scholarly journals Region-Specific Neurovascular Decoupling Associated With Cognitive Decline in Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Song’an Shang ◽  
Hongying Zhang ◽  
Yuan Feng ◽  
Jingtao Wu ◽  
Weiqiang Dou ◽  
...  

Background: Cognitive deficits are prominent non-motor symptoms in Parkinson’s disease (PD) and have been shown to involve the neurovascular unit (NVU). However, there is a lack of sufficient neuroimaging research on the associated modulating mechanisms. The objective of this study was to identify the contribution of neurovascular decoupling to the pathogenesis of cognitive decline in PD.Methods: Regional homogeneity (ReHo), a measure of neuronal activity, and cerebral blood flow (CBF), a measure of vascular responses, were obtained from patients with PD with mild cognitive impairment (MCI) and normal cognition (NC) as well as matched healthy controls (HCs). Imaging metrics of neurovascular coupling (global and regional CBF-ReHo correlation coefficients and CBF-ReHo ratios) were compared among the groups.Results: Neurovascular coupling was impaired in patients with PD-MCI with a decreased global CBF-ReHo correlation coefficient relative to HC subjects (P < 0.05). Regional dysregulation was specific to the PD-MCI group and localized to the right middle frontal gyrus, right middle cingulate cortex, right middle occipital gyrus, right inferior parietal gyrus, right supramarginal gyrus, and right angular gyrus (P < 0.05). Compared with HC subjects, patients with PD-MCI showed higher CBF-ReHo ratios in the bilateral lingual gyri (LG), bilateral putamen, and left postcentral gyrus and lower CBF-ReHo ratios in the right superior temporal gyrus, bilateral middle temporal gyri, bilateral parahippocampal gyri, and right inferior frontal gyrus. Relative to the HC and PD-NC groups, the PD-MCI group showed an increased CBF-ReHo ratio in the left LG, which was correlated with poor visual–spatial performance (r = −0.36 and P = 0.014).Conclusion: The involvement of neurovascular decoupling in cognitive impairment in PD is regionally specific and most prominent in the visual–spatial cortices, which could potentially provide a complementary understanding of the pathophysiological mechanisms underlying cognitive deficits in PD.

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Alexandru Hanganu ◽  
Oury Monchi

Cognitive impairment in patients with Parkinson’s disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson’s disease and to take into consideration the near-future possibilities of their implementation into clinical practice.


2021 ◽  
pp. 1-12
Author(s):  
Rachael A. Lawson ◽  
Caroline H. Williams-Gray ◽  
Marta Camacho ◽  
Gordon W. Duncan ◽  
Tien K. Khoo ◽  
...  

Background: Cognitive impairment is common in Parkinson’s disease (PD), with 80% cumulatively developing dementia (PDD). Objective: We sought to identify tests that are sensitive to change over time above normal ageing so as to refine the neuropsychological tests predictive of PDD. Methods: Participants with newly diagnosed PD (n = 211) and age-matched controls (n = 99) completed a range of clinical and neuropsychological tests as part of the ICICLE-PD study at 18-month intervals over 72 months. Impairments on tests were determined using control means (<1-2SD) and median scores. Mild cognitive impairment (PD-MCI) was classified using 1-2SD below normative values. Linear mixed effects modelling assessed cognitive decline, while Cox regression identified baseline predictors of PDD. Results: At 72 months, 46 (cumulative probability 33.9%) participants had developed PDD; these participants declined at a faster rate in tests of global cognition, verbal fluency, memory and attention (p <  0.05) compared to those who remained dementia-free. Impaired baseline global cognition, visual memory and attention using median cut-offs were the best predictors of early PDD (area under the curve [AUC] = 0.88, p <  0.001) compared to control-generated cut-offs (AUC = 0.76–0.84, p <  0.001) and PD-MCI (AUC] = 0.64–0.81, p <  0.001). Impaired global cognition and semantic fluency were the most useful brief tests employable in a clinical setting (AUC = 0.79, p <  0.001). Conclusion: Verbal fluency, attention and memory were sensitive to change in early PDD and may be suitable tests to measure therapeutic response in future interventions. Impaired global cognition, attention and visual memory were the most accurate predictors for developing a PDD. Future studies could consider adopting these tests for patient clinical trial stratification.


Author(s):  
Iván Galtier ◽  
Antonieta Nieto ◽  
María Mata ◽  
Jesús N. Lorenzo ◽  
José Barroso

ABSTRACT Objective: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) in Parkinson’s disease (PD) are considered as the risk factors for dementia (PDD). Posterior cortically based functions, such as visuospatial and visuoperceptual (VS-VP) processing, have been described as predictors of PDD. However, no investigations have focused on the qualitative analysis of the Judgment of Line Orientation Test (JLOT) and the Facial Recognition Test (FRT) in PD-SCD and PD-MCI. The aim of this work was to study the VS-VP errors in JLOT and FRT. Moreover, these variables are considered as predictors of PDD. Method: Forty-two PD patients and 19 controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Analyses of errors were conducted following the procedure described by Ska, Poissant, and Joanette (1990). Follow-up assessment was conducted to a mean of 7.5 years after the baseline. Results: PD-MCI patients showed a poor performance in JLOT and FRT total score and made a greater proportion of severe intraquadrant (QO2) and interquadrant errors (IQO). PD-SCD showed a poor performance in FRT and made mild errors in JLOT. PD-MCI and QO2/IQO errors were independent risk factors for PDD during the follow-up. Moreover, the combination of both PD-MCI diagnosis and QO2/IQO errors was associated with a greater risk. Conclusions: PD-MCI patients presented a greater alteration in VS-VP processing observable by the presence of severe misjudgments. PD-SCD patients also showed mild difficulties in VS-SP functions. Finally, QO2/IQO errors in PD-MCI are a useful predictor of PDD, more than PD-MCI diagnosis alone.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Emily J. Henderson ◽  
Howard Chu ◽  
Daisy M. Gaunt ◽  
Alan L. Whone ◽  
Yoav Ben-Shlomo ◽  
...  

Background.MoCA is widely used in Parkinson’s disease (PD) to assess cognition. The Test Your Memory (TYM) test is a cognitive screening tool that is self-administered.Objectives.We sought to determine (a) the optimal value of TYM to discriminate between PD patients with and without cognitive deficits on MoCA testing, (b) equivalent MoCA and TYM scores, and (c) interrater reliability in TYM testing.Methods.We assessed the discriminant ability of TYM and the equivalence between TYM and MoCA scores and measured the interrater reliability between three raters.Results.Of the 135 subjects that completed both tests, 55% had cognitive impairment according to MoCA. A MoCA score of 25 was equivalent to a TYM score of 43-44. The area under the receiver operator characteristic (ROC) curve for TYM to differentiate between PD-normal and PD-cognitive impairment was 0.82 (95% CI 0.75 to 0.89). The optimal cutoff to distinguish PD-cognitive impairment from PD-normal was ≤45 (sensitivity 90.5%, specificity 59%) thereby correctly classifying 76.3% of patients with PD-cognitive impairment. Interrater agreement was high (0.97) and TYM was completed in under 7 minutes (interquartile range 5.33 to 8.52 minutes).Conclusions.The TYM test is a useful and less resource intensive screening test for cognitive deficits in PD.


Sensors ◽  
2021 ◽  
Vol 21 (5) ◽  
pp. 1788
Author(s):  
Sara Rosenblum ◽  
Ariella Richardson ◽  
Sonya Meyer ◽  
Tal Nevo ◽  
Maayan Sinai ◽  
...  

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder affecting patient functioning and quality of life. Aside from the motor symptoms of PD, cognitive impairment may occur at early stages of PD and has a substantial impact on patient emotional and physical health. Detecting these early signs through actual daily functioning while the patient is still functionally independent is challenging. We developed DailyCog—a smartphone application for the detection of mild cognitive impairment. DailyCog includes an environment that simulates daily tasks, such as making a drink and shopping, as well as a self-report questionnaire related to daily events performed at home requiring executive functions and visual–spatial abilities, and psychomotor speed. We present the detailed design of DailyCog and discuss various considerations that influenced the design. We tested DailyCog on patients with mild cognitive impairment in PD. Our case study demonstrates how the markers we used coincide with the cognitive levels of the users. We present the outcome of our usability study that found that most users were able to use our app with ease, and provide details on how various features were used, along with some of the difficulties that were identified.


2019 ◽  
Author(s):  
Edward N. Wilson ◽  
Michelle S. Swarovski ◽  
Patricia Linortner ◽  
Marian Shahid ◽  
Abigail J. Zuckerman ◽  
...  

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD) and affects 1% of the population above 60 years old. Although PD commonly manifests with motor symptoms, a majority of patients with PD subsequently develop cognitive impairment which often progresses to dementia, a major cause of morbidity and disability. PD is characterized by α-synuclein accumulation that frequently associates with amyloid beta (Aβ) and tau fibrils, the hallmarks of AD neuropathologic changes; this co-occurrence suggests that onset of cognitive decline in PD may be associated with appearance of pathologic Aβ and/or tau. Recent studies have highlighted the appearance of the soluble form of the Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) receptor in CSF during development of AD. Given the known association of microglial activation with advancing PD, we investigated whether CSF and/or plasma sTREM2 increased with progression to PD dementia. We examined 165 participants consisting of 17 cognitively normal elderly, 45 PD patients with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF Aβ and tau levels revealed that CSF sTREM2 concentrations were elevated in PD subgroups with abnormal tau, but not Aβ, CSF concentration. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in PD that is associated with cognitive decline.One sentence summaryCSF sTREM2 correlates with CSF tau in PD


2020 ◽  
Author(s):  
Arturo Moreno ◽  
Nijee Luthra ◽  
Luke Bonham ◽  
Jonathan Lin ◽  
Lauren Broestl ◽  
...  

Abstract Aging is the primary risk factor for Parkinson’s disease (PD) and cognitive impairment from PD is a major and unmet biomedical challenge. Klotho, a pleiotropic protein, extends lifespan and enhances cognition. Whether longevity factors such as klotho can counteract PD-related mortality and deficits in mice or associate with resistance to PD in humans is unknown. Here we show that transgenic elevation of klotho increased lifespan, improved synaptic and cognitive, but not motor, functions in mice, and decreased steady state α-synuclein levels in the brains of mice that express wildtype human α-synuclein. In humans, a genetic variant of KLOTHO that increases circulating klotho levels associated with better executive cognition and less CSF abnormalities of α-synuclein in individuals with PD. Thus, klotho can counteract cognitive deficits related to PD, possibly modulating α-synuclein levels – and these findings may be relevant to new therapeutic pathways for human PD.


2020 ◽  
Vol 117 (3) ◽  
pp. 58-67
Author(s):  
Anastasiia Shkodina ◽  
Kateryna Tarianyk ◽  
Dmytro Boiko

The article summarizes the arguments and counter-arguments within the scientific discussion on the impact of sleep disorders on the development of cognitive decline in patients with Parkinson's disease. The main purpose of the study is to study the possibility of predicting the development of cognitive decline by assessing the severity of sleep disorders and their differences in the presence of cognitive impairment. Systematization of literature sources and approaches to solving the problem showed that sleep disorders develop in the early stages of Parkinson's disease and are often accompanied by cognitive impairment. Cognitive decline is manifested throughout Parkinson's disease and ranges from moderate in the early stages to dementia in the late stages. The relevance of the study of the relationship between sleep disorders and cognitive functions lies in the possibility of further improving the prediction of the development of cognitive decline in order to effectively correct it. Treatment of sleep disorders can be accompanied by improved memory and even morphological changes in the brain. Therefore, the question arises about the possibility of correcting cognitive decline by influencing sleep disorders. The methodology of the study included assessment of the overall status of patients on a unified scale of Parkinson's disease, Montreal cognitive rating scale and sleep scale in Parkinson's disease. The duration of the study was 8 months. Patients with Parkinson's disease were selected as the study. The article presents the results of a survey of patients who show that patients with Parkinson's disease and cognitive decline showed a predominance of motor disorders, sleep disorders and the overall score on the sleep scale in Parkinson's disease. In the presence of cognitive decline more pronounced disorders of motor functions in everyday life, which can lead to sleep disorders and its quality. The study empirically confirms and theoretically proves that the assessment of sleep disorders can be used to predict the risk of developing cognitive impairment in patients with Parkinson's disease. The results of this study may be useful for improving the early diagnosis and prevention of cognitive impairment in patients with Parkinson's disease, which, in turn, leads to improved quality of treatment of these patients. Such changes can directly affect the choice of therapeutic tactics and improve the quality of life of patients with Parkinson's disease. The question of the features of various sleep disorders and their prognostic value in relation to cognitive decline in patients with various forms of Parkinson's disease remains open.


Author(s):  
Francis R. Loayza ◽  
Ignacio Obeso ◽  
Rafael González Redondo ◽  
Federico Villagra ◽  
Elkin Luis ◽  
...  

AbstractRecent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the pre-supplementary motor area and the inferior frontal gyrus are key components of the right hemisphere “inhibitory network”. Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson’s disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson’s disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided Parkinson’s disease. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson’s disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which requires engagement of additional regions, not observed in controls, to successfully stop ongoing actions.


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