Cognitive and morphometric features of mild cognitive impairment reversion in early patients with Parkinson's disease.

INTRODUCTION: Mild cognitive impairment is a common feature of Parkinson's disease (PD-MCI), even at the earliest disease stages. Growing evidence supports the instability of PD-MCI over time, without a consistent linear evolution to dementia, and in some patients, the potential of reversion to normal cognition. However, which features are associated with reversion from PD-MCI to normal cognition in early PD-MCI are not fully known. METHODS: In our longitudinal study of early drug naïve PD patients, 65 of 134 (48 %) patients had PD-MCI at baseline. Study participants underwent comprehensive assessments at baseline and 1-year follow-up. Sixteen (24.6 %) patients with PD-MCI reverted to normal cognition (Reverters), and 49 (75.4 %) had persistent PD-MCI (Non-Reverters) after 1-year follow-up. We performed single- and multiple-variable logistic regression analyses to identify baseline variables predicting reversion of PD-MCI to normal cognition after 1-year. We also compared brain morphometric measures (cortical thickness and volumes) at baseline between the PD-MCI Reverters and Non-Reverters. RESULTS: Higher educational level and better performance on measures of attention and memory at baseline predicted the reversion to normal cognition at 1-year follow-up. Reverters had greater cortical thickness in the left inferior temporal gyrus than Non-Reverters. CONCLUSIONS: Our results show PD-MCI with a higher chance of reverting to normal cognition over time have a higher educational level, better frontotemporal-related cognitive function, and increased thickness of the inferior temporal lobe gyrus. These findings may potentially help researchers to select the candidates for clinical trials focusing on the treatment of cognitive impairment in the early stages of PD.

Memory Phenotypes In Early, De Novo Parkinson's Disease Patients with Mild Cognitive Impairment.

BACKGROUND: Memory deficits in mild cognitive impairment related to Parkinson's disease (PD-MCI) are quite heterogeneous, and there is no general agreement on their genesis. OBJECTIVES: To define memory phenotypes in de novo PD-MCI and their associations with motor and non-motor features and patients' quality of life. METHODS: From a sample of 183 early de novo patients with PD, cluster analysis was applied to neuropsychological measures of memory function of 82 patients with PD-MCI (44.8%). The remaining patients free of cognitive impairment were considered as a comparison group (n = 101). Cognitive measures and structural magnetic resonance imaging-based neural correlates of memory function were used to substantiate the results. RESULTS: A three-cluster model produced the best solution. Cluster A (65.85%) included memory unimpaired patients; Cluster B (23.17%) included patients with mild episodic memory disorder related to a "prefrontal executive-dependent phenotype"; Cluster C (10.97%) included patients with severe episodic memory disorder related to a "hybrid phenotype," where hippocampal-dependent deficits co-occurred with prefrontal executive-dependent memory dysfunctions. Cognitive and brain structural imaging correlates substantiated the findings. The three phenotypes did not differ in terms of motor and non-motor features, but the attention/executive deficits progressively increased from Cluster A, through Cluster B, to Cluster C. This last cluster had worse quality of life compared to others. CONCLUSIONS: Our results demonstrated the memory heterogeneity of de novo PD-MCI, suggesting existence of three distinct memory-related phenotypes. Identification of such phenotypes can be fruitful in understanding the pathophysiological mechanisms underlying PD-MCI and its subtypes and in guiding appropriate treatments. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Validation of new diagnostic criteria for fatigue in patients with Parkinson disease.

BACKGROUND AND PURPOSE: Although disabling fatigue is common in Parkinson disease (PD), available consensus-based diagnostic criteria have not yet been empirically validated. The aim of this study was to evaluate the clinimetric properties of the criteria. METHODS: A sample of outpatients with PD was evaluated for demographic, clinical, behavioral, and cognitive features. Fatigue was diagnosed according to the new diagnostic criteria and was rated by means of the Parkinson Fatigue Scale (PFS) and Fatigue Severity Scale (FSS). Acceptability, concurrent and discriminant validity, and interrater reliability were evaluated with binary logistic regression analyses and Cohen kappa (κ). RESULTS: Of 241 included patients, 17 (7.1%) met the diagnostic criteria for PD-related fatigue. Eight of nine symptoms described in Section A of the diagnostic criteria occurred in >50% of patients with fatigue. Acceptability (missing data = 0.8%) of the criteria was good, as was their concurrent validity with the PFS (odds ratio = 3.65) and FSS (odds ratio = 3.63). The discriminant validity of fatigue criteria with other PD-related behavioral and cognitive features was good (odds ratio < 1.68). The interrater reliability was excellent (κ = 0.92). CONCLUSIONS: This is the first study to test the clinimetric properties of case definition diagnostic criteria for PD-related fatigue. Our results suggest that current diagnostic criteria may be useful in both clinical practice and research. Future longitudinal studies should examine their long-term stability.

The psychological correlates of fatigue in Parkinson's disease: Contribution of maladaptive metacognitive beliefs.

INTRODUCTION: Psychological factors can underlie fatigue in neurological disorders, but its relationship to fatigue in Parkinson's disease (PD) has not been explored. We assessed the association between maladaptive metacognitive beliefs and presence of fatigue in PD. METHODS: Ninety-eight consecutive outpatients with PD (61% male; median age: 66.50 years) were assessed in terms of demographic, clinical, medication treatment, cognitive, or behavioural characteristics including metacognitive beliefs (Metacognitions Questionnaire-30 or MCQ). Fatigue was ascertained by PD-related diagnostic criteria. Univariate statistical approach (Mann-Whitney and Pearson chi-square tests) was used to compare PD patients with (f-PD) or without (nf-PD) fatigue in terms of demographic, clinical, medication treatment, cognitive, behavioural, and metacognitive measures. RESULTS: Twenty-one PD patients (21%) displayed fatigue. The f-PD group scored higher on the MCQ-total score, MCQ-Cognitive Confidence subscale, and all behavioral measures (ps < 0.01) relative to nf-PD. They also had a more advanced Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale-III score. CONCLUSION: Maladaptive metacognitive beliefs such as the lack of cognitive confidence may play a key role to trigger and maintain fatigue in PD. Future studies, using a multivariate statistical approach, are needed to confirm these preliminary findings in a larger sample of patients with fatigue and to assess if modification of such metacognitive beliefs has the potential to ameliorate fatigue in PD.

Correlates of the discrepancy between objective and subjective cognitive functioning in non-demented patients with Parkinson's disease.

BACKGROUND: Subjective complaints of cognitive deficits are not necessarily consistent with objective evidence of cognitive impairment in Parkinson's disease (PD). Here we examined the factors associated with the objective-subjective cognitive discrepancy. METHODS: We consecutively enrolled 90 non-demented patients with PD who completed the Parkinson's Disease Cognitive Functional Rating Scale (subjective cognitive measure) and the Montreal Cognitive Assessment (MoCA; objective cognitive measure). The patients were classified as "Overestimators", "Accurate estimators", and "Underestimators" on the basis of the discrepancy between the objective vs. subjective cognitive measures. To identify the factors distinguishing these groups from each other, we used chi-square tests or one-way analyses of variance, completed by logistic and linear regression analyses. RESULTS: Forty-nine patients (54.45%) were classified as "Accurate estimators", 29 (32.22%) as "Underestimators", and 12 (13.33%) as "Overestimators". Relative to the other groups, the "Underestimators" scored higher on the Fatigue Severity Scale (FSS), Beck Depression Inventory (BDI), and Parkinson Anxiety Scale (p < 0.01). Logistic regression confirmed that FSS and BDI scores distinguished the "Underestimators" group from the others (p < 0.05). Linear regression analyses also indicated that FSS and BDI scores positively related to objective-subjective cognitive discrepancy (p < 0.01). "Overestimators" scored lower than other groups on the MoCA's total score and attention and working memory subscores (p < 0.01). CONCLUSION: In more than 45% of consecutive non-demented patients with PD, we found a 'mismatch' between objective and subjective measures of cognitive functioning. Such discrepancy, which was related to the presence of fatigue and depressive symptoms and frontal executive impairments, should be carefully evaluated in clinical setting.

Correlates of Psychological Distress in Patients with Parkinson's Disease During the COVID-19 Outbreak.

BACKGROUND: Following the severe consequences of the COVID-19 outbreak, on March 9, 2020, the Italian government implemented extraordinary measures to limit viral transmission, including restrictive quarantine measures. This resulted in a rapid and profound change of people's daily lives. OBJECTIVE: We assessed the psychological impact of the 40-day quarantine in a large cohort of patients with Parkinson's disease (PD) and caregivers. Moreover, we analyzed whether prelockdown clinical features may be associated with subjective response of patients with PD to this traumatic event. METHODS: A total of 94 patients with PD were enrolled in the study. The Impact of Event Scale-Revised, the Kessler Psychological Distress Scale, and the 12-item Zarit Burden Inventory were obtained from patients and caregivers by email. A multivariate regression analysis was performed to determine whether prelockdown clinical motor and nonmotor features were associated with the psychological impact of lockdown. RESULTS: Regression analyses showed that prelockdown levels of anxiety, treatment-related motor complications, patients' quality of life, and lockdown hours per day were significantly associated with psychological impact measures of the 40-day quarantine. In addition, we showed that caregiver burden was correlated with overall patient autonomy and attention/memory impairment. CONCLUSIONS: We identified specific PD motor and nonmotor features potentially predisposing to higher psychological impact of stressful situations, such as quarantine. This may help guide postpandemic interventions and preventive strategies to avoid further impairment of psychological well-being in patients with PD.

Correlates of psychological distress in epileptic patients during the COVID-19 outbreak.

INTRODUCTION: Following the severe consequences of the coronavirus disease 2019 (COVID-19) outbreak, on March 9th, 2020 the Italian Government implemented extraordinary measures to limit viral transmission, including restrictive quarantine measures. Psychological distress represents the seizure-precipitating factor most often reported by patients with epilepsy. To date, no studies have analyzed the role played by the different dimensions of psychological distress quarantine-induced in patients with epilepsy. MATERIALS AND METHODS: We included a total of 40 patients, 18 suffered from generalized, and 22 from focal epilepsy. The patients previously seen in the outpatient clinic during the pre-lockdown period between January and February 2020 were reevaluated after the lockdown period. Psychological distress was evaluated by using the three subscales of Impact of Event Scale-Revised (IES-R). Finally, we employed logistic regression analyses to explore the demographic and clinical features associated to high scores on IES-R. RESULTS: Patients with higher scores on IES-R Intrusion and IES-R Avoidance subscales demonstrated an increased number of epileptic attacks compared to prelockdown period. Multivariate logistic regression analyses showed that a specific subgroup of patients (i.e., older, female with more anxious symptoms) are at higher risk of increased seizure frequency. CONCLUSIONS: Our study confirmed that the frequency of epileptic seizures increased during lockdown when compared to pre-lockdown period. The early identification of patients more vulnerable to worsening is crucial to limit the risk of requiring hospital or clinical treatment during the COVID-19 outbreak.

Comparison of alternate and original forms of the Montreal Cognitive Assessment (MoCA): an Italian normative study.

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a screening test widely used in clinical practice and suited for detection of Mild Cognitive Impairment. Alternate forms of the MoCA were developed to avoid "learning effect" in serial assessments, and the present study aimed at investigating inter-form parallelism and at providing normative values for the Italian versions of MoCAs 2 and 3. METHOD: Three separate convenience samples were recruited: the first (n = 78) completed three alternate MoCA versions for ascertaining inter-form parallelism; the second (n = 302) and the third (n = 413) samples were administered MoCA 2 or 3 to compute normative data. RESULTS: A three-step procedure complemented by confirmatory factor analysis and a mixed factorial ANOVA suggested that the three MoCA versions are not strictly parallel. Multiple linear regression analysis revealed that age and education significantly influenced MoCA 2 and 3 total scores. No significant effect of sex was found. From the derived linear equation, correction grids for MoCA 2 and 3 raw scores were built and equivalent scores computed. Inferential cutoff for adjusted scores, estimated using a non-parametric technique, were 17.49 for MoCA 2 and 18.34 for MoCA 3. Correlation analysis showed strong correlations of MoCA 2 (r = 0.69, p < .001) and MoCA 3 (r = 0.61, p < .001) adjusted total scores with MMSE adjusted scores. CONCLUSION: The three MoCA forms are not strictly parallel. Specifically developed normative data must be adopted for using MoCA in serial cognitive assessments for clinical and research studies.

Regression-based normative data and equivalent scores for Trail Making Test (TMT): an updated Italian normative study.

OBJECTIVES: The Trail Making Test (TMT) is widely used to assess psychomotor speed and attentional set-shifting. Since the regression-based norms and equivalent scores (ESs) for the TMT Italian version trace back to more than 20 years ago, we aimed at providing updated normative data for basic (Part A and Part B) and derived (Score B-A and Score B/A) TMT scores collected in a larger sample with an extended age range. METHODS: Three hundred fifty-five Italian volunteers stratified for sex (166 men), age decades (age range 20-90 years), and educational level (from primary school to university) completed the TMT and the Montreal Cognitive Assessment (MoCA). RESULTS: Multiple linear regression analyses revealed that age and educational level significantly influenced performances on basic and derived TMT scores except for B/A, which was associated only with the educational level. From the derived linear equations, correction grids for basic and derived TMT raw scores were developed. Inferential cutoff scores, estimated using a non-parametric technique, and ES were computed. Basic and derived TMT scores showed a good test-retest reliability (all rs ≥ 0.50); Part B (rs = - 0.48, p < 0.001) and Score B-A (rs = - 0.49, p < 0.001) were moderately associated with MoCA total score. CONCLUSIONS: This study confirms the association of basic and derived TMT raw scores with sociodemographic variables and provides updated correction grids and ES for assessing the attentional/executive functions in clinical and research fields.