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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Montreal Cognitive Assessment (MOCA; Santangelo et al., 2015).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
SHAM-REAL tDCS Group
Participants randomly assigned to this group will receive a first cycle of SHAM multifocal tDCS (8 sessions, twice a week) and a second cycle of REAL multifocal tDCS (8 sessions, twice a week). During both cycles participant will receive cognitive stimulation treatment after brain simulation.
干预措施: StarStim 32, Neuroelectrics, Spain - Real multifocal tDCS (Device)
SHAM-REAL tDCS Group
Participants randomly assigned to this group will receive a first cycle of SHAM multifocal tDCS (8 sessions, twice a week) and a second cycle of REAL multifocal tDCS (8 sessions, twice a week). During both cycles participant will receive cognitive stimulation treatment after brain simulation.
干预措施: StarStim 32, Neuroelectrics, Spain - Sham multifocal tDCS (Device)
SHAM-REAL tDCS Group
Participants randomly assigned to this group will receive a first cycle of SHAM multifocal tDCS (8 sessions, twice a week) and a second cycle of REAL multifocal tDCS (8 sessions, twice a week). During both cycles participant will receive cognitive stimulation treatment after brain simulation.
干预措施: Cognitive treatment (Behavioral)
REAL-SHAM tDCS Group
Participants randomly assigned to this group will receive a first cycle of REAL multifocal tDCS (8 sessions, twice a week) and a second cycle of SHAM multifocal tDCS (8 sessions, twice a week). During the two cycles participant will receive cognitive stimulation treatment after brain simulation.
干预措施: StarStim 32, Neuroelectrics, Spain - Real multifocal tDCS (Device)
REAL-SHAM tDCS Group
Participants randomly assigned to this group will receive a first cycle of REAL multifocal tDCS (8 sessions, twice a week) and a second cycle of SHAM multifocal tDCS (8 sessions, twice a week). During the two cycles participant will receive cognitive stimulation treatment after brain simulation.
干预措施: StarStim 32, Neuroelectrics, Spain - Sham multifocal tDCS (Device)
REAL-SHAM tDCS Group
Participants randomly assigned to this group will receive a first cycle of REAL multifocal tDCS (8 sessions, twice a week) and a second cycle of SHAM multifocal tDCS (8 sessions, twice a week). During the two cycles participant will receive cognitive stimulation treatment after brain simulation.
干预措施: Cognitive treatment (Behavioral)
结局指标
主要结局
Montreal Cognitive Assessment (MOCA; Santangelo et al., 2015).
时间窗: 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.
MOCA is a brief neuropsychological tool for screening global cognitive functioning specifically designed for MCI and early stages of dementia. The score ranges 0-30; the higher the score the higher the level of general cognitive functioning.
Frontal Assessment Battery (FAB; Appollonio et al., 2005).
时间窗: 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.
FAB is a screening neuropsychological battery for evaluation of executive functioning. Total score ranges 0-18; the higher the score, the higher the level of executive functioning.
Free and Cued Selective Reminding Test (FCSRT; Frasson et al., 2011).
时间窗: 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.
FCSRT is a neuropsychological tool designed to assess episodic memory domain. The test provides separate scores for free, cued and total immediate recall (scores 0-36), and scores for free, cued and total delayed recall (scores 0-12); the higher the scores, the higher the memory performance
Stroop Colour and Word Test (Caffarra et al., 2002).
时间窗: 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.
The Stroop Test is a neuropsychological test assessing cognitive interference and inhibition. The test provides two measures, i.e. overall number of errors and time to complete the test, with lower scores indicating better performance.
Geriatric Depression Scale (GDS; Galeoto et al., 2018).
时间窗: 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.
GDS is an evaluation tool to diagnose older adult's depression. This questionnaire is designed for the older person and defines his/her degree of satisfaction, quality of life, and feelings. The total score ranges 0-30 with higher scores indicating higher levels of depression.
次要结局
- EEG Power Spectrum(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.)
- Independence in Everyday Life - ADL(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.)
- Independence in Everyday Life - IADL(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.)
研究者
Luigi Trojano
Professor
University of Campania Luigi Vanvitelli