Dataset Information

Enhancement of Executive Functions but Not Memory by Multidomain Group Cognitive Training in Patients with Parkinson's Disease and Mild Cognitive Impairment: A Multicenter Randomized Controlled Trial.

ABSTRACT:

Background

Meta-analyses have demonstrated cognitive training (CT) benefits in Parkinson's disease (PD) patients. However, the patients' cognitive status has only rarely been based on established criteria. Also, prediction analyses of CT success have only sparsely been conducted.

Objective

To determine CT effects in PD patients with mild cognitive impairment (PD-MCI) on cognitive and noncognitive outcomes compared to an active control group (CG) and to analyze CT success predictors.

Methods

Sixty-four PD-MCI patients (age: 67.61?±?7.70; UPDRS-III: 26.58?±?13.54; MoCA: 24.47?±?2.78) were randomized to either a CT group or a low-intensity physical activity CG for six weeks (twice weekly, 90 minutes). Outcomes were assessed before and after training. MANOVAs with follow-up ANOVAs and multiple regression analyses were computed.

Results

Both interventions were highly feasible (participation, motivation, and evaluation); the overall dropout rate was 4.7%. Time?×?group interaction effects favoring CT were observed for phonemic fluency as a specific executive test (p=0.018, ? _p ²=0.092) and a statistical trend for overall executive functions (p=0.095, ? _p ²=0.132). A statistical trend for a time?×?group interaction effect favoring CG was shown for the digit span backward as a working memory test (p=0.098, ? _p ²=0.043). Regression analyses revealed cognitive baseline levels, education, levodopa equivalent daily dose, motor scores, and ApoE status as significant predictors for CT success.

Conclusions

CT is a safe and feasible therapy option in PD-MCI, yielding executive functions improvement. Data indicate that vulnerable individuals may show the largest cognitive gains. Longitudinal studies are required to determine whether CT may also attenuate cognitive decline in the long term. This trial is registered with DRKS00010186.

SUBMITTER: Kalbe E

PROVIDER: S-EPMC7721510 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Enhancement of Executive Functions but Not Memory by Multidomain Group Cognitive Training in Patients with Parkinson's Disease and Mild Cognitive Impairment: A Multicenter Randomized Controlled Trial.

Kalbe Elke E Folkerts Ann-Kristin AK Ophey Anja A Eggers Carsten C Elben Saskia S Dimenshteyn Karina K Sulzer Patricia P Schulte Claudia C Schmidt Nele N Schlenstedt Christian C Berg Daniela D Witt Karsten K Wojtecki Lars L Liepelt-Scarfone Inga I

Parkinson's disease 20201130

<h4>Background</h4>Meta-analyses have demonstrated cognitive training (CT) benefits in Parkinson's disease (PD) patients. However, the patients' cognitive status has only rarely been based on established criteria. Also, prediction analyses of CT success have only sparsely been conducted.<h4>Objective</h4>To determine CT effects in PD patients with mild cognitive impairment (PD-MCI) on cognitive and noncognitive outcomes compared to an active control group (CG) and to analyze CT success predictor ...[more]

PMID: 33312495

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Project description:BackgroundMeta-analyses indicate positive effects of cognitive training (CT) in patients with Parkinson's disease (PD), however, most previous studies had small sample sizes and did not evaluate long-term follow-up. Therefore, a multicenter randomized controlled, single-blinded trial (Train-ParC study) was conducted to examine CT effects in PD patients with mild cognitive impairment (PD-MCI). Immediately after CT, an enhancement of executive functions was demonstrated. Here, we present the long-term results 6 and 12 months after CT.MethodsAt baseline, 64 PD-MCI patients were randomized to a multidomain CT group (n = 33) or to a low-intensity physical activity training control group (PT) (n = 31). Both interventions included 90 min training sessions twice a week for 6 weeks. 54 patients completed the 6 months (CT: n = 28, PT: n = 26) and 49 patients the 12 months follow-up assessment (CT: n = 25, PT: n = 24). Primary study outcomes were memory and executive functioning composite scores. Mixed repeated measures ANOVAs, post-hoc t tests and multiple regression analyses were conducted.ResultsWe found a significant time x group interaction effect for the memory composite score (p = 0.006, η2 = 0.214), but not for the executive composite score (p = 0.967, η2 = 0.002). Post-hoc t tests revealed significant verbal and nonverbal memory improvements from pre-intervention to 6 months, but not to 12 months follow-up assessment in the CT group. No significant predictors were found for predicting memory improvement after CT.ConclusionsThis study provides Class 1 evidence that multidomain CT enhances memory functioning in PD-MCI after 6 months but not after 12 months, whereas executive functioning did not change in the long-term.Clinical trial registrationGerman Clinical Trials Register (ID: DRKS00010186), 21.3.2016 (The study registration is outlined as retrospective due to an administrative delay. The first patient was enrolled three months after the registration process was started. A formal confirmation of this process from the German Clinical Trials Register can be obtained from the authors.).

Project description:BackgroundMild cognitive impairment (MCI) is a symptom characterizing cognitive decline and a transitional state between normal aging and dementia; however, there is no definitive diagnosis and treatment for MCI. Neurofeedback (NF), which is a training mechanism that employs operant conditioning to regulate brain activity, has been increasingly investigated concerning its beneficial effects for dementia and MCI.MethodsThis study investigated cognitive improvement and hemodynamic changes in the prefrontal cortex (PFC) following NF training in patients with MCI. Five patients with MCI received NF training for enhanced beta band activity in the dorsolateral PFC-16 sessions for 8 weeks-with each session divided into 9 5-minute trials. The primary outcome measure was a cognitive assessment tool: the Korean version of the Montreal Cognitive Assessment. The secondary outcome measures were the Central Nervous System Vital Signs for neurocognitive testing, hemodynamic changes using functional near-infrared spectroscopy in the PFC during a working-memory task, and Beck Depression Inventory scores.ResultsAfter completing the training, patients' cognitive function significantly improved in domains such as composite memory, cognitive flexibility, complex attention, reaction time, and executive function. Increased electroencephalogram beta power was observed over NF training sessions (Spearman rank correlation test: r?=?0.746, P?=?.001). The threshold value for gaining positive feedback from pre-NF baseline on beta power significantly increased (Spearman rank correlation test: r?=?0.805, P?=?.001). Hemodynamic response in PFC changed after NF training, and individual differences were identified. Specifically, hypoactivation of the hemodynamic response by emotional distraction recovered following NF training.ConclusionWe suggest that patients' cognitive processing efficiency was improved by the NF training. These beneficial results suggest that NF training may have potential therapeutic applications to prevent the progression from MCI to dementia.Trial registration numberClinical Research Information Service (KCT0003433).

Project description:The ability to dynamically use various aspects of cognition is essential to daily function, and reliant on dopaminergic transmission in cortico-striatal circuitry. Our aim was to investigate both striatal and cortical dopaminergic changes in patients with Parkinson's disease with mild cognitive impairment, who represent a vulnerable group for the development of dementia. We hypothesized severe striatal dopamine denervation in the associative (i.e. cognitive) region and cortical D2 receptor abnormalities in the salience and executive networks in Parkinson's disease with mild cognitive impairment compared with cognitively normal patients with Parkinson's disease and healthy control subjects. We used positron emission tomography imaging with dopaminergic ligands (11)C-dihydrotetrabenazine, to investigate striatal dopamine neuron integrity in the associative subdivision and (11)C-FLB 457, to investigate cortical D2 receptor availability in patients with Parkinson's disease (55-80 years of age) with mild cognitive impairment (n = 11), cognitively normal patients with Parkinson's disease (n = 11) and age-matched healthy control subjects (n = 14). Subjects were administered a neuropsychological test battery to assess cognitive status and determine the relationship between dopaminergic changes and cognitive performance. We found that patients with mild cognitive impairment had severe striatal dopamine depletion in the associative (i.e. cognitive) subdivision as well as reduced D2 receptor availability in the bilateral insula, a key cognitive hub, compared to cognitively normal patients and healthy subjects after controlling for age, disease severity and daily dopaminergic medication intake. Associative striatal dopamine depletion was predictive of D2 receptor loss in the insula of patients with Parkinson's disease with mild cognitive impairment, demonstrating interrelated striatal and cortical changes. Insular D2 levels also predicted executive abilities in these patients as measured using a composite executive z-score obtained from neuropsychological testing. Furthermore we assessed cortical thickness to ensure that D2 receptor changes were not confounded by brain atrophy. There was no difference between groups in cortical thickness in the insula, or any other cortical region of interest. These findings suggest that striatal dopamine denervation combined with insular D2 receptor loss underlie mild cognitive impairment in Parkinson's disease and in particular decline in executive function. Furthermore, these findings suggest a crucial and direct role for dopaminergic modulation in the insula in facilitating cognitive function.

Dataset Information

Enhancement of Executive Functions but Not Memory by Multidomain Group Cognitive Training in Patients with Parkinson's Disease and Mild Cognitive Impairment: A Multicenter Randomized Controlled Trial.

Background

Objective

Methods

Results

Conclusions

Publications

Enhancement of Executive Functions but Not Memory by Multidomain Group Cognitive Training in Patients with Parkinson's Disease and Mild Cognitive Impairment: A Multicenter Randomized Controlled Trial.

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