A Non-invasive, Multimodal Approach to Restore Functional Networks and Cognition in Alzheimer's Disease and Frontotemporal Dementia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Change in Behavioral Symptom Severity (NPI)
研究概览
简要总结
This pilot study aims to test clinical and connectivity changes following non-invasive stimulation of disease-specific networks in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Brain network stimulation will be carried out with transcranial direct current stimulation (tDCS). Target networks will be the default mode network (DMN) and salience network (SN). Twenty AD and 20 bvFTD patients will be recruited and assessed with a comprehensive clinical, behavioral and cognitive battery, and 3 Tesla MRI scan (including resting-state functional MRI, arterial spin labeling, diffusion tensor imaging, structural MRI) at three time-points: baseline, after tDCS, and after 6 months. Patients will be randomized to 2 arms: anodal stimulation of the disease-specific network (DMN in AD, SN in bvFTD) or cathodal stimulation of the anti-correlated network (SN in AD, DMN in bvFTD). The intervention will consist of 10 tDCS sessions over two weeks. Cerebrospinal fluid (CSF) samples will be collected at baseline for biomarker's assessment; blood samples will be collected at each time-point to assess changes in peripheral inflammatory markers. Blood and CSF collection will be optional. A sample of 20 elderly controls will be included for baseline comparisons.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of AD or bvFTD according to current clinical criteria (Albert et al., 2011; Rascovsky et al., 2011)
- •Ability to provide written informed consent
- •Availability of a collateral source
排除标准
- •Moderate/severe dementia
- •Presence of any medical or psychiatric illness that could interfere in completing assessments
- •Exclusion Criteria for MRI and tDCS:
- •metal implants, pace-makers, prosthetic heart valves
- •claustrophobia
- •history of epilepsy
- •pregnancy
- •Exclusion Criteria for controls:
- •Current or past history of clinical, neurological, or psychiatric conditions that could interfere with the assessment (e.g., transient ischemic attack, ictus, head trauma, epilepsy, multiple sclerosis, neuropathy, mood disorders, substance abuse)
结局指标
主要结局
Change in Behavioral Symptom Severity (NPI)
时间窗: Baseline, post tDCS (week 3)
The Neuropsychiatric Inventory (NPI) is a behavioral scale administered to the caregiver assessing 12 dimensions: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, nighttime behaviors, and appetite/eating. Each dimension has multiple screening questions relating to symptoms. If the answer to the screening questions is "Yes", the dimensional-score is the product of frequency (1=occasionally to 4=very frequently) and severity (1=Mild to 3=Severe) of symptoms. Dimensional-scores are summed (from 0 to 144). Higher scores indicate greater behavioral disturbances. Negative changes at post tDCS compared to baseline represent an improvement on the scale.
Change in Clinical Disease Severity (CDR)
时间窗: Baseline, post tDCS (week 3)
CDR - Clinical Dementia Rating score The clinical dementia rating (CDR) is a clinical global rating scale administered to both the participant and the caregiver, assessing 6 domains of participant function: memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care. Each domain is based on a 5-point scale ranging from no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 to severe impairment=3. The global CDR score is computed via a memory-weighted averaging algorithm of the six domain scores and ranges from 0 to 5. The CDR-sum of boxes (CDR-SB) is the sum of the individual domain scores and ranges from 0 to 18. Higher scores indicate more clinical impairment. Negative changes at post tDCS compared to baseline represent an improvement on the scale.
Change in Behavioral Symptom Severity (FBI)
时间窗: Baseline, post tDCS (week 3)
The Frontal Behavioral Inventory (FBI) is a 24-item inventory designed to assess behavior and personality changes via caregiver. Item-level scores range from 0=none, 1=mild/occasional, 2=moderate, 3=severe/most of the time. Item-scores are summed (from 0 to 72). Higher scores indicate greater behavioral/personality disturbances. Negative changes at post tDCS compared to baseline represent an improvement on the scale.
Change in Functional Connectivity
时间窗: Baseline, post tDCS (week 3)
Default mode network (DMN) and salience network (SN) mean functional connectivity is assessed on resting state functional MRI. Functional connectivity is standardized to Z scores and thresholded at Z\>2. Higher values denote greater functional connectivity. A positive change at post tDCS compared to baseline represents an increase in resting-state functional connectivity.
Change in Cerebral Blood Flow
时间窗: Baseline, post tDCS (week 3)
Default mode network (DMN) and salience network (SN) mean cerebral blood flow is assessed on arterial spin labeling. Cerebral blood flow is computed by averaging values across the DMN and SN regions of interest. Cerebral blood flow is a measure of brain perfusion, higher values denoting higher perfusion. A positive change at post tDCS compared to baseline represents an increase in perfusion.
次要结局
- Change in Cognition: Executive Function(Baseline, post tDCS (week 3))
- Change in Structural Connectivity: FA(Baseline, post tDCS (week 3))
- Change in Cognition: Memory(Baseline, post tDCS (week 3))
- Change in Cognition: Language(Baseline, post tDCS (week 3))
- Change in Cognition: Emotion Recognition(Baseline, post tDCS (week 3))
- Change in Cognition: Visuospatial Function(Baseline, post tDCS (week 3))
- Change in Structural Connectivity: MD, AxD, RaD(Baseline, post tDCS (week 3))
研究者
Michela Pievani
Principal Investigator
IRCCS Centro San Giovanni di Dio Fatebenefratelli