Neuromodulation of Language and Memory Networks in Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Boston Naming Test
研究概览
简要总结
The purpose of this study is to assess the effects of non-invasive brain stimulation on memory and language ability in patients with two phenotypic variations of underlying Alzheimer disease pathology: amnestic mild cognitive impairment (aMCI) and logopenic variant of primary progressive aphasia (lvPPA). This study will use repetitive Transcranial Magnetic Stimulation (rTMS) to stimulate nodes of networks that are thought to be affected in these two conditions. Specifically, a node of the Default Mode Network (DMN)-the angular gyrus (AG)-will be stimulated in aMCI patients; and a node of the language network-the posterior inferior frontal gyrus (pIFG) will be stimulated in patients with lvPPA.
We will use functional connectivity MRI (fcMRI) to assess changes in functional network architecture following the stimulation. We will also assess putative cognitive improvements resulting from the stimulation by in-depth language testing in lvPPA patients and in-depth memory testing in aMCI patients.
详细描述
Specific Aims
Aim 1: To investigate the feasibility of selective rTMS modulation of the Default Mode Network (DMN) vs. language network in patients with aMCI and lvPPA. We will assess the reliability of the rTMS/fcMRI approach to network modulation by studying the same subjects over repeated sessions, with the same methodology, including appropriate sham stimulation conditions.
Hypothesis 1a: Changes in network functional connectivity following excitatory rTMS to AG (a node of the DMN) and pIFG (a node of the language network) across identical stimulation sessions separated in time, will show minimal within subject variability in aMCI and lvPPA patients, respectively, thus confirming the reliability of the approach and the reproducibility of prior findings demonstrating connectivity changes within the DMN and language networks.
Hypothesis 1b: High frequency rTMS to pIFG will reliably increase pIFG-SMG-pMTG functional connectivity within the language network; high frequency rTMS to AG will reliably increase functional connectivity between pIPL and HF in the DMN.
Hypothesis 1c: The changes in network functional connectivity will be selective, in that stimulation to AG (in the DMN) will not modulate connectivity within the language network, while stimulation to pIFG (in the language network) will not modulate DMN connectivity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
All participants will undergo SHAM stimulation as a control condition. They will be blinded as to whether they are receiving active or SHAM stimulation.
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients, age 18-90, who carry a diagnosis of either the logopenic variant (lvPPA) of PPA or amnestic MCI (aMCI). Patients must have been observed for at least one year by a specialized clinician.
- •The presence of underlying AD pathology must be verified by a prior amyloid-PET and/or Tau-PET imaging (done as part of a prior protocol), or CSF biomarkers of AD pathology.
- •Patients with lvPPA must have at least mild to moderate language impairment.
- •Patients with aMCI must meet criteria for this condition, including the presence of at least mild to moderate episodic memory impairment.
- •Patients must be native English speakers.
- •Patients must have a study partner (e.g. spouse, sibling, adult child, friend) who can accompany them to all study visits.
排除标准
- •Any history of seizures, unexplained loss of consciousness or a first-degree family member with epilepsy (to ensure safety to receive rTMS).
- •Any history of significant co-occurring neurological illness unrelated to the neurodegenerative disease in question (e.g. multiple sclerosis), or significant medical problems (e.g. poorly controlled diabetes/hypertension or cancer within 5 years).
- •Active symptoms of major depressive disorder, bipolar disorder, schizophrenia, substance use disorder or significant premorbid intellectual disability according to DSM criteria.
- •MRI evidence of significant (e.g. confluent leukoariosis or stroke) cerebrovascular disease, hydrocephalus or the presence of a space-occupying intra-cranial mass.
- •Contraindications to MRI or rTMS including: cardiac pacemaker or pacemaker wires, neurostimulators, implanted pumps, metal in the body (rods, plates, screws, shrapnel, dentures, IUD), surgical aneurysm clips in the head, previous neurosurgery or cochlear implants.
- •In line with published MGH IRB guidelines for rTMS, pregnancy must be ruled out by urine ß-HCG if answers to screening questions suggest that pregnancy is possible and if female participants are premenopausal and of child-bearing age. Subjects will not be able to enroll if they are breastfeeding.
研究组 & 干预措施
Active stimulation
Active rTMS will be administered with a MagPro X100 stimulator (MagVenture, Denmark), using a 70 mm figure-of-eight liquid cooled coil capable of doing active or sham stimulation (e.g. the Cool B70 coil or the Cool B65 A/P coil). Active rTMS will be delivered at 80-120% of a patient's resting or active motor threshold. rTMS will be administered in an excitatory pattern as 20Hz. Stimulation parameters will remain well within established safety guidelines (Rossi et al. 2009).
干预措施: repetitive transcranial magnetic stimulation (rTMS) (Device)
SHAM stimulation
SHAM stimulation will also be administered with a MagPro X100 stimulator (MagVenture, Denmark), using a 70 mm figure-of-eight liquid cooled coil capable of doing active or sham stimulation (e.g. the Cool B70 coil or the Cool B65 A/P coil). SHAM rTMS will be delivered at 80-120% of a patient's resting or active motor threshold. SHAM stimulation will be delivered to the exact same cortical targets as active rTMS. While no electromagnetic stimulation will be delivered during SHAM, the sounds will approximate active stimulation and skin electrodes will approximate the sensation of active rTMS. Inclusion of a sham condition in this protocol is critical to measure whether or not the stimulation is improving memory or language performance, or whether practice effects or other non-specific effects are responsible for any changes in memory or language performance which may be observed.
干预措施: repetitive transcranial magnetic stimulation (rTMS) (Device)
结局指标
主要结局
Boston Naming Test
时间窗: Up to 5 weeks
A test of confrontation naming of drawn pictures.
Western Aphasia Battery-repetition
时间窗: Up to 5 weeks
A test of the ability to repeat phonetically complex phrases
Western Aphasia Battery-reading comprehension
时间窗: Up to 5 weeks
A test of the ability to correctly comprehend read material
Western Aphasia Battery-spelling
时间窗: Up to 5 weeks
A test of the ability to spell irregular words.
Controlled Oral Word Association Test
时间窗: Up to 5 weeks
A test of word generation, e.g. generation of as many words as possible beginning with a certain letter of the alphabet.
Cambridge Semantic Battery
时间窗: Up to 5 weeks
A test of semantic knowledge through word-pairings.
The Northwestern Anagram Test
时间窗: Up to 5 weeks
A test of non-verbal production of sentences.
Picture Description Test
时间窗: Up to 5 weeks
A test in which patients write a paragraph describing a picture, such as a picnic or the cookie theft picture.
Changes in intrinsic functional connectivity
时间窗: Up to 5 weeks
Changes in region-to-region functional connectivity within the stimulated networks will be assessed, e.g. changes in connectivity in the DMN will be assessed in aMCI patients and changes in the language network will be assessed in lvPPA patients.
次要结局
未报告次要终点
研究者
Mark Eldaief, MD
Assistant Professor of Neurology
Massachusetts General Hospital