Cognitive training (CT) is an increasingly popular, non-pharmacological intervention for improving cognitive functioning in neurodegenerative diseases and healthy aging. Although meta-analyses support the efficacy of CT in improving cognitive functioning, the neural mechanisms underlying the effects of CT are still unclear. We performed a systematic review of literature in the PubMed, Embase and PsycINFO databases on controlled CT trials (N > 20) in aging and neurodegenerative diseases with pre-and post-training functional MRI outcomes up to November 23rd 2018 (PROSPERO registration number CRD42019103662). Twenty articles were eligible for our systematic review. We distinguished between multi-domain and single-domain CT. CT induced both increases and decreases in task-related functional activation, possibly indicative of an inverted U-shaped curve association between regional brain activity and task performance. Functional connectivity within 'cognitive' brain networks was consistently reported to increase after CT while a minority of studies additionally reported increased segregation of frontoparietal and default mode brain networks. Although we acknowledge the large heterogeneity in type of CT, imaging methodology, in-scanner task paradigm and analysis methods between studies, we propose a working model of the effects of CT on brain activity and connectivity in the context of current knowledge on compensatory mechanisms that are associated with aging and neurodegenerative diseases.

Background Cognitive dysfunction is highly prevalent in Parkinson’s disease (PD) and a large proportion of patients eventually develops PD-related dementia. Currently, no effective treatment is available. Cognitive training is effective in relieving cognitive dysfunctions in several –neurodegenerative– diseases, and earlier small-scale trials have shown positive results for PD. In this randomized controlled trial, we assess the efficacy of online home-based cognitive training, its long-term effects, as well as the underlying neural correlates in a large group of PD patients. Methods In this double-blind randomized controlled trial we will include 140 non-demented patients with idiopathic PD that experience significant subjective cognitive complaints. Participants will be randomized into a cognitive training group and an active control group. In both groups, participants will individually perform an online home-based intervention for eight weeks, three times a week during 45 min. The cognitive training consists of thirteen games that focus on executive functions, attention and processing speed with an adaptive difficulty. The active control comprises three games that keep participants cognitively engaged without a training component. Participants will be subjected to extensive neuropsychological assessments at baseline and after the intervention, and at six months, one year and two years of follow-up. A subset of participants (40 in each treatment condition) will undergo structural and functional magnetic resonance imaging. The primary outcome of this study is the performance on the Tower of London task. Secondary outcomes are objective and subjective cognitive functioning, conversion to PD-related mild cognitive impairment or dementia, functional and structural connectivity and network topological indices measured with magnetic resonance imaging. None of the outcome measures are part of the cognitive training program. Data will be analyzed using multivariate mixed-model analyses and odds ratios. Discussion This study is a large-scale cognitive training study in PD patients that evaluates the efficacy in relieving cognitive dysfunction, and the underlying mechanisms. The strengths of this study are the large sample size, the long follow-up period and the use of neuroimaging in a large subsample. The study is expected to have a low attrition and a high compliance rate given the home-based and easily-accessible intervention in both conditions. Trial registration ClinicalTrials.gov ID NCT02920632 . Registered September 30, 2016. Electronic supplementary material The online version of this article (10.1186/s12883-019-1403-6) contains supplementary material, which is available to authorized users.