2011 Apr;59(4):704-16. doi: 10.1111/j.1532-5415.2011.03323.x. Epub 2011 Mar 25.

  PMID: 21438861 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.

  PMID: 29592650 BACKGROUND

• Bamidis PD, Vivas AB, Styliadis C, Frantzidis C, Klados M, Schlee W, Siountas A, Papageorgiou SG. A review of physical and cognitive interventions in aging. Neurosci Biobehav Rev. 2014 Jul;44:206-20. doi: 10.1016/j.neubiorev.2014.03.019. Epub 2014 Apr 4.

  PMID: 24705268 BACKGROUND

• Zhu X, Yin S, Lang M, He R, Li J. The more the better? A meta-analysis on effects of combined cognitive and physical intervention on cognition in healthy older adults. Ageing Res Rev. 2016 Nov;31:67-79. doi: 10.1016/j.arr.2016.07.003. Epub 2016 Jul 14.

  PMID: 27423932 BACKGROUND

• Law LL, Barnett F, Yau MK, Gray MA. Effects of combined cognitive and exercise interventions on cognition in older adults with and without cognitive impairment: a systematic review. Ageing Res Rev. 2014 May;15:61-75. doi: 10.1016/j.arr.2014.02.008. Epub 2014 Mar 12.

  PMID: 24632497 BACKGROUND

• Karssemeijer EGA, Aaronson JA, Bossers WJ, Smits T, Olde Rikkert MGM, Kessels RPC. Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis. Ageing Res Rev. 2017 Nov;40:75-83. doi: 10.1016/j.arr.2017.09.003. Epub 2017 Sep 12.

  PMID: 28912076 BACKGROUND

• McEwen SC, Siddarth P, Rahi B, Kim Y, Mui W, Wu P, Emerson ND, Lee J, Greenberg S, Shelton T, Kaiser S, Small GW, Merrill DA. Simultaneous Aerobic Exercise and Memory Training Program in Older Adults with Subjective Memory Impairments. J Alzheimers Dis. 2018;62(2):795-806. doi: 10.3233/JAD-170846.

  PMID: 29480182 BACKGROUND

• Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WT. Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5568-72. doi: 10.1073/pnas.87.14.5568.

  PMID: 1695380 BACKGROUND

• van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13427-31. doi: 10.1073/pnas.96.23.13427.

  PMID: 10557337 BACKGROUND

• Kleim JA, Markham JA, Vij K, Freese JL, Ballard DH, Greenough WT. Motor learning induces astrocytic hypertrophy in the cerebellar cortex. Behav Brain Res. 2007 Mar 28;178(2):244-9. doi: 10.1016/j.bbr.2006.12.022. Epub 2007 Jan 25.

  PMID: 17257689 BACKGROUND

• Hotting K, Roder B. Beneficial effects of physical exercise on neuroplasticity and cognition. Neurosci Biobehav Rev. 2013 Nov;37(9 Pt B):2243-57. doi: 10.1016/j.neubiorev.2013.04.005. Epub 2013 Apr 25.

  PMID: 23623982 BACKGROUND

• Lista I, Sorrentino G. Biological mechanisms of physical activity in preventing cognitive decline. Cell Mol Neurobiol. 2010 May;30(4):493-503. doi: 10.1007/s10571-009-9488-x. Epub 2009 Dec 30.

  PMID: 20041290 BACKGROUND

• Novkovic T, Mittmann T, Manahan-Vaughan D. BDNF contributes to the facilitation of hippocampal synaptic plasticity and learning enabled by environmental enrichment. Hippocampus. 2015 Jan;25(1):1-15. doi: 10.1002/hipo.22342. Epub 2014 Aug 28.

  PMID: 25112659 BACKGROUND

• Vaynman S, Ying Z, Gomez-Pinilla F. Exercise induces BDNF and synapsin I to specific hippocampal subfields. J Neurosci Res. 2004 May 1;76(3):356-62. doi: 10.1002/jnr.20077.

  PMID: 15079864 BACKGROUND

• Gomez-Pinilla F, Vaynman S, Ying Z. Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. Eur J Neurosci. 2008 Dec;28(11):2278-87. doi: 10.1111/j.1460-9568.2008.06524.x.

  PMID: 19046371 BACKGROUND

• Neeper SA, Gomez-Pinilla F, Choi J, Cotman C. Exercise and brain neurotrophins. Nature. 1995 Jan 12;373(6510):109. doi: 10.1038/373109a0. No abstract available.

  PMID: 7816089 BACKGROUND

• Gunstad J, Benitez A, Smith J, Glickman E, Spitznagel MB, Alexander T, Juvancic-Heltzel J, Murray L. Serum brain-derived neurotrophic factor is associated with cognitive function in healthy older adults. J Geriatr Psychiatry Neurol. 2008 Sep;21(3):166-70. doi: 10.1177/0891988708316860. Epub 2008 May 23.

  PMID: 18503034 BACKGROUND

• Erickson KI, Miller DL, Roecklein KA. The aging hippocampus: interactions between exercise, depression, and BDNF. Neuroscientist. 2012 Feb;18(1):82-97. doi: 10.1177/1073858410397054. Epub 2011 Apr 29.

  PMID: 21531985 BACKGROUND

• Nascimento CM, Pereira JR, de Andrade LP, Garuffi M, Talib LL, Forlenza OV, Cancela JM, Cominetti MR, Stella F. Physical exercise in MCI elderly promotes reduction of pro-inflammatory cytokines and improvements on cognition and BDNF peripheral levels. Curr Alzheimer Res. 2014;11(8):799-805. doi: 10.2174/156720501108140910122849.

  PMID: 25212919 BACKGROUND

• McMorris T, Davranche K, Jones G, Hall B, Corbett J, Minter C. Acute incremental exercise, performance of a central executive task, and sympathoadrenal system and hypothalamic-pituitary-adrenal axis activity. Int J Psychophysiol. 2009 Sep;73(3):334-40. doi: 10.1016/j.ijpsycho.2009.05.004. Epub 2009 May 18.

  PMID: 19454298 BACKGROUND

• Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM. Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease. Neurobiol Aging. 2007 Mar;28(3):327-35. doi: 10.1016/j.neurobiolaging.2006.02.007. Epub 2006 Mar 29.

  PMID: 16574280 BACKGROUND

• Klimesch W, Sauseng P, Hanslmayr S. EEG alpha oscillations: the inhibition-timing hypothesis. Brain Res Rev. 2007 Jan;53(1):63-88. doi: 10.1016/j.brainresrev.2006.06.003. Epub 2006 Aug 1.

  PMID: 16887192 BACKGROUND

• Richard Clark C, Veltmeyer MD, Hamilton RJ, Simms E, Paul R, Hermens D, Gordon E. Spontaneous alpha peak frequency predicts working memory performance across the age span. Int J Psychophysiol. 2004 Jun;53(1):1-9. doi: 10.1016/j.ijpsycho.2003.12.011.

  PMID: 15172130 BACKGROUND

• Vlahou EL, Thurm F, Kolassa IT, Schlee W. Resting-state slow wave power, healthy aging and cognitive performance. Sci Rep. 2014 May 29;4:5101. doi: 10.1038/srep05101.

  PMID: 24869503 BACKGROUND

• Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Brain Res Rev. 1999 Apr;29(2-3):169-95. doi: 10.1016/s0165-0173(98)00056-3.

  PMID: 10209231 BACKGROUND

• Li Y, Zhao Z, Cai J, Gu B, Lv Y, Zhao L. The Frequency-Dependent Aerobic Exercise Effects of Hypothalamic GABAergic Expression and Cardiovascular Functions in Aged Rats. Front Aging Neurosci. 2017 Jun 30;9:212. doi: 10.3389/fnagi.2017.00212. eCollection 2017.

  PMID: 28713263 BACKGROUND

• Bondi MW, Edmonds EC, Jak AJ, Clark LR, Delano-Wood L, McDonald CR, Nation DA, Libon DJ, Au R, Galasko D, Salmon DP. Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. J Alzheimers Dis. 2014;42(1):275-89. doi: 10.3233/JAD-140276.

  PMID: 24844687 BACKGROUND

• Bondi MW, Jak AJ, Delano-Wood L, Jacobson MW, Delis DC, Salmon DP. Neuropsychological contributions to the early identification of Alzheimer's disease. Neuropsychol Rev. 2008 Mar;18(1):73-90. doi: 10.1007/s11065-008-9054-1. Epub 2008 Mar 18.

  PMID: 18347989 BACKGROUND

• Clark LR, Delano-Wood L, Libon DJ, McDonald CR, Nation DA, Bangen KJ, Jak AJ, Au R, Salmon DP, Bondi MW. Are empirically-derived subtypes of mild cognitive impairment consistent with conventional subtypes? J Int Neuropsychol Soc. 2013 Jul;19(6):635-45. doi: 10.1017/S1355617713000313. Epub 2013 Apr 3.

  PMID: 23552486 BACKGROUND

• Edmonds EC, Delano-Wood L, Clark LR, Jak AJ, Nation DA, McDonald CR, Libon DJ, Au R, Galasko D, Salmon DP, Bondi MW; Alzheimer's Disease Neuroimaging Initiative. Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors. Alzheimers Dement. 2015 Apr;11(4):415-24. doi: 10.1016/j.jalz.2014.03.005. Epub 2014 May 22.

  PMID: 24857234 BACKGROUND

• Nuriel T, Angulo SL, Khan U, Ashok A, Chen Q, Figueroa HY, Emrani S, Liu L, Herman M, Barrett G, Savage V, Buitrago L, Cepeda-Prado E, Fung C, Goldberg E, Gross SS, Hussaini SA, Moreno H, Small SA, Duff KE. Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer's disease-like pathology. Nat Commun. 2017 Nov 13;8(1):1464. doi: 10.1038/s41467-017-01444-0.

  PMID: 29133888 BACKGROUND

• Jak AJ, Bondi MW, Delano-Wood L, Wierenga C, Corey-Bloom J, Salmon DP, Delis DC. Quantification of five neuropsychological approaches to defining mild cognitive impairment. Am J Geriatr Psychiatry. 2009 May;17(5):368-75. doi: 10.1097/JGP.0b013e31819431d5.

  PMID: 19390294 BACKGROUND

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 BACKGROUND

• Miller KJ, Siddarth P, Gaines JM, Parrish JM, Ercoli LM, Marx K, Ronch J, Pilgram B, Burke K, Barczak N, Babcock B, Small GW. The memory fitness program: cognitive effects of a healthy aging intervention. Am J Geriatr Psychiatry. 2012 Jun;20(6):514-23. doi: 10.1097/JGP.0b013e318227f821.

  PMID: 21765343 BACKGROUND

• Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E, Kramer AF. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci. 2003 Feb;58(2):176-80. doi: 10.1093/gerona/58.2.m176.

  PMID: 12586857 BACKGROUND

• Foster C, Jackson AS, Pollock ML, Taylor MM, Hare J, Sennett SM, Rod JL, Sarwar M, Schmidt DH. Generalized equations for predicting functional capacity from treadmill performance. Am Heart J. 1984 Jun;107(6):1229-34. doi: 10.1016/0002-8703(84)90282-5. No abstract available.

  PMID: 6720550 BACKGROUND

• Polacchini A, Metelli G, Francavilla R, Baj G, Florean M, Mascaretti LG, Tongiorgi E. A method for reproducible measurements of serum BDNF: comparison of the performance of six commercial assays. Sci Rep. 2015 Dec 10;5:17989. doi: 10.1038/srep17989.

  PMID: 26656852 BACKGROUND

• Segal SK, Cotman CW, Cahill LF. Exercise-induced noradrenergic activation enhances memory consolidation in both normal aging and patients with amnestic mild cognitive impairment. J Alzheimers Dis. 2012;32(4):1011-8. doi: 10.3233/JAD-2012-121078.

  PMID: 22914593 BACKGROUND

• Will PM, Walter JD. Exercise testing: improving performance with a ramped Bruce protocol. Am Heart J. 1999 Dec;138(6 Pt 1):1033-7. doi: 10.1016/s0002-8703(99)70067-0.

  PMID: 10577432 BACKGROUND

• Balady GJ, Chaitman B, Driscoll D, Foster C, Froelicher E, Gordon N, Pate R, Rippe J, Bazzarre T. Recommendations for cardiovascular screening, staffing, and emergency policies at health/fitness facilities. Circulation. 1998 Jun 9;97(22):2283-93. doi: 10.1161/01.cir.97.22.2283. No abstract available.

  PMID: 9631884 BACKGROUND

• Gualtieri CT, Johnson LG. Reliability and validity of a computerized neurocognitive test battery, CNS Vital Signs. Arch Clin Neuropsychol. 2006 Oct;21(7):623-43. doi: 10.1016/j.acn.2006.05.007. Epub 2006 Oct 2.

  PMID: 17014981 BACKGROUND

Related Links

• World Health Organization (WHO) definitions
• Rivermead Behavioural Memory Test - Third Edition (RBMT-3)
• Use of the Functional Activities Questionnaire in Older Adults with Dementia
• Multifactorial Memory Questionnaire

Limitations and Caveats

Early termination due to small number of participants recruited and low intervention completion rates led to small numbers of subjects analyzed. One of the participants that completed the study in the intervention arm had a mid-trial concussion. Data are not interpretable.

Results Point of Contact

• Title: Dr. Jennifer Bramen
• Organization: Saint John's Cancer Institute

jennifer.bramen@providence.org

310-525-0865

Study Officials

• Jennifer Bramen, PhD

  Saint John's Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: The study will include two arms: Arm 1: activity monitoring only control (CON), Arm 2: active intervention with mSIM program (mSIM) plus activity monitoring (via Fitbit), to evaluate the efficacy of the mSIM intervention on memory performance and everyday functioning. The 'Activity monitoring only' arm will serve as the control group. Study objectives include measuring treatment related changes in memory performance and everyday functioning along with putative biomarkers of the behavioral changes.

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: December 4, 2019
• Study Start: October 1, 2019
• Primary Completion: April 17, 2023
• Study Completion: April 17, 2023
• Last Updated: January 14, 2025
• Results First Posted: January 14, 2025

Record last verified: 2025-01

Locations

US (1)