Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relations...Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.展开更多
The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent bu...The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.展开更多
The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly referred to as COVID-19, brings myriad challenges to research conducted among those more susceptible to the virus. Accordi...The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly referred to as COVID-19, brings myriad challenges to research conducted among those more susceptible to the virus. According to the United States (US) Centers for Disease Control (CDC), eight out of ten re-ported COVID-19 deaths are among people > 65 years of age and older. Nonetheless, researchers must continue the crucial work of investigating and understanding diseases that affect the elderly. The focus of this white paper is to assess the challenges associated with research within the elderly population with neurocognitive conditions. Specifically, this paper addresses the need for the standardized administration of performance measures (e.g., neurocognitive assessments) among a dementia population while ensuring the physical safety of participants. Consideration is given to the administration of performance measures and the availability and feasibility of administering these measures remotely to a population that may have difficulty using novel technologies. In implementing remote research assessments, it is suggested that researchers fol-low a GAMMA approach by: 1) establishing clear Guidance on remote visit expectations and processes;2) establishing Appropriate exclusionary criteria in the development of the study design;3) providing subjects Appropriate study Materials for visual processing;4) incorporating Multiple data sources in the overall study design (e.g., caregiver input);and 5) Acknowledging that there will be study limitations as researchers use emerging technology with this patient population, and using mitigation strategies for these limitations where possible.展开更多
Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ...Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ChI in Parkinson’s disease dementia (PDD) remains controversial. The objective of this systematic review and meta-analysis was to assess the effects of ChI in PDD. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE and Cochrane library up to March 2014 using the descriptors “Parkinson’s disease”, “dementia in Parkinson’s disease”, “cognition”, “acetylcholinesterase inhibitors”, “cholinesterase inhibitors”, “anticholinesterase agents”, “rivastigmine”, “donepezil” and “galantamine” (Pubmed search strategy). All randomized, doubleblinded, placebo-controlled trials that met the eligibility criteria and assessed the effects of ChI in PDD were considered for analysis. There were no restrictions regarding paper language. Summary effect-sizes were presented as standardized mean differences (SMD) and the pooled analysis was performed with a fixed-effects model. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Results: After a comprehensive search, 175 references were retrieved. From these, five randomized trials involving 946PDD subjects were included in the review. Four studies used donepezil and only one study used rivastigmine. The pooled analysis of five studies that assessed the effects of ChI in MMSE total score showed a SMD of 0.24 (CI 95% 0.11 - 0.38). Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). There was no significant heterogeneity between the studies. Conclusions: The results of this systematic review and meta- analysis suggest that ChI improves cognitive impairment in PDD subjects. Despite statistically significant, the translation of these results into relevant clinical improvement should be taken with caution, as the studies did not address what would be considered a clinically significant result.展开更多
Background： Rapid eye movement （REM） sleep behavior disorder （RBD） may be a risk factor for cognitive impairment in patients with Parkinson＆#39;s disease （PD）.However, little is known regarding the relation be...Background： Rapid eye movement （REM） sleep behavior disorder （RBD） may be a risk factor for cognitive impairment in patients with Parkinson＆#39;s disease （PD）.However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment.The aim of this study was： （1） to investigate the domains of cognitive impairment in patients with PD and RBD, and （2） to explore risk factors for PD-mild cognitive impairment （PD-MCI） and the relationship between RBD severity and impairment in different cognitive domains in PD.Methods： The participants were grouped as follows： PD without RBD （PD-RBD;n =42）, PD with RBD （PD ＋ RBD;n =32）, idiopathic RBD （iRBD;n =15）, and healthy controls （HCs;n =36）.All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function.The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD ＋ RBD groups.Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong （RBDQ-HK） and the RBD Screening Questionnaire （RBDSQ）, then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.Results： Compared to PD-RBD subjects, PD ＋ RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher （P 〈 0.05）.During neuropsychological testing, PD ＋ RBD patients performed worse than PD-RBD patients, including delayed memory function, especially.The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD ＋ RBD, iRBD, and HC groups, respectively.RBD was an important factor for the PD-MCI variance （odds ratio =5.204, P =0.018）.During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B （errors） and Auditory Verbal Learning Test （delayed recall） and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure （copy） results.Conclusions： When PD-RBD and PD ＋ RBD patients have equivalent motor symptoms, PD ＋ RBD patients still have more olfactory dysfunction and worse daytime somnolence.RBD is an important risk factor for MCI, including delayed memory.Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.展开更多
Parkinson＇s disease （PD）, a complex neurodegenerative disease, is characterized by the loss of dopamine neurons in the substantia nigra ot the midbraln. PD patients have varying degrees of cognitive impairment （CI...Parkinson＇s disease （PD）, a complex neurodegenerative disease, is characterized by the loss of dopamine neurons in the substantia nigra ot the midbraln. PD patients have varying degrees of cognitive impairment （CI） that we term PD-CI. However, the etiology of these changes remains unexplained. We chose three Uygur male patients with PD-CI and three healthy controls of the same of nationality and sex to explore the pathogenesis of Xinjiang Uygur PD-CI using microarray-based gene expression profiling of monocytes.展开更多
Background:Parkinson’s Disease(PD)with mild cognitive impairment(MCI)(PD-MCI)represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia.Although ...Background:Parkinson’s Disease(PD)with mild cognitive impairment(MCI)(PD-MCI)represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia.Although transcranial direct current stimulation(tDCS)has been demonstrated to improve motor and non-motor symptoms in PD,to date,no study has investigated the effects of tDCS on Theory of Mind(ToM),i.e.,the ability to understand and predict other people’s behaviours,in PD-MCI.Methods:In this randomized,double-blind,sham-controlled study,we applied active tDCS over the medial frontal cortex(MFC)to modulate ToM performance in twenty patients with PD-MCI.Twenty matched healthy controls(HC)were also enrolled and were asked to perform the ToM task without receiving tDCS.Results:In the patients with PD-MCI,i)ToM performance was worse than that in the HC,ii)ToM abilities were poorer in those with fronto-executive difficulties,and iii)tDCS over the MFC led to significant shortening of latency for ToM tasks.Conclusions:We show for the first time that active tDCS over the MFC enhances ToM in patients with PD-MCI,and suggest that non-invasive brain stimulation could be used to ameliorate ToM deficits observed in these patients.展开更多
Background:There is limited evidence on caregiver outcomes associated with mild cognitive impairment in patients with Parkinson’s disease(PD-MCI)and the coping strategies used by these caregivers.Methods:To investiga...Background:There is limited evidence on caregiver outcomes associated with mild cognitive impairment in patients with Parkinson’s disease(PD-MCI)and the coping strategies used by these caregivers.Methods:To investigate this relationship,we examined levels of burden,depression,anxiety,coping strategies and positive aspects of caregiving in the informal caregivers of 96 PD patients.The PD patients were classified using MDS-Task Force Level II criteria as showing either normal cognition(PD-N;n=51),PD-MCI(n=30)or with dementia(PDD;n=15).Results:Mean Zarit Burden Interview(ZBI)score increased significantly between carers of PD-N(M=13.39,SD=12.22)compared to those of PD-MCI patients(M=22.00,SD=10.8),and between carers of PD-MCI and PDD patients(M=29.33,SD=9.59).Moreover,the proportion of carers showing clinically significant levels of burden(ZBI score≥21)also increased as the patients’cognitive status declined(18% for PD-N;60% for PD-MCI;and 80%for PDD)and was mirrored by an increasing amount of time spent providing care by the caregivers.Caregiver ZBI score was independent of patient neuropsychiatric symptoms,motor function,disease duration and time that caregivers spent caregiving.Caregiver use of different coping strategies increased with worsening cognition.However,we found only equivocal evidence that the use of problem-focused,emotion-focused and dysfunctional coping mediated the association between patient cognitive status and caregiver burden,because the inverse models that used caregiver burden as the mediator were also significant.Conclusions:The study highlights the impact of Parkinson’s disease on those providing care when the patient’s cognition is poor,including those with MCI.Caregiver well-being has important implications for caregiver support,nursing home placement and disease course.展开更多
Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain...Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain activity of PD patients with MCI （PD-MCI） relative to cognitively normal PD patients （PD-CN） and healthy control （HC） subjects. In this work, 13 PD-MCI patients, 16 PD-CN patients, and 16 HC subjects completed resting state functional MRI. Spontaneous brain activity was measured by calculating amplitude of low frequency fluctuation （ALFF） values across the whole brain. Between-group differences and correlations between ALFF values and cognitive test scores were analyzed. ALFF values decreased in the right superior temporal gyrus and increased in the left middle temporal gyrus and left superior frontal gyms of PD-MCI patients compared with PD-CN patients. In the PD-MCI group, ALFF values in the left middle temporal gyrus were negatively correlated with Montreal Cognitive Assessment and vocabulary test scores, and the ALFF values in the left superior frontal gyms were negatively correlated with vocabulary test scores. Our study demonstrates that PD-MCI is associated with abnormal spontaneous brain activity in the temporal and frontal lobes. These findings inform the underlying neural mechanism of cognitive impairment in PD.展开更多
Background:Mild cognitive impairment in Parkinson’s disease(PD-MCI)is a common clinical condition.Understanding its pathology and clinical features is important for early intervention before the onset of dementia.In ...Background:Mild cognitive impairment in Parkinson’s disease(PD-MCI)is a common clinical condition.Understanding its pathology and clinical features is important for early intervention before the onset of dementia.In the past,variable definitions and differences in neuropsychological batteries generated divergent results of the affected cognitive patterns.Main body:The introduction of PD-MCI criteria by the Movement Disorders Society(MDS)Task Force provides a more uniform system for defining and measuring PD-MCI and may improve the validity of future research.PD-MCI is likely to be heterogeneous since it can coexist with Alzheimer’s disease and/or Lewy body pathologies in PD.Pathogeneses of neuropsychiatric disturbances,such as depression,anxiety and apathy,are associated with PD with or without MCI.In addition,cognitive reserve formed by patients’unique life experiences may influence the outward cognitive performance despite the presence of the aforementioned pathogeneses and hence alter the diagnosis of MCI.Conclusion:The overlap of cognitive impairment across different neurodegenerative diseases suggests that PD-MCI is likely to result from a mixture of complex pathophysiologies,rather than being a distinct pathologic entity.Differentiating MCI from other organic symptoms in PD would facilitate novel therapeutic strategies.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 81971006 (to DSG), 82101263 (to CXT)Jiangsu Province Science Foundation for Youths,No. BK20210903 (to CXT)+2 种基金Research Foundation for Talented Scholars of Xuzhou Medical University,No. RC20552114 (to CXT)Science&Technology Program of Xuzhou,No. KC19016 (to JC)Project of Xuzhou Medical University,No. 2018KJ06 (to JC)。
文摘Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.
基金supported by the National Natural Science Foundation of China,No.82071419Key Research and Development Program of Guangzhou,No.202206010086+1 种基金High-level Hospital Construction Project,No.DFJH201907Supporting Research Funds for Outstanding Young Medical Talents in Guangdong Province,No.KJ012019442(all to YZ)。
文摘The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.
文摘The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly referred to as COVID-19, brings myriad challenges to research conducted among those more susceptible to the virus. According to the United States (US) Centers for Disease Control (CDC), eight out of ten re-ported COVID-19 deaths are among people > 65 years of age and older. Nonetheless, researchers must continue the crucial work of investigating and understanding diseases that affect the elderly. The focus of this white paper is to assess the challenges associated with research within the elderly population with neurocognitive conditions. Specifically, this paper addresses the need for the standardized administration of performance measures (e.g., neurocognitive assessments) among a dementia population while ensuring the physical safety of participants. Consideration is given to the administration of performance measures and the availability and feasibility of administering these measures remotely to a population that may have difficulty using novel technologies. In implementing remote research assessments, it is suggested that researchers fol-low a GAMMA approach by: 1) establishing clear Guidance on remote visit expectations and processes;2) establishing Appropriate exclusionary criteria in the development of the study design;3) providing subjects Appropriate study Materials for visual processing;4) incorporating Multiple data sources in the overall study design (e.g., caregiver input);and 5) Acknowledging that there will be study limitations as researchers use emerging technology with this patient population, and using mitigation strategies for these limitations where possible.
文摘Introduction: Dementia is frequently associated with Parkinson’s disease, especially in later stages. Efficacy of cholinesterase inhibitors (ChI) in Alzheimer’s dementia is well established. However, treatment with ChI in Parkinson’s disease dementia (PDD) remains controversial. The objective of this systematic review and meta-analysis was to assess the effects of ChI in PDD. Methods: A comprehensive literature search was performed in MEDLINE, EMBASE and Cochrane library up to March 2014 using the descriptors “Parkinson’s disease”, “dementia in Parkinson’s disease”, “cognition”, “acetylcholinesterase inhibitors”, “cholinesterase inhibitors”, “anticholinesterase agents”, “rivastigmine”, “donepezil” and “galantamine” (Pubmed search strategy). All randomized, doubleblinded, placebo-controlled trials that met the eligibility criteria and assessed the effects of ChI in PDD were considered for analysis. There were no restrictions regarding paper language. Summary effect-sizes were presented as standardized mean differences (SMD) and the pooled analysis was performed with a fixed-effects model. Outcomes considered for analysis were the Mini Mental Status Exam (MMSE) score and the cognition scale for evaluation of dementia ADAS-Cog. The degree of heterogeneity between included studies was assessed through the I2 test. Results: After a comprehensive search, 175 references were retrieved. From these, five randomized trials involving 946PDD subjects were included in the review. Four studies used donepezil and only one study used rivastigmine. The pooled analysis of five studies that assessed the effects of ChI in MMSE total score showed a SMD of 0.24 (CI 95% 0.11 - 0.38). Three studies considered the effects of ChI on Adas-Cog and the pooled results showed a SMD of 0.21 (CI 95% 0.07 - 0.35). There was no significant heterogeneity between the studies. Conclusions: The results of this systematic review and meta- analysis suggest that ChI improves cognitive impairment in PDD subjects. Despite statistically significant, the translation of these results into relevant clinical improvement should be taken with caution, as the studies did not address what would be considered a clinically significant result.
文摘Background： Rapid eye movement （REM） sleep behavior disorder （RBD） may be a risk factor for cognitive impairment in patients with Parkinson＆#39;s disease （PD）.However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment.The aim of this study was： （1） to investigate the domains of cognitive impairment in patients with PD and RBD, and （2） to explore risk factors for PD-mild cognitive impairment （PD-MCI） and the relationship between RBD severity and impairment in different cognitive domains in PD.Methods： The participants were grouped as follows： PD without RBD （PD-RBD;n =42）, PD with RBD （PD ＋ RBD;n =32）, idiopathic RBD （iRBD;n =15）, and healthy controls （HCs;n =36）.All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function.The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD ＋ RBD groups.Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong （RBDQ-HK） and the RBD Screening Questionnaire （RBDSQ）, then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.Results： Compared to PD-RBD subjects, PD ＋ RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher （P 〈 0.05）.During neuropsychological testing, PD ＋ RBD patients performed worse than PD-RBD patients, including delayed memory function, especially.The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD ＋ RBD, iRBD, and HC groups, respectively.RBD was an important factor for the PD-MCI variance （odds ratio =5.204, P =0.018）.During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B （errors） and Auditory Verbal Learning Test （delayed recall） and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure （copy） results.Conclusions： When PD-RBD and PD ＋ RBD patients have equivalent motor symptoms, PD ＋ RBD patients still have more olfactory dysfunction and worse daytime somnolence.RBD is an important risk factor for MCI, including delayed memory.Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.
基金This study was supported by grants from the National Natural Science Foundation of China （No.81160143） and Xinjiang Uygur Autonomous Region Science and Technology Supporting Project in Xinjiang（No.201191162）.
文摘Parkinson＇s disease （PD）, a complex neurodegenerative disease, is characterized by the loss of dopamine neurons in the substantia nigra ot the midbraln. PD patients have varying degrees of cognitive impairment （CI） that we term PD-CI. However, the etiology of these changes remains unexplained. We chose three Uygur male patients with PD-CI and three healthy controls of the same of nationality and sex to explore the pathogenesis of Xinjiang Uygur PD-CI using microarray-based gene expression profiling of monocytes.
基金Mauro Adenzato was supported by the University of Turin(Ricerca scientifica finanziata dall’Università“Cognizione sociale e attaccamento in popolazioni cliniche e non cliniche”)Ivan Enrici was supported by University of Turin grants(Ricerca scientifica finanziata dall’Università“Linea Generale”and“Linea Giovani”).
文摘Background:Parkinson’s Disease(PD)with mild cognitive impairment(MCI)(PD-MCI)represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia.Although transcranial direct current stimulation(tDCS)has been demonstrated to improve motor and non-motor symptoms in PD,to date,no study has investigated the effects of tDCS on Theory of Mind(ToM),i.e.,the ability to understand and predict other people’s behaviours,in PD-MCI.Methods:In this randomized,double-blind,sham-controlled study,we applied active tDCS over the medial frontal cortex(MFC)to modulate ToM performance in twenty patients with PD-MCI.Twenty matched healthy controls(HC)were also enrolled and were asked to perform the ToM task without receiving tDCS.Results:In the patients with PD-MCI,i)ToM performance was worse than that in the HC,ii)ToM abilities were poorer in those with fronto-executive difficulties,and iii)tDCS over the MFC led to significant shortening of latency for ToM tasks.Conclusions:We show for the first time that active tDCS over the MFC enhances ToM in patients with PD-MCI,and suggest that non-invasive brain stimulation could be used to ameliorate ToM deficits observed in these patients.
文摘Background:There is limited evidence on caregiver outcomes associated with mild cognitive impairment in patients with Parkinson’s disease(PD-MCI)and the coping strategies used by these caregivers.Methods:To investigate this relationship,we examined levels of burden,depression,anxiety,coping strategies and positive aspects of caregiving in the informal caregivers of 96 PD patients.The PD patients were classified using MDS-Task Force Level II criteria as showing either normal cognition(PD-N;n=51),PD-MCI(n=30)or with dementia(PDD;n=15).Results:Mean Zarit Burden Interview(ZBI)score increased significantly between carers of PD-N(M=13.39,SD=12.22)compared to those of PD-MCI patients(M=22.00,SD=10.8),and between carers of PD-MCI and PDD patients(M=29.33,SD=9.59).Moreover,the proportion of carers showing clinically significant levels of burden(ZBI score≥21)also increased as the patients’cognitive status declined(18% for PD-N;60% for PD-MCI;and 80%for PDD)and was mirrored by an increasing amount of time spent providing care by the caregivers.Caregiver ZBI score was independent of patient neuropsychiatric symptoms,motor function,disease duration and time that caregivers spent caregiving.Caregiver use of different coping strategies increased with worsening cognition.However,we found only equivocal evidence that the use of problem-focused,emotion-focused and dysfunctional coping mediated the association between patient cognitive status and caregiver burden,because the inverse models that used caregiver burden as the mediator were also significant.Conclusions:The study highlights the impact of Parkinson’s disease on those providing care when the patient’s cognition is poor,including those with MCI.Caregiver well-being has important implications for caregiver support,nursing home placement and disease course.
基金supported by the National Natural Science Foundation of China(81271429 and 81571228)
文摘Mild cognitive impairment （MCI） is common in patients with Parkinson＇s disease （PD）, yet the underlying neural mechanisms of this disease state remain unclear. We investigated alterations in the spontaneous brain activity of PD patients with MCI （PD-MCI） relative to cognitively normal PD patients （PD-CN） and healthy control （HC） subjects. In this work, 13 PD-MCI patients, 16 PD-CN patients, and 16 HC subjects completed resting state functional MRI. Spontaneous brain activity was measured by calculating amplitude of low frequency fluctuation （ALFF） values across the whole brain. Between-group differences and correlations between ALFF values and cognitive test scores were analyzed. ALFF values decreased in the right superior temporal gyrus and increased in the left middle temporal gyrus and left superior frontal gyms of PD-MCI patients compared with PD-CN patients. In the PD-MCI group, ALFF values in the left middle temporal gyrus were negatively correlated with Montreal Cognitive Assessment and vocabulary test scores, and the ALFF values in the left superior frontal gyms were negatively correlated with vocabulary test scores. Our study demonstrates that PD-MCI is associated with abnormal spontaneous brain activity in the temporal and frontal lobes. These findings inform the underlying neural mechanism of cognitive impairment in PD.
基金This work was supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme(TCR12dec010)administered by the Singapore Ministry of Health’s National Medical Research Councilthe Singapore Millennium Foundation。
文摘Background:Mild cognitive impairment in Parkinson’s disease(PD-MCI)is a common clinical condition.Understanding its pathology and clinical features is important for early intervention before the onset of dementia.In the past,variable definitions and differences in neuropsychological batteries generated divergent results of the affected cognitive patterns.Main body:The introduction of PD-MCI criteria by the Movement Disorders Society(MDS)Task Force provides a more uniform system for defining and measuring PD-MCI and may improve the validity of future research.PD-MCI is likely to be heterogeneous since it can coexist with Alzheimer’s disease and/or Lewy body pathologies in PD.Pathogeneses of neuropsychiatric disturbances,such as depression,anxiety and apathy,are associated with PD with or without MCI.In addition,cognitive reserve formed by patients’unique life experiences may influence the outward cognitive performance despite the presence of the aforementioned pathogeneses and hence alter the diagnosis of MCI.Conclusion:The overlap of cognitive impairment across different neurodegenerative diseases suggests that PD-MCI is likely to result from a mixture of complex pathophysiologies,rather than being a distinct pathologic entity.Differentiating MCI from other organic symptoms in PD would facilitate novel therapeutic strategies.
