Can a serious game-based cognitive training attenuate cognitive decline related to Alzheimer's disease? Protocol for a randomized controlled trial

Abstract

Background: Alzheimer's disease (AD) is a major public health issue. Cognitive interventions such as computerized cognitive trainings (CCT) are effective in attenuating cognitive decline in AD. However, in those at risk of dementia related to AD, results are heterogeneous. Efficacy and feasibility of CCT needs to be explored in depth. Moreover, underlying mechanisms of CCT effects on the three cognitive domains typically affected by AD (episodic memory, semantic memory and spatial abilities) remain poorly understood.

Methods: In this bi-centric, randomized controlled trial (RCT) with parallel groups, participants (planned N = 162, aged 60-85 years) at risk for AD and with at least subjective cognitive decline will be randomized to one of three groups. We will compare serious game-based CCT against a passive wait list control condition and an active control condition (watching documentaries). Training will consist of daily at-home sessions for 10 weeks (50 sessions) and weekly on-site group meetings. Subsequently, the CCT group will continue at-home training for an additional twenty-weeks including monthly on-site booster sessions. Investigators conducting the cognitive assessments will be blinded. Group leaders will be aware of participants' group allocations. Primarily, we will evaluate change using a compound value derived from the comprehensive cognitive assessment for each of three cognitive domains. Secondary, longitudinal functional and structural magnetic resonance imaging (MRI) and evaluation of blood-based biomarkers will serve to investigate neuronal underpinnings of expected training benefits.

Discussion: The present study will address several shortcomings of previous CCT studies. This entails a comparison of serious game-based CCT with both a passive and an active control condition while including social elements crucial for training success and adherence, the combination of at-home and on-site training, inclusion of booster sessions and assessment of physiological markers. Study outcomes will provide information on feasibility and efficacy of serious game-based CCT in older adults at risk for AD and will potentially generalize to treatment guidelines. Moreover, we set out to investigate physiological underpinnings of CCT induced neuronal changes to form the grounds for future individually tailored interventions and neuro-biologically informed trainings.

Trial registration: This RCT was registered 1st of July 2020 at clinicaltrials.gov (Identifier NCT04452864).

Keywords: Alzheimer’s disease; Cognitive training; Computerized cognitive training; Magnetic resonance imaging; Mild cognitive impairment; Serious games; Subjective cognitive decline; Training adherence.

Fig. 1

a Study Design: In the three study arms participants perform a cognitive assessment four times with an interval of 3 months in-between. Neuroimaging is performed at baseline and after 3 months in all study arms. After 6 months neuroimaging is performed in the cognitive training and the waitlist control group and after 9 months in the waitlist control group only. Blood samples are collected once, in the first group appointment. b Assessment: Each assessment has a duration of approximately 3 hours if neuroimaging is included. Abbreviations Figure a: CCT = Computerized cognitive training, CG = Control group, A = Assessment, o = Neuroimaging. Abbreviations Figure b: MoCA = Montreal Cognitive Assessment, AVLT = Auditory verbal learning test, GNT = Graded naming test, fMRI = Functional magnetic resonance Imaging, ASL = Arterial spin labelling