N-palmitoylethanolamine (PEA) plays a key role in preventing Aβ-mediated neuroinflammation and neurotoxicity in murine models. It has been demonstrated that PEA provides anti-neuroinflammatory, pain-relieving and neuroprotective actions even in humans. In this project, we aim to evaluate these anti-neuroinflammatory effects via the cognitive evaluation and biochemical analyses of a 12-month oral administration of PEA in subjects with mild cognitive impairment (MCI). Subjects with MCI will be randomized to placebo or PEA groups, and followed for another 6 months. Cognitive abilities and neurological inflammation will be examined at baseline and after treatment. The specific objectives of the project are to ascertain whether: (i) PEA influences the scores of the neuropsychological and behavioral evaluations after one-year treatment, comparing PEA-treated and placebo subjects in both MCI and control groups; (ii) PEA can change the inflammatory and neuronal damage markers of blood and urine in MCI subjects; and (iii) these changes correlate with the clinical scores of participating subjects.

Cognitive impairment (CI) represents a common symptom in patients suffering from multiple sclerosis (MS), which can affect every stage of the disease course. Recent studies seem to support cognitive rehabilitation (CR) for minimizing the CI consequences. We reviewed the currently available evidence on the non-pharmacological approaches to CI, with the aim of giving an overview of the treatments used worldwide, from the traditional methods to the most recent techniques. A search of the literature was conducted on PubMed (articles in English performed in the last five years on humans). A total of 37 articles met our eligibility criteria after screening titles, abstracts and full-text and were divided into three main groups: in-presence interventions; studies performed via tele-rehabilitation and miscellaneous. Despite the great heterogeneity of the intervention and assessment methods, the evidence suggests that a non-pharmacological approach can improve MS-related CI. Cognitive rehabilitation seems effective and well established, as well as the use of computerized CR having the benefit of being even more appealing. Limited conclusions can be drawn on group CR due to the small number of studies focused on this kind of intervention. Some of the innovative approaches (virtual reality, EEG-based neurofeedback, brain stimulation, exercise, diet modification) may play a role in future studies and should be deeply explored.

(1) Background: Emotional recognition (ER), the ability to read into others’ minds and recognize others’ emotional states, is important in social environment adaptation. Recently it has been found that ER difficulties affect patients with multiple sclerosis (pMS) and relate to different gray matter atrophy patterns from secondary progressive (SP-pMS) and relapsing–remitting (RR-pMS). The aim of this study was to compare the performances of the two MS phenotypes on the Reading the Mind in the Eyes test (RMEt) and other cognitive, mood and fatigue measures. We also examined associations between performance on the RMEt and cognitive, mood and fatigue variables. (2) Methods: A total of 43 pMS (27RR-pMS/16SP-pMS) underwent a clinical assessment, the RMEt, the cognitive battery, and completed mood and fatigue questionnaires. Both groups’ performances on the RMEt were then correlated with all these measures. (3) Results: the RMEt scores of RR-pMS were significantly correlated with the impairment degree in some cognitive scores. SP-pMS scores correlated mainly with fatigue, anxiety, anger and depression. (4) Conclusions: ER performances relate to cognitive aspects in RR-pMS, whereas mainly to mood outcomes in the SP-pMS group. We can hypothesize that deficits in ER are a further sign of disease progression. Our data support the different roles of cognitive and emotional deficits related to different disease courses and lesional correlates.

MS clinical features vary between patients. In approximately 60% of cases, cognitive deficits are associated with motor disabilities, with consequences on both walking and maintaining balance and cognitive efficiency. Multimodal programs are very infrequent for MS patients and cognitive rehabilitation is not provided by the Italian health system, which only favors access to motor rehabilitation. Dual-task studies showed how motor and cognitive skills are closely associated. Therefore, physiotherapy exercises may favor an indirect improvement in cognition. The aim of this study is to understand which rehabilitative approach may increase both cognitive and motor efficiency, avoiding the waste of time and resources. In this multi-site single-blind parallel controlled clinical trial, we will compare three rehabilitative approaches: cognitive training, motor training and combined cognitive–motor training. We also aim to evaluate: whether self-perception and objective improvement correspond; the impact of each rehabilitation program on patients’ QoL, mood and self-perception; and long-term effects. A total of 60 patients will be randomly assigned to one of the three treatments for two 45-min sessions/week for 12 weeks. All participants will undergo a complete cognitive, motor, clinical assessment together with mood, self-perception, and QoL questionnaires before, immediately after and 6 months after the training period.