scholarly journals Memantine for the Patients with Mild Cognitive Impairment in Parkinson’s Disease: A Pharmacological fMRI Study

2021 ◽  
Author(s):  
Shoji Kawashima ◽  
Noriyuki Matsukawa ◽  
RCIP-Nagoya Study Group
Keyword(s):  
Parkinson’S Disease ◽  
Working Memory ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Spatial Working Memory ◽  
Clinical Status ◽  
Visuospatial Working Memory ◽  
Increased Risk ◽  
The Impact

Abstract Background:Mild cognitive impairment of Parkinson’s disease (PD-MCI) represents increased risk of future cognitive decline. The characteristics of PD-MCI are impairments in executive function and visuospatial recognition. The visuospatial n-back test has a merit that it can assess both cognitive domains. Concerning the treatment of PD-MCI and dementia in PD (PDD), many studies have reported efficacy of cholinesterase inhibitors. Similarly, some studies reported efficacy of memantine for PDD, showing that it improved clinical status or behavioral symptoms. However, therapeutic evidence of memantine for PD-MCI has not been unestablished. Methods: We aimed to investigate whether memantine can alter brain function of the patients with PD-MCI, using functional MRI. In comparison between memantine and placebo, we explored the difference in regions associated with visuospatial n-back test. The 0-back test reflects visuospatial recognition, and the 1-back and 2-back tests reflect visuospatial working memory. This study followed a randomized double-blind crossover design. Patients in the memantine group were given memantine at 5 mg/day in the first week, and the dose was increased by 5 mg/day per week, with the final dose of 20 mg/day. The patients in the placebo group were given a placebo following the same regimen. The population in this study constitutes 10 patients who completed follow-up. During maximum dose administration, fMRI scanning and neuropsychological tests were performed. Group comparisons between memantine and placebo were performed.Results: There were no significant regions enhanced by memantine comparing with placebo at any load of n-back tests. In contrast, exploring regions reduced by memantine, we found significant reduction of activations within right lingual gyrus and left superior frontal gyrus in comparison between 2-back and 0-back test. A number of correct answers of the 2-back test and time to complete Trail Making Test-A were worse at memantine intervention. Reduced brain activations were associated with worse visuo-spatial working memory caused by memantine.Conclusions:This study reports memantine did not improve visuospatial working memory of the patients with PD-MCI. Treatment of PD should be planned carefully considering the impact for cognitive function. Further study is needed to establish new therapeutic strategy of the patients with PD-MCI.

scholarly journals Visuospatial n-back test for early detection of mild cognitive impairment in patients with Parkinson’s Disease : an fMRI study

2020 ◽  
Author(s):  
Shoji Kawashima ◽  
Yoko Shimizu ◽  
Yoshino Ueki ◽  
Noriyuki Matsukawa
Keyword(s):  
Parkinson’S Disease ◽  
Working Memory ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Detection ◽  
Functional Neuroimaging ◽  
Common Symptom ◽  
Visuospatial Working Memory ◽  
Increased Risk

AbstractBackgroundCognitive impairment is a common symptom in the patients with Parkinson’s disease (PD). In delineating a therapeutic plan, the early diagnosis of mild cognitive impairment in PD (PD-MCI) is important. Patients with PD-MCI have severe impairment in frontal executive function and/or visuospatial recognition. However, the clinical assessment of these functions is not routinely performed.MethodIn this study, we aimed to clarify the advantage of visuospatial version of the n-back test as a tool for the early detection of neuropsychological change in the patients with PD-MCI. The score of 0-back test reflects visuospatial recognition, and the scores of 1-back and 2-back reflect visuospatial working memory. PD-MCI was classified according to the criteria provided by the Movement Disorder Society Task Force for mild cognitive impairment in PD. We recruited 13 patients with PD-MCI, and 15 patients with cognitive normal PD. Using functional MRI (fMRI), we also aimed to clarify the specific brain regions associated with the impairment of visuospatial working memory.ResultWe demonstrated that the correct answer rate of patients with PD-MCI was lower in the 2-back test than patients with PD-CN. However, we did not find statistical difference in the 0-back test. These results indicate the preservation of visuospatial recognition and the impairment of visuospatial working memory in the patients with PD-MCI. We revealed the reduced activation within the middle frontal gyrus (MFG) and the inferior parietal lobule (IPL) during the 2-back test in the patients with PD-MCI. It may be associated with the severity of cortico-striatal dysfunction in the dopaminergic neural network which is associated with Lewy body pathology.ConclusionThe visuospatial n-back test has advantages for use in rapid and early detection of impaired visual recognition and working memory. The combination of functional neuroimaging and neuropsychological tests may provide markers for the increased risk of dementia before the development of an irreversible disease-specific pathology.

scholarly journals Effects of Home-Based Working Memory Training on Visuo-Spatial Working Memory in Parkinson’s Disease: A Randomized Controlled Trial

2020 ◽  
Vol 12 ◽  
pp. 117957351989946 ◽  
Author(s):  
Kathrin Giehl ◽  
Anja Ophey ◽  
Paul Reker ◽  
Sarah Rehberg ◽  
Jochen Hammes ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Working Memory ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Spatial Working Memory ◽  
Controlled Trial ◽  
Memory Training ◽  
Randomized Controlled ◽  
Home Based

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)

scholarly journals Impairment of the visuospatial working memory in the patients with Parkinson’s Disease: an fMRI study

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shoji Kawashima ◽  
Yoko Shimizu ◽  
Yoshino Ueki ◽  
Noriyuki Matsukawa
Keyword(s):  
Parkinson’S Disease ◽  
Working Memory ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Correct Answer ◽  
Brain Regions ◽  
Middle Frontal Gyrus ◽  
Common Symptom ◽  
Visuospatial Working Memory ◽  
Parietal Lobule

Abstract Background Mild cognitive impairment (MCI) is a common symptom in the patients with Parkinson’s disease (PD). The characteristics of cognitive impairment in PD are executive function (including working memory) and visuo-perceptual processing. The visuospatial n-back test has the merit of minimizing the influence of educational biases involved in the verbal n-back test. Furthermore, it can assess both visuospatial recognition and working memory in a single test. Methods We aimed to clarify the advantage of the visuospatial n-back test as a tool for detecting impairments of working memory in PD. We enrolled 28 right-handed patients with PD (18 males, 10 females) and 12 age-matched healthy controls (HC; 7 males, 5 females). Thirteen patients were classified as MCI (PD-MCI), and 15 as cognitively normal PD (PD-CN). Using functional MRI (fMRI), we explored the specific brain regions associated with the performance of the n-back test in the PD-MCI, PD-CN, and HC groups. The 0-back test assesses visuospatial recognition, while the 1-back and 2-back tests assess visuospatial working memory. Group comparisons were performed for three loads of this test. Results Patients with PD performed significantly worse in terms of the correct answer rates of all n-back tests compared with HC. fMRI analyses performed during the 2-back test revealed reduced activation in the bilateral dorsolateral prefrontal cortex, middle frontal gyrus (MFG), and parietal lobule in the PD group compared with the HC group. In contrast, the fMRI result during the 0-back test showed only a marginal difference in the frontal lobe. On comparisons of task performance between the PD-MCI and PD-CN groups, we found that the correct answer rate in the 2-back test was lower in the PD-MCI group than in the PD-CN group. However, scores of the 0-back and 1-back tests were not significantly different between the two groups. The fMRI findings revealed that activations within the middle frontal gyrus (MFG) and inferior parietal lobule (IPL) during the 2-back test were reduced in the patients with PD-MCI when compared to those with PD-CN. Conclusions This study reports reduced activation of the MFG and IPL in patients with PD-MCI. These regions may be associated with the pathophysiology of working memory impairment in patients with PD, which involves fronto-striatal network dysfunction.

scholarly journals Semantic Fluency Deficits and Associated Brain Activity in Parkinson’s Disease Patients With Mild Cognitive Impairment

2021 ◽  
Author(s):  
Jihyun Yang ◽  
Katie L McMahon ◽  
David A Copland ◽  
Dana Pourzinal ◽  
Gerard J Byrne ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Verbal Fluency ◽  
Brain Activity ◽  
Angular Gyrus ◽  
Semantic Fluency ◽  
Compensatory Mechanisms ◽  
Increased Risk

Abstract Parkinson’s disease (PD) patients with poor verbal fluency have an increased risk of developing dementia. This study examines the neural mechanisms underpinning semantic fluency deficits in PD patients with mild cognitive impairment (PD-MCI) compared to patients without MCI (PD-NC) and healthy controls (HC). Thirty-seven (37) PD patients completed a cognitive assessment battery to identify MCI (13 PD-MCI). Gender- and age-matched 20 HC also participated. Participants were scanned (3T Siemens PRISMA) whilst performing semantic fluency, semantic switching, and automatic speech tasks. The number of responses, error rate, and fMRI data for semantic generation and semantic switching were analyzed. Participants also completed a series of verbal fluency tests outside the scanner, including letter fluency. Patients with PD-MCI performed significantly worse than PD-NC and HC during semantic fluency and semantic switching tasks. Patients with PD-MCI showed greater activity in the right angular gyrus compared to PD-NC and HC during semantic switching. Increased right angular activity correlated with worse verbal fluency performance outside the scanner. Our study showed that PD-MCI patients perform more poorly on semantic fluency than either PD-NC or HC groups. Increased right angular gyrus activity in patients with PD-MCI during semantic switching suggests early compensatory mechanisms predicting the risk of future dementia in PD.

Assessment of Cognitive-Driven Performance-Based Activities of Daily Living Dysfunction in Parkinson’s Disease

2019 ◽  
Vol 26 (4) ◽  
pp. 430-440
Author(s):  
Patricia Sulzer ◽  
Alena Bäumer ◽  
Huong Giang Hoang ◽  
Sara Becker ◽  
Hannah Dorothea Lönneker ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Activities Of Daily Living ◽  
Daily Living ◽  
Neuropsychological Test ◽  
Motor Dysfunction ◽  
Efficient Performance ◽  
Increased Risk

AbstractObjectives:Parkinson’s disease (PD) patients with mild cognitive impairment (PD-MCI) have an increased risk of developing dementia (PDD). As activities of daily living (ADL) impairment is mandatory for the diagnosis of PDD, assessing early signs of instrumental ADL (iADL) dysfunction, especially in PD-MCI, is essential. In PD, self- and caregiver-reported iADL performance is often confounded by motor dysfunction and mood. Objective and time-efficient performance-based measurements are needed to screen for cognitive-related iADL dysfunction. We evaluated the Erlangen Test of Activities of Daily Living in Mild Dementia and Mild Cognitive Impairment (ETAM) in PD and determined its value for characterizing a subgroup of PD-MCI patients with mild performance-based iADL impairment.Methods:Twenty-one cognitively normal PD patients (PD-NC), 24 PD-MCI patients, and 18 healthy controls (HC) were analyzed. Assessments included the ETAM, a comprehensive neuropsychological test battery, iADL, mood, and motor measurements.Results:PD-MCI patients scored significantly lower on the ETAM total score compared to PD-NC patients (p = .002), whereas HC and PD-NC patients did not statistically differ. No HC scored lower than 27 points (diagnostic cutoff for mild iADL impairment); only PD-MCI patients scored below this cutoff (29.2%) suggesting the ETAM is able to characterize a PD-MCI subgroup with early iADL impairment. PD-MCI patients below the cutoff were more impaired in the attention domain (p = .04).Conclusions:The ETAM is a potentially valuable clinical assessment, able to detect first signs of iADL dysfunction in PD-MCI. Further studies in larger cohorts are needed to evaluate the prognostic ability for predicting PDD.

scholarly journals Influence of Different Cut-Off Values on the Diagnosis of Mild Cognitive Impairment in Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Inga Liepelt-Scarfone ◽  
Susanne Graeber ◽  
Anne Feseker ◽  
Gülsüm Baysal ◽  
Jana Godau ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Predictive Accuracy ◽  
Neuropsychological Testing ◽  
Population Based ◽  
Healthy Population ◽  
Increased Risk ◽  
Definition Of

Comparable to Alzheimer's disease, mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with an increased risk for dementia. However different definitions of PD-MCI may have varying predictive accuracy for dementia. In a cohort of 101 nondemented Parkinson patients who underwent neuropsychological testing, the frequency of PD-MCI subjects and PD-MCI subtypes (i.e., amnestic/nonamnestic) was determined by use of varying healthy population-based cut-off values. We also investigated the association between defined PD-MCI groups and ADL scales. Varying cut-off values for the definition of PD-MCI were found to affect frequency of PD-MCI subjects (9.9%–92.1%) and, maybe more important, lead to a “shift” of proportion of detected PD-MCI subtypes especially within the amnestic single-domain subtype. Models using a strict cut-off value were significantly associated with lower ADL scores. Thus, the use of defined cut-off values for the definition of PD-MCI is highly relevant for comparison purposes. Strict cut-off values may have a higher predictive value for dementia.

scholarly journals EEG-Derived Functional Connectivity Patterns Associated with Mild Cognitive Impairment in Parkinson’s Disease

2021 ◽  
Vol 11 (3) ◽  
pp. 40
Author(s):  
Alejandro Armando Peláez Suárez ◽  
Sheila Berrillo Batista ◽  
Ivonne Pedroso Ibáñez ◽  
Enrique Casabona Fernández ◽  
Marinet Fuentes Campos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Working Memory ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Path Length ◽  
Clustering Coefficient ◽  
Eyes Closed ◽  
The Mean

Objective: To evaluate EEG-derived functional connectivity (FC) patterns associated with mild cognitive impairment (MCI) in Parkinson’s disease (PD). METHODS: A sample of 15 patients without cognitive impairment (PD-WCI), 15 with MCI (PD-MCI), and 26 healthy subjects were studied. The EEG was performed in the waking functional state with eyes closed, for the functional analysis it was used the synchronization likelihood (SL) and graph theory (GT). RESULTS: PD-MCI patients showed decreased FC in frequencies alpha, in posterior regions, and delta with a generalized distribution. Patients, compared to the healthy people, presented a decrease in segregation (lower clustering coefficient in alpha p = 0.003 in PD-MCI patients) and increased integration (shorter mean path length in delta (p = 0.004) and theta (p = 0.002) in PD-MCI patients). There were no significant differences in the network topology between the parkinsonian groups. In PD-MCI patients, executive dysfunction correlated positively with global connectivity in beta (r = 0.47) and negatively with the mean path length at beta (r = −0.45); alterations in working memory were negatively correlated with the mean path length at beta r = −0.45. CONCLUSIONS: PD patients present alterations in the FC in all frequencies, those with MCI show less connectivity in the alpha and delta frequencies. The neural networks of the patients show a random topology, with a similar organization between patients with and without MCI. In PD-MCI patients, alterations in executive function and working memory are related to beta integration.

scholarly journals Posterior Cortical Cognitive Deficits Are Associated With Structural Brain Alterations in Mild Cognitive Impairment in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Quentin Devignes ◽  
Romain Viard ◽  
Nacim Betrouni ◽  
Guillaume Carey ◽  
Gregory Kuchcinski ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cortical Thickness ◽  
Mean Diffusivity ◽  
Magnetic Resonance Imaging Scan ◽  
Caudate Nuclei ◽  
Increased Risk ◽  
Significant Difference

Context: Cognitive impairments are common in patients with Parkinson’s disease (PD) and are heterogeneous in their presentation. The “dual syndrome hypothesis” suggests the existence of two distinct subtypes of mild cognitive impairment (MCI) in PD: a frontostriatal subtype with predominant attentional and/or executive deficits and a posterior cortical subtype with predominant visuospatial, memory, and/or language deficits. The latter subtype has been associated with a higher risk of developing dementia.Objective: The objective of this study was to identify structural modifications in cortical and subcortical regions associated with each PD-MCI subtype.Methods: One-hundred and fourteen non-demented PD patients underwent a comprehensive neuropsychological assessment as well as a 3T magnetic resonance imaging scan. Patients were categorized as having no cognitive impairment (n = 41) or as having a frontostriatal (n = 16), posterior cortical (n = 25), or a mixed (n = 32) MCI subtype. Cortical regions were analyzed using a surface-based Cortical thickness (CTh) method. In addition, the volumes, shapes, and textures of the caudate nuclei, hippocampi, and thalami were studied. Tractometric analyses were performed on associative and commissural white matter (WM) tracts.Results: There were no between-group differences in volumetric measurements and cortical thickness. Shape analyses revealed more abundant and more extensive deformations fields in the caudate nuclei, hippocampi, and thalami in patients with posterior cortical deficits compared to patients with no cognitive impairment. Decreased fractional anisotropy (FA) and increased mean diffusivity (MD) were also observed in the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the striato-parietal tract, and the anterior and posterior commissural tracts. Texture analyses showed a significant difference in the right hippocampus of patients with a mixed MCI subtype.Conclusion: PD-MCI patients with posterior cortical deficits have more abundant and more extensive structural alterations independently of age, disease duration, and severity, which may explain why they have an increased risk of dementia.

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