Working Memory and Physical Exercise Training in Patients With Mild Cognitive Impairment

Official title

Adaptive Working Memory and Physical Exercise Training to Improve Brain and Mitochondrial Function in MCI

Overview

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.

Interventions

• Behavioral Progressive aerobic exercise
  Progressive aerobic exercise
• Behavioral Adaptive cognitive training
  Adaptive cognitive training
• Behavioral Combined
  Combine adaptive cognitive and progressive aerobic exercise training

Primary outcome measures

• Changes in Brain structure measures [Time frame: At baseline and at 4 weeks after the corresponding training program.]
• Changes in brain cortical thickness measures [Time frame: At baseline and at 4 weeks after the corresponding training program.]
• Changes in Brain microstructure measures [Time frame: 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 [Time frame: At baseline and at 4 weeks after the corresponding training program.]
• Changes in Brain Activation on functional MRI [Time frame: At baseline and at 4 weeks after the corresponding training program.]
• Changes in cognitive performance, emotions, and motor function based on NIH toolbox [Time frame: 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) [Time frame: At baseline and at 4 weeks after the corresponding training program.]
• Changes in Blood Bioenergetic Markers [Time frame: At baseline and at 4 weeks after the corresponding training program.]

Secondary outcome measures (1)

• VO2peak [Time frame: At baseline and within one week after the corresponding training program.]

Eligibility criteria

Inclusion criteria

• Adult men and women of all races and ethnicities who are 50-80 years of age will be eligible.
• Only sedentary adults will be eligible (engaging in structured activity for exercise <3x/week) for Progressive aerobic exercise or Combined training
• Ability to use, and accessibility to, an iPad or computer is required for the Adaptive cognitive training and Combined training.
• Fluent in English.
• The diagnosis of MCI will first be confirmed at the screening evaluation using the clinical dementia rating (CDR) scale and the Montreal Cognitive Assessment (MoCA). We will also evaluate their ADL using instrumental activities of daily living (IADL) to ensure they have preserved independence in functional abilities despite the cognitive deficits. The primary caregivers will be interviewed (either in person or by phone) for the participants' IADL to corroborate the independent functional status.

Exclusion criteria

• Does not have access to a computer or internet to perform the Cogmed® training AND is unwilling to come to the lab for the training.
• Unable to undergo an MRI investigation based on claustrophobia or metal foreign bodies.
• Symptomatic heart disease, Coronary artery disease, congestive heart failure, uncontrolled hypertension, uncontrolled diabetes (HbA1c>10%), significant cardiovascular disorders (on EKG and graded exercise test) that would prevent the participant from the exercise training; neurologic, musculoskeletal, or other condition that limits the subject's ability to complete study physical assessments.
• Estimated verbal Intelligence Quotient (IQ) below 70 (based on the Wechsler Test of Adult Reading) which would invalidate the informed consent process for the study.
• Self-reported moderate to severe substance use disorder(s) (e.g., self-reported intake >3 oz liquor, or three 4 oz glasses of wine, or three 12 oz cans of beer per day or illicit drug use).
• Severe chronic or acute medical or other (non-MCI) neuropsychiatric conditions that might confound the cognitive or brain imaging measures (e.g., liver function tests >2.5 normal range or evidence for renal failure).
• Body mass index >40 kg/m2.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Supportive care

Study locations

United States · 1 center

• University of Maryland Baltimore — Baltimore

Publications

• 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. PMID 24895057
• 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. PMID 28837640
• 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. PMID 28737289
• 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. PMID 35444526
• 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. PMID 29101632
• 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. PMID 29098063
• 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. PMID 23158761
• 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. PMID 16585053

Identifiers

NCT: NCT05948930 · HP-00105789

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗