Multi-Domain Exercise and Memory in Adults Relative to ApoE Genotype: A fMRI Study

The current project utilizes a single-blinded, double arm, 6-month randomized controlled trial to assess the effects of a multi-domain exercise program on memory performance, as well as cortical activities during the memory tasks in cognitively intact adults (i.e., 45-70 years). In addition, the potential moderator role of apolipoprotein epsilon-4 (ApoE e4) status and the mediator role of the brain-derived neurotrophic factor (BDNF) will be explored.

Aging has been adversely associated with the deterioration of cognitive and brain functions. Most research on the effects of regular exercise on cognitive and brain functions has been focused on exercise programs with a single mode of exercise. Studies focusing on the effects of exercise programs with multi-domains on cognitive function and cortical functionality are sparse in late-middle-aged and older adults. In addition, while growing evidence has revealed the beneficial effects of regular exercise on cognitive function, scientific evidence regarding the effects of multi-domain exercise programs on cognitive function and brain function in late-middle-aged and older adults who are with or without the genetic risk for Alzheimer's disease (AD) is scarce. Lastly, the potential mediator role of the brain-derived neurotrophic factor (BDNF) in individuals is required to be explored.

In the current study, a single-blinded, double arm, 6-month randomized controlled trial has been utilized to assess the effects of a multi-domain exercise program containing multiple physical fitness components, meditation, and social interaction on memory, as well as cortical functionalities during the memory tasks in cognitively intact adults (i.e., 45-70 years). Specifically, the project aims to examine: (1) the causal links between a multi-domain exercise program composed of various physical fitness components, meditation, and social interaction against a control group on the memory performance in cognitively intact adults aged between 45 and 70 years with or without a genetic risk for AD, (2) the cortical functionality through functional images collected through a series of functional magnetic resonance images (fMRI), and (3) the potential influence of apolipoprotein epsilon-4 (ApoE e4) and BDNF on the effects of exercise.

One hundred eligible individuals will participate in the current study and will be randomly assigned into either the 6-month multi-domain exercise group (exercise group) or the online educational course group (control group).

All participants' physical fitness, cognitive function, and cortical functionalities via fMRI scanning will be assessed at the Baseline (Baseline-Assessments) and at the cessation of the 6-month intervention (Post-Assessments). The potential moderating role of ApoE genotypes and the mediation role of BDNF will be explored. Participation in this study will take approximately 7 months.

Eligibility Criteria:
Inclusion Criteria:

* Normal or corrected-to-normal vision
* Able to speak and read Chinese
* Scores of Mini-Mental Status Examination \>= 25
* Physical Activity Readiness Questionnaire score \< 0
* Able to conduct the exercise with moderate intensity
* Meet the criteria to undergo magnetic resonance imaging
* Provide informed consent

Exclusion Criteria:

* Diagnosed or self-reported cognitive problems (e.g., mild cognitive impairment or dementia)
* Diagnosed or self-reported physical disease (e.g., untreated hypertension and chronic heart disease, stroke, brain tumor, musculoskeletal disorders, other exercise contradictions)
* Diagnosed or self-reported major psychiatric illness (e.g., major depression, schizophrenia)
* Diagnosed or self-reported neurodegenerative disease (e.g., Alzheimer's disease and other dementias, Parkinson's disease (PD) and PD-related disorders, Huntington's disease)
* History of alcohol or drug abuse
* History of chemotherapy
* Traveling consecutively for three weeks or more during the study
* Unwillingness to be randomized to one of the two groups
* Currently participating in another study trial

Exclusion Criteria for functional magnetic resonance images (fMRI):

Participants will be excluded if s/he has a contraindication to fMRI scanning, such as aneurysm clip, implanted neural stimulator, cochlear implant, any implanted device, cardiac pacemaker. To ensure volunteers are eligible for the current project, they will be asked to fill out a questionnaire to inform whether they have conditions (e.g. paralyzed hemidiaphragm) or present unnecessary risks (e.g., pregnancy) during the recruitment period.