Clinical Research Directory

Biomarker-based Trial of NPC-1 for Alzheimer's Pathology

The goal of this early phase, open-label, single arm clinical trial is to determine the 6-month effects and tolerability of NPC1 (parthenolide and ipriflavone) on biomarkers of Alzheimer's Disease among adults with objective indicators of seeding AD pathology that also have subjective cognitive concerns, Mild Cognitive Impairment, or Alzheimer's Disease (AD)

Personalized Assessment of High-definition Slow-oscillatory Transcranial Direct Current Stimulation (So-tDCS) in Older Adults With Subjective Cognitive and Sleep Complaints

Background: Subjective cognitive decline (SCD) is considered to be the early risk stage of dementia. Untreated SCD comorbid with sleep disturbances may accelerate the progression of neurodegeneration (β-amyloid and tau) and lead to cognitive deficits. At present, non-pharmacological interventions for managing SCD and sleep disturbances are very limited. High-definition slow-oscillatory transcranial direct current stimulation (so-tDCS) is a newly developed frequency-specific modality of brain stimulation for promoting brain health and cognition. Notably, neurophysiological feature (impedance) during tDCS was found to be related to treatment outcomes and adverse effects (skin injury). Objectives: We propose to 1) develop a high-performing neurophysiological signal detector for tDCS and test its feasibility and flexibility in a randomized clinical trial; 2) investigate the short-term and long-term effects of high-definition so-tDCS on SCD, sleep quality and plasma Aβ and p-tau levels; 3) examine the values of neurophysiological signals in predicting the treatment outcomes at individual level. Design: A randomized, double-blind, sham-controlled trial. Methods: Chinese right-handed older adults with SCD and sleep disturbances will be randomly assigned to a 4-week intervention of either high-definition 0.75 Hz so-tDCS or sham tDCS, with 40 participants per arm. Pre-treatment magnetic resonance imaging (MRI) scans will be collected to exclude the cases with major neurological disease and quantify individual's brain features. Galvanic skin response, subjective cognitive complaints, sleep quality, plasma p-tau and β-amyloid levels and domain-specific cognition will be assessed at baseline, 4th week, 8th week and 12th week. Program adherence and adverse effects will be monitored throughout the whole intervention.

The Signature of Alzheimer's Disease in Subjective Cognitive Decline

This study focuses on improving early detection of Alzheimer's disease (AD) in patients with subjective cognitive decline (SCD), a preclinical stage of cognitive impairment, in the context of emerging disease-modifying therapies (DMTs). Current biomarkers, such as brain MRI, PET scans, and cerebrospinal fluid (CSF) markers, are highly accurate but costly, invasive, and not widely accessible. The study aims to provide cost-effective, scalable tools for early identification of individuals at risk, enabling personalized assessment and timely DMT administration. Objectives: * Evaluate the accuracy of innovative, easily accessible biomarkers in predicting biologically confirmed AD. * Assess the predictive utility of previously studied methods for SCD patients. * Explore new approaches, including automated speech analysis, to identify cognitive decline. * Evaluate genetic contributions to AD risk. * Integrate data from these various modalities using machine learning to create a predictive model for AD in SCD patients. Study Design: This is a multicenter, longitudinal, low-intervention study conducted at IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy (UO1) and the Center for Research and Innovation in Dementia, Careggi Hospital, Florence, Italy (UO2). Eligible participants are adults with SCD, intact daily functioning, and Mini-Mental State Examination (MMSE) scores \>24. Exclusion criteria include neurological or systemic diseases, major psychiatric disorders, substance use, or prior head injury. Participants undergo: * Detailed medical and family history collection. * Comprehensive neuropsychological, personality, and independence in daily activities assessment * EEG recording in resting state. * Blood sampling for plasma biomarkers (Aβ42, Aβ40, p-tau181, p-tau217, t-tau, NfL, GFAP). * CSF biomarker analysis (Aβ42, Aβ40, p-tau, t-tau). * Genetic analysis of AD-related genes (PSEN1, PSEN2, APOE, TREM2, ABCA7, BDNF, HTT). * Speech recording and analysis using standardized tasks to extract features for automated evaluation. The study expects to create a machine learning-based predictive model combining biomarker, neuropsychological, EEG, speech, and genetic data to improve early detection and guide personalized patient care. Procedures: * Neuropsychological evaluations occur at baseline and two-year follow-up. * Language recordings are conducted in controlled settings using standardized picture description tasks. * EEG is recorded using 21-channel systems. * Blood and CSF samples are collected, processed, and stored at -80°C for subsequent analysis at respective institutional laboratories. * Plasma biomarkers are analyzed with Simoa technology; CSF biomarkers are analyzed using chemiluminescent enzyme immunoassay (CLEIA). * Genetic analyses employ PCR, high-resolution melting analysis (HRMA), sequencing, and capillary electrophoresis as appropriate for specific genes or polymorphisms. The study expects to create a machine learning-based predictive model combining biomarker, neuropsychological, EEG, speech, and genetic data to improve early detection and guide personalized patient care.

EARLY-COGN^3 - Smart Digital Solutions for EARLY Treatment of COGnitive Disability: a Neuropsychological, Neurophysiological and Neurobiological Perspective in Chronic Neurological Diseases - PNRR-MCNT2-2023-12377069

The increase in life expectancy in recent decades has led to a large number of people living into old age and an increased risk of developing Chronic Neurological Diseases (CNDs) such as neurodegenerative diseases. A higher cumulative risk of dementia has been largely demonstrated in Mild Cognitive Impairment (MCI) and Subjective Cognitive Complaints (SCCs) subjects and in Parkinson's Disease (PD) patients, as compared to the general population. These disorders result in an impairment of the individual's abilities to perform daily tasks. As their disease progresses, patients become dependent on medical services and on family support. Given the limited effectiveness of pharmacological treatments, non-pharmacological interventions to prevent and treat cognitive deficits and the associated difficulties with activities of daily living in neurodegenerative disease patients have gained attention in recent years and, among these, cognitive training offers a potential approach for dementia prevention and improvement of cognitive function. A critical aspect of cognitive training programs is that the most promising interventions have involved intensive in-person sessions that are unlikely to be cost-effective or feasible for large-scale implementation. Within the framework of non-pharmacological interventions, the use of technology to assist the person at risk and/or with mild dementia at home and to extend rehabilitation services in the treatment of dementia has gradually gained importance. Telerehabilitation technologies allow to provide services remotely in patients' homes, allowing access to health care to patients living in rural settings or with mobility difficulties. In addition, the telerehabilitation modality offers the advantage of providing rehabilitation within the natural environment of the patient's home, making the treatment more realistic and possibly more generalizable to the person's daily life. The present project proposes to test a home-based asynchronous cognitive telerehabilitation program aimed at enhancing the continuum of care for MCI, SCCs and PD, using technology. The proposed study is a single blind randomized controlled trial (RCT) involving subjects with CNDs randomly assigned to one out of two intervention groups: i) the tele@cognitive group, who will receive at-home cognitive telerehabilitation (tele@cognitive treatment); ii) the Active Control Group (ACG), who will receive at-home unstructured cognitive stimulation. The aim of the project will be threefold: \[1\] to test the short-term and long-term efficacy of tele@cognitive protocol as compared to an unstructured cognitive at-home rehabilitation in the treatment of a cohort of patients with CNDs; \[2\] to explore the changes induced by tele@cognitive intervention on biomolecular and neurophysiological markers; \[3\] to explore potential cognitive, neurobiological and neurophysiological predictors of response to tele@cognitive treatment.