Improving Neurological Health with Acetylcholine via Neuroplasticity-based Computerized Exercise in Mild Cognitive Impairment (INHANCE-MCI)

Acetylcholine plays a key role in regulating synaptic plasticity and mediating crucial aspects of cognitive function. Unfortunately, binding levels of acetylcholine decline by an estimated 2.5% per decade throughout the lifespan, with sharper decreases observed in individuals with mild cognitive impairment. Computerized brain training may enhance cholinergic neurotransmission, potentially slowing cognitive decline associated with these deficits. In the current proposal, we will deploy a computerized cognitive training program (INHANCE-MCI), inspired by the positive findings of the recently completed INHANCE study (2R44AG039965-05). This cognitive training intervention was partially developed through two successful SBIR-funded Phase II programs (R44AG039965; R44NS071780). The program will integrate two validated but historically independent computerized exercises that, based on prior research, may synergistically reduce the long-term risk of dementia onset. This prospective, double-blind, parallel-arm, active-controlled clinical trial will randomize patients with mild cognitive impairment to intervention or active control and evaluate changes in cholinergic function, cognitive performance, and functional abilities. The broader objectives of the project are two-fold: (1) to uncover the mechanisms through which specific forms of brain training deliver cognitive and functional gains to address the rapid rise in neurodegenerative diseases and (2) to promote widespread availability of the program. An effective, low-cost, and highly scalable program, available across platforms (web, iOS, Android) on both internet-connected and offline devices, offers the potential for global reach, extending the accessibility of brain health strategies in at-risk adults. With such computerized tools in hand, we can enhance the lives of patients and their families, alleviate the significant financial burden associated with cognitive impairment, and make strides toward creating a healthier society and a more efficient healthcare system.