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R Fallows,
K McCoy,
J Hertza,
E Klosson,
B Estes,
I Stroescu,
Cm Salinas,
A Stringer,
S. Aronson,
W Macallister, [......],
T White,
J Gold,
A Vincent,
T Roebuck-Spencer,
A Bowles,
K Gilliland,
A Watts,
F Ahmed,
A Yon,
B Gordon
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ABSTRACT: Objective: The seminal paper on cerebellar cognitive affective syndrome by Schmahmann and Sherman (1998), and subsequent studies, has expanded our understanding of the role of the cerebellum beyond motor functioning to psychological and cognitive functioning. However, many of these studies have examined patients between 1 week and 5 years post-injury and have tended to exclude patients with prior neurological injuries. Thus, the objective of this case study was to examine cerebellar injury in the context of remote traumatic brain injury (TBI) and describe the long-term cognitive, psychological, and psychosocial sequelae of injury in a 33-year-old, right-handed, Caucasian veteran (S.M.). Method: At age 23, S.M. was referred for neuroimaging by psychiatry due to concern that a TBI from age 16 was the cause of recent onset aggressive behavior. Multiple neuroimaging studies showed no neuroanatomical sequelae of TBI, but revealed a right cerebellar arteriovenous malformation (AVM). Embolization resulted in >50% removal of the AVM, but uncovered an intranidal aneurysm. Repeat neuroimaging revealed a large hemorrhage within the cerebellum with the mass effect and hydrocephalus; subsequent treatment resulted in a complicated 5-month hospital stay. Results: Neuropsychological evaluation conducted 10 years after injury revealed deficits in basic attention, working memory, and information processing speed with relatively intact executive functioning and memory. Physical deficits, including ataxia, dysarthria, and spasticity, and psychological difficulties, including impulsivity and low frustration tolerance, were more prominent and caused significant psychosocial distress, impacting interpersonal relationships. Conclusions: This case highlights the cognitive residual of cerebellar injury and the potential long-term impact on psychological and social functioning.
Archives of Clinical Neuropsychology 09/2011; 26(6):470-567. · 2.18 Impact Factor
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Joseph H Friedman,
P Agarwal,
R Alcalay,
K J Black,
K L Chou,
L Cote,
P Dayalu,
S Frank,
J Hartlein,
R A Hauser, [......],
C Moskowitz,
B Ravina,
D Riley,
J Sanchez-Ramos,
D K Simon,
T Simuni,
J Sutton,
P Tuite, D Weintraub,
T Zesiewicz
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ABSTRACT: Hallucinations, delusions, and compulsive behaviors are frequent iatrogenic complications of the treatment of motor dysfunction in Parkinson's disease (PD). Although these have been studied, and the phenomenology described, there are few detailed descriptions of the various psychiatric problems our treated PD patients live with that allow physicians who do not have a great deal of experience with PD patients to appreciate the extent of their altered lives. This report is a compilation of vignettes describing these behavioral problems that the treating neurologist or psychiatrist attributed to the medications used for treating PD.
The International journal of neuroscience 06/2011; 121(8):472-6. · 0.86 Impact Factor
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ABSTRACT: Cognitive decline associated with Parkinson disease (PD) is common and highly disabling. Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease.
A total of 45 patients with PD were enrolled in this prospective cohort study and had at least 1 yearly longitudinal follow-up evaluation. CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale (DRS-2). CSF was tested for amyloid β 1-42 (Aβ(1-42)), p-tau(181p), and total tau levels using the Luminex xMAP platform. Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time.
Lower baseline CSF Aβ(1-42) was associated with more rapid cognitive decline. Subjects with CSF Aβ(1-42) levels ≤192 pg/mL declined an average of 5.85 (95% confidence interval 2.11-9.58, p = 0.002) points per year more rapidly on the DRS-2 than subjects above that cutoff, after adjustment for age, disease duration, and baseline cognitive status. CSF total tau and p-tau(181p) levels were not significantly associated with cognitive decline.
Reduced CSF Aβ(1-42) was an independent predictor of cognitive decline in patients with PD. This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD. This biomarker may provide clinically useful prognostic information, particularly if combined with other risk factors for cognitive impairment in PD.
Neurology 09/2010; 75(12):1055-61. · 8.31 Impact Factor
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D Weintraub,
S Mavandadi,
E Mamikonyan,
A D Siderowf,
J E Duda,
H I Hurtig,
A Colcher,
S S Horn,
S Nazem,
T R Ten Have,
M B Stern
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ABSTRACT: Depression and antidepressant use, especially selective serotonin reuptake inhibitors (SSRIs), are common in Parkinson disease (PD). The objective of this clinical trial was to assess the efficacy of atomoxetine, a selective norepinephrine reuptake inhibitor (SNRI), for the treatment of clinically significant depressive symptoms and common comorbid neuropsychiatric symptoms in PD.
A total of 55 subjects with PD and an Inventory of Depressive Symptomatology-Clinician (IDS-C) score > or = 22 were randomized to 8 weeks of atomoxetine or placebo treatment (target dosage = 80 mg/day). Depression response (> 50% decrease in IDS-C score or Clinical Global Impression-Improvement [CGI-I] score of 1 or 2) was assessed using intention-to-treat modeling procedures. Secondary outcomes included global cognition, daytime sleepiness, anxiety, apathy, and motor function.
There were no between-groups differences in a priori-defined response rates. Using a more liberal response criterion of > 40% decrease in IDS score from baseline, there was a trend (p = 0.08) favoring atomoxetine. Patients receiving atomoxetine experienced significantly greater improvement in global cognition (p = 0.003) and daytime sleepiness (p = 0.001), and atomoxetine was well-tolerated.
Atomoxetine treatment was not efficacious for the treatment of clinically significant depressive symptoms in PD, but was associated with improvement in global cognitive performance and daytime sleepiness. Larger studies of SNRIs in PD for disorders of mood, cognition, and wakefulness are appropriate.
This interventional study provides Class II evidence that atomoxetine (target dosage = 80 mg/day) is not efficacious in improving clinically significant depression in PD.
Neurology 08/2010; 75(5):448-55. · 8.31 Impact Factor
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ABSTRACT: Due to the high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson disease (PD), routine cognitive screening is important for the optimal management of patients with PD. The Montreal Cognitive Assessment (MoCA) is more sensitive than the commonly used Mini-Mental State Examination (MMSE) in detecting MCI and dementia in patients without PD, but its validity in PD has not been established.
A representative sample of 132 patients with PD at 2 movement disorders centers was administered the MoCA, MMSE, and a neuropsychological battery with operationalized criteria for deficits. MCI and PD dementia (PDD) criteria were applied by an investigator blinded to the MoCA and MMSE results. The discriminant validity of the MoCA and MMSE as screening and diagnostic instruments was ascertained.
Approximately one third of the sample met diagnostic criteria for a cognitive disorder (12.9% PDD and 17.4% MCI). Mean (SD) MoCA and MMSE scores were 25.0 (3.8) and 28.1 (2.0). The overall discriminant validity for detection of any cognitive disorder was similar for the MoCA and the MMSE (receiver operating characteristic area under the curve [95% confidence interval]): MoCA (0.79 [0.72, 0.87]) and MMSE (0.76 [0.67, 0.85]), but as a screening instrument the MoCA (optimal cutoff point = 26/27, 64% correctly diagnosed, lack of ceiling effect) was superior to the MMSE (optimal cutoff point = 29/30, 54% correctly diagnosed, presence of ceiling effect).
The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, has adequate psychometric properties as a screening instrument for the detection of mild cognitive impairment or dementia in Parkinson disease. However, a positive screen using either instrument requires additional assessment due to suboptimal specificity at the recommended screening cutoff point.
Neurology 11/2009; 73(21):1738-45. · 8.31 Impact Factor
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American Journal of Psychiatry - AMER J PSYCHIAT. 01/2008; 165(2):261-261.
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ABSTRACT: Depressive disorders may affect up to 50% of patients with Parkinson disease (PD) and are associated with increased disability and reduced quality of life. No previous study has systematically examined the impact of depressive symptoms in early, untreated PD.
We administered the 15-item Geriatric Depression Scale (GDS-15) as part of two NIH-sponsored phase II clinical trials in PD, enrolling 413 early, untreated PD subjects. We used linear mixed models to examine the relationship of depressive symptoms, measured by the GDS-15, with motor function and activities of daily living (ADLs), as measured by the Unified PD Rating Scale (UPDRS). A time-dependent Cox model was used to examine the effect of demographic and clinical outcome measures as predictors of investigator-determined time to need for symptomatic therapy for PD.
A total of 114 (27.6%) subjects screened positive for depression during the average 14.6 months of follow-up. Forty percent of these subjects were neither treated with antidepressants nor referred for further psychiatric evaluation. Depression, as assessed by the GDS-15, was a significant predictor of more impairment in ADLs (p < 0.0001) and increased need for symptomatic therapy of PD (hazard ratio = 1.86; 95% CI 1.29, 2.68).
Clinically important depressive symptoms are common in early Parkinson disease (PD), but are often not treated. Depressive symptoms are an important contributor to disability and the decision to start symptomatic therapy for motor-related impairment in early PD, highlighting the broad importance of identifying and treating depression in this population.
Neurology 08/2007; 69(4):342-7. · 8.31 Impact Factor
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A Siderowf,
A Newberg,
K L Chou,
M Lloyd,
A Colcher,
H I Hurtig,
M B Stern,
R L Doty,
P D Mozley,
N Wintering,
J E Duda, D Weintraub,
P J Moberg
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ABSTRACT: In vivo imaging of the dopamine transporter with [99mTc]TRODAT-1 (TRODAT) and olfactory testing have both been proposed as potential biomarkers in Parkinson disease (PD).
To evaluate the relationship between TRODAT SPECT imaging, odor identification skills, and motor function in patients with early PD.
Twenty-four patients with a clinical diagnosis of early-stage PD (mean Hoehn & Yahr stage = 1.4) underwent TRODAT imaging, Unified PD Rating Scale (UPDRS) ratings of motor function, and administration of the University of Pennsylvania Smell Identification Test (UPSIT). Brain images were obtained using a standardized processing protocol and specific uptake ratios for striatal regions of interest were calculated. Partial correlations between the imaging indices, disease duration, UPSIT scores, and UPDRS motor scores were then calculated.
UPSIT scores were correlated with TRODAT uptake in the striatum as a whole (r = 0.66, p = 0.001). The putamen showed the strongest correlation with the UPSIT (r = 0.74; p < 0.001). The correlation between dopamine transporter density in the caudate and UPSIT was moderate (r = 0.36, p = 0.11), but was not significant.
Olfactory function is highly correlated with dopamine transporter imaging abnormalities in early Parkinson disease (PD). Further studies are warranted to determine whether changes over time in these two measures are also correlated in early PD.
Neurology 05/2005; 64(10):1716-20. · 8.31 Impact Factor
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ABSTRACT: The management of early Parkinson’s disease (PD) involves the treatment of motor symptoms, and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews efficacy and safety data for the newest PD treatment options, as well as for established therapies. Part 2 of the article, presented here, reviews key data relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.
European Neurology. 08/1970; 61(4):206-215.
