Background: Postural instability (PI) in Parkinson's disease (PD) is associated with depression a... more Background: Postural instability (PI) in Parkinson's disease (PD) is associated with depression and apathy based on UPDRS scores. We sought to examine the link using more objective PI measures. Methods: Demographic, clinical, depression and apathy data were recorded for PD patients prospectively recruited from an outpatient university movement disorders clinic. PI was objectively evaluated using the standing center of pressure sway area. Results: Thirty-seven PD patients participated in the study. Bivariate analysis revealed that PI was significantly correlated to both apathy (p = 0.018) and depression (p = 0.014). Hierarchical regression revealed that apathy significantly predicted PI but depression did not significantly add to the prediction. Also, depression did not significantly predict PI and the addition of apathy did not increase this prediction. Conclusion: Apathy and depression are both associated with objective measures of PI, and apathy appears a stronger predictor of PI than depression. Concomitant improvement in PI may be important to consider when measuring apathy or depression interventions in PD.
We present the pre to post bilateral globus pallidus interna (GPi) deep brain stimulation neurops... more We present the pre to post bilateral globus pallidus interna (GPi) deep brain stimulation neuropsychological profiles of a 69-year-old patient with a 12-year history of X-linked dystonia-Parkinsonism (XDP). Pre-operative cognitive function was impaired in almost all domains and this impaired performance was not dependent on his medications. Following DBS, changes in neuropsychological functioning were examined using Reliable Change Indices and standardized z-score comparisons. Results showed reductions in processing speed in the context of stable performance in language and visuospatial domains. Postoperative improvements occurred on a cognitive screening measure, verbal memory, and a test of problem-solving skills. This is the first report on an individual with XDP who was cognitively impaired, but had good outcome following GPi bilateral stimulation to treat debilitating motor symptoms. The possible mechanisms for his stable cognitive performance include the target of his DBS, reduced medication dosage, and improvement in dystonia that may in turn have reduced patient's pain.
Objective-There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this pro... more Objective-There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this prospective blinded randomized trial was to compare the cognitive and mood effects of unilateral subthalamic nucleus (STN) vs. unilateral globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with Parkinson disease (PD). Methods-Fifty-two subjects with moderate-to-advanced PD were randomized to either unilateral STN or GPi DBS. Right or alternatively left sided stimulation was chosen to address the side of the body with the most bothersome symptoms. The co-primary outcome measures were the change in the 8 subscales of the Visual Analog Mood Scale (VAMS), and the change in the 2 versions of verbal fluency (i.e. semantic and letter), at 7 months post-DBS in the optimal setting compared to the pre-DBS state. In addition, at 7 months post-DBS, after subjects underwent initial evaluation off medications and on optimized DBS therapy, they were tested in four randomized and counterbalanced conditions (optimal DBS, ventral DBS, dorsal DBS, and off DBS) while remaining off medication. Secondary outcome measures then compared the differences in the VAMS items and verbal fluency subscales within the 4 DBS conditions at 7 months, and the change in the VAMS items and verbal fluency subscales from the pre-DBS state to the other 3 DBS conditions (ventral, dorsal and off) at 7 months. Results-Forty-five subjects (23 GPi and 22 STN) completed the protocol. The study revealed no significant difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes from pre-to post-DBS in the optimal setting (Hotelling's T 2 test: p=0.16 and 0.08 respectively). When comparing the 4 DBS conditions at 7 months, subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally to the optimal stimulation site. When comparing the other 3 DBS conditions (ventral, dorsal and off DBS) to the pre-DBS state, the STN group showed a larger deterioration of letter verbal fluency scores than the GPi group, especially in the off DBS state. A 12-point mean improvement in the UPDRS motor subscale was seen post DBS, but there was no significant difference between targets.
Prospective studies conducted during the last decade have shown that the majority of patients wit... more Prospective studies conducted during the last decade have shown that the majority of patients with Parkinson’s disease (PD) develop dementia. In addition, using a variety of definitions and methods, more recent research suggests that approximately a quarter of PD patients without dementia have mild cognitive impairment (PD-MCI). Furthermore, several studies have shown that approximately 20% have MCI even at time
A growing body of literature supports the view that essential tremor (ET) involves alteration of ... more A growing body of literature supports the view that essential tremor (ET) involves alteration of cerebellar-thalamo-cortical networks which can result in working memory and executive deficits. In this study, we tested the hypothesis that individuals with ET would exhibit worse performance on memory tasks requiring more intrinsic organization and structuring (i.e., word lists) relative to those with fewer 'executive' demands (i.e., stories), similar to that previously observed in individuals with Parkinson's disease (PD). Participants included a convenience sample of 68 ET patients and 68 idiopathic PD patients, retrospectively matched based on age, education, and sex. All patients underwent routine neuropsychological evaluation assessing recent memory, auditory attention/working memory, language, and executive function. Memory measures included the Hopkins Verbal Learning Test-R and WMS-III Logical Memory. Both ET and PD patients performed significantly worse on word lis...
Objective This prospective investigation examined: 1) processing speed and working memory relativ... more Objective This prospective investigation examined: 1) processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson's disease, and 2) the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory. Methods Participants completed a neuropsychological protocol, Unified Parkinson's Disease Rating Scale, brain MRI, and fasting blood draw to rule out vascular contributors. Within group a priori anatomical contributors included bilateral frontal thickness, caudate nuclei volume, and prefrontal white matter fractional anisotropy.
The subjects were six 8-to 11-year-old boys with attention deficits enrolled in their school&... more The subjects were six 8-to 11-year-old boys with attention deficits enrolled in their school's resource specialist program for learning disabled children. The effects of baseline conditions, teacher-administered reinforcers, and self-administered reinforcers were evaluated ...
Five patients with left hemispatial neglect and five aphasic control subjects were given a hemisp... more Five patients with left hemispatial neglect and five aphasic control subjects were given a hemispatial pointing task. They were instructed to point to an imaginary point in space perpendicular to the midline of the chest. Right hemisphere-damaged subjects with neglect deviated more into the hemispace ipsilateral to the lesion than left hemisphere-damaged controls. This task did not require sensory input from left hemispace, and the defective performance cannot be attributed to sensory inattention or to impaired gaze or memory. The finding is compatible with hemispatial akinesia.
Patients with hemispatial neglect perform activities poorly in the hemispace contralateral to the... more Patients with hemispatial neglect perform activities poorly in the hemispace contralateral to the lesion. We postulate that hemispatial neglect induced by right hemisphere lesions may be associated with a directional hypokinesia: initiation of movements toward the hemispace contralateral to the lesion is affected more than movements toward the lesion. We tested 6 patients with hemispatial neglect caused by right hemisphere damage, 7 with left hemisphere damage and no neglect, and 12 controls. Patients with left hemispatial neglect initiated responses to left hemispace more slowly than toward right hemispace.
Objective: Parkinson&... more Objective: Parkinson's disease (PD) is a neurodegenerative disorder resulting in a wide variety of symptoms. The current study examined the influence of apathy, depression and motor symptoms on quality of life (QoL) in PD patients. Information was drawn from an 18-month period. Method: Participants (N = 397) were assessed for apathy (Apathy Scale; Starkstein et al., 1992), depression (Beck Depression Inventory-II; Beck, Steer, Ball & Ranieri, 1996), motor severity (Unified Parkinson's Disease Rating Scale, Part III; UPDRS; Fahn, Elton & Committee, 1987), and QoL (Parkinson's Disease Questionnaire-39; Jenkinson, Fitzpatrick, Peto, Greenhall, & Hyman,1997) at 3 time points: an initial clinical evaluation (baseline), a 6-month follow-up, and an 18-month follow-up. Latent growth-curve models were used to determine the influence of apathy, depression, and motor symptoms on QoL trajectories. Results: Greater difficulties with QoL at baseline showed the strongest relationship to more severe depression symptoms, followed by more severe motor symptoms, younger age, and less education (all p values < .001). Worsening of QoL over the 18-month period was only predicted by a worsening of depression (p = .003). The relationship between QoL and depression symptoms remained significant in a subsample of nondepressed PD patients. Conclusion: Overall, findings from the current study suggest that self-reported QoL among PD patients is primarily related to depression. Future efforts to improving clinical care of PD patients may benefit by focusing on improving psychosocial adjustment or treatments targeting depression. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Brain magnetic resonance image (MRI) registration alters structure orientation, size, and/or shap... more Brain magnetic resonance image (MRI) registration alters structure orientation, size, and/or shape. To determine whether linear registration methods (image transformation to 6, 9, and 12° of freedom) alter structural volume and cognitive associations, we examined transformation alterations to the caudate nucleus within individuals diagnosed with Parkinson's disease (PD) and demographically matched non-PD peers. Volumes from native and six were expected be significantly different from 9 and 12° of freedom methods. Caudate nucleus volumes were expected to be associated with measures of processing speed and mental flexibility, but the strength of the association based on transformation approach was unknown. MRI brain scans from individuals with Parkinson's disease (n = 40) and age-matched controls (n = 40) were transformed using 6, 9, and 12° of freedom to an average brain template. Correlations controlling for total intracranial volume assessed expected structural-behavioral a...
The Parkinson&amp... more The Parkinson's disease questionnaire-39 (PDQ-39) is a common measure of health related quality of life (HRQoL) that is widely used with Parkinson disease (PD) patients. Previous evidence suggests that the PDQ-39 reflects at least 8 dimensions (i.e., Emotion, Cognitions, Mobility, etc). To date, little research has examined the external/convergent validity of the Cognitions and Emotional Well-being domains of the PDQ-39. A convenience sample of 303 PD patients underwent a comprehensive multi-domain neuropsychological evaluation, including tests of execution function, episodic verbal memory, processing speed, language and working memory, as well as completing measures of depression, apathy, state and trait anxiety and HRQoL (PDQ-39). Hierarchical regressions were conducted in order to examine the relationship between scores on neuropsychological tests and the Cognitions index, as well as mood measures and the Emotional Well-being index of the PDQ-39. Neuropsychological test performance did not account for a significant amount of variance in the PDQ-39 Cognitions index scores. Instead, it was depression that significantly contributed to the Cognitions index, above and beyond neuropsychological performance. The PDQ-39 Emotional Well-being index was also related to mood measures, primarily depression and trait anxiety. The PDQ-39 Cognition index may be more related to mood functioning, as opposed to cognitive functioning, and should not be considered a "proxy" for cognitive functioning. Future studies are needed to better explain the construct of this index.
A patient with verbal amnesia and a propensity to direct his attention to the right following a r... more A patient with verbal amnesia and a propensity to direct his attention to the right following a retrosplenial area lesion was studied with positron emission tomography using [F-IS] fluorodeoxyglucose.
We reviewed our deep brain stimulation patient database to describe hardware complications which ... more We reviewed our deep brain stimulation patient database to describe hardware complications which resulted from implantable pulse generator mobility, a phenomenon referred to as Twiddler's syndrome. A prospectively collected database of adverse events for all patients operated on at the University of Florida was queried searching for hardware malfunctions. Of 362 total leads implanted in 226 patients since 2002, there were 17 hardware malfunctions. Three of them were due to Twiddler's syndrome, representing 1.3% of patients (3 of 226 patients) and 1.4% of leads (5 of 362 leads). The subjects had characteristic presentations including re-emergence of symptoms, pain along the path of the hardware, abnormal impedances/current drain and radiographic signs of twisting/fracture. In all cases securing the implantable pulse generator within the chest pocket resolved the issue. Twiddler's syndrome in the population of movement disorder patients treated with deep brain stimulation is an uncommon but important adverse event. It possesses a characteristic presentation and with appropriate diagnostic evaluation it is treatable and future occurrences are preventable.
To collect the information necessary to design the methods and outcome variables for a larger tri... more To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome. We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS. A university movement disorders center. Five patients with implanted DBS. A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness. This study provides safety and proof of concept that a scheduled DBS approach could improve motor and vocal tics in Tourette syndrome. Refinements in neurostimulator battery life, outcome measure selection, and flexibility in programming settings can be used to enhance outcomes in a future larger study. Scheduled stimulation holds promise as a potential first step for shifting movement and neuropsychiatric disorders toward more responsive neuromodulation approaches. clinicaltrials.gov Identifier: NCT01329198.
Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose... more Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinson's disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity. Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables. Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinson's Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function. Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated.
The pathology of Alzheimer's Disease (AD) is believed to appear first in the transentorhinal/ento... more The pathology of Alzheimer's Disease (AD) is believed to appear first in the transentorhinal/entorhinal cortex. The usefulness, however, of entorhinal volumetric measurements to discriminate among normal and prodromal stage AD patients is debated. Some attribute this reduced discrimination ability to difficulties with magnetic resonance imaging (MRI) depiction and measurement of this structure (Xu Y, Jack et al., 2001). Objective(s): The purpose of this study was to assess intra and inter rater reliability of three different entorhinal cortex volumetric measurement approaches to identify if one of these protocols is most appropriate for visualization and quantification purposes. Methods: Volumetric MRI scans (3.0T Siemens; MP Rage sequences) were obtained on 24 nondemented older adults (mean ageϭ71.09Ϯ6.44; Mini Mental State Exam ϭ 28.96Ϯ1.19). Volumetric analysis was conducted with MEA-SURE (Barta et al., 1997). Each entorhinal cortex was measured twice using three different volumetric protocols: 1) Insausti et al (1998) that uses collateral sulcus (CS) depth to define ROI boundary; 2) Goncharova et al that excludes the CS; 3) an experimental "Full" technique that includes the entire CS. Conclusions: Intraclass correlation coefficients showed high intra-rater reliability for all three entorhinal protocols (Insausti, rϭ.98; Goncharova, rϭ.97; Full, rϭ.96). Inter-rater reliability was highest with the Full technique (rϭ .95) and lowest with the Insausti et al protocol (rϭ.86). There was adequate association among all three techniques (ICC among all three approaches, rϭ.92). Our preliminary findings suggest that the entorhinal cortex can be measured reliably on MRI using any of three volumetric protocols. The lowest rater reliability was identified for the Insausti et al (1998) protocol. This protocol requires a rater to subjectively alter their measurement approach based on CS depth. Strengths and weakness of measurement approach along with the range of volumes will be discussed.
A masked facial expression, one of the hallmark features of Parkinson disease (PD), can form the ... more A masked facial expression, one of the hallmark features of Parkinson disease (PD), can form the basis for misattributions by others about a patient's mood or interest levels. Reports of preserved intensity of internal emotional experience in PD participants raise the question of whether patients are aware of their outward expressivity levels. The aim of the present study was to determine whether PD participants exhibit deficits in overall emotional expressivity, and if so, whether they are aware of these deficits. We evaluated 37 non-demented PD participants and 21 comparison participants using the Berkeley Expressivity Questionnaire (BEQ). To examine awareness of emotional expressivity, we compared participant self-ratings of their own expressivity to ratings made by family members or close friends. Participants also completed questionnaires regarding depression and apathy and underwent motor examination and cognitive screening. PD participants' self-ratings of emotional expressivity were significantly lower than comparison participants' self-ratings. Even so, the PD participants viewed themselves as experiencing equivalent levels of emotional intensity to comparison participants, based on analysis of the BEQ subscales. Informant and PD participant self-ratings did not differ, indicating that PD participants accurately appraise the extent of their reduced expressivity. These findings suggest that anosognosia for emotional expressivity is not a prominent feature of nondemented Parkinson disease. Importantly, PD participants are aware of their reduced expressivity and report experiencing emotions as intensely as comparison participants. These findings highlight the view that diminished emotional expressivity in PD should not be mistaken for decreased subjective emotional experience.
Background: Postural instability (PI) in Parkinson's disease (PD) is associated with depression a... more Background: Postural instability (PI) in Parkinson's disease (PD) is associated with depression and apathy based on UPDRS scores. We sought to examine the link using more objective PI measures. Methods: Demographic, clinical, depression and apathy data were recorded for PD patients prospectively recruited from an outpatient university movement disorders clinic. PI was objectively evaluated using the standing center of pressure sway area. Results: Thirty-seven PD patients participated in the study. Bivariate analysis revealed that PI was significantly correlated to both apathy (p = 0.018) and depression (p = 0.014). Hierarchical regression revealed that apathy significantly predicted PI but depression did not significantly add to the prediction. Also, depression did not significantly predict PI and the addition of apathy did not increase this prediction. Conclusion: Apathy and depression are both associated with objective measures of PI, and apathy appears a stronger predictor of PI than depression. Concomitant improvement in PI may be important to consider when measuring apathy or depression interventions in PD.
We present the pre to post bilateral globus pallidus interna (GPi) deep brain stimulation neurops... more We present the pre to post bilateral globus pallidus interna (GPi) deep brain stimulation neuropsychological profiles of a 69-year-old patient with a 12-year history of X-linked dystonia-Parkinsonism (XDP). Pre-operative cognitive function was impaired in almost all domains and this impaired performance was not dependent on his medications. Following DBS, changes in neuropsychological functioning were examined using Reliable Change Indices and standardized z-score comparisons. Results showed reductions in processing speed in the context of stable performance in language and visuospatial domains. Postoperative improvements occurred on a cognitive screening measure, verbal memory, and a test of problem-solving skills. This is the first report on an individual with XDP who was cognitively impaired, but had good outcome following GPi bilateral stimulation to treat debilitating motor symptoms. The possible mechanisms for his stable cognitive performance include the target of his DBS, reduced medication dosage, and improvement in dystonia that may in turn have reduced patient's pain.
Objective-There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this pro... more Objective-There is a paucity of level-one evidence comparing STN and GPi DBS. Our aim in this prospective blinded randomized trial was to compare the cognitive and mood effects of unilateral subthalamic nucleus (STN) vs. unilateral globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with Parkinson disease (PD). Methods-Fifty-two subjects with moderate-to-advanced PD were randomized to either unilateral STN or GPi DBS. Right or alternatively left sided stimulation was chosen to address the side of the body with the most bothersome symptoms. The co-primary outcome measures were the change in the 8 subscales of the Visual Analog Mood Scale (VAMS), and the change in the 2 versions of verbal fluency (i.e. semantic and letter), at 7 months post-DBS in the optimal setting compared to the pre-DBS state. In addition, at 7 months post-DBS, after subjects underwent initial evaluation off medications and on optimized DBS therapy, they were tested in four randomized and counterbalanced conditions (optimal DBS, ventral DBS, dorsal DBS, and off DBS) while remaining off medication. Secondary outcome measures then compared the differences in the VAMS items and verbal fluency subscales within the 4 DBS conditions at 7 months, and the change in the VAMS items and verbal fluency subscales from the pre-DBS state to the other 3 DBS conditions (ventral, dorsal and off) at 7 months. Results-Forty-five subjects (23 GPi and 22 STN) completed the protocol. The study revealed no significant difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes from pre-to post-DBS in the optimal setting (Hotelling's T 2 test: p=0.16 and 0.08 respectively). When comparing the 4 DBS conditions at 7 months, subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally to the optimal stimulation site. When comparing the other 3 DBS conditions (ventral, dorsal and off DBS) to the pre-DBS state, the STN group showed a larger deterioration of letter verbal fluency scores than the GPi group, especially in the off DBS state. A 12-point mean improvement in the UPDRS motor subscale was seen post DBS, but there was no significant difference between targets.
Prospective studies conducted during the last decade have shown that the majority of patients wit... more Prospective studies conducted during the last decade have shown that the majority of patients with Parkinson’s disease (PD) develop dementia. In addition, using a variety of definitions and methods, more recent research suggests that approximately a quarter of PD patients without dementia have mild cognitive impairment (PD-MCI). Furthermore, several studies have shown that approximately 20% have MCI even at time
A growing body of literature supports the view that essential tremor (ET) involves alteration of ... more A growing body of literature supports the view that essential tremor (ET) involves alteration of cerebellar-thalamo-cortical networks which can result in working memory and executive deficits. In this study, we tested the hypothesis that individuals with ET would exhibit worse performance on memory tasks requiring more intrinsic organization and structuring (i.e., word lists) relative to those with fewer 'executive' demands (i.e., stories), similar to that previously observed in individuals with Parkinson's disease (PD). Participants included a convenience sample of 68 ET patients and 68 idiopathic PD patients, retrospectively matched based on age, education, and sex. All patients underwent routine neuropsychological evaluation assessing recent memory, auditory attention/working memory, language, and executive function. Memory measures included the Hopkins Verbal Learning Test-R and WMS-III Logical Memory. Both ET and PD patients performed significantly worse on word lis...
Objective This prospective investigation examined: 1) processing speed and working memory relativ... more Objective This prospective investigation examined: 1) processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson's disease, and 2) the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory. Methods Participants completed a neuropsychological protocol, Unified Parkinson's Disease Rating Scale, brain MRI, and fasting blood draw to rule out vascular contributors. Within group a priori anatomical contributors included bilateral frontal thickness, caudate nuclei volume, and prefrontal white matter fractional anisotropy.
The subjects were six 8-to 11-year-old boys with attention deficits enrolled in their school&... more The subjects were six 8-to 11-year-old boys with attention deficits enrolled in their school's resource specialist program for learning disabled children. The effects of baseline conditions, teacher-administered reinforcers, and self-administered reinforcers were evaluated ...
Five patients with left hemispatial neglect and five aphasic control subjects were given a hemisp... more Five patients with left hemispatial neglect and five aphasic control subjects were given a hemispatial pointing task. They were instructed to point to an imaginary point in space perpendicular to the midline of the chest. Right hemisphere-damaged subjects with neglect deviated more into the hemispace ipsilateral to the lesion than left hemisphere-damaged controls. This task did not require sensory input from left hemispace, and the defective performance cannot be attributed to sensory inattention or to impaired gaze or memory. The finding is compatible with hemispatial akinesia.
Patients with hemispatial neglect perform activities poorly in the hemispace contralateral to the... more Patients with hemispatial neglect perform activities poorly in the hemispace contralateral to the lesion. We postulate that hemispatial neglect induced by right hemisphere lesions may be associated with a directional hypokinesia: initiation of movements toward the hemispace contralateral to the lesion is affected more than movements toward the lesion. We tested 6 patients with hemispatial neglect caused by right hemisphere damage, 7 with left hemisphere damage and no neglect, and 12 controls. Patients with left hemispatial neglect initiated responses to left hemispace more slowly than toward right hemispace.
Objective: Parkinson&... more Objective: Parkinson's disease (PD) is a neurodegenerative disorder resulting in a wide variety of symptoms. The current study examined the influence of apathy, depression and motor symptoms on quality of life (QoL) in PD patients. Information was drawn from an 18-month period. Method: Participants (N = 397) were assessed for apathy (Apathy Scale; Starkstein et al., 1992), depression (Beck Depression Inventory-II; Beck, Steer, Ball & Ranieri, 1996), motor severity (Unified Parkinson's Disease Rating Scale, Part III; UPDRS; Fahn, Elton & Committee, 1987), and QoL (Parkinson's Disease Questionnaire-39; Jenkinson, Fitzpatrick, Peto, Greenhall, & Hyman,1997) at 3 time points: an initial clinical evaluation (baseline), a 6-month follow-up, and an 18-month follow-up. Latent growth-curve models were used to determine the influence of apathy, depression, and motor symptoms on QoL trajectories. Results: Greater difficulties with QoL at baseline showed the strongest relationship to more severe depression symptoms, followed by more severe motor symptoms, younger age, and less education (all p values < .001). Worsening of QoL over the 18-month period was only predicted by a worsening of depression (p = .003). The relationship between QoL and depression symptoms remained significant in a subsample of nondepressed PD patients. Conclusion: Overall, findings from the current study suggest that self-reported QoL among PD patients is primarily related to depression. Future efforts to improving clinical care of PD patients may benefit by focusing on improving psychosocial adjustment or treatments targeting depression. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Brain magnetic resonance image (MRI) registration alters structure orientation, size, and/or shap... more Brain magnetic resonance image (MRI) registration alters structure orientation, size, and/or shape. To determine whether linear registration methods (image transformation to 6, 9, and 12° of freedom) alter structural volume and cognitive associations, we examined transformation alterations to the caudate nucleus within individuals diagnosed with Parkinson's disease (PD) and demographically matched non-PD peers. Volumes from native and six were expected be significantly different from 9 and 12° of freedom methods. Caudate nucleus volumes were expected to be associated with measures of processing speed and mental flexibility, but the strength of the association based on transformation approach was unknown. MRI brain scans from individuals with Parkinson's disease (n = 40) and age-matched controls (n = 40) were transformed using 6, 9, and 12° of freedom to an average brain template. Correlations controlling for total intracranial volume assessed expected structural-behavioral a...
The Parkinson&amp... more The Parkinson's disease questionnaire-39 (PDQ-39) is a common measure of health related quality of life (HRQoL) that is widely used with Parkinson disease (PD) patients. Previous evidence suggests that the PDQ-39 reflects at least 8 dimensions (i.e., Emotion, Cognitions, Mobility, etc). To date, little research has examined the external/convergent validity of the Cognitions and Emotional Well-being domains of the PDQ-39. A convenience sample of 303 PD patients underwent a comprehensive multi-domain neuropsychological evaluation, including tests of execution function, episodic verbal memory, processing speed, language and working memory, as well as completing measures of depression, apathy, state and trait anxiety and HRQoL (PDQ-39). Hierarchical regressions were conducted in order to examine the relationship between scores on neuropsychological tests and the Cognitions index, as well as mood measures and the Emotional Well-being index of the PDQ-39. Neuropsychological test performance did not account for a significant amount of variance in the PDQ-39 Cognitions index scores. Instead, it was depression that significantly contributed to the Cognitions index, above and beyond neuropsychological performance. The PDQ-39 Emotional Well-being index was also related to mood measures, primarily depression and trait anxiety. The PDQ-39 Cognition index may be more related to mood functioning, as opposed to cognitive functioning, and should not be considered a "proxy" for cognitive functioning. Future studies are needed to better explain the construct of this index.
A patient with verbal amnesia and a propensity to direct his attention to the right following a r... more A patient with verbal amnesia and a propensity to direct his attention to the right following a retrosplenial area lesion was studied with positron emission tomography using [F-IS] fluorodeoxyglucose.
We reviewed our deep brain stimulation patient database to describe hardware complications which ... more We reviewed our deep brain stimulation patient database to describe hardware complications which resulted from implantable pulse generator mobility, a phenomenon referred to as Twiddler's syndrome. A prospectively collected database of adverse events for all patients operated on at the University of Florida was queried searching for hardware malfunctions. Of 362 total leads implanted in 226 patients since 2002, there were 17 hardware malfunctions. Three of them were due to Twiddler's syndrome, representing 1.3% of patients (3 of 226 patients) and 1.4% of leads (5 of 362 leads). The subjects had characteristic presentations including re-emergence of symptoms, pain along the path of the hardware, abnormal impedances/current drain and radiographic signs of twisting/fracture. In all cases securing the implantable pulse generator within the chest pocket resolved the issue. Twiddler's syndrome in the population of movement disorder patients treated with deep brain stimulation is an uncommon but important adverse event. It possesses a characteristic presentation and with appropriate diagnostic evaluation it is treatable and future occurrences are preventable.
To collect the information necessary to design the methods and outcome variables for a larger tri... more To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome. We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS. A university movement disorders center. Five patients with implanted DBS. A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness. This study provides safety and proof of concept that a scheduled DBS approach could improve motor and vocal tics in Tourette syndrome. Refinements in neurostimulator battery life, outcome measure selection, and flexibility in programming settings can be used to enhance outcomes in a future larger study. Scheduled stimulation holds promise as a potential first step for shifting movement and neuropsychiatric disorders toward more responsive neuromodulation approaches. clinicaltrials.gov Identifier: NCT01329198.
Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose... more Objective. Health comorbidities, particularly cardiovascular risk factors, are well known to pose risks for cognitive decline in older adults. To date, little attention has focused on the impact of these comorbidities on Parkinson's disease (PD). This study examined the prevalence and contribution of comorbidities on cognitive status in PD patients, above and beyond the effects of disease severity. Methods. A cross sectional design was used, including neuropsychological data on 341 PD patients without severe cognitive decline. Comorbidity data were collected via medical chart review. Data were analyzed using a series of multiple hierarchical regressions, controlling for PD-related disease variables. Results. Overall sample characteristics are 69% male, disease duration 9.7 years, Unified Parkinson's Disease Rating Scale 26.4, and age 64.7 years. Hypercholesterolemia (41.6%), hypertension (38.1%), and hypotension (30.2%) were the most reported comorbidities. The presence of hypertension significantly contributed to domains of executive function and verbal memory. The cooccurrence of orthostatic hypotension moderated the relationship between hypertension and executive function. Conclusions. This study on a large cohort of PD patients provides evidence for a detrimental influence of health comorbidities, particularly hypertension, on cognitive domains that have traditionally been conceptualized as being frontally and/or temporally mediated.
The pathology of Alzheimer's Disease (AD) is believed to appear first in the transentorhinal/ento... more The pathology of Alzheimer's Disease (AD) is believed to appear first in the transentorhinal/entorhinal cortex. The usefulness, however, of entorhinal volumetric measurements to discriminate among normal and prodromal stage AD patients is debated. Some attribute this reduced discrimination ability to difficulties with magnetic resonance imaging (MRI) depiction and measurement of this structure (Xu Y, Jack et al., 2001). Objective(s): The purpose of this study was to assess intra and inter rater reliability of three different entorhinal cortex volumetric measurement approaches to identify if one of these protocols is most appropriate for visualization and quantification purposes. Methods: Volumetric MRI scans (3.0T Siemens; MP Rage sequences) were obtained on 24 nondemented older adults (mean ageϭ71.09Ϯ6.44; Mini Mental State Exam ϭ 28.96Ϯ1.19). Volumetric analysis was conducted with MEA-SURE (Barta et al., 1997). Each entorhinal cortex was measured twice using three different volumetric protocols: 1) Insausti et al (1998) that uses collateral sulcus (CS) depth to define ROI boundary; 2) Goncharova et al that excludes the CS; 3) an experimental "Full" technique that includes the entire CS. Conclusions: Intraclass correlation coefficients showed high intra-rater reliability for all three entorhinal protocols (Insausti, rϭ.98; Goncharova, rϭ.97; Full, rϭ.96). Inter-rater reliability was highest with the Full technique (rϭ .95) and lowest with the Insausti et al protocol (rϭ.86). There was adequate association among all three techniques (ICC among all three approaches, rϭ.92). Our preliminary findings suggest that the entorhinal cortex can be measured reliably on MRI using any of three volumetric protocols. The lowest rater reliability was identified for the Insausti et al (1998) protocol. This protocol requires a rater to subjectively alter their measurement approach based on CS depth. Strengths and weakness of measurement approach along with the range of volumes will be discussed.
A masked facial expression, one of the hallmark features of Parkinson disease (PD), can form the ... more A masked facial expression, one of the hallmark features of Parkinson disease (PD), can form the basis for misattributions by others about a patient's mood or interest levels. Reports of preserved intensity of internal emotional experience in PD participants raise the question of whether patients are aware of their outward expressivity levels. The aim of the present study was to determine whether PD participants exhibit deficits in overall emotional expressivity, and if so, whether they are aware of these deficits. We evaluated 37 non-demented PD participants and 21 comparison participants using the Berkeley Expressivity Questionnaire (BEQ). To examine awareness of emotional expressivity, we compared participant self-ratings of their own expressivity to ratings made by family members or close friends. Participants also completed questionnaires regarding depression and apathy and underwent motor examination and cognitive screening. PD participants' self-ratings of emotional expressivity were significantly lower than comparison participants' self-ratings. Even so, the PD participants viewed themselves as experiencing equivalent levels of emotional intensity to comparison participants, based on analysis of the BEQ subscales. Informant and PD participant self-ratings did not differ, indicating that PD participants accurately appraise the extent of their reduced expressivity. These findings suggest that anosognosia for emotional expressivity is not a prominent feature of nondemented Parkinson disease. Importantly, PD participants are aware of their reduced expressivity and report experiencing emotions as intensely as comparison participants. These findings highlight the view that diminished emotional expressivity in PD should not be mistaken for decreased subjective emotional experience.
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