Mild behavioral impairment in Parkinson's disease: Data from the Parkinson's disease cognitive impairment study (PACOS)

Neuropsychiatric symptoms (NPS) have been frequently described in Parkinson's disease (PD), even in the earliest stages of the disease. Recently the construct of mild behavioral impairment (MBI) has been proposed as an at-risk state for incident cognitive decline and dementia. The aim of the present study is to evaluate the prevalence and associated factors of MBI in PD. Cross-sectional data from 429 consecutive PD patients enrolled in the PArkinson's disease COgnitive impairment Study (PACOS) were included in the study. All subjects underwent neuropsychological assessment, according to the MDS Level II criteria. NPS were evaluated with the Neuropsychiatric Inventory. Multivariate logistic regression models were used to evaluate clinical and behavioral characteristics, which are associated with PD-MBI. The latter was ascertained in 361 (84.1%) subjects of whom 155 (36.1%) were newly diagnosed patients (disease duration ≥1 year) and 206 (48.0%) had a disease duration <1 year. Furthermore, 68 (15.9%) out of 429 subjects were PDw (without MBI). Across the MBI domains, Impulse Dyscontrol was significantly more prevalent among PD-MBI with disease duration <1 year than newly diagnosed patients. The frequency of Social Inappropriateness and Abnormal Perception significantly increased throughout the entire PD-MBI sample with increasing Hoehn andYahr (H&Y) stages. PD-MBI in newly diagnosed PDwas significantly associated with H&Y stage (OR 2.35, 95% CI 1.05-5.24) and marginally with antidepressant drug use (OR 2.94, 95% CI 0.91-9.47), while in patients with a disease duration >1 year was associated with UPDRS-ME (OR 3.37, 95% CI 1.41-8.00). The overall MBI frequency in the PACOS sample was 84% and 36% among newly diagnosed patients. The presence of MBI mainly related to motor impairment and disability

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

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 ± 9.7 years, mean disease duration of 5.6 ± 5.5 years with a mean UPDRS-ME score of 31.7 ± 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

Transcranial random noise stimulation over the primary motor cortex in PD-MCI patients: a crossover, randomized, sham-controlled study

Mild cognitive impairment (MCI) is a very common non-motor feature of Parkinson’s disease (PD) and the non-amnestic single-domain is the most frequent subtype. Transcranial random noise stimulation (tRNS) is a non-invasive technique, which is capable of enhancing cortical excitability. As the main contributor to voluntary movement control, the primary motor cortex (M1) has been recently reported to be involved in higher cognitive functioning. The aim of this study is to evaluate the effects of tRNS applied over M1 in PD-MCI patients in cognitive and motor tasks. Ten PD-MCI patients, diagnosed according to the Movement Disorder Society, Level II criteria for MCI, underwent active (real) and placebo (sham) tRNS single sessions, at least 1 week apart. Patients underwent cognitive (Digit Span Forward and Backward, Digit Symbol, Visual Search, Letter Fluency, Stroop Test) and motor assessments (Unified Parkinson’s Disease Rating Scale [UPDRS-ME], specific timed trials for bradykinesia, 10-m walk and Timed up and go tests) before and after each session. A significant improvement in motor ability (UPDRS-ME and lateralized scores, ps from 0.049 to 0.003) was observed after real versus sham tRNS. On the contrary, no significant differences were found in other motor tasks and cognitive assessment both after real and sham stimulations. These results confirm that tRNS is a safe and effective tool for improving motor functioning in PD-MCI. Future studies using a multisession tRNS applied over multitargeted brain areas (i.e., dorsolateral prefrontal cortex and M1) are required to clarify the role of tRNS regarding rehabilitative intervention in PD

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

Changes in Motor, Cognitive, and Behavioral Symptoms in Parkinson's Disease and Mild Cognitive Impairment During the COVID-19 Lockdown

Objective: The effects of the COVID-19 lockdown on subjects with prodromal phases of dementia are unknown. The aim of this study was to evaluate the motor, cognitive, and behavioral changes during the COVID-19 lockdown in Italy in patients with Parkinson's disease (PD) with and without mild cognitive impairment (PD-MCI and PD-NC) and in patients with MCI not associated with PD (MCInoPD). Methods: A total of 34 patients with PD-NC, 31 PD-MCI, and 31 MCInoPD and their caregivers were interviewed 10 weeks after the COVID-19 lockdown in Italy, and changes in cognitive, behavioral, and motor symptoms were examined. Modified standardized scales, including the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society, Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II, were administered. Multivariate logistic regression was used to evaluate associated covariates by comparing PD-NC vs. PD-MCI and MCInoPD vs. PD-MCI. Results: All groups showed a worsening of cognitive (39.6%), pre-existing (37.5%), and new (26%) behavioral symptoms, and motor symptoms (35.4%) during the COVID-19 lockdown, resulting in an increased caregiver burden in 26% of cases. After multivariate analysis, PD-MCI was significantly and positively associated with the IADL lost during quarantine (OR 3.9, CI 1.61–9.58), when compared to PD-NC. In the analysis of MCInoPD vs. PD-MCI, the latter showed a statistically significant worsening of motor symptoms than MCInoPD (OR 7.4, CI 1.09–45.44). Regarding NPI items, nighttime behaviors statistically differed in MCInoPD vs. PD-MCI (16.1% vs. 48.4%, p = 0.007). MDS-UPDRS parts I and II revealed that PD-MCI showed a significantly higher frequency of cognitive impairment (p = 0.034), fatigue (p = 0.036), and speech (p = 0.013) than PD-NC. On the contrary, PD-MCI showed significantly higher frequencies in several MDS-UPDRS items compared to MCInoPD, particularly regarding pain (p = 0.001), turning in bed (p = 0.006), getting out of bed (p = 0.001), and walking and balance (p = 0.003). Conclusion: The COVID-19 quarantine is associated with the worsening of cognitive, behavioral, and motor symptoms in subjects with PD and MCI, particularly in PD-MCI. There is a need to implement specific strategies to contain the effects of quarantine in patients with PD and cognitive impairment and their caregivers

Executive functioning and serum lipid fractions in Parkinson’s disease—a possible sex-effect: the PACOS study

The association between dyslipidemia and cognitive performance in Parkinson’s disease (PD) patients still needs to be clarified. Aim of the study was to evaluate the presence of possible associations between serum lipids fractions and executive dysfunction also exploring the sex-specific contribute of lipids level on cognition. Patients from the PACOS cohort, who underwent a complete serum lipid profile measures (total cholesterol-TC, low-density lipoprotein cholesterol-LDL, high-density lipoprotein cholesterol-HDL and triglycerides-TG) were selected. Adult Treatment Panel III guidelines of the National Cholesterol Education Program were used to classify normal/abnormal lipid fractions. Executive functioning was assessed with the Frontal Assessment Battery (FAB). Logistic regression was performed to assess associations between lipids fractions and FAB score. Correlations between lipids fractions and FAB score were explored. Sex-stratified analysis was performed. Three hundred and forty-eight PD patients (148 women; age 66.5 ± 9.5 years; disease duration 3.9 ± 4.9 years) were enrolled. Women presented significantly higher TC, LDL and HDL than men. In the whole sample, any association between lipid profile measures and FAB score was found. Among women, a positive association between hypertriglyceridemia and FAB score under cutoff was found (OR 3.4; 95%CI 1.29–9.03; p value 0.013). A statistically significant negative correlation was found between the FAB score and triglyceride serum levels (r = − 0.226; p value 0.005). Differently, among men, a statistically significant negative association between hypercholesterolemia and FAB score under cutoff (OR 0.4; 95%CI 0.17–0.84; p value 0.018) and between high LDL levels and FAB score under cutoff (OR 0.4; 95%CI 0.18–0.90; p value 0.027) were found. Our data suggest a sex-specific different role of lipids in executive functioning

Voxel-Based Morphomerty study in patients with amnestic Mild Cognitive Impairment and Alzheimer's Disease: population-based data from the Zabùt Aging Project

Aims and objectives Compare the preliminary results of a voxel-based morphometry (VBM) analysis performed in patients with amnestic Mild Cognitive Impairment (aMCI) and Alzheimer’s disease (AD) in comparison to a control group with normal aging brain (NAB). Methods and materials 83 brain MRI scans were obtained a using 1.5T unit (Sag 3D T1w-FSPGR IR preped ASSET sequence was used for the VBM analysis that was performed with FSL’s sienax tool) during the Zabùt Aging Project (ZAP), a population-based, cohort study regarding aging and dementia conducted in Southern Italy. After the exclusion of subjects with severe leucoaraiosis, silent cerebral infarcts or any other findings that could affect the results, 58 suitale subjects (27 males and 31 females, mean age 72.95/SD6.66 (range 61-85); naMCI=21, nAD=19, nNAB=18) were included. The results were compared using t-test (p = 0.05).VBM result example. Top left: axial Multiple Planar Reconstruction (MPR). VBM extracted tissues: csf in blue (top center), gray matter in red (top right), white matter in yellow (bottom center) and all three components (bottom right). Bottom left (in pink) the result of the brain extraction process (FSL’s BET). Results Statistically significant differences were found between total gray matter volumes (TGMv) (p = 0.002) and total brain volume (TBv) (p = 0.004) in AD vs NAB; between TGMv (p = 0.005) and TBv (p = 0.004) in aMCI vs AD. No statistically significant differences were observed in VBM data between aMCI and NAB or between the white matter volumes within groups. Conclusion Our results, reflect what already reported the scientific literature and confirm the importance of VBM for the quantitative assessment of brain atrophy in subjects with cognitive impairment. The VBM prospective evaluation of aMCI subjects will help to clarify specific areas involved in AD-type neurodegenerative progression