Abstract

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.

Keywords: Parkinson's disease; cognitive; memory; mild cognitive impairment; non-motor symptoms.

Abstract

Background: The occurrence of cognitive dysfunctions and psychological symptoms, as well as their mutual relationships, in migraine patients are still debated. The aim of the study was to characterize the cognitive profile and psychological symptoms (i.e. depression, anxiety and apathy) in drug-naïve migraine without aura (MwoA) patients.

Methods: Seventy-two consecutive MwoA patients, referred to the Italian University Headache Clinic and 72 healthy subjects (HCs) were enrolled. Patients, during an attack-free period, and HCs completed Montreal Cognitive Assessment (MoCA), Beck Depression Inventory-II (BDI-II), Self-version of Apathy Evaluation Scale (AES-S) and State and Trait Anxiety Inventory (STAI-Y-1 and 2). Clinical parameters of disease severity (i.e. disease duration, migraine attacks per month, mean pain intensity during migraine attacks, migraine disability and impact on daily life) were recorded.

Results: Although performance of MwoA patients on MoCA was above Italian cut-off threshold (<15.5) suggesting presence of cognitive impairment, MwoA patients achieved significantly lower scores than HCs on total MoCA scale (22.3 ± 2.7 versus 25.4 ± 2.3) and on its attention (4.9 ± 1.1 versus 5.6 ± 0.7), memory (1.8 ± 1.4 versus 3.1 ± 1.3), visuospatial (3.2 ± 0.9 versus 3.6 ± 0.6) and executive subscales (2.6 ± 1.1 versus 3.1 ± 0.8). In addition, we observed significant correlations between MoCA executive domain subscore and the attack-related disability score (MIDAS). As for behavioral profile, the percentage of depressive symptoms (4.2 %), high state and trait anxiety (13.9 and 9.7 %, respectively), and apathy (11.1 %) in MwoA patients were similar to that of HCs. No significant associations of behavioural symptoms with cognitive performance and clinical parameters were found.

Conclusions: Drug-naïve MwoA patients are characterized by subtle cognitive dysfunctions and low percentage of behavioural symptoms. The results support the importance of searching for subclinical cognitive disturbances in patients with MwoA, who deserve to be followed-up to verify whether they develop clinically relevant disorders over time.

Keywords: Apathy; Cognitive deficits; Depression; Migraine; MoCA; Montreal cognitive assessment.

Abstract

Introduction: Migraine shows a significantly higher prevalence in women, especially during reproductive age when menstrual-related hormonal fluctuations represent the most common migraine trigger. Indeed, over 50% of patients report a higher occurrence of migraine attacks during the perimenstrual window. Menstrual migraine attacks are consistently referred to as more disabling, less responsive to symptomatic treatments, longer in duration, and more prone to relapse than non-menstrual migraine attacks. Evidence strongly suggests that estrogen fluctuations are involved in migraine attacks worsening during the perimenstrual window through several mechanisms directly or indirectly involving the CGRP pathway. We aimed to evaluate whether mAbs blocking CGRP-ligand or receptor (CGRP-mAbs) could represent an effective and safe preventive treatment for menstrual migraine attacks in patients with menstrual-related migraine (MRM) with previous treatment failures.

Methods: Forty patients with MRM with at least three previous treatment failures received monthly CGRP-mAbs. At the baseline and after six CGRP-mAbs administrations, patients underwent to extensive interviews to assess frequency, duration, intensity, and responsiveness to painkiller intake of migraine attacks occurring during the perimenstrual window.

Results: After six administrations of CGRP-mAbs we observed a reduction of median menstrual migraine frequency (from 5 to 2 days per month), pain intensity (from 8/10 to 6/10), and attacks duration (from 24 to 8 h) (p < 0.001). Nevertheless, a significant increase in the percentage of responding to migraine painkillers was observed from 42.5% at baseline to 95% at T1 (p < 0.001).

Conclusions: CGRP-mAbs could represent a safe and effective preventive therapeutic strategy able to reduce the disabling burden of menstrual migraine attack frequency, duration, intensity, and significantly improve the response to painkillers. These findings could be related to and further indirectly prove the greater influence of CGRP-mediated mechanisms in the pathophysiology of menstrual migraine attacks.

Keywords: Calcitonin gene-related peptide monoclonal antibody; Menstrual migraine; Menstrual-related migraine; Migraine.

Abstract

Background: In the context of a causal relationship between stress and migraine, coping strategies are aimed at managing stressful life events and reducing the distressing emotions connected to them.

Methods: Sixty-one consecutive patients with migraine without aura (MwoA) and sixty-one healthy controls (HCs) completed three self-report questionnaires assessing a broad range of coping (cognitive and behavioural) strategies: the Coping Orientation to Problems Experienced (COPE), the Coping Inventory for Stressful Situation (CISS), and the Proactive Coping Inventory (PCI). Moreover, the Perceived Stress Scale (PSS), a scale measuring self-perception of stress, global cognitive functioning, depressive symptoms, apathy, state, and trait anxiety, was administered to all participants.

Results: No significant difference was found on the scales and subscales of PCI and CISS as well as in the PSS between MwoA patients and HCs. However, the two groups showed different scores in the subscale "turning to religion" of COPE (22.08 ± 5.19 in migraineurs vs. 24.70 ± 4.44 in HCs, p = 0.003). A significant negative correlation of the turning to religion score with the HIT-6 score was found.

Conclusions: The present study revealed that MwoA patients show a significantly reduced use of the "turning to religion" approach, an emotion-focused coping strategy. Although migraine patients appeared to be less oriented to transcendent (that means a reduced utilization of an adaptive coping strategy), they did not perceive daily living as more stressful than HCs. Finally, the reduced utilization of the "turning to religion" coping strategy is associated with a great impact of migraine on ability to function on the job or at school, at home, and in social situations in migraine patients.

Abstract

We conducted a systematic review and meta-analysis aimed at establishing robust prevalence estimates and identifying clinical correlates of fatigue in PD. From 2,459 titles and abstracts, we selected 44 relevant studies (n = 7427 patients). Overall, the meta-analysis showed a prevalence of fatigue of 50% in PD. This prevalence estimate, however, was significantly moderated by study heterogeneity in measurement scales and cut-off thresholds. In contrast, demographic features, disease severity, cognitive impairment, and depression did not moderate prevalence estimates. Moreover, fatigue prevalence did not differ between de novo and treated PD patients. Compared to nonfatigued patients, fatigued patients had sligthly higher age (1.44 years), disease duration (0.93 years), l-dopa equivalent daily dose (50.89 units), UPDRS-III (4.99 points), and H & Y (0.33 points), as well as risk of comorbid depression (risk ratio = 1.89) and had a little lower MMSE score (-0.66 points). Fatigue was moderately associated with apathy (Hedges' g = 0.55), anxiety (Hedges' g = 0.67), daytime somnolence (Hedges' g = 0.43), sleep disturbances (Hedges' g = 0.66), and poorer quality of life (Hedges' g = 1.23). Our analyses suggest that fatigue is a frequent, independent nonmotor symptom in PD appearing early and persisting throughout the disease course, and that establishing uniform diagnostic criteria for PD-related fatigue is critical. In addition, several nonmotor symptoms appear to be associated with fatigue and negatively impact quality of life. Pharmacological and nonpharmacological interventions targeting fatigue and associated symptoms may improve quality of life in patients with PD. © 2018 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; fatigue; meta-analysis; prevalence; review.