Clinical trial NCT06668610: A Multifocal TDCS-EEG Protocol for Improving Symptoms of Mild Cognitive Impairment and Early Dementia
Official title: An Integrated Multifocal TDCS-EEG Protocol for Improving Cognitive and Affective Symptoms in Mild Cognitive Impairment and Early Stages of Dementia: a Crossover Double-blind Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Mild Cognitive Impairment (MCI)
Dementia
Alzheimer Disease, Early Onset
Alzheimer Disease
Frontotemporal Degeneration (FTD)
Neurocognitive Decline
Keywords: non invasive brain stimulation (NIBS)
transcranial direct current stimulation (tDCS)
electroencephalography (EEG)
crossover
randomised controlled trial
mild cognitive impairment
early stage dementia
multifocal brain stimulation
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
First posted: 2024-10-31
Enrollment: 50
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study will adopt a double-blinded crossover randomised controlled design. The whole intervention will consist of two treatment phases (sham vs real multifocal stimulation) and multiple assessment phases performed before and after each rehabilitation cycle (T1, T2, T3). Recruited participants will be randomly assigned to a "SHAM-REAL" stimulation group or a "REAL-SHAM" stimulation group by computer-generated random numbers. Throughout the entirety of the study, all participants will undergo conventional cognitive stimulation therapy, involving paper-and-pencil exercise and computerised activity on several cognitive domains including memory, attention, and executive functions (Bahar-Fuchs et al., 2019; Woods et al., 2012).
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if an integrated protocol using multifocal non invasive brain stimulation and brain recording combined with cognitive training is effective in treating cognitive and affective symptomatology in patients with mild cognitive impairment and early stages of dementia. The main questions it aims to answer are:

* Does multifocal non-invasive brain stimulation reduce cognitive and affective symptoms in patients with mild cognitive impairment and early stages of dementia?
* Do some specific factors, such as education and cognitive reserve, affect the extent of the possible outcomes achievable from the intervention?
* Do electrophysiological measures contribute identifying responders and non-responders to the treatment? Researchers will compare real non-invasive brain stimulation to a placebo stimulation (reproducing the same feeling of stimulation without actually stimulating the brain) combined with cognitive rehabilitation on general cognition measures and depression symptoms.

Participants will

* Undergo two treatment cycles (real stimulation or placebo over frontal and temporal ares of the left hemisphere) combined with cognitive training twice a week for two months.
* Complete neuropsychological evaluations before the first rehabilitation cycle and at the end of each rehabilitation cycle.

Caregivers will provide information on functional daily living activities for their relatives.

Detailed description: The global prevalence of dementia is expected to continue to rise. Recent estimates forecast that the number of people with dementia worldwide will increase to 152 million cases in 2050. This calls for the development of effective prevention and treatment strategies. Recently, the benefits of non-pharmacological interventions for the intervention in dementia and its preclinical conditions are being explored. Within this contex, transcranial direct current stimulation (tDCS), represents a safe and straightforward approach to modulate brain excitability with the potential to reduce symptomatology in individuals with dementia and Mild Cognitive Impairment (MCI).

The objective of this study is to evaluate a protocol for the treatment of the cognitive and affective symptoms in dementia and MCI with several specific novel features.

First, the protocol adopts multifocal stimulation of relevant brain structures involved in the genesis of the symptoms. While previous studies focused on specific areas in the frontal and temporal cortex in separate treatment conditions, the present study employes multifocal tDCS over such structures to strengthen distribution of direct current over the left fronto-temporal network, and to possibly boost the achievable outcomes.

Second, to address the issue of heterogeneity of stimulation effects, the study combines electrophysiological measures (EEG) with brain stimulation to monitor the effect of brain stimulation following specific polarities, also considering possible individual differences in response to stimulation. Such a protocol would allow identifying responders (and non responders) to stimulation, thus targeting individuals which may benefit (or not) from a given intervention.

Third, the study will further explore the variability in response to brain stimulation raised by previous studies, considering the relationship between some demographic and psychological factors with clinical and electrophysiological outcomes. Previous studies have shown a buffering effect of age and education on global cognitive response following brain stimulation, and a relevant association of cognitive functioning with cognitive reserve. The contribution of these variables will be explored in the study to provide a more complex interpretation of either positive or null effects associated with the intervention.

Eligibility criteria: Inclusion Criteria:

* age between 55 and 85 years;
* diagnosis of minor neurocognitive disorder, or major neurocognitive disorder with mild severity, according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5; APA 2013) with a Clinical Dementia Rating Scale (CDR) of .05 or 1 (Morris, 1993);
* right handedness.

Exclusion Criteria:

* brain events with an acute aetiology (stroke, traumatic brain injury, neoplastic ablation);
* psychiatric disorders (schizophrenia, psychosis, bipolar disorder) and assumption of psychotropic drugs;
* diagnosis of moderate or severe major neurocognitive disorders (DSM-5; APA 2013) with CDR scores equal or above 2 (Morris, 1993);
* any condition with may also hypothetically interfere with electrophysiological recording and neurostimulation (metallic implants in the brain, cochlear implant, pacemakers, or suffering from epilepsy) (Antal et al., 2017; Bikson et al., 2016).

Primary outcomes:
measure: Montreal Cognitive Assessment (MOCA; Santangelo et al., 2015).
timeFrame: The test will be used to monitor cognitive functions before the first cycle (T1, at week 0) and at the end of the first (T2; at week 4) and second cycle (T3; at week 8) of the intervention. Each cycle is 28 days.
measure: Frontal Assessment Battery (FAB; Appollonio et al., 2005).
timeFrame: The test will be used to monitor cognitive functions before the first cycle (T1, at week 0) and at the end of the first (T2; at week 4) and second cycle (T3; at week 8) of the intervention. Each cycle is 28 days.
measure: Free and Cued Selective Reminding Test (FCSRT; Frasson et al., 2011).
timeFrame: The test will be used to monitor cognitive functions before the first cycle (T1, at week 0) and at the end of the first (T2; at week 4) and second cycle (T3; at week 8) of the intervention. Each cycle is 28 days.
measure: Stroop Colour and Word Test (Caffarra et al., 2002).
timeFrame: The test will be used to monitor cognitive functions before the first cycle (T1, at week 0) and at the end of the first (T2; at week 4) and second cycle (T3; at week 8) of the intervention. Each cycle is 28 days.
measure: Geriatric Depression Scale (GDS; Galeoto et al., 2018).
timeFrame: The test will be used to monitor affective symptoms before the first cycle (T1, at week 0) and at the end of the first (T2; at week 4) and second cycle (T3; at week 8) of the intervention. Each cycle is 28 days.
Secondary outcomes:
measure: EEG Power Spectrum
timeFrame: EEG recordings will be performed before and after the first (at week 0), eight (at week 4), ninth (at week 5) and sixtheenth (at week 8) intervention sessions. The scale will be completed by caregivers. Each intervention cycle is 28 days.
measure: Independence in Everyday Life - ADL
timeFrame: The scale will be used to monitor symptoms before the first cycle (T1, at week 0) and at the end of the first (T2; at week 4) and second cycle (T3; at week 8) of the intervention. The scale will be completed by caregivers. Each cycle is 28 days.
measure: Independence in Everyday Life - IADL
timeFrame: The scale will be used to monitor independence before the first cycle (T1, at week 0) and at the end of the first (T2; at week 4) and second cycle (T3; at week 8) of the intervention. The scale will be completed by caregivers. Each cycle is 28 days.
Other outcomes:
Locations:
city: Caserta
country: Italy
facility: Department of Psychology, University of Campania "Luigi Vanvitelli"
Study officials:
References: