Cognitive phenotyping of GBA1-Parkinson's disease: A study on deep brain stimulation outcomes.

BACKGROUND: Heterozygous variants in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson's Disease (PD). GBA1-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in GBA1-PD, are debated. METHODS: This study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into GBA1-PD and non-GBA1-PD groups, with non-GBA1-PD further divided into cognitive fast-progressors and slow-progressors. RESULTS: GBA1 variants were present in 13.5 % of patients. GBA1-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-GBA1-PD. Non-GBA1-PD fast-progressors exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but slow-progressors showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD). CONCLUSIONS: GBA1-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-GBA1-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, GBA1-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status.

Impact of Stimulation Frequency on Verbal Fluency Following Bilateral Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

OBJECTIVE: The effects of stimulation frequency on verbal fluency (VF) following subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) are not well understood. The present study examines the impact stimulation frequency has on VF following bilateral STN-DBS in PD. METHODS: Prospective study of 38 consecutive patients with PD with low frequency STN-DBS (LFS) (n = 10) and high frequency STN-DBS (HFS) (n = 14), and a non-operated PD control group consisting of patients with fluctuating response to dopaminergic medication (n = 14) homogeneous in age, education, disease duration, and global cognitive function. Patients were evaluated on VF tasks (letter, semantic, action verbs, alternating). A one-way analysis of variance (ANOVA) was conducted to assess distinctions between groups. Pre- and post-surgical comparisons of fluencies were performed for operated groups. A mixed ANOVA was applied to the data to evaluate the interaction between treatment (HFS vs. LFS) and time (pre- vs. post-surgery). Strategy use (clustering and switching) was evaluated. RESULTS: Semantic and letter fluency performance revealed significant differences between HFS and LFS groups. Pre- and post-surgical comparisons revealed HFS negatively affected letter, semantic, and action fluencies, but LFS had no effect on VF. No interaction effect or main effect of treatment was found. Main effect of time was significant for semantic and action fluencies indicating a decrease in postoperative fluency performance. Patients with LFS produced larger average cluster sizes than patients with HFS. CONCLUSION: LFS may be less detrimental to VF, but these findings suggest that VF decline following STN-DBS is not caused by stimulation frequency alone.

Tau seeding activity in skin biopsy differentiates tauopathies from synucleinopathies.

Most neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need. Since tau protein is highly expressed in skin of tauopathies patients, we aimed to exploit the ultrasensitive seeding activity assay (SAA) to assess tau seeding activity in skin of patients with tauopathies. In this multicentric, case-control study, patients with tauopathies and synucleinopathies were consecutively recruited and sex-matched to healthy controls (HC). Subjects underwent a double 3 mm skin biopsy in cervical area and ankle. Skin tau-SAA, using TauK18 and TauK19 as reaction substrates for 4R and 3R isoforms, seeding score, clinical scales, biochemical and morphological characterization of SAA end-products were evaluated. We analyzed 58 subjects: 24 tauopathies (18 progressive supranuclear palsy, PSP, and 6 corticobasal degeneration, CBD), 20 synucleinopathies (14 Parkinson's disease, PD, and 6 multiple system atrophy, MSA), and 14 HC. PSP and CBD showed higher tau seeding activity at both anatomical sites. A greater sensitivity of 4R-SAA than 3R-SAA was observed. 4R tau-SAA identified tauopathies with 71% sensitivity and 93% specificity. Accuracy was higher for PSP than CBD: PSP vs HC / PD (AUC 0.825), while CBD vs HC / PD (AUC 0.797), and PSP vs MSA (AU 0.778). SAA end-products showed differences in biochemical and morphological characterization according to the anatomical site. Skin tau-SAA identifies tauopathies with good accuracy and can be used to implement the in-vivo clinical diagnosis of patients with neurodegenerative diseases. Further characterization of peripheral tau seed in skin may elucidate the structure of tau deposits in brain.

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease.

BACKGROUND: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. METHODS: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. RESULTS: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). CONCLUSIONS: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD.

Associations Between Diabetic Retinopathy and Parkinson's Disease: Results From the Catalonian Primary Care Cohort Study.

The purpose of this study was to assess the risk of occurrence of Parkinson's disease (PD) among subjects with type 2 diabetes and diabetic retinopathy (DR) in our large primary health care database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated the number of events, time to event, cumulative incidence, and incidence rates of PD for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the probability of occurrence between DR and PD. In total, 26,453 type 2 diabetic subjects with DR were identified in the database, and 216,250 subjects without DR at inclusion. During the follow-up period, 1,748 PD events occurred. PD incidence rate and cumulative incidence were higher among subjects with DR (16.95 per 10,000 person-years and 0.83%, respectively). In the unadjusted analysis, subjects with DR were at 1.25 times higher risk (hazard ratio: 1.22, 95% confidence interval: 1.06; 1.41) of developing PD during the study period. However, we did not find any statistically significant HR for DR in any models after adjusting for different risk factors (age, sex, duration of diabetes, smoking, body mass index, glycosylated hemoglobin, comorbidities). In conclusion, in our primary health care population database, DR was not associated with an increased risk of PD after adjusting for different risk factors. In our retrospective cohort study, age, male sex, and diabetes duration were independent risk factors for developing PD.

Serum neurofilament light chain levels reflect cortical neurodegeneration in de novo Parkinson's disease.

INTRODUCTION: Cognitive impairment and dementia are highly prevalent non-motor complications in Parkinson's disease (PD) with deleterious consequences for patients and caregivers. With no treatment currently available, finding and validating minimally-invasive biomarkers of neurodegeneration in this population represents an urgent need for clinical trials targeting its prevention or delay. Recently, serum neurofilament light chain (NfL) levels have been identified as a promising biomarker of neural loss, but whether they reflect cortical neurodegeneration in early PD stages has not been addressed. METHODS: From the Parkinson's Progression Markers Initiative (PPMI), we selected 133 de novo PD patients and 56 healthy controls (HC) with available structural neuroimaging and serum NfL data. We then studied whether NfL levels were abnormal in the PD group with respect to HC, and whether they correlated with cognitive indicators and cortical macro (cortical thinning) and microstructural (increased intracortical mean diffusivity) degeneration. RESULTS: Serum NfL levels were significantly increased in the PD group (p = 0.010), and were also related to worse cognitive performance and a cortical macro and microstructural compromise (p < 0.05 corrected). These associations were observed both cross-sectionally and longitudinally within a one-year follow-up period. Topographically, NfL levels reflected posterior-cortical deterioration rather than frontal damage. Importantly, NfL levels were not associated with striatal SPECT-DAT uptake or ß-amyloid burden. DISCUSSION: Our results show that serum NfL levels reflect cortical neurodegeneration from the very early stages of PD. Moreover, its brain structural correlates and its lack of relationship with dopaminergic depletion or amyloidosis suggests that NfL could track the underlying pathological process leading to PD dementia.

CLU rs11136000 promotes early cognitive decline in Parkinson's disease.

BACKGROUND: The C allele of the rs11136000 genetic variant of the clusterin gene has been associated with increased risk of Alzheimer's disease. However, a comprehensive characterization of the role of this genetic variant in early cognitive deterioration in PD is lacking. METHODS: Using the Parkinson's Progression Markers Initiative database, we compared baseline and 5-year cognitive performance between high-risk and low-risk clusterin genotypes. RESULTS: At baseline, recently diagnosed and drug-naive de novo PD patients with the high-risk clusterin genotype showed lower cognitive scores in memory and executive function tests. These differences were even higher at the 5-year follow-up, when they showed a higher prevalence of clinically diagnosed mild cognitive impairment or dementia. They also showed cortical thinning at baseline and increased annual thinning in frontal and posterior cortical regions. DISCUSSION: Our results provide evidence of this clusterin genotype promoting early cognitive deterioration in PD, but further research is needed to delineate the specific neurodegenerative pathways underlying this clinical association. © 2020 International Parkinson and Movement Disorder Society.

Differential Expression of Striatal ΔFosB mRNA and FosB mRNA After Different Levodopa Treatment Regimens in a Rat Model of Parkinson's Disease.

Levodopa-induced dyskinesia (LID) is the main side effect associated with levodopa treatment and represents the biggest challenge for Parkinson's disease therapy. While the overexpression of ΔFosB transcription factor is related to the development of LID, few studies have been undertaken on fosB gene transcriptional regulation induced by levodopa in vivo. The aim of this study is to evaluate the expression of ΔFosB mRNA and FosB mRNA in the striatum after acute, chronic, and subchronic levodopa treatment in rats with unilateral 6-OHDA-lesion in the medial forebrain bundle. qRT-PCR was used to compare the levels of ΔFosB and FosB mRNA expression in the dopamine-denervated striatum following levodopa treatment. While the results obtained after a single levodopa dose indicate a significant increase of ∆FosB mRNA expression in the striatum 1 h post-injection, the levels returned to baseline values after 24 h. After subchronic levodopa treatment, the levels of ∆FosB and FosB mRNA expression were lower 1 h post-administration of levodopa in comparison with acute effect. However, after chronic levodopa treatment, ∆FosB mRNA expression in the striatum persisted in dyskinetic rats only, and positive correlation was found between the levels of ∆FosB mRNA expression 1 h after levodopa administration and the level of dyskinetic severity. In summary, acute levodopa treatment led to highly increased levels of ∆FosB mRNA expression in the striatum. While repeated administration induced a partial desensitization of the fosB gene in the striatum, it did not suppress its activity completely, which could explain why dyskinesia appears after chronic levodopa treatment.

Parkinson's Disease: Impulsivity Does Not Cause Impulse Control Disorders but Boosts Their Severity.

Introduction: Impulse control disorders (ICDs) are a common complication of Parkinson's disease (PD) receiving dopamine agonist (DAA) Impulsivity is considered an underlying mechanism but evidence of this relationship is scarce. To explore the relationship between impulsivity and the presence and severity of ICD in PD. Methods: Prospective cross-sectional study of consecutive PD outpatients. Patients with dementia or previously known ICDs were excluded. Two measures of impulsivity were assessed: Barratt Impulsiveness Scale (BIS-11) for impulsiveness trait (main exposure) and commission errors in the Continuous Performance Test (CE) for motor inhibition. Main outcomes were diagnosis of ICD based on a comprehensive clinical interview and severity of ICD based on the Questionnaire for Impulsive-Compulsive Disorders. Results: Of 100 patients (mean [SD] age, 67.2 [8.8], 54 male), 31 had ICD. Patients with ICDs were 5.3 years younger (p = 0.01), used more frequently dopamine agonist (p = 0.02), alcohol (p = 0.009) and tobacco (p = 0.02). They were not more impulsive on BIS-11 (56 vs. 58, p = 0.23, adjusted p = 0.46) and CE (p = 0.96). No relationship was found between dopaminergic medications and impulsivity or ICD severity. Among patients with ICD, impulsivity was correlated with ICD severity (BIS-11 r = 0.33, p = 0.001, adjusted p = 0.002, CE r = 0.53, p = 0.006). Multivariate regression analysis confirmed the independent predictive role of both measures. Conclusions: Impulsivity is not associated with increased prevalence of ICD in PD but it is strongly linked to ICD severity. When considering dopamine replacement therapy, assessment of impulsivity may be a useful approach to detect those patients at risk of severe forms of ICD.

Angiotensin Type 1 Receptor Antagonists Protect Against Alpha-Synuclein-Induced Neuroinflammation and Dopaminergic Neuron Death.

The loss of dopaminergic neurons and α-synuclein accumulation are major hallmarks of Parkinson's disease (PD), and it has been suggested that a major mechanism of α-synuclein toxicity is microglial activation. The lack of animal models that properly reproduce PD, and particularly the underlying synucleinopathy, has hampered the clarification of PD mechanisms and the development of effective therapies. Here, we used neurospecific adeno-associated viral vectors serotype 9 coding for either the wild-type or mutated forms of human alpha-synuclein (WT and SynA53T, respectively) under the control of a synapsin promoter to further induce a marked dopaminergic neuron loss together with an important microglial neuroinflammatory response. Overexpression of neuronal alpha-synuclein led to increased expression of angiotensin type 1 receptors and NADPH oxidase activity, together with a marked increase in the number of OX-6-positive microglial cells and expression of markers of phagocytic activity (CD68) and classical pro-inflammatory/M1 microglial phenotype markers such as inducible nitric oxide synthase, tumor necrosis factor alpha, interleukin-1ß, and IL-6. Moreover, a significant decrease in the expression of markers of immunoregulatory/M2 microglial phenotype such as the enzyme arginase-1 was constantly observed. Interestingly, alpha-synuclein-induced changes in microglial phenotype markers and dopaminergic neuron death were inhibited by simultaneous treatment with the angiotensin type 1 blockers candesartan or telmisartan. Our results suggest the repurposing of candesartan and telmisartan as a neuroprotective strategy for PD.

Update in therapeutic strategies for Parkinson's disease.

PURPOSE OF REVIEW: To review recent advances in therapeutics for motor and nonmotor symptoms of Parkinson's disease. RECENT FINDINGS: Neuroprotection remains a large area of investigation with preliminary safety data on alpha synuclein immunotherapy and glucagon-like peptide-1 agonists. Novel Monoamine Oxidase B and Caetchol-O-methyltransferase-inhibitors for motor fluctuations have shown benefit and are recently approved for clinical use. Long-acting amantadine has also been approved to reduce dyskinesia. Alternative delivery strategies (sublingual, inhaled) dopaminergics may prove useful for rapid reversal of Parkinson's disease motor symptoms. Advanced therapies (surgery and infusional therapies) continue to be useful in subgroups of patients for motor complications with improved safety and also benefit on some nonmotor symptoms, including neuropsychiatric issues. Specific therapeutics for cognition, swallowing, sleep, and mood disorders had moderate to limited benefits. Exercise-based therapy appears beneficial at all stages of Parkinson's disease. SUMMARY: The motor symptoms of Parkinson's disease can be reasonably treated and managed. However, therapies to slow or prevent disease progression remain a focus of research. Despite increased studies, treating nonmotor symptoms remains a challenge and an ongoing priority.

Adenosine A2A-receptor antagonism and pathophysiology of Parkinson's disease and drug-induced movement disorders.

Parkinson's disease and drug-induced movement disorders (DIMDs) have commonalities in etiology based on impaired dopamine-based neurotransmission. Adenosine A(2A)-receptor antagonism may provide a new mechanism through which these disorders can be managed. In the motor circuit, tonic output from the globus pallidus and substantia nigra regulates movement via opposing excitatory and inhibitory inputs to the cerebral cortex through the direct and indirect pathways. Increased activity of the direct pathway increases movement via an inhibitory effect on thalamocortical projection neurons; increased activity of the indirect pathway has the opposite effect. Regulation of these pathways is mediated primarily by reciprocal inhibitory interactions between dopamine and adenosine receptors on neurons of these pathways. Adenosine A(2A) receptors are colocalized with dopamine D(2) receptors on the indirect pathway neurons, with A(2A) activation opposing the effect of D(2) activation. The A(2A) receptors' role in the pathophysiology of Parkinson's disease and DIMDs is evidenced by the upregulation of A(2A) receptors in patients with Parkinson's disease and patients receiving long-term administration of dopamine blockers. Further, A(2A)-receptor antagonists are effective in reversing parkinsonian motor deficits and extrapyramidal symptoms in animal models of Parkinson's disease and DIMDs. Understanding the role of A(2A)-receptor antagonism in the pathophysiology of Parkinson's disease and DIMD has therapeutic implications.

Facial emotion recognition impairment in patients with Parkinson's disease and isolated apathy.

Apathy is a frequent feature of Parkinson's disease (PD), usually related with executive dysfunction. However, in a subgroup of PD patients apathy may represent the only or predominant neuropsychiatric feature. To understand the mechanisms underlying apathy in PD, we investigated emotional processing in PD patients with and without apathy and in healthy controls (HC), assessed by a facial emotion recognition task (FERT). We excluded PD patients with cognitive impairment, depression, other affective disturbances and previous surgery for PD. PD patients with apathy scored significantly worse in the FERT, performing worse in fear, anger, and sadness recognition. No differences, however, were found between nonapathetic PD patients and HC. These findings suggest the existence of a disruption of emotional-affective processing in cognitive preserved PD patients with apathy. To identify specific dysfunction of limbic structures in PD, patients with isolated apathy may have therapeutic and prognostic implications.

Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease.

We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off-stimulation, regardless of the sequence of stimulation. In open assessment, both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group.

PDD-Short Screen: a brief cognitive test for screening dementia in Parkinson's disease.

The diagnosis of Parkinson's disease with dementia (PDD) is currently based on clinical criteria (DSM-IV, MDS-Task Force). In daily practice and research studies, these criteria still depend on the subjective impression of the examiner. Brief screening tests (BST) are helpful in identifying patients with PD with dementia, which can be difficult in patients with advanced PD. We aimed to develop a BST for PD, the PDD-Short Screen (PDD-SS), to accurately and quickly screen for PDD. In this prospective study, 70 patients with nondemented (age 73.8 +/- 4.4) and 32 demented (age 73.8 +/- 4.4) PD regularly attending a Movement Disorders Clinic were included. Diagnosis of dementia was based on DSM-IV criteria, CDR score >or=1, and PD-CRS total score

Homocysteine and cognitive impairment in Parkinson's disease: a biochemical, neuroimaging, and genetic study.

The role of the plasma level of homocysteine (Hcy), as a primary outcome, and the effect of silent cerebrovascular lesions and genetic variants related to Hcy metabolism, as secondary outcomes, in the cognitive decline and dementia in Parkinson's disease (PD) were studied. This case-control study focused on 89 PD patients of minimum 10 years of evolution and older than 60 years, who were neuropsychologically classified either as cognitively normal (n = 37), having mild cognitive impairment (Petersen criteria) (n = 22), or suffering from dementia (DSM-IV) (n = 30), compared with cognitively normal age-matched control subjects (n = 30). Plasma levels of Hcy, vitamins B12 and B6, folic acid, polymorphisms in genes related to Hcy metabolism (MTHFR, MTR, MTRR, and CBS) and silent cerebrovascular events were analyzed. Plasma levels of Hcy were increased in PD patients (P = 0.0001). There were no differences between the groups of patients. The brain vascular burden was similar among PD groups. There was no association between polymorphisms in the studied genes and the Hcy plasma levels or cognitive status in PD patients. We found no evidence for a direct relationship between Hcy plasma levels and cognitive impairment and dementia in PD. No indirect effect through cerebrovascular disease or genetic background was found either.

Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families.

Within the past few years, there has been a significant change in identifying and characterizing the FMR1 premutation associated phenotypes. The premutation has been associated with elevated FMR1 mRNA levels and slight to moderate reductions in FMRP levels. Furthermore, it has been established that approximately 20% of female premutation carriers present primary ovarian insufficiency (POI) and that fragile X-associated tremor/ataxia syndrome (FXTAS) occurs in one-third of all male premutation carriers older than 50 years. Besides POI and FXTAS, new disorders have recently been described among individuals (especially females) with the FMR1 premutation. Those pathologies include thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia. However there are few reports related to FXTAS penetrance among female premutation carriers or regarding these disorders recently associated to the FMR1 premutation. Therefore, we have evaluated 398 fragile X syndrome (FXS) families in an attempt to provide an estimation of the premutation associated phenotypes penetrance. Our results show that signs of FXTAS are detected in 16.5% of female premutation carriers and in 45.5% of premutated males older than 50 years. Furthermore, among females with the FMR1 premutation, penetrance of POI, thyroid disease and chronic muscle pain is 18.6, 15.9 and 24.4%, respectively. The knowledge of this data might be useful for accurate genetic counselling as well as for a better characterization of the clinical phenotypes of FMR1 premutation carriers.

Diagnosis and management of essential tremor and dystonic tremor.

Essential tremor (ET) is the most common adult movement disorder. Traditionally considered as a benign disease, it can cause an important physical and psychosocial disability. Drug treatment for ET remains poor and often unsatisfactory. Current therapeutic strategies for ET are reviewed according to the level of discomfort caused by tremor. For mild tremor, nonpharmacological strategies consist of alcohol and acute pharmacological therapy; for moderate tremor, pharmacological therapies (propranolol, gabapentin, primidone, topiramate, alprazolam and other drugs); and for severe tremor, the role of functional surgery is emphasised (thalamic deep brain stimulation, thalamotomy). The more specific treatment of head tremor with the use of botulinum toxin is also discussed. Several points are discussed to guide the immediate research into this disease in the near future. Dystonic tremor is a common symptom in dystonia. Diagnostic criteria for dystonic tremor and differential diagnosis with psychogenic tremor and ET are described. Treatment of dystonic tremor matches the treatment of dystonia. In cases of symptomatic dystonic tremor similar to ET, therapeutic strategies would be the same as for ET.

Cut-off score of the Mattis Dementia Rating Scale for screening dementia in Parkinson's disease.

The prevalence of dementia in Parkinson's disease (PD) is close to 30%, and its incidence is 4 to 6 times higher than in age-matched general population. PD with dementia (PDD) is mainly characterized by a predominant and progressive frontal-subcortical impairment. The Mattis Dementia Rating Scale (MDRS) is a commonly used screening test that sensitively measures the degree of frontal-subcortical defects. Although the MDRS has been validated as a screening test of cognitive dysfunction in nondemented PD patients (PD-ND), its utility for screening dementia in PD is unknown. In order to validate the MDRS for diagnosis of PDD it was prospectively administered to 92 PD patients (57 PD-ND, 35 PDD) fulfilling UK-PDSBB criteria. Dementia was diagnosed according to DSM-IV-TR and a Clinical Dementia Rating (CDR) scale score >or=1. Univariate, logistic regression, and ROC curve analysis were carried out to measure the discriminative power of MDRS in PDD. Regression analysis showed MDRS total scores to independently differentiate PD-ND from PDD (P < 0.001). Age and education did not predict the presence of dementia. ROC curve analysis showed a cut-off score of