Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is characterized by a gradual decline in cognitive processes and functional abilities. It significantly impacts patients, caregivers, and society as a whole. Individuals with amnestic Mild Cognitive Impairment (a-MCI) are at greater risk for progression to AD than normal healthy older adults. Given that cognitive functioning is still relatively intact in a-MCI, it is a particularly promising target for cognitive training interventions, which capitalize on preserved cognitive abilities. However, there are few well-controlled training studies in MCI. The prefrontal cortex (PFC) is a promising and viable target for cognitive training in MCI. The proposed repetition lag training procedure (RLTP) is a theoretically based, clinically relevant, and innovative incremented difficulty training procedure that is designed to train the PFC-supported general cognitive process of recollection and has shown promise in preliminary studies in high functioning older adults and MCI patients. The proposed pilot clinical trial will test the effects of the RLTP in combination with a theoretically and empirically supported pre-training program in mnemonic strategy use in a single blind randomized controlled design in a-MCI patients, with a 9-month post-intervention follow-up period. Outcome measures were carefully selected to cover a wide range of domains: cognitive neuropsychological, self-report and behavioral measures of everyday functioning and awareness of memory impairment/metamemory, quality of life, caregiver burden, and neuropsychiatric symptoms.
Specific Aim 1 is to test the hypothesis that a-MCI patients will improve on the repetition lag task following training.
Specific Aim 2 is to test the hypothesis that a-MCI patients who are exposed to the training intervention (experimental group) will show greater improvement in cognitive, functional, and neuropsychiatric measures from baseline to post- training, relative to a-MCI patients who are not exposed to the intervention but who have a similar amount of contact with staff, time in the laboratory, and cognitive stimulation (control group).
Specific Aim 3 is to test the hypothesis that better baseline performance on executive function and metamemory tasks and higher education level will be associated with higher post-training improvement scores, and that higher depressive symptoms and age will be associated with lower post-training scores.
Specific Aim 4 is to test the degree to which training benefits are maintained at follow-up. Findings will provide clinically relevant information about the short- and long-term effects of an innovative training procedure that has the potential to improve daily functioning. They will also enhance scientific understanding of the malleability of PFC-based processes in response to training interventions in MCI, the role of these processes in individual treatment response, and the ability of such training to slow AD symptom progression. Data will also provide information about the relative sensitivity of different cognitive and functional measures, and about specific training parameters, response predictors and follow-up effects, which will be used to refine the design of a full-scale clinical trial.

Public Health Relevance

Individuals with amnestic Mild Cognitive Impairment (a-MCI) are at greater risk for progression to Alzheimer's Disease (AD) than normal healthy older adults. This pilot clinical trial will test the ability of an innovative and theoretically based memory training intervention to improve cognitive, neuropsychiatric and everyday functioning in a-MCI patients, to maintain that improvement across a 9-month follow-up period, and to slow progression of AD symptoms.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BBBP-N (52))
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Ryan, Laurie M
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Johns Hopkins University
Schools of Medicine
United States
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