Evaluating a frontostriatal working-memory updating-training paradigm in Parkinson's disease: the iPARK trial, a double-blinded randomized controlled trial.
ABSTRACT: BACKGROUND:Cognitive decline and dementia are common in Parkinson's disease (PD). Cognitive deficits have been linked to the depletion of dopamine in the nigrostriatal pathway, but pharmacological treatments for PD have little evidence of improving or delaying cognitive decline. Therefore, exploring non-pharmacological treatment options is important. There have been some promising results of cognitive training interventions in PD, especially for improvements in working memory and executive functions. Yet, existing studies are often underpowered, lacking appropriate control condition, long term follow-up, a thorough description of the intervention and characteristics of the participants. Working memory updating training has previously shown to increase striatal activation in healthy young and old participants as well as dopaminergic neurotransmission in healthy young participants. In the light of dopamine dysfunction in PD, with negative effects on both motor and cognitive functions it is of interest to study if an impaired striatal system can be responsive to a non-invasive, non-pharmacological intervention. METHODS AND DESIGN:The iPARK trial is a double-blinded, randomized controlled trial with a parallel-group design that aims to recruit 80 patients with PD (during the period 02/2017-02/2023). Included patients need to have PD, Hoehn and Yahr staging I-III, be between 45 to 75?years of age and not have a diagnosis of dementia. All patients will undergo 30?sessions (6-8?weeks) of web-based cognitive training performed from home. The target intervention is a process-based training program targeting working memory updating. The placebo program is a low dose short-term memory program. A battery of neuropsychological tests and questionnaires will be performed before training, directly after training, and 16?weeks after training. DISCUSSION:We expect that the iPARK trial will provide novel and clinically useful information on whether updating training is an effective cognitive training paradigm in PD. Further, it will hopefully contribute to a better understanding of cognitive function in PD and provide answers regarding cognitive plasticity as well as determining critical factors for a responsive striatal system. TRIAL REGISTRATION:Clinicaltrials.gov registry number: NCT03680170 , registry name: "Cognitive Training in Parkinson's Disease: the iPARK study", retrospectively registered on the 21st of September 2018. The inclusion of the first participant was the 1st of February 2017.
Project description:In Parkinson's disease (PD), the fronto-striatal network is involved in motor and cognitive symptoms. Working memory (WM) updating training engages this network in healthy populations, as observed by improved cognitive performance and increased striatal BOLD signal. This two-part study aimed to assess the feasibility of WM updating training in PD and measure change in cognition, movement and functional brain response in one individual with PD after WM updating training. A feasibility and single-subject (FL) study were performed in which patients with PD completed computerized WM updating training. The outcome measures were the pre-post changes in criterion and transfer cognitive tests; cognitive complaints; psychological health; movement kinematics; and task-related BOLD signal. Participants in the feasibility study showed improvements on the criterion tests at post-test. FL displayed the largest improvements on the criterion tests and smaller improvements on transfer tests. Furthermore, FL reported improved cognitive performance in everyday life. A shorter onset latency and smoother upper-limb goal-directed movements were measured at post-test, as well as increased activation within the striatum and decreased activation throughout the fronto-parietal WM network. This two-part study demonstrated that WM updating training is feasible to complete for PD patients and that change occurred in FL at post-test in the domains of cognition, movement and functional brain response.
Project description:It is currently not known what are the best working memory training strategies to offset the age-related declines in fluid cognitive abilities. In this randomized clinical double-blind trial, older adults were randomly assigned to one of two types of working memory training - one group was trained on a predictable memory updating task (PT) and another group was trained on a novel, unpredictable memory updating task (UT). Unpredictable memory updating, compared to predictable, requires greater demands on cognitive control (Basak and Verhaeghen, 2011a). Therefore, the current study allowed us to evaluate the role of cognitive control in working memory training. All participants were assessed on a set of near and far transfer tasks at three different testing sessions - before training, immediately after the training, and 1.5 months after completing the training. Additionally, individual learning rates for a comparison working memory task (performed by both groups) and the trained task were computed. Training on unpredictable memory updating, compared to predictable, significantly enhanced performance on a measure of episodic memory, immediately after the training. Moreover, individuals with faster learning rates showed greater gains in this episodic memory task and another new working memory task; this effect was specific to UT. We propose that the unpredictable memory updating training, compared to predictable memory updating training, may a better strategy to improve selective cognitive abilities in older adults, and future studies could further investigate the role of cognitive control in working memory training.
Project description:Working memory (WM) represents a core cognitive function with a major striatal contribution, and thus WM deficits, commonly observed in Parkinson's disease (PD), could also relate to many other problems in PD patients. Our online study aimed to determine the subdomains of WM that are particularly affected in PD and to clarify the links between WM and everyday cognitive deficits, other executive functions, psychiatric and PD symptoms, as well as early cognitive impairment. Fifty-two mild-to-moderate PD patients and 54 healthy controls performed seven WM tasks tapping selective updating, continuous monitoring, or maintenance of currently active information. Self-ratings of everyday cognition, depression, and apathy symptoms, as well as screenings of global cognitive impairment, were also collected. The data were analyzed using structural equation modeling. Of the three WM domains, only selective updating was directly predictive of PD group membership. More widespread WM deficits were observed only in relation to global cognitive impairment in PD patients. Self-rated everyday cognition or psychiatric symptoms were not linked to WM performance but correlated with each other. Our findings suggest that WM has a rather limited role in the clinical manifestation of PD. Nevertheless, due to its elementary link to striatal function, the updating component of WM could be a candidate for a cognitive marker of PD also in patients who are otherwise cognitively well-preserved.
Project description:During the past decade, working memory training has attracted much interest. However, the training outcomes have varied between studies and methodological problems have hampered the interpretation of results. The current study examined transfer after working memory updating training by employing an extensive battery of pre-post cognitive measures with a focus on near transfer. Thirty-one healthy Finnish young adults were randomized into either a working memory training group or an active control group. The working memory training group practiced with three working memory tasks, while the control group trained with three commercial computer games with a low working memory load. The participants trained thrice a week for five weeks, with one training session lasting about 45 minutes. Compared to the control group, the working memory training group showed strongest transfer to an n-back task, followed by working memory updating, which in turn was followed by active working memory capacity. Our results support the view that working memory training produces near transfer effects, and that the degree of transfer depends on the cognitive overlap between the training and transfer measures.
Project description:Previous work demonstrates that working-memory (WM) updating training results in improved performance on a letter-memory criterion task, transfers to an untrained n-back task, and increases striatal dopamine (DA) activity during the criterion task. Here, we sought to replicate and extend these findings by also examining neurochemical correlates of transfer. Four positron emission tomography (PET) scans using the radioligand raclopride were performed. Two of these assessed DAD2 binding (letter memory; n-back) before 5 weeks of updating training, and the same two scans were performed post training. Key findings were (a) pronounced training-related behavioral gains in the letter-memory criterion task, (b) altered striatal DAD2 binding potential after training during letter-memory performance, suggesting training-induced increases in DA release, and (c) increased striatal DA activity also during the n-back transfer task after the intervention, but no concomitant behavioral transfer. The fact that the training-related DA alterations during the transfer task were not accompanied by behavioral transfer suggests that increased DA release may be a necessary, but not sufficient, condition for behavioral transfer to occur.
Project description:Objective:We investigated if a 5-week computerized adaptive working memory training program (Cogmed®) of 20 to 25 sessions would be effective in improving the working memory capacity and other neuropsychological functions compared to a non-adaptive working memory training program (active-controlled) in adult patients with mild cognitive impairment (MCI). Methods:This randomized double-blinded active control trial included 68 individuals aged 43 to 88 years, 45 men and 23 women, who were diagnosed with MCI at four Memory clinics. The study sample was randomized by block randomization to either adaptive or non-adaptive computerized working memory training. All participants completed the training, and were assessed with a comprehensive neuropsychological test battery before the intervention, and at 1 and 4 months after training. Results:Compared to the non-adaptive training group, the adaptive training group did not show significantly greater improvement on the main outcome of working memory performance at 1 and 4 months after training. Conclusion:No difference were found between the two types of training on the primary outcome of working memory, or on secondary outcomes of cognitive function domains, in this sample of MCI patients. Hence, the hypothesis that the adaptive training program would lead to greater improvements compared to the non-adaptive training program was not supported. Within group analyses was not performed due to the stringent RCT design.
Project description:Normal aging is associated with a gradual decline in executive functions such as set-shifting, inhibition, and updating, along with a progressive decline of neurotransmitter systems including the dopamine system. Modulation from the dopamine system is thought to be critical for the gating of information during working memory. Given the known relationships between executive aging, cognition, and dopamine, this study aims to explore the neurobiology underlying age-related changes in working memory updating using fMRI with healthy subjects from across the adult age spectrum. Our results indicate that older age is associated with poorer performance, reduced meso-cortico-striatal activation, and reduced functional coupling between the caudate and the VLPFC during the updating task. Additionally, caudate activation is associated with improved accuracy and VLPFC activation with faster reaction times in the full sample. Thus, older subjects' under-recruitment of and reduced functional coupling between these regions may specifically underlie age-related changes in working memory updating. These results are consistent with computational models of executive cognition and dopamine-mediated age-related cognitive decline.
Project description:HIV-associated neurocognitive impairments that impact daily function persist in the era of effective antiretroviral therapy. Cognitive training, a promising low-cost intervention, has been shown to improve neurocognitive functioning in some clinical populations. We tested the feasibility, acceptability, and preliminary effects of computerized cognitive training to improve working memory in persons living with HIV infection (PLWH) and working memory impairment. In this randomized clinical trial, we assigned 21 adult PLWH to either an experimental cognitive training intervention or an attention-matched control training intervention. Participants completed 12 training sessions across 10 weeks with assessments at baseline and post-training. Session attendance was excellent and participants rated the program positively. Participants in the experimental arm demonstrated improved working memory function over time; participants in the control arm showed no change. Our results suggest that cognitive training may be a promising intervention for working memory impairment in PLWH and should be evaluated further.
Project description:Repetitive negative thinking (RNT) is a proximal risk factor implicated in the onset and maintenance of common mental health problems such as depression and anxiety. Adolescence may be a key developmental window in which to target RNT and prevent the emergence of such disorders. Impairments in updating the contents of working memory are hypothesised to causally contribute to RNT, and some theorists have suggested these difficulties may be specific to the manipulation of negative information. The present study compared the effects of computerised adaptive working memory updating training (in which the task becomes more difficult as performance improves) to a non-adaptive control task in reducing levels of RNT. 124 healthy young people were randomised to 20 sessions of (i) working memory updating training using neutral stimuli, (ii) working memory updating training using negative stimuli, or (iii) non-adaptive working memory updating training. Adaptive working memory updating training using neutral, but not negative, stimuli resulted in significant improvements to working memory updating for negative material, as assessed using an unpractised task, and significant reductions in susceptibility to state RNT. These findings demonstrate proof-of-concept that working memory updating training has the potential to reduce susceptibility to episodes of state RNT.
Project description:Background:Cognitive impairment is a very frequent and severe nonmotor symptom of Parkinson's disease (PD). Early intervention in this at-risk group for cognitive decline may be crucial for long-term preservation of cognitive functions. Computerized working memory training (WMT) has been proven beneficial in non-PD patient populations, but such evidence is still needed for patients with PD. Objective:This study aimed to evaluate the effect of WMT on visuo-spatial working memory (WM) in cognitively unimpaired patients with PD. Methods:A single-blind randomized controlled trial encompassing 76 patients with PD but no cognitive impairment according to level II diagnostic criteria was conducted. Thirty-seven patients engaged in home-based adaptive WMT 5 times per week for a period of 5?weeks, whereas the remaining patients were in the waiting list arm of the study (control group [CG]). Working memory performance was evaluated using a computerized task before and after intervention and at 14-week follow-up, allowing to quantify the precision of WM on a continuous scale, ie, to test not only if an item was remembered but also how well the location of this item was retained. Results:Coincidently, the WMT group showed slightly worse WM performance compared with the CG at baseline, which was ameliorated after WMT. This training-induced effect remained stable until follow-up. Conclusion:Patients showing relatively low WM performance, despite not formally diagnosable as Parkinson's disease with mild cognitive impairment (PD-MCI), seem to benefit from home-based WMT. Thus, WMT could potentially be implemented in future trials as a time- and cost-efficient route to counteract subtle cognitive changes in early disease stages. Trial registration:German Clinical Trial Register (drks.de, DRKS00009379).