This study evaluates the efficacy and mechanism of internet-based cognitive control training on episodic memory function in patients with amnestic Mild Cognitive Impairment(aMCI). Half of participants will receive adaptive internet-based cognitive control training program, while the other half will receive a fixed, primary difficulty level task.

Background:

Alzheimer's disease (AD) is a common dementia in elderly populations, and amnestic mild cognitive impairment (aMCI) refers to a transitional stage between normal aging and early dementia. Patients with aMCI are at higher risks of evolving toward AD. Although it has been widely recognized that early intervention of aMCI holds the potential to delay or even reverse the cognitive impairment, no treatment is available yet. Episodic memory dysfunction is the characteristic impairment in aMCI, cognitive control training significantly improved executive function in patients with aMCI . Whether and how cognitive control training improves episodic memory function in patients with aMCI remains largely unknown.

Objectives:

The primary objective of this double-blinded, randomized RCT is to assess whether internet-based cognitive control training in patients with amnestic Mild Cognitive Impairment improves their episodic memory function. The second objective is to evaluate the effect of cognitive control training on neural plasticity, including brain activation and white matter integrity, which are assessed by functional and structural MRI.

Patients and Methods:

The proposed study is a single-center, double-blinded, randomized controlled trial that will include 70 patients diagnosed with aMCI from the neurology clinics at The First Affiliated Hospital, Zhejiang University. The patients will be randomized to either a training or a control group. The intervention is internet-based cognitive control training performed for 30 minutes over 60 sessions. Neuropsychological assessment and functional magnetic resonance imaging (MRI) will be performed before and 12 weeks after training.

Relevance:

Currently there is no known treatment available for aMCI. The proposed study is to determine the efficacy of cognitive control training on episodic memory function in patients with aMCI. Secondly, using functional and structural MRI, this study is to reveal the potential mechanism underlying cognitive control training.

Inclusion Criteria:

• Literate Chinese, aged 50 years and older
• Complaint about memory loss and confirmed by an informant
• Cognitive impairment in memory domain, adjusted for age and education
• Normal or near-normal performance on general cognitive function and no or minimum impairment of daily life activities
• Clinical dementia rating (CDR) =0.5, Mini-Mental State Examination (MMSE) score ≥ 20 (primary school) or ≥ 24 (junior school or above)
• Failure to meet the criteria for dementia

Exclusion Criteria:

• history of clinically significant stroke
• neurological diseases that may lead to neurological distortion, including schizophrenia, severe anxiety or depression, frontotemporal dementia，Huntington disease, brain tumor, parking disease, metabolic encephalopathy, encephalitis, multiple sclerosis, epilepsy, brain trauma, normal pressure hydrocephalus
• systemic diseases that may lead to neurological distortion, including hypothyroidism, folic acid deficiency, vitamin B12 deficiency, severe anemia, specific infection such as HIV and syphilis
• clinically significant gastrointestinal, renal, hepatic, respiratory, endocrine, or cardiovascular system disease;
• cancer, alcoholism, drug addiction;
• severe aphasia, physical disabilities, or any other factor that may preclude completion of neuropsychological testing;
• use of medications that may affect cognitive functioning, including tranquilizers, anti-anxiolytics, hypnotics, nootropics, and cholinomimetic agents;
• inability to undergo a brain MRI.