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 ◽  
...  

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.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyoungwon Baik ◽  
Seon Myeong Kim ◽  
Jin Ho Jung ◽  
Yang Hyun Lee ◽  
Seok Jong Chung ◽  
...  

AbstractWe investigated the efficacy of donepezil for mild cognitive impairment in Parkinson’s disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson’s Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.


2017 ◽  
Vol 24 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Anna Isabel Garcia-Diaz ◽  
Barbara Segura ◽  
Hugo Cesar Baggio ◽  
Maria Jose Marti ◽  
Francesc Valldeoriola ◽  
...  

AbstractBackground: Diagnosis of mild cognitive impairment in Parkinson’s disease (PD) is relevant because it is a marker for evolution to dementia. However, the selection of suitable tests to evaluate separate cognitive domains in mild cognitive impairment related to PD remains an open question. The current work aims to investigate the neuroanatomical correlates of several visuospatial/visuoperceptual tests using the same sample and a multimodal MRI approach. Methods: The study included 36 PD patients and 20 healthy subjects matched for age, sex, and education. The visuospatial/visuoperceptual tests selected were: Pentagon Copying Test (PCT), Judgment of Line Orientation Test (JLOT), Visual Form Discrimination Test (VFDT), Facial Recognition Test (FRT), Symbol Digit Modalities Test (SMDT), and clock copying task (CLOX2). FreeSurfer was used to assess cortical thickness, and tract-based spatial statistics was used for fractional anisotropy analysis. Results: Lower performance in the PCT, JLOT, and SDMT was associated with extensive cortical thickness reductions in lateral parietal and temporal regions. VFDT and CLOX2 did not show this common pattern and correlated with more limited medial occipito-temporal and occipito-parietal regions. Performance in all visuospatial/visuoperceptual tests correlated with fractional anisotropy in the corpus callosum. Conclusions: Our findings show that JLOT, SDMT, and PCT, in addition to differentiating patients from controls, are suitable visuospatial/visuoperceptual tests to reflect cortical thinning in lateral temporo-parietal regions in PD patients. We did not observe the dissociation between dorsal and ventral streams that was expected according to the neuropsychological classification of visuospatial and visuoperceptual tests. (JINS, 2018, 24, 33–44)


2021 ◽  
Author(s):  
Jihyun Yang ◽  
Katie L McMahon ◽  
David A Copland ◽  
Dana Pourzinal ◽  
Gerard J Byrne ◽  
...  

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.


2020 ◽  
Author(s):  
Shoji Kawashima ◽  
Yoko Shimizu ◽  
Yoshino Ueki ◽  
Noriyuki Matsukawa

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.


2019 ◽  
Vol 26 (4) ◽  
pp. 430-440
Author(s):  
Patricia Sulzer ◽  
Alena Bäumer ◽  
Huong Giang Hoang ◽  
Sara Becker ◽  
Hannah Dorothea Lönneker ◽  
...  

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.


2021 ◽  
Vol 18 ◽  
Author(s):  
Sara García ◽  
Olaya Amor-Gutiérrez ◽  
María Palomares-Albarrán ◽  
Celia Toyos-Rodríguez ◽  
Fernando Cuetos ◽  
...  

Aims: There are several candidate biomarkers for AD and PD which differ in sensitivity, specificity, cost-effectiveness, invasiveness, logistical and technical demands. This study is aimed to test whether plasma concentration of unfolded p53 may help to discriminate among the neurodegenerative processes occurring in Mild Cognitive Impairment, Alzheimer’s disease and Parkinson's disease. Method: An electrochemical immunosensor was used to measure unfolded p53 in plasma samples of 20 Mild Cognitive Impairment (13 males/7 females; mean age 74.95±5.31), 20 Alzheimer’s (11 males/9 females; mean age: 77.25±7.79), 15 Parkinson’s disease patients (12 males/3 females; mean age: 68.60 ± 7.36) and its respective age/sex/studies-matched controls. Result: We observed a significantly higher concentration of unfolded p53 in the plasma of patients of each of the three pathologies with respect to their control groups (p=0.000). Furthermore, the plasma concentration of unfolded p53 was significantly higher in Alzheimer’s disease patients in comparison with Mild Cognitive Impairment patients (p=0.000) and Parkinson’s disease patients (p=0.006). No significant difference between Mild Cognitive Impairment and Parkinson’s disease patients was observed (p=0.524). Conclusion: Our results suggest that unfolded p53 concentration in the plasma may be a useful biomarker for an undergoing neuropathological process that may be common, albeit with a different intensity, to different diseases.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Inga Liepelt-Scarfone ◽  
Susanne Graeber ◽  
Anne Feseker ◽  
Gülsüm Baysal ◽  
Jana Godau ◽  
...  

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.


2021 ◽  
Author(s):  
Shoji Kawashima ◽  
Noriyuki Matsukawa ◽  
RCIP-Nagoya Study Group

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.


2020 ◽  
Vol 17 (4) ◽  
pp. 480-486
Author(s):  
Wei Pu ◽  
Xudong Shen ◽  
Mingming Huang ◽  
Zhiqian Li ◽  
Xianchun Zeng ◽  
...  

Objective: Application of diffusion tensor imaging (DTI) to explore the changes of FA value in patients with Parkinson's disease (PD) with mild cognitive impairment. Methods: 27 patients with PD were divided into PD with mild cognitive impairment (PD-MCI) group (n = 7) and PD group (n = 20). The original images were processed using voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Results: The average age of pd-mci group was longer than that of PD group, and the course of disease was longer than that of PD group. Compared with PD group, the voxel based analysis-fractional anisotropy (VBA-FA) values of PD-MCI group decreased in the following areas: bilateral frontal lobe, bilateral temporal lobe, bilateral parietal lobe, bilateral subthalamic nucleus, corpus callosum, and gyrus cingula. Tract-based spatial statistics-fractional anisotropy (TBSS-FA) values in PD-MCI group decreased in bilateral corticospinal tract, anterior cingulum, posterior cingulum, fornix tract, bilateral superior thalamic radiation, corpus callosum(genu, body and splenium), bilateral uncinate fasciculus, bilateral inferior longitudinal fasciculus, bilateral superior longitudinal fasciculus, bilateral superior fronto-occipital fasciculus, bilateral inferior fronto-occipital fasciculus, and bilateral parietal-occipital tracts. The mean age of onset in the PD-MCI group was greater than that in the PD group, and the disease course was longer than that in the PD group. Conclusion: DTI-based VBA and TBSS post-processing methods can detect abnormalities in multiple brain areas and white matter fiber tracts in PD-MCI patients. Impairment of multiple cerebral cortex and white matter fiber pathways may be an important causes of cognitive dysfunction in PD-MCI.


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