Cognitive training and neuroplasticity in mild cognitive impairment (COG-IT): protocol for a two-site, blinded, randomised, controlled treatment trial

Abstract

Introduction: Mild cognitive impairment (MCI) is common in older adults and represents a high-risk group for progression to Alzheimer's disease (AD). Medication trials in MCI have generally failed, but new discoveries with brain plasticity in ageing have led to the study of cognitive training as a potential treatment to improve cognitive abilities. Computerised cognitive training (CCT) involves computerised cognitive exercises that target specific cognitive abilities and neural networks to potentially improve cognitive functioning through neuroplasticity.

Methods and analysis: In a two-site study (New York State Psychiatric Institute/Columbia University Medical Center and Duke University Medical Center), we will randomise 100 patients with MCI (Wechsler Memory Scale-III Logical Memory II score 0-11; Folstein Mini Mental State Examination ≥23) to home-based CCT (suite of exercises: memory, matching, spatial recognition, processing speed) or a home-based active control condition (computerised crossword puzzle training (CPT)) with 12 weeks of intensive training followed by regular booster sessions up to 78 weeks. All patients will receive standard neuropsychological and functional assessments in clinic as well as structural/functional brain MRI scans at study entry and endpoint. We will test if CCT, versus CPT, leads to improved cognitive functioning, transfers to functional ability and tasks of everyday life and impacts hippocampal volume changes and changes in the default mode network of the brain measured by resting-state functional MRI.

Ethics and dissemination: The study will be conducted following ethics approval and written informed consent will be obtained from all subjects. Study results will be disseminated via publication, clinicaltrials.gov, media and conference presentations. This will be the first controlled long-term trial to evaluate the effects of home-based CCT versus computerised CPT on cognitive abilities and functional measures and neural outcomes as determined by MRI indices in patients with MCI. Positive results from trial may support further development of home-based CCT.

Trial registration number: ClinicalTrials.gov identifier (NCT03205709).

Keywords: clinical trials; delirium and cognitive disorders; dementia; magnetic resonance imaging.

Conflict of interest statement

Competing interests: JLD, LSP, TEG, JRS, SNR, NAK, HFA, CAH, SNT, EP, JRP have no competing interests. PMD has received research grants and advisory fees from several companies in this field for other studies, and owns shares in several companies whose products are not discussed here. DPD serves as a consultant on advisory boards to Acadia, Avanir, Genentech, Eisai, and Neuronix.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Conceptual model in the intervention phase patients are randomly assigned to either CCT or CPT. To evaluate cognitive status, the primary outcome measure will be the ADAS-Cog 11, the secondary outcome measure will be the neuropsychological testing composite score and the exploratory outcome measure will be the neurocognitive performance test. To evaluate functional status, the primary outcome measure will be the UPSA and the secondary outcome measure will be the FAQ. To evaluate changes in neural circuitry, the primary outcome measures will include hippocampal volume (MRI) and DMN connectivity (fMRI). AD, Alzheimer’s disease; ADAS-Cog, 11 Alzheimer’s Disease Assessment Scale—Cognitive Subscale 11; CCT, computerised cognitive training; CPT, crossword puzzle training; DMN, default mode network; FAQ, Functional Assessment Questionnaire; fMRI functional MRI; MCI mild cognitive impairment; UPSA UCSD Performance-Based Skills Assessment.