Does an association between cigarette smoking and Parkinson's Disease-related psychosis exist? Insights from a large non-demented cohort

Background: Parkinson's Disease-related Psychosis (PDP) encompasses a spectrum of symptoms ranging from "minor" hallucinations to formed hallucinations and delusions. Notably, cognitive impairment has been recognized as the strongest risk factor for PDP. Several evidences suggest a possible role of cigarette smoking in both cognition and psychotic syndromes. Objectives: To evaluate the possible independent association between cigarette smoking and PDP in a large cohort of non-demented PD patients. Methods: A cohort of non-demented PD patients was selected from the FRAGAMP study population. All participants underwent a standardised structured questionnaire to assess demographic, clinical and environmental exposure data. Clinical features were assessed using UPDRS, HY stage, AIMS, MMSE and Hamilton Rating Scale for Depression. Presence of psychotic symptoms was assessed using UPDRS-I.2 score. Diagnosis of PDP was made according to NINDS/NIMH criteria. Results: Four hundred eighty-five non-demented PD patients were enrolled [292 men (60.2%); mean age +/- SD 65.6 +/- 9.8]. Among them, 28 (5.8%) had PDP. Multivariate analysis, adjusting by HY stage, MMSE and LED, shown an independent association between PDP and "nightmares-abnormal movements during sleep" and current smoking [adjOR 7.39 (95%CI 1.45-37.69; P-value 0.016)]. Conclusions: Our findings provide interesting insights about the possible role of current smoking in facilitating the occurrence of psychotic symptoms in PD

Influence of Drugs on Mild Cognitive Impairment in Parkinson's Disease: Evidence from the PACOS Study

Background: polytherapy and the anticholinergic activity of several drugs negatively influence cognition in the elderly. However, little is known on the effect on Mild Cognitive Impairment (MCI) in Parkinson's Disease (PD). Methods: patients with PD belonging to the baseline PACOS cohort with full pharmacological data have been included in this study. MCI diagnosis was made according to the MDS level II criteria. Polytherapy was defined as patients assuming >= 6 drugs. The anticholinergic burden has been calculated using the Anticholinergic Drug Scale (ADS). Molecules have been classified according to the ATC classification. Association with MCI has been assessed with a multivariate logistic regression analysis with MCI as the dependent variable. Results: pharmacological data were available for 238 patients (mean age 64.7 +/- 9.7). One hundred (42.0%) were diagnosed with MCI. No association was found in the full multivariate model (correcting for age, sex, disease duration, education, UPDRS-ME, LEDD-DAs) with either polytherapy or the ADS. Concerning drug classes, anti-hypertensive medications were positively associated with PD-MCI (OR 2.02;95%CI 1.04-3.89; p=0.035) while gastroprotective agents were negatively associated (OR 0.51; 95%CI 0.27-0.99; p=0.047). Conclusion: the magnitude of polytherapy and anticholinergic drugs burden does not appear to modulate MCI risk in PD, probably due to cautious prescription patterns. The effect of anti-hypertensive and gastroprotective agents on PD-MCI risk, while needing further confirmations, could be relevant for clinical practice

Retinal Thickness in Essential Tremor and Early Parkinson Disease: Exploring Diagnostic Insights

International audienceBackground: Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD. Methods: Macular layers and peripapillary retinal nerve fiber layer (RNFL) thickness among ET, early PD, and healthy controls (HCs) were assessed using OCT. Results: Forty-two eyes from 23 ET, 41 eyes from 21 early PD, and 33 eyes from 17 HCs were analyzed. Macular RNFL, ganglion cell layer, inner plexiform layer, and inner nuclear layer were thinner in PD as compared with ET and even more in HCs. Differences between ET and PD were more evident when considering the TD-PD subgroup, especially for RNFL. Among ET patients, thickness of the inner macular layers showed negative linear relationship with both age at onset and disease duration. Peripapillary temporal quadrant thinning was found in ET compared with HCs. Conclusions: Macular inner retina was thinner in patients with ET and early PD compared with HCs. These findings suggest that the retinal assessment may have a utility in the differential diagnosis between ET and PD

Clinical-Instrumental patterns of neurodegeneration in Essential Tremor: A data-driven approach

International audienceIntroduction: Essential Tremor (ET) is increasingly recognized as a complex disorder with additional clinical signs other than tremor. It is still unknown whether a unique pathophysiologic or neurodegenerative process underlies progression and prognosis of the disease. The aim of the study was to identify ET phenotypes through a clinicalinstrumental data-driven approach and to characterize possible patterns of neurodegeneration.Methods: ET patients were categorized using spatio-temporal and kinematic variables related to mobility and dynamic stability processed by motion transducers. Differences between the identified groups in clinicaldemographic variables, neuropsychological performances and retinal parameters by Optical Coherence Tomography (OCT) segmentation analysis were tested.Results: Twenty-five ET patients were studied. Based on clustering of kinematic and spatio-temporal gait parameters,two independent groups were identified: cluster “A” (N = 15) and cluster “B” (N = 10). Compared to group A, group B had overall worse performance in mobility, especially on turning tasks. Identified clusters did not differ in terms of age, age at onset and disease duration. Patients in group B had more head tremor and more severe action tremor in the upper limbs as compared to group A, demonstrating also worse performances on cognitive assessments. Based on OCT analysis, group B presented a reduced thickness of the retinal inner layer as compared to group A, suggesting underlying neurodegenerative processes.Conclusions: The presence of gait and mobility impairment, associated with midline tremor, cognitive decline and retinal degeneration suggests a subtype of ET associated with neurodegeneration

Risk factors of Parkinson\u2019s disease: simultaneous assessment, interactions and etiological subtypes

Objective: To perform a simultaneous evaluation of potential risk/protective factors of Parkinson's disease (PD) in order to identify independent risk/protective factors, assess interaction among factors and determine whether identified risk factors predict etiological subtypes of PD. Methods: We designed a large case-control study assessing 31 protective/risk factors of PD, including environmental and lifestyle factors, comorbidities, and drugs. The study enrolled 694 PD patients and 640 healthy controls from six neurological centers. Data were analyzed by logistic regression models, additive interaction models, and cluster analysis. Results: The simultaneous assessment of 31 putative risk/protective factors of PD showed that only coffee consumption (odds ratio [OR]: 0.6; 95% confidence interval [CI]: 0.4-0.9), smoking (OR: 0.7; 95% CI: 0.6-0.9), physical activity (OR: 0.8; 95% CI: 0.7-0.9), family history of PD (OR: 3.2; 95% CI: 2.2- 4.8), dyspepsia (OR: 1.8; 95% CI:1.3-2.4), exposure to pesticides (OR: 2.3; 95% CI:1.3- 4.2), oils (OR: 5.6; 95% CI: 2.3-13.7), metals (OR: 2.8; 95% CI: 1.5-5.4), and general anesthesia (OR: 6.1; 95% CI: 2.9-12.7) were independently associated with PD. There was no evidence of interaction among risk/protective factors, but cluster analysis identified four subtypes with different risk factor profiles. In Group 1, all patients had a family history of PD, while dyspepsia or exposure to toxic agents were present in 30% of patients. In Group 2 and 3, a family history of PD was lacking, while exposure to toxic agents (Group 2) and dyspepsia (Group 3) played major roles. Group 4 consisted of patients with no risk factors. Conclusions: This study demonstrated that nine factors independently modify PD risk by coexisting in the same patient rather than interacting with others. Our study suggests the need for future preventive strategies aimed at reducing the coexistence of different risk factors within the same subject