Morphometric magnetic resonance imaging cortico-subcortical features in Parkinson's disease with mild cognitive impairment.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) patients with cognitive impairment undergo progressive atrophy of several cortical and subcortical areas. The aim was to study the magnetic resonance imaging (MRI) morphometric features of PD patients with mild cognitive impairment (MCI). METHODS: Patients from the Parkinson's Disease Cognitive Impairment Study (PACOS) cohort with an available structural volumetric brain MRI and morphometric measurements of the midbrain and pons areas, middle cerebellar peduncle, superior cerebellar peduncle width and midbrain anteroposterior diameter (A-Pdiam) were included. MCI was diagnosed according to the Movement Disorder Society level II criteria. Additionally, cortical thickness analysis was performed and correlated with morphometric brainstem measurements. RESULTS: Morphometric measurements were available for 168 subjects, of whom 67 (39.9%) were diagnosed with PD-MCI. The mean age (± standard deviation) of the sample was 64.2 ± 9.8. Amongst patients, 84 (50%) were men with a disease duration of 5.2 ± 5.4 years and a Unified Parkinson's Disease Rating Scale-Motor Examination score of 32.1 ± 12.9. In the univariate and multivariate analysis, after adjusting for age, sex, years of schooling and disease duration, MCI was associated with midbrain area (odds ratio 0.98; 95% confidence interval 0.96-0.99; p = 0.048) and A-Pdiam (odds ratio 0.63; 95% confidence interval 0.46-0.86; p = 0.005). Furthermore, 121 PD patients underwent cortical thickness analysis, which showed the presence of cortical thinning in lateral orbitofrontal regions of patients with PD-MCI. No correlation was found between cortical thickness and brainstem morphometric measurements. CONCLUSIONS: A mild midbrain atrophy and the presence of frontal cortical thickness reduction might be considered a structural MRI feature of PD patients with MCI.

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

INTRODUCTION: 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 clinical-instrumental 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 clinical-demographic 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.

An updated protocol for the cost-effective and weekend-free culture of human induced pluripotent stem cells.

The protocol provided here describes methodologies for making a highly cost-effective, chemically defined medium for culturing hiPSCs we call B8 medium. The typical cost of B8 medium is US$10 per liter, which with modifications included here is more affordable than standard media. We provide simple protocols for making B8 supplement aliquots, making the basal media DMEM/F12, Matrigel-coated plates, thawing, passaging, culturing, and cryopreserving hiPSCs. We show typical differentiation results and provide a comprehensive troubleshooting guide. For complete details on the use and execution of this protocol, please refer to Kuo et al. (2020).

Cognitive impairment and levodopa induced dyskinesia in Parkinson's disease: a longitudinal study from the PACOS cohort.

Aim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson's disease Cognitive impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dose, UPDRS-ME and LID were recorded at baseline and follow-up. To identify possible neuropsychological predictors associated with the probability of LID development at follow-up, Cox proportional-hazards regression model was used. Out of 139 PD patients enrolled (87 men, mean age 65.7 ± 9.4), 18 (12.9%) were dyskinetic at baseline. Out of 121 patients non-dyskinetic at baseline, 22 (18.1%) developed LID at follow-up. The impairment of the attention and executive domains strongly predicted the development of LID (HR 4.45;95%CI 1.49-13.23 and HR 3.46; 95%CI 1.26-9.48 respectively). Impairment of the attention and executive domains increased the risk of dyskinesia reflecting the alteration of common cortical network.

Vascular risk factors, white matter lesions and cognitive impairment in Parkinson's disease: the PACOS longitudinal study.

BACKGROUND: Vascular risk factors (VRFs) may be associated with cognitive decline in early Parkinson's disease (PD) but results are inconclusive. The identification of modifiable risk factors is relevant for prevention and treatment. METHODS: Parkinson's disease (PD) patients of the PACOS cohort who underwent a baseline and follow-up neuropsychological evaluation were enrolled in the study. PD with Mild Cognitive Impairment (MCI) and dementia (PDD) were diagnosed according to the MDS criteria. A Baseline 1.5 T brain MRI was used to calculate the white matter lesions (WMLs) burden using the Wahlund visual scale. Laboratory data, presence of hypertension, diabetes and use of anti-hypertensive drugs were collected and the Framingham Risk (FR) score was calculated. VRFs predicting PD-MCI and PDD were evaluated using Cox proportional hazard regression model. RESULTS: Out of 139 enrolled patients, 84 (60.4%) were classified as normal cognition (NC) and 55 (39.6%) as MCI at baseline. At follow-up 28 (33.3%) PD-NC developed MCI and 4 (4.8%) PDD (follow-up time 23.5 ± 10.3 months). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD. At multivariate analysis among PD-NC a systolic blood pressure (SBP) > 140 mmHg was the stronger predictor of MCI (adjHR 4.04; 95% CI 1.41-11.3) while the presence of MCI at baseline (adj HR 7.55; 95% CI 1.76-32.3) and a severe WMLs burden (adj HR 2.80; 95% CI 0.86-9.04) were the strongest predictors of PDD, even if this latter association has a trend towards significance. CONCLUSION: Hypertension represents the most important modifiable risk factor for PD-MCI in the PACOS cohort, increasing the risk of about four times.

Cardiovascular autonomic function and MCI in Parkinson's disease.

INTRODUCTION: dysautonomic dysfunction and cognitive impairment represent the most disabling non-motor features of Parkinson's Disease (PD). Recent evidences suggest the association between Orthostatic Hypotension (OH) and PD-Dementia. However, little is known on the interactions between cardiovascular dysautonomia and Mild Cognitive Impairment (MCI). We aimed to evaluate the association between cardiovascular dysautonomia and MCI in patients with PD. METHODS: non-demented PD patients belonging to the PACOS cohort underwent a comprehensive instrumental neurovegetative assessment including the study of both parasympathetic and sympathetic function (30:15 ratio, Expiratory-Inspiratory ratio [E-I] and presence of Orthostatic Hypotension [OH]). Diagnosis of MCI was made according to the MDS criteria level II. RESULTS: we enrolled 185 PD patients of whom 102 (55.1%) were men, mean age was 64.6 ±â€¯9.7 years, mean disease duration of 5.6 ±â€¯5.5 years with a mean UPDRS-ME score of 31.7 ±â€¯10.9. MCI was diagnosed in 79 (42.7%) patients. OH was recorded in 52 (28.1%) patients, altered 30:15 ratio was recorded in 39 (24.1%) patients and an altered E-I ratio was found in 24 (19.1%) patients. Presence of MCI was associated with an altered 30:15 ratio (adjOR 2.83; 95%CI 1.25-6.40) but not with an altered E-I ratio, while OH was associated only with the amnestic MCI subgroup (OR 2.43; 95% CI 1.05-5.06). CONCLUSION: in our study sample, MCI was mainly associated with parasympathetic dysfunction in PD.

Incidence of Mild Cognitive Impairment and Dementia in Parkinson's Disease: The Parkinson's Disease Cognitive Impairment Study.

Background: Cognitive impairment in Parkinson's disease (PD) includes a spectrum varying from Mild Cognitive Impairment (PD-MCI) to PD Dementia (PDD). The main aim of the present study is to evaluate the incidence of PD-MCI, its rate of progression to dementia, and to identify demographic and clinical characteristics which predict cognitive impairment in PD patients. Methods: PD patients from a large hospital-based cohort who underwent at least two comprehensive neuropsychological evaluations were retrospectively enrolled in the study. PD-MCI and PDD were diagnosed according to the Movement Disorder Society criteria. Incidence rates of PD-MCI and PDD were estimated. Clinical and demographic factors predicting PD-MCI and dementia were evaluated using Cox proportional hazard model. Results: Out of 139 enrolled PD patients, 84 were classified with normal cognition (PD-NC), while 55 (39.6%) fulfilled the diagnosis of PD-MCI at baseline. At follow-up (mean follow-up 23.5 ± 10.3 months) 28 (33.3%) of the 84 PD-NC at baseline developed MCI and 4 (4.8%) converted to PDD. The incidence rate of PD-MCI was 184.0/1000 pyar (95% CI 124.7-262.3). At multivariate analysis a negative association between education and MCI development at follow-up was observed (HR 0.37, 95% CI 0.15-0.89; p = 0.03). The incidence rate of dementia was 24.3/1000 pyar (95% CI 7.7-58.5). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD, giving an incidence rate of 123.5/1000 pyar (95% CI 70.3-202.2). A five time increased risk of PDD was found in PD patients with MCI at baseline (RR 5.09, 95% CI 1.60-21.4). Conclusion: Our study supports the relevant role of PD-MCI in predicting PDD and underlines the importance of education in reducing the risk of cognitive impairment.

Mild cognitive impairment in Parkinson's disease: the Parkinson's disease cognitive study (PACOS).

Approximately 30% of Parkinson's disease (PD) patients show impaired cognitive performance, which is suggestive of Mild Cognitive Impairment (MCI), representing a predictor of dementia, especially when present at diagnosis. The objective of the study was to evaluate the frequency and clinical predictors of MCI in a large hospital-based cohort of PD patients. We collected cross-sectional data from the Parkinson's disease cognitive impairment study (PACOS), a multicenter study involving two Movement Disorder centers, which are located in south Italy. The PD subjects were diagnosed according to the UK Brain Bank criteria and they underwent an extensive neuropsychological assessment. PD-MCI was diagnosed according to the Movement Disorder Society task force criteria for MCI. PD severity was evaluated in accordance with the Unified PD Rating Scale-Motor Examination (UPDRS-ME) and the Hoehn and Yahr scales. The study included 659 PD patients (57.5% men; mean age 67.0 ± 9.7 years), with a mean disease duration of 3.8 ± 4.6 years and a mean UPRDS-ME score of 25.8 ± 12.3. PD-MCI was diagnosed in 261 (39.6%) subjects and in 82 (31.7%) of 259 newly diagnosed patients (disease duration ≤ 1 year). An amnestic MCI multidomain phenotype was the most frequent MCI subtype (39.1% of the overall sample and 43.9% in newly diagnosed PD). A positive significant association between MCI, age and motor scores was found at multivariate logistic regression analysis, while a negative association was observed between educational level and MCI. In conclusion and in agreement with the literature data, the prevalence of MCI recorded in the PACOS sample was approximately 40 and 32% amongst newly diagnosed patients.