Background: Scientific research increasingly focuses on visual symptoms of people with Parkinson’... more Background: Scientific research increasingly focuses on visual symptoms of people with Parkinson’s disease (PD). However, this mostly involves functional measures, whereas self-reported data are equally important for guiding clinical care. Objective: This review provides an overview of the nature and prevalence of self-reported visual complaints by people with PD, compared to healthy controls. Methods: A systematic literature search was performed. Studies from three databases (PubMed, PsycInfo, and Web of Science) were screened for eligibility. Only studies that reported results of visual self-reports in people with idiopathic PD were included. Results: One hundred and thirty-nine eligible articles were analyzed. Visual complaints ranged from function-related complaints (e.g., blurred vision, double vision, increased sensitivity to light or changes in contrast sensitivity) to activity-related complaints (e.g., difficulty reading, reaching, or driving). Visual complaints were more pr...
Objective To identify and substantiate the occurrence, extent and location of retinal degeneratio... more Objective To identify and substantiate the occurrence, extent and location of retinal degeneration in de novo Parkinson’s disease patients (PD) compared to primary open angle glaucoma patients (POAG) and healthy controls (HC). Background PD patients experience visual symptoms and retinal degeneration. Studies using spectral-domain optical coherence tomography (SD-OCT) have shown retinal thinning in PD, resembling the glaucoma pattern. This study investigated the retinal thinning in de novo Ldopa-naive PD patients, to analyse if the profile of retinal thinning could serve as a biomarker for PD. Methods SD-OCT data were collected in de novo Ldopa-naive PD patients at the University Medical Center Groningen. A 5x5 mm OD macular scan was made. These scans were compared to age-matched POAG patients and HC’s. Good quality scans (≥4); segmented by Iowa Reference Algorithms [1], were divided by ETDRS 9-sector grid, and were meta-analyzed by cell-layers (Cohen’s d; 95% CI). Results In total ...
The diagnosis of Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) is based on ... more The diagnosis of Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) is based on an arbitrary distinction between the time of onset of cognitive and motor symptoms. Both diagnoses share many features, like the presence of Lewy bodies, the core symptomatology and the core neurochemical deficits. However, the cognitive symptoms are more severe in DLB, very likely due to extensive beta-amyloid deposits in the cortex, the parkinsonian symptoms are more severe in PDD, due to the more extensive loss of presynaptic dopaminergic neurons and the hippocampal atrophy is more extensive in DLB, very likely due to a loss of fronto-hippocampal projections. Therefore DLB and PDD seem to be part of a spectrum of Lewy body pathologies, which may be accompanied by other protein deposits, like beta-amyloid, causing a different seventy and timing of the symptoms. The cognitive symptoms and hallucinations can be treated by cholinesterase inhibitors and anti-psychotics. DLB patients mostly...
INTRODUCTION The postural instability gait difficulty motor subtype of patients with Parkinson... more INTRODUCTION The postural instability gait difficulty motor subtype of patients with Parkinson's disease (PIGD-PD) has been associated with more severe cognitive pathology and a higher risk on dementia compared to the tremor-dominant subtype (TD-PD). Here, we investigated whether the microstructural integrity of the cholinergic projections from the nucleus basalis of Meynert (NBM) was different between these clinical subtypes. METHODS Diffusion-weighted imaging data of 98 newly-diagnosed unmedicated PD patients (44 TD-PD and 54 PIGD-PD subjects) and 10 healthy controls, were analysed using diffusion tensor imaging, focusing on the white matter tracts associated with cholinergic projections from the NBM (NBM-WM) as the tract-of-interest. Quantitative tract-based and voxel-based analyses were performed using FA and MD as the estimates of white matter integrity. RESULTS Voxel-based analyses indicated significantly lower FA in the frontal part of the medial and lateral NBM-WM tract of both hemispheres of PIGD-PD compared to TD-PD. Relative to healthy control, several clusters with significantly lower FA were observed in the frontolateral NBM-WM tract of both disease groups. Furthermore, significant correlations between the severity of the axial and gait impairment and NBM-WM FA and MD were found, which were partially mediated by NBM-WM state on subjects' attentional performance. CONCLUSIONS The PIGD-PD subtype shows a loss of microstructural integrity of the NBM-WM tract, which suggests that a loss of cholinergic projections in this PD subtype already presents in de novo PD patients.
BACKGROUND The supplementary motor area (SMA) is implicated in stereotypic multi-limb movements s... more BACKGROUND The supplementary motor area (SMA) is implicated in stereotypic multi-limb movements such as walking with arm swing. Gait difficulties in Parkinson's Disease (PD) include reduced arm swing, which is associated with reduced SMA activity. OBJECTIVE To test whether enhanced arm swing improves Parkinsonian gait and explore the role of the SMA in such an improvement. METHODS Cortical activity and gait characteristics were assessed by ambulant EEG, accelerometers and video recordings in 27 PD patients with self-reported gait difficulties and 35 healthy participants when walking normally. Within these two groups, 19 PD patients additionally walked with enhanced arm swing and 30 healthy participants walked without arm swing. Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation analysis of recordings from Fz over the putative SMA and gait analysis was performed. RESULTS Baseline PD gait, characterized by reduced arm swing among other features, exhibited reduced within-step Event Related Desynchronization (ERD)/Synchronization (ERS) alternation (Fz; 20-50Hz), accompanied by a reduced step length and walking speed. All became similar to normal gait when patients walked with enhanced arm swing. When healthy controls walked without arm swing, their alternating ERD-ERS pattern decreased, mimicking baseline PD gait. CONCLUSION Enhanced arm swing may serve as a driving force to overcome impaired gait control in PD patients by restoring reduced ERD-ERS alternation over the putative SMA. Accompanied by increased step length and walking speed, this provides a neural underpinning of arm swing as an effective rehabilitation concept for improving Parkinsonian gait.
BackgroundThe most common genetic risk factor for Parkinson's disease known is a damaging var... more BackgroundThe most common genetic risk factor for Parkinson's disease known is a damaging variant in the GBA1 gene. The entire GBA1 gene has rarely been studied in a large cohort from a single population. The objective of this study was to assess the entire GBA1 gene in Parkinson's disease from a single large population.MethodsThe GBA1 gene was assessed in 3402 Dutch Parkinson's disease patients using next‐generation sequencing. Frequencies were compared with Dutch controls (n = 655). Family history of Parkinson's disease was compared in carriers and noncarriers.ResultsFifteen percent of patients had a GBA1 nonsynonymous variant (including missense, frameshift, and recombinant alleles), compared with 6.4% of controls (OR, 2.6; P < 0.001). Eighteen novel variants were detected. Variants previously associated with Gaucher's disease were identified in 5.0% of patients compared with 1.5% of controls (OR, 3.4; P < 0.001). The rarely reported complex allele p.D14...
Journal of Chromatography B: Biomedical Sciences and Applications, 1997
Analytical methods are described for the selective, rapid and sensitive determination of R- and S... more Analytical methods are described for the selective, rapid and sensitive determination of R- and S-apomorphine, apocodeine and isoapocodeine and the glucuronic acid and sulfate conjugates in plasma and urine. The methods involve liquid-liquid extraction followed by high-performance liquid chromatography with electrochemical detection. The glucuronide and sulfate conjugates are determined after enzymatic hydrolysis. For the assay of R- and S-apomorphine a 10 microm Chiralcel OD-R column is used and the voltage of the detector is set at 0.7 V. The mobile phase is a mixture of aqueous phase (pH 4.0)-acetonitrile (65:35, v/v). At a flow-rate of 0.9 ml min(-1) the total run time is ca. 15 min. The detection limits are 0.3 and 0.6 ng ml(-1) for R- and S- apomorphine, respectively (signal-to-noise ratio 3). The intra- and inter-assay variations are &amp;amp;amp;amp;lt;5% in the concentration range of 2.5-25 ng ml(-1) for plasma samples, and &amp;amp;amp;amp;lt;4% in the concentration range of 40-400 ng ml(-1) for urine samples. For the assay of apomorphine, apocodeine and isoapocodeine, a 5 microm C18 column was used and the voltage of the detector set at 0.825 V. Ion-pairing chromatography was used. The mobile phase is a mixture of aqueous phase (pH 3.0)-acetonitrile (75:25, v/v). At a flow-rate of 0.8 ml min(-1) the total run time is ca. 14 min. The detection limits of this assay are 1.0 ng ml(-1) for apomorphine and 2.5 ng ml(-1) for both apocodeine and isoapocodeine (signal-to-noise ratio 3). The inter-assay variations are 5% in the concentration range of 5-40 ng ml(-1) for plasma samples and 7% in the concentration range of 50-500 ng ml(-1) for urine samples. The glucuronic acid and sulfate conjugates of the various compounds are hydrolysed by incubation of the samples with beta-glucuronidase and sulfatase type H-1, respectively. Hydrolysis was complete after 5 h of incubation. No measurable degradation of apomorphine, apocodeine and isoapocodeine occurred during the incubation. A pharmacokinetic study of apomorphine, following the intravenous infusion of 30 microg kg(-1) for 15 min in a patient with Parkinson&amp;amp;amp;amp;#39;s disease, demonstrates the utility of the methods: both the pharmacokinetic parameters of the parent drug and the appearance of apomorphine plus metabolites in urine could be determined.
BackgroundLittle is known about visual hallucinations (VH) in psychosis. We investigated the prev... more BackgroundLittle is known about visual hallucinations (VH) in psychosis. We investigated the prevalence and the role of bottom-up and top-down processing in VH. The prevailing view is that VH are probably related to altered top-down processing, rather than to distorted bottom-up processing. Conversely, VH in Parkinson's disease are associated with impaired visual perception and attention, as proposed by the Perception and Attention Deficit (PAD) model. Auditory hallucinations (AH) in psychosis, however, are thought to be related to increased attention.MethodOur retrospective database study included 1119 patients with non-affective psychosis and 586 controls. The Community Assessment of Psychic Experiences established the VH rate. Scores on visual perception tests [Degraded Facial Affect Recognition (DFAR), Benton Facial Recognition Task] and attention tests [Response Set-shifting Task, Continuous Performance Test-HQ (CPT-HQ)] were compared between 75 VH patients, 706 non-VH pati...
We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patien... more We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patients with Parkinson's disease (PD) by means of clinical assessments and patient diaries 12 months after surgery. STN-DBS reduced the UPDRS part III off-medication score by 33%, and successively improved complete daily on-time without dyskinesia at 12 months significantly. In conclusion, our study demonstrates the efficacy of chronic STN-DBS on motor features in a selected population of advanced PD patients. In addition to clinical assessments, patients' diaries serve as an essential tool to evaluate the functional motor status after STN-DBS.
Background: Scientific research increasingly focuses on visual symptoms of people with Parkinson’... more Background: Scientific research increasingly focuses on visual symptoms of people with Parkinson’s disease (PD). However, this mostly involves functional measures, whereas self-reported data are equally important for guiding clinical care. Objective: This review provides an overview of the nature and prevalence of self-reported visual complaints by people with PD, compared to healthy controls. Methods: A systematic literature search was performed. Studies from three databases (PubMed, PsycInfo, and Web of Science) were screened for eligibility. Only studies that reported results of visual self-reports in people with idiopathic PD were included. Results: One hundred and thirty-nine eligible articles were analyzed. Visual complaints ranged from function-related complaints (e.g., blurred vision, double vision, increased sensitivity to light or changes in contrast sensitivity) to activity-related complaints (e.g., difficulty reading, reaching, or driving). Visual complaints were more pr...
Objective To identify and substantiate the occurrence, extent and location of retinal degeneratio... more Objective To identify and substantiate the occurrence, extent and location of retinal degeneration in de novo Parkinson’s disease patients (PD) compared to primary open angle glaucoma patients (POAG) and healthy controls (HC). Background PD patients experience visual symptoms and retinal degeneration. Studies using spectral-domain optical coherence tomography (SD-OCT) have shown retinal thinning in PD, resembling the glaucoma pattern. This study investigated the retinal thinning in de novo Ldopa-naive PD patients, to analyse if the profile of retinal thinning could serve as a biomarker for PD. Methods SD-OCT data were collected in de novo Ldopa-naive PD patients at the University Medical Center Groningen. A 5x5 mm OD macular scan was made. These scans were compared to age-matched POAG patients and HC’s. Good quality scans (≥4); segmented by Iowa Reference Algorithms [1], were divided by ETDRS 9-sector grid, and were meta-analyzed by cell-layers (Cohen’s d; 95% CI). Results In total ...
The diagnosis of Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) is based on ... more The diagnosis of Lewy body dementia (LBD) and Parkinson's disease dementia (PDD) is based on an arbitrary distinction between the time of onset of cognitive and motor symptoms. Both diagnoses share many features, like the presence of Lewy bodies, the core symptomatology and the core neurochemical deficits. However, the cognitive symptoms are more severe in DLB, very likely due to extensive beta-amyloid deposits in the cortex, the parkinsonian symptoms are more severe in PDD, due to the more extensive loss of presynaptic dopaminergic neurons and the hippocampal atrophy is more extensive in DLB, very likely due to a loss of fronto-hippocampal projections. Therefore DLB and PDD seem to be part of a spectrum of Lewy body pathologies, which may be accompanied by other protein deposits, like beta-amyloid, causing a different seventy and timing of the symptoms. The cognitive symptoms and hallucinations can be treated by cholinesterase inhibitors and anti-psychotics. DLB patients mostly...
INTRODUCTION The postural instability gait difficulty motor subtype of patients with Parkinson... more INTRODUCTION The postural instability gait difficulty motor subtype of patients with Parkinson's disease (PIGD-PD) has been associated with more severe cognitive pathology and a higher risk on dementia compared to the tremor-dominant subtype (TD-PD). Here, we investigated whether the microstructural integrity of the cholinergic projections from the nucleus basalis of Meynert (NBM) was different between these clinical subtypes. METHODS Diffusion-weighted imaging data of 98 newly-diagnosed unmedicated PD patients (44 TD-PD and 54 PIGD-PD subjects) and 10 healthy controls, were analysed using diffusion tensor imaging, focusing on the white matter tracts associated with cholinergic projections from the NBM (NBM-WM) as the tract-of-interest. Quantitative tract-based and voxel-based analyses were performed using FA and MD as the estimates of white matter integrity. RESULTS Voxel-based analyses indicated significantly lower FA in the frontal part of the medial and lateral NBM-WM tract of both hemispheres of PIGD-PD compared to TD-PD. Relative to healthy control, several clusters with significantly lower FA were observed in the frontolateral NBM-WM tract of both disease groups. Furthermore, significant correlations between the severity of the axial and gait impairment and NBM-WM FA and MD were found, which were partially mediated by NBM-WM state on subjects' attentional performance. CONCLUSIONS The PIGD-PD subtype shows a loss of microstructural integrity of the NBM-WM tract, which suggests that a loss of cholinergic projections in this PD subtype already presents in de novo PD patients.
BACKGROUND The supplementary motor area (SMA) is implicated in stereotypic multi-limb movements s... more BACKGROUND The supplementary motor area (SMA) is implicated in stereotypic multi-limb movements such as walking with arm swing. Gait difficulties in Parkinson's Disease (PD) include reduced arm swing, which is associated with reduced SMA activity. OBJECTIVE To test whether enhanced arm swing improves Parkinsonian gait and explore the role of the SMA in such an improvement. METHODS Cortical activity and gait characteristics were assessed by ambulant EEG, accelerometers and video recordings in 27 PD patients with self-reported gait difficulties and 35 healthy participants when walking normally. Within these two groups, 19 PD patients additionally walked with enhanced arm swing and 30 healthy participants walked without arm swing. Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation analysis of recordings from Fz over the putative SMA and gait analysis was performed. RESULTS Baseline PD gait, characterized by reduced arm swing among other features, exhibited reduced within-step Event Related Desynchronization (ERD)/Synchronization (ERS) alternation (Fz; 20-50Hz), accompanied by a reduced step length and walking speed. All became similar to normal gait when patients walked with enhanced arm swing. When healthy controls walked without arm swing, their alternating ERD-ERS pattern decreased, mimicking baseline PD gait. CONCLUSION Enhanced arm swing may serve as a driving force to overcome impaired gait control in PD patients by restoring reduced ERD-ERS alternation over the putative SMA. Accompanied by increased step length and walking speed, this provides a neural underpinning of arm swing as an effective rehabilitation concept for improving Parkinsonian gait.
BackgroundThe most common genetic risk factor for Parkinson's disease known is a damaging var... more BackgroundThe most common genetic risk factor for Parkinson's disease known is a damaging variant in the GBA1 gene. The entire GBA1 gene has rarely been studied in a large cohort from a single population. The objective of this study was to assess the entire GBA1 gene in Parkinson's disease from a single large population.MethodsThe GBA1 gene was assessed in 3402 Dutch Parkinson's disease patients using next‐generation sequencing. Frequencies were compared with Dutch controls (n = 655). Family history of Parkinson's disease was compared in carriers and noncarriers.ResultsFifteen percent of patients had a GBA1 nonsynonymous variant (including missense, frameshift, and recombinant alleles), compared with 6.4% of controls (OR, 2.6; P < 0.001). Eighteen novel variants were detected. Variants previously associated with Gaucher's disease were identified in 5.0% of patients compared with 1.5% of controls (OR, 3.4; P < 0.001). The rarely reported complex allele p.D14...
Journal of Chromatography B: Biomedical Sciences and Applications, 1997
Analytical methods are described for the selective, rapid and sensitive determination of R- and S... more Analytical methods are described for the selective, rapid and sensitive determination of R- and S-apomorphine, apocodeine and isoapocodeine and the glucuronic acid and sulfate conjugates in plasma and urine. The methods involve liquid-liquid extraction followed by high-performance liquid chromatography with electrochemical detection. The glucuronide and sulfate conjugates are determined after enzymatic hydrolysis. For the assay of R- and S-apomorphine a 10 microm Chiralcel OD-R column is used and the voltage of the detector is set at 0.7 V. The mobile phase is a mixture of aqueous phase (pH 4.0)-acetonitrile (65:35, v/v). At a flow-rate of 0.9 ml min(-1) the total run time is ca. 15 min. The detection limits are 0.3 and 0.6 ng ml(-1) for R- and S- apomorphine, respectively (signal-to-noise ratio 3). The intra- and inter-assay variations are &amp;amp;amp;amp;lt;5% in the concentration range of 2.5-25 ng ml(-1) for plasma samples, and &amp;amp;amp;amp;lt;4% in the concentration range of 40-400 ng ml(-1) for urine samples. For the assay of apomorphine, apocodeine and isoapocodeine, a 5 microm C18 column was used and the voltage of the detector set at 0.825 V. Ion-pairing chromatography was used. The mobile phase is a mixture of aqueous phase (pH 3.0)-acetonitrile (75:25, v/v). At a flow-rate of 0.8 ml min(-1) the total run time is ca. 14 min. The detection limits of this assay are 1.0 ng ml(-1) for apomorphine and 2.5 ng ml(-1) for both apocodeine and isoapocodeine (signal-to-noise ratio 3). The inter-assay variations are 5% in the concentration range of 5-40 ng ml(-1) for plasma samples and 7% in the concentration range of 50-500 ng ml(-1) for urine samples. The glucuronic acid and sulfate conjugates of the various compounds are hydrolysed by incubation of the samples with beta-glucuronidase and sulfatase type H-1, respectively. Hydrolysis was complete after 5 h of incubation. No measurable degradation of apomorphine, apocodeine and isoapocodeine occurred during the incubation. A pharmacokinetic study of apomorphine, following the intravenous infusion of 30 microg kg(-1) for 15 min in a patient with Parkinson&amp;amp;amp;amp;#39;s disease, demonstrates the utility of the methods: both the pharmacokinetic parameters of the parent drug and the appearance of apomorphine plus metabolites in urine could be determined.
BackgroundLittle is known about visual hallucinations (VH) in psychosis. We investigated the prev... more BackgroundLittle is known about visual hallucinations (VH) in psychosis. We investigated the prevalence and the role of bottom-up and top-down processing in VH. The prevailing view is that VH are probably related to altered top-down processing, rather than to distorted bottom-up processing. Conversely, VH in Parkinson's disease are associated with impaired visual perception and attention, as proposed by the Perception and Attention Deficit (PAD) model. Auditory hallucinations (AH) in psychosis, however, are thought to be related to increased attention.MethodOur retrospective database study included 1119 patients with non-affective psychosis and 586 controls. The Community Assessment of Psychic Experiences established the VH rate. Scores on visual perception tests [Degraded Facial Affect Recognition (DFAR), Benton Facial Recognition Task] and attention tests [Response Set-shifting Task, Continuous Performance Test-HQ (CPT-HQ)] were compared between 75 VH patients, 706 non-VH pati...
We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patien... more We assessed the efficacy of chronic stimulation of the subthalamic nucleus (STN-DBS) in 20 patients with Parkinson's disease (PD) by means of clinical assessments and patient diaries 12 months after surgery. STN-DBS reduced the UPDRS part III off-medication score by 33%, and successively improved complete daily on-time without dyskinesia at 12 months significantly. In conclusion, our study demonstrates the efficacy of chronic STN-DBS on motor features in a selected population of advanced PD patients. In addition to clinical assessments, patients' diaries serve as an essential tool to evaluate the functional motor status after STN-DBS.
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