Are neuropsychological tests useful in screening for the genetic risk of Parkinson's disease?

We evaluated whether assessments of cognitive flexibility, memory, mood, somatic complaints, personality traits and finger tapping rate could be used to screen persons of at least 40 years of age for their possible genetic risk for idiopathic Parkinson's disease (PD). Thirty-five asymptomatic first-degree relatives (FPD) of PD families with at least two affected members were compared with 29 relatives (SPD) of sporadic PD patients and with 32 controls. After covarying for age and intelligence, FPD had lower scores in verbal fluency, achieved fewer categories and had more errors in the Wisconsin Card Sorting Test; they exhibited more impulsiveness, strain and less extraversion on personality assessment. FPD did not differ from SPD in any of these items. The global assessment of neuropsychological test performance, mood changes, somatic complaints, personality traits and fine motor abilities is of no help in differentiating persons at a putative genetic risk for PD from those without such risk.     

Are importance ratings useful in the assessment of subjective quality of life in schizophrenic patients?

Subjective quality of life (QOL) is predominantly measured as satisfaction in various life domains. However, this approach has often been criticized for not taking individual preferences into account. A combination of importance and satisfaction ratings allows for the different weights that different life domains have in a person's QOL. The present study aimed to investigate empirically the usefulness of combined satisfaction and importance ratings in the assessment of schizophrenic patients. In a cross-sectional study, 149 schizophrenic patients and 106 healthy controls rated their satisfaction with and the importance of 19 different life domains. Results of multidimensional scaling suggested that satisfaction and importance ratings tap different concepts in mentally healthy controls and schizophrenic patients. However, as compared with satisfaction ratings, importance ratings were even more shifted towards the positive pole of the scale and showed less variance. Very high correlations were found between the pure and the weighted satisfaction scores. No additional variance could be accounted for with regard to psychopathology, age or sex. Although a combination of satisfaction and importance ratings fits better with the subjective concept of QOL on a theoretical level, the results of this study do not support the application of this model in QOL assessment in schizophrenic patients. Copyright © 1999 Whurr Publishers Ltd.     

Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinson's disease?

Patients with Parkinson's disease often complain of fatigue, and although cardiac sympathetic denervation is thought to be associated with fatigue, this link remains unclear. Previously, we detected cardiac sympathetic denervation in patients with Parkinson's disease using dobutamine, a selective beta‐1 stimulant. To clarify the involvement of autonomic dysfunction in fatigue in Parkinson's disease, we conducted autonomic function tests on 33 patients with Parkinson's disease (mean age, 66.1 ± 5.6 years; 20 men, 13 women) and evaluated their relationships to fatigue. We divided patients into 2 groups, fatigued (n = 12) and nonfatigued (n = 21), based on an average score ≥ 3.3 on the Parkinson fatigue scale. Autonomic function tests included the coefficient of variation of R–R intervals, head‐up tilt test, norepinephrine and dobutamine infusion tests, and cardiac ¹²³I‐metaiodobenzylguanidine scintigraphy. The coefficient of variation of R–R intervals and the systolic blood pressure changes accompanying the head‐up tilt test did not show significant differences between the 2 groups; however, the pressor responses in the norepinephrine and dobutamine infusion tests were significantly greater in the fatigued group than in the nonfatigued group. The ¹²³I‐metaiodobenzylguanidine heart‐to‐mediastinal uptake ratio was lower in the fatigued group than in the nonfatigued group. Partial correlation analyses, using disease duration and Hoehn and Yahr stage as control variables, also demonstrated significant correlations between the Parkinson fatigue scale score and the results of the autonomic function tests and cardiac ¹²³I‐metaiodobenzylguanidine uptake. Our results suggest that autonomic dysfunction, including cardiac sympathetic denervation, is associated with fatigue in patients with Parkinson's disease. © 2011 Movement Disorder Society     

How useful is (123I) beta-CIT SPECT in the diagnosis of Parkinson's disease?

Because clinical features of parkinsonism can occur in other forms of parkinsonian syndromes in addition to Parkinson's disease, neuroimaging may have a role in determining true disease status. Iodine-123 ((123)I) (2beta-carboxymethoxy-3beta-[4-iodophenyl] tropane) or ((123)I) beta-CIT is a recently developed diagnostic biomarker of Parkinson's disease that provides in vivo information about nigrostriatal degeneration. In clinical trials, beta-CIT single photon emission computed tomography (SPECT) has been shown to be a highly sensitive diagnostic tool in differentiating clinically probable Parkinson's disease from normal subjects and essential tremor patients. As a tool for differentiating Parkinson's disease from atypical parkinsonian syndromes, ((123)I) beta-CIT SPECT may have more limited use because of more extensive postsynaptic pathology in the latter. Differentiating among various parkinsonian syndromes may be improved by methodological refinements, a combined strategy of imaging presynaptic and postsynaptic sites, or by metabolic imaging.     

Are dementia and depression in Parkinson's disease related?

INTRODUCTION: Depression and dementia are common problems in PD. As the depression and dementia of PD share many symptoms such as apathy, anhedonia, anergia, and agitation, it is reasonable to ask if they are related. METHODS: 106 consecutive PD patients, unselected for depression or dementia were evaluated for depression using the Hamilton Depression Scale (Ham-D21). They were also evaluated using a modified neuropsychiatric inventory (NPI). Following the above, 100 consecutive PD patients were evaluated for dementia using Folstein's Mini Mental Status Examination (MMSE). They were also evaluated using the modified NPI. RESULTS: 29 of the first series of patients, 27%, were depressed, score of > or =14 on the Ham-D21. 8 of the second series of consecutive patients, 18%, were demented, score < or =24 on the MMSE. Depressed and demented patients were significantly more likely to suffer from apathy, anhedonia, mood lability, daytime drowsiness, paranoia, and hallucinations. Demented patients were significantly older, had PD longer, were more disabled and more likely to be depressed. COMMENT: The commonality of certain symptoms in demented and depressed patients suggests that dementia and depression in PD may be related and that, in PD depression may be a fore-runner of dementia. Five year follow-up of these patients supports this suggestion.     

Are dopaminergic pathways involved in theory of mind? A study in Parkinson's disease

The "orbitofrontal" and "cingulate" frontostriatal loops and the mesolimbic dopaminergic system that modulates their function have been implicated in theory of mind (ToM). Parkinson's disease (PD) provides a model for assessing their role in humans. Results of the handful of previous studies of ToM in PD providing preliminary evidence of impairment remain controversial, mainly because the patients included in these studies were not accurately described, making it difficult to determine whether their ToM deficits were due to general cognitive deterioration or to a more specific dopaminergic deficit. The aim of our study was therefore to re-examine previous results highlighting ToM in PD and to explore the involvement of the dopaminergic pathways in ToM. ToM was investigated in 17 newly diagnosed PD patients (early PD group), 27 PD patients in the advanced stages of the disease (advanced PD group) and 26 healthy matched controls (HC), using two ToM tasks: a visual one, which is thought to reflect the "affective" ToM subcomponent ("Reading the Mind in the Eyes"), and a verbal one, which is thought to reflect both the "affective" and the "cognitive" ToM subcomponents (faux pas recognition). Furthermore, the early PD group was studied in two conditions: with and without dopamine replacement therapy (DRT). We failed to find any significant difference in ToM between the early PD patients and the HC group. Furthermore, there was no difference between the early PD patients in the medicated and unmedicated conditions. Conversely, the advanced PD patients scored poorly on the intention attribution question ("cognitive" ToM score) in the faux pas recognition task. The present results suggest that the deficit in ToM only occurs in the more advanced stages of the disease. In addition, our results would appear to indicate that these advanced PD patients present "cognitive" ToM impairment rather than global ("cognitive" and "affective") ToM impairment. In other words, the ToM deficit would appear to be present in PD patients where the degenerative process has spread beyond the dopaminergic pathways, but not in early PD patients where neuronal loss is thought to be restricted to the nigrostriatal and mesolimbic dopaminergic systems. In conclusion, our results suggest that the dopaminergic pathways are not involved in ToM.     

Is a computational model useful to understand the effect of deep brain stimulation in Parkinson's disease?

A growing number of computational models have been proposed over the last few years to help explain the therapeutic effect of deep brain stimulation (DBS) on motor disorders in Parkinson's disease (PD). However, none of these has been able to explain in a convincing manner the physiological mechanisms underlying DBS. Can these models really contribute to improving our understanding? The model by Rubin and Terman [31] represents one of the most comprehensive and biologically plausible models of DBS published recently. We examined the validity of the model, replicated its simulations and tested its robustness. While our simulations partially reproduced the results presented by Rubin and Terman [31], several issues were raised including the high complexity of the model in its non simplified form, the lack of robustness of the model with respect to small perturbations, the nonrealistic representation of the thalamus and the absence of time delays. Computational models are indeed necessary, but they may not be sufficient in their current forms to explain the effect of chronic electrical stimulation on the activity of the basal ganglia (BG) network in PD.     

In vivo alpha-synuclein overexpression in rodents: a useful model of Parkinson's disease?

Mutations in alpha-synuclein were the first genetic defect linked to Parkinson's disease (PD). The relevance of alpha-synuclein to sporadic PD is strongly supported by the presence of alpha-synuclein aggregates in neurons of patients. This has prompted the development of numerous animal models based on alpha-synuclein overexpression, primarily through genetic methods in mice and viral transduction in rats. In mice, different promoters and transgenes lead to a wide variety of phenotypes accompanied by non-existent, late onset, or non-specific neurodegeneration. Rapid neurodegeneration, in contrast, is observed after viral transduction but is limited to the targeted region and does not mimic the broad pathology observed in the disease. Overall, each model reproduces a subset of features of PD and can be used to identify therapeutic targets and test disease-modifying therapies. The predictive value of all models of the disease, however, remains speculative in the absence of effective neuroprotective treatments for PD in humans.     

Are patients with Parkinson's disease suicidal?

Using the National Center of Health Statistics' mortality statistics databases for 1991 through 1996 (12,430,473 deaths), we isolated 144,364 individuals 40 years of age or older with a primary diagnosis of Parkinson's disease (PD). Of these, 122 died by suicide. The rate of suicide in the general population was about 10 times higher than in patients with PD (0.8% compared with only 0.08%, respectively). These different rates of suicide cannot be attributed to differences in age, gender, race, education, or marital status. Compared with patients with suicidal PD, patients with PD who died from other causes manifested significantly lower rates of affective disorders. The referent population exhibited a higher rate of malignancy and a lower rate of depression. The findings suggest that marital status, mood disorder, and somatic comorbidity provide only a limited understanding of completed suicide.     

Are the Effects of rTMS in Parkinson's Disease Clinically Relevant?

Introduction. Earlier studies have shown that brain stimulation by means of repetitive Transcranial Magnetic Stimulation (rTMS) over the primary motor cortex can decrease the motor impairments in Parkinson's disease (PD). The present study focused on the clinical relevance of rTMS in the treatment of PD.

Method. Thirteen PD patients received a minimum of 10 sessions of 2,000 pulses 5 Hz rTMS over the hand and leg area over the primary motor cortex, with a stimulation intensity of 120% of the motor threshold. In our analysis an effect could be considered as clinically relevant if the quality of life (QoL) improved with 30% or more.

Results. Paired-sample t-tests revealed a significant improvement of Unified Parkinson's Disease Rating Scale score, walking speed, and mood. A minority of the patients (38%) who underwent rTMS showed an improvement in QoL of greater than 30%. The improvements on QoL correlated significantly to scores of motor improvements on the Unified Parkinson's Disease Rating Scale but not to improvements in mood as assessed by the Geriatric Depression Scale. The use of rTMS did not demonstrate any effects on tremor, freezing of gait, and activities of daily life, and rTMS had no effect on the stage of disease. It mainly improved rigidity, finger and hand movements, and leg agility.

Conclusion. This study shows that although there can be significant group effects of rTMS on PD symptoms, these significant effects do not automatically imply that these are clinically relevant. Therefore we advise that future studies in the field of neuromodulation (rTMS, neurofeedback, etc.) also focus more on the clinical relevance of the treatment under investigation rather than only report “significant group differences.”     

Are quantitative and clinical measures of bradykinesia related in advanced Parkinson's disease?

Introduction

Bradykinesia is usually assessed using clinical rating scales. In some circumstances, a laboratory assessment of bradykinesia using tools of higher resolution is required. One task often used for the evaluation of bradykinesia is a rapid alternating movement (RAM) of the hand. However, the relationship between clinical scores of bradykinesia and the properties of a RAM task assessed quantitatively has yet to be determined.

Objective

Identify which of the commonly used properties of a RAM task are related to a clinical score of bradykinesia and assess the strength of this relationship.

Methods

Nineteen patients with idiopathic Parkinson's disease were tested ON and OFF medication. They performed three trials of the RAM task and were assessed clinically using the Unified Parkinson's disease rating scale in each condition and with each hand.

Results

A statistically significant correlation was observed between the clinical score of bradykinesia and two of the properties of the RAM task; namely mean and maximal velocity.

Comparison with existing methods

These results indicate that a RAM task does provide a measure of bradykinesia but it is only moderately correlated to a clinical rating of this motor symptom.

Conclusion

We propose that the results from the RAM task represent a measure of “core bradykinesia” while a clinical evaluation represents a composite score of bradykinesia, movement amplitude and motor coordination.     

Skin biopsy for assessment of autonomic denervation in Parkinson’s disease

Summary. Autonomic dysfunction in Parkinson’s disease (PD) is considered a late complication of the disease or an adverse effect of anti-parkinsonian medications. Morphological changes are demonstrated only by postmortem examination. The study objective was to evaluate peripheral autonomic neural involvement in PD using punch skin biopsy. The study sample included 22 patients (mean age 50 ± 7.7 years, mean disease duration 5.3 ± 3.8 years) and 19 controls. Four-millimeter skin biopsies were immunohistochemically stained with anti-PGP 9.5 antibody. Autonomic innervation of the blood vessels, sweat glands, and erector pili muscles was assessed and rated from 0 (normal) to 2 (severe). Cutaneous autonomic innervation was decreased in patients compared to controls. Semi quantitative analysis demonstrated reduced autonomic innervation of the blood vessels (1.0 ± 0.8 vs. 0.42 ± 0.8 in controls; p < 0.02), of sweat glands (0.95 ± 0.67 vs. 0.47 ± 0.61; p < 0.02) and of the erector pili muscles (1.06 ± 0.55 vs 0.21 ± 0.42; p < 0.001). This method demonstrates that the peripheral autonomic system is affected in PD at early stage of the disease and that autonomic involvement in PD may be more prevalent than previously thought. R. Dabby and R. Djaldetti contributed equally to this work