Clinical trials

Mild Cognitive Impairment (MCI) is a clinical condition with a heterogeneous etiology and clinical course characterized by objective cognitive deficits not severe enough to cause clear functional limitations or to warrant a diagnosis of dementia. Since MCI represents a risk factor for progression to various forms of dementia, timely preventive intervention is essential, although outpatient cognitive rehabilitation for this population is still limited by issues related to service accessibility. This study aims to investigate the effectiveness of a multimodal group cognitive rehabilitation intevention designed to be accessible for patients with MCI and sustainable in clinical practice. The primary objective of the study is to evaluate the effects of the intervention on cognitive, behavioural, and functional profile of patients with MCI, compared with an active control group. Outcome measures will be collected for all participants at T0 (baseline), T1 (after 12 weeks of intervention), and T2 (3 months after the end of the intervention and approximately 6 months from baseline), in order to assess both short-term and long-term effects of the intervention. The secondary objective is to explore the relationship between changes in outcome measures in the experimental group following the intervention and patients' demographic and clinical characteristics, with the aim of identifying potential predictors of a greater response to the intervention. Treatment accessibility, which guided the study design, will be evaluated though dropout and attendance rates, use of the provided tools and responses to the final satisfaction questionnaire. The experimental group will receive a multimodal cognitive rehabilitation intervention, including (a) a multi-domain cognitive training and (b) a lifestyle intervention, consisting of psychoeducational sessions on neuroprotective factors and supported by the use of a web-based application accessible via computer and tablet. The intervention program will be delivered in small groups, with two 60-minute sessions per week over 12 weeks. The intervention was designed to enhance accessibility and sustainability by limiting intervention intensity and duration, using technology, and delivering group-based rehabilitation in groups that are not highly homogeneous. This approach is expected to result in a better cost-benefit balance and greater transferability to clinical practice. The control group will receive an informational booklet on neuroprotective factors, including practical daily-life recommendations to reduce risk profiles. Forty patients with MCI and their informants will be recruited and randomly assigned to the experimental or control group. Participants in the experimental group will be further divided into small subgroups based on the presence of memory impairment.

Parkinson's disease (PD) presents a complex challenge due to its progressive neurodegenerative nature, affecting various bodily systems. Despite decades of research, understanding its onset and progression remains unclear, complicating early diagnosis and treatment. Recent advances in PD pathophysiology suggest promising treatments to slow disease progression, yet reversing cellular degeneration remains elusive. With novel therapies emerging, the need for early detection tools is urgent. However, validated biomarkers for PD diagnosis are lacking, relying on subjective scales like Hoehn and Yahr or costly medical imaging techniques. The accumulation of misfolded α-Synuclein (α-Syn) proteins in PD pathology has sparked interest, but defining diagnostic roles requires further investigation. Recent findings of α-Syn in neuronal-derived extracellular vesicles (NDEVs) from PD patients suggest a potential for novel diagnostic methods. Our proposed project, VαMPiRE, aims to conduct a longitudinal study involving 600 PD and 600 non-PD participants using a cluster-adjusted case-control methodology, to explore α-Syn isoforms and related biomarkers in NDEVs for early PD detection. We plan to develop and validate an innovative in-vitro diagnostic (IVD) test capable of detecting PD's earliest stages and estimating disease prognosis and progression. Utilizing AI models to generate data analysis algorithms and collaboration with leading analytical laboratories and IVD manufacturers, we aim to ensure the reliability and feasibility of the developed prototype. Through consortium efforts, we envision licensing the generated intellectual property to drive the commercialization of our results. Two round of blood sample extractions will be performed within a 24-month gap to PD participants and a single baseline for non-PD controls. All participants will be regularly followed up during this 24-month period to monitor disease evolution and treatment, and non-PD controls developing the disease will be part of a third cohort (expected to be around 24 subjects according to 4% incidence) that will confirm the sensitivity of the test in asymptomatic subjects. The unique aspect of the project is that we anticipate being able to detect theses 4% of non-PD participants that will go on to develop the disease, therefore demonstrating the value of these biomarkers to identify PD early. The prototype will be validated for its discriminative capacity, using the first baseline set of PD and non-PD samples, and for its ability to detect the PD-progression comparing baseline and 24-months data plus blood samples. Improved early screening could allow for 270,000 new cases of PD to be detected earlier, improve the disease management of 9.4 M people currently diagnosed of PD and avoid losing a total of 5.8 million disability adjusted life years (DALYs) by 2028 leading also the development of better treatments.

The first aim of the observational study is the translation, cross-cultural adaptation and validation of functional and behavioral scales used in the diagnosis of neurodegenerative diseases, for which a formal version in Italian is not available at present. In particular, the study includes the following functional and behavioral scales: the Katz's index (Basic Activities of Daily Living, BADL), the Lawton and Brody's scale (Instrumental Activities of Daily Living, IADL), the Everyday Cognition questionnaire (E-Cog), the Neuropsychiatric Inventory Questionnaire (NPI-Q) for assessing the Behavioral and Psychological Symptoms of Dementia. Furthermore, a modified Italian version of the Functional Activities Questionnaire (FAQ), which integrates and updates the content of the original items (e.g., addressing the use of technologies, M-FAQ) will be used in the validation study. The second aim is to evaluate the psychometric properties of the M-FAQ, the ECog, and the NPI-Q in terms of reliability and validity. The third aim is to apply a Receiver Operating Characteristic (ROC) curve analysis to identify cut-offs of IADL, M-FAQ and ECOG to discriminate between different clinical groups (i.e., neurologically unimpaired elderly; Subjective Cognitive Decline, SCD; Mild Cognitive Impairment, MCI; mild Alzheimer's Disease, AD). Neurologically unimpaired elderly participants (over 60 years old) and participants with SCD, MCI, mild AD, and their caregivers/informants will undergo: i) administration of the translated versions of the scales; ii) administration of a Cognitive Reserve questionnaire. For SCD, MCI and AD participants, data from the clinical neuropsychological evaluation will also be collected, while paper-and-pencil psychometric tests to assess global cognitive functioning (Mini Mental State Examination) and logical-abstract reasoning (Raven's Colored Matrices) will be administered to the neurologically unimpaired participants.