Elena Campana

Background/Objective: Mild cognitive impairment (MCI) often represents the prodromal stage of neurodegenerative dementia. Identification of Alzheimer disease (AD) and other dementias in the MCI stage is essential for early intervention. Transcranial magnetic stimulation (TMS) has gained interest as a non-invasive method to evaluate cortical excitability and neurotransmitter function. This systematic review aims to evaluate the diagnostic utility of TMS-derived indices, such as short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI) in MCI populations. Methods: Following PRISMA guidelines, 14 studies were selected, encompassing 476 MCI patients. Reported outcomes related to TMS measures (SAI, SICI, ICF, LICI) were reviewed across various MCI phenotypes. Results: Most studies report reduced SAI, a marker of cholinergic dysfunction, in amnestic MCI and MCI due to AD. Alterations in SICI and ICF, markers of GABAergic and glutamatergic dysfunction, were more variable, mainly observed in MCI of non-AD type. LICI showed no consistent changes. One study demonstrated increased clinicians’ diagnostic confidence when TMS data were incorporated. Conclusions: TMS measures hold promise as a non-invasive tool for early and differential diagnosis of MCI. Further standardized and longitudinal research is needed to confirm its clinical applicability.

Background: In recent years, there has been increasing interest in the application of repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct-Current Stimulation (tDCS) to enhance and rehabilitate the language abilities in individuals with neurodegenerative diseases. Objective: The aim of this narrative literature review is to investigate the usefulness of rTMS and tDCS to improve language abilities in people with Primary Progressive Aphasia (PPA). Methods: This narrative literature review was conducted through a search of the PubMed online database to identify studies investigating the effects of multiple sessions of rTMS or tDCS on language abilities in PPA patients, applied either as stand-alone interventions or in combination with language treatment. Results: Thirty-three studies fulfilled the inclusion criteria; five studies employed rTMS without language treatment; two studies applied tDCS as stand-alone intervention; twenty-two studies combined tDCS with language treatment; and four studies assessed the effects of tDCS during verbal task without language treatment. Conclusions: rTMS and tDCS applied with or without concomitant language treatment appear to be promising interventions for enhancing language abilities in PPA, with sustained effects reported over time. Further research is necessary to optimise stimulation protocols and to improve our understanding of their long-term effects. Moreover, randomised controlled trials (RCTs) with larger sample sizes are critically needed to clarify the true impact of brain stimulation in PPA, with a focus on changes in cognitive and functional performance, neural activity, and potential molecular correlates.

Rehabilitation is an important player in preventing and reducing the high impact of disability on everyday functioning in chronic neurological diseases (CNDs), especially if timely, intensive, and multidimensional. However, to date, rehabilitation is often a service accessible only to a few people, and the issue of a progressive decrease in treatment adherence still remains to be addressed. This study protocol describes an RCT whose aim is to test the effectiveness in terms of adherence of DANCE Rehabilitation EXperience (DANCEREX-DTx), a new digital therapeutic solution which combines a holistic, multidimensional program based on dance and music with an innovative motivational system. The randomized, single-blind, controlled trial will involve 192 patients with CNDs from three rehabilitation centers in Italy. Participants will be randomized (with an allocation ratio of 2:2:1) into three interventions: (1) DANCEREX treatment, (2) multidimensional dance-based program, and (3) educational program. Groups will be assessed at the baseline (T0), after intervention (T1-after 12 weeks), and after six months from enrollment (T2). The primary outcome will be treatment adherence in terms of the number of drop-outs and the percentage of attended sessions on the total prescribed. Moreover, a multifaceted evaluation, including quality of life and clinical/functional measures, will be conducted at each time-point. Surrogate measures (neuroimaging and neurobiological) will be collected at T0 and T1. Finally, usability and acceptability will be assessed at T1. We expect the validation, in terms of usability, acceptability, and effectiveness of DANCEREX-DTx as an innovative rehabilitation program able to respond in a sustainable way to the great need for rehabilitation of people with CNDs. With DANCEREX-DTx, we aspire to change the hospital-centered paradigm of rehabilitation care to bring it to the patients' homes, making them active in their treatment path and promoting motivation and adherence to treatment from the initial stages of the disease.Trial registration: The trial was registered in the clinicaltrials.gov database (identifier NCT06112639) on 2023-11-01.

Background: Healthy cognitive functioning is a primary component of well-being, independence, and successful aging. Cognitive deficits can arise from various conditions, such as brain injury, mental illness, and neurological disorders. Rehabilitation is a highly specialized service limited to patients who have access to institutional settings. In response to this unmet need, telehealth solutions are ideal for triggering the migration of care from clinics to patients’ homes. Objectives: The aim of EARLY-COGN^3 will be threefold: (1) to test the efficacy of a digital health at-home intervention (tele@cognitive protocol) as compared to an unstructured cognitive at-home rehabilitation in a cohort of patients with Chronic Neurological Diseases (CNDs); (2) to investigate its effects on the biomolecular and neurophysiological marker hypothesizing that people with CNDs enrolled in this telerehabilitation program will develop changes in biological markers and cortical and subcortical patterns of connectivity; (3) to analyze potential cognitive, neurobiological, and neurophysiological predictors of response to the tele@cognitive treatment. Method: In this single-blind, randomized, and controlled pilot study, we will assess the short- and long-term efficacy of cognitive telerehabilitation protocol (tele@cognitive) as compared to an unstructured cognitive at-home rehabilitation (Active Control Group—ACG) in a cohort of 60 people with Mild Cognitive Impairment (MCI), Subjective Cognitive Complaints (SCCs), or Parkinson’s Disease (PD). All participants will undergo a clinical, functional, neurocognitive, and quality of life assessment at the baseline (T0), post-treatment (5 weeks, T1), and at the 3-month (T2) follow-up. Neurophysiological markers and biomolecular data will be collected at T0 and T1. Conclusions: EARLY-COGN^3 project could lead to a complete paradigm shift from the traditional therapeutic approach, forcing a reassessment on how CNDs could take advantage of a digital solution. (clinicaltrials.gov database, ID: NCT06657274)

Primary Progressive Aphasia (PPA) is a syndrome due to different neurodegenerative disorders selectively disrupting language functions. PPA specialist care is underdeveloped. There are very few specialists (neurologists, psychiatrists, neuropsychologists, and speech therapists) and few hospital- or community-based services dedicated to the diagnosis and continuing care of people with PPA. Currently, healthcare systems struggle to provide adequate coverage of care that is too often fragmented, uncoordinated, and unresponsive to the needs of people with PPA and their families. Recently, attention has been gained by non-invasive brain stimulation techniques that allow a personalized treatment approach, such as transcranial Direct Current Stimulation (tDCS). The MAINSTREAM trial looks forward to introducing and evaluating therapeutic innovations such as tDCS coupled with language therapy in rehabilitation settings. A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia, MAINSTREAM (ID: 3430931) was registered in the clinicaltrials.gov database (identifier: NCT05730023) on 15 February 2023.