Transcranial direct current stimulation in typical and atypical Alzheimer's disease

经颅直流电刺激治疗典型和非典型阿尔茨海默病

• 批准号: 10260455
• 负责人: Kyrana Tsapkini
• 金额: $ 75.9万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10260455
• 关键词: Affect; Aftercare; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Amnesia; Anodes; Anomia; Aphasia; Area; Atrophic; Auditory; Behavior Therapy; Biological Markers; Brain; Brain region; Caregivers; Categories; Characteristics; Clinical Trials; Cognition; Cognitive; Complex; Controlled Clinical Trials; Coupling; Development; Diffusion Magnetic Resonance Imaging; Disease; Double-Blind Method; Elderly; Electrical Stimulation of the Brain; Evaluation; Event; Failure; Foundations; Functional Magnetic Resonance Imaging; Future; Health system; Hippocampus (Brain); Image; Impaired cognition; Individual; Inferior frontal gyrus; Intervention; Language; Language Development; Language Disorders; Learning; Left; Magnetic Resonance Spectroscopy; Measures; Membrane Potentials; Memory; Methodology; Multi-Institutional Clinical Trial; Names; Nerve Degeneration; Neurocognitive; Neurodegenerative Disorders; Neurons; Neurotransmitters; Oral; Painless; Parahippocampal Gyrus; Patients; Pattern; Performance; Pharmaceutical Preparations; Phenotype; Physiological; Prefrontal Cortex; Prevalence; Primary Progressive Aphasia; Publishing; Quality of life; Questionnaires; Randomized Controlled Clinical Trials; Rest; Semantics; Site; Sleep; Structure; Sum; Symptoms; Synapses; Synaptic Transmission; Syndrome; Techniques; Testing; Therapeutic; Therapeutic Effect; Training; Variant; Verbal Learning; actigraphy; alternative treatment; angular gyrus; base; cingulate cortex; classical conditioning; cognitive function; cognitive task; effective therapy; gamma-Aminobutyric Acid; improved; learning outcome; lexical retrieval; neurological rehabilitation; neuroregulation; post intervention; prevent; relating to nervous system; statistics; theories; treatment effect

Alzheimer’s disease (AD) is the leading neurodegenerative disease of aging with devasting effects on all cognitive functions of patients and a great toll on caregivers and the health system. Given the recent failures of disease-modifying drugs, the current focus is in preventing or mitigating synaptic damage that correlates with cognitive decline in AD patients. Transcranial Direct Current Stimulation (tDCS) is a safe, non-invasive, non- painful electrical stimulation of the brain that is shown to act as a primer at the synaptic level when administered along with behavioral therapy, mostly involving language, learning and memory. Previous studies have shown that tDCS over the left angular gyrus (AG) improves language associative learning in the elderly through changes in functional connectivity between the AG and the hippocampus. Our previous, double-blind, sham controlled, clinical trial on the effects of tDCS in neurodegenerative disorders has also shown augmented effects of lexical retrieval for tDCS. With regard to the mechanisms of tDCS effects in the brain, tDCS modulates the functional connectivity between the stimulated area and other task-related areas, as well as the inhibitory neurotransmitter GABA. In the present study we will compare the effects of active vs. sham tDCS over the AG—an area that is part of the default mode network (DMN) but also a language area, particularly important for semantic integration and event processing—in two predominant AD variants: probable AD with amnesic phenotype and probable AD with non-amnesic (language deficit) phenotype also described as logopenic variant PPA with AD pathology (aphasic AD). We aim to: (1) determine whether active high-definition tDCS (HD-tDCS) targeting the left AG combined with a Word-List Learning Intervention (WordLLI) will improve verbal learning; (2) identify the changes in functional connectivity between the stimulated area (AG) and other structurally and functionally connected areas using resting-state functional magnetic resonance imaging (rsfMRI), i.e., areas of the default mode network (DMN); (3) identify changes in the inhibitory neurotransmitter GABA at the stimulation site and magnetic resonance spectroscopy (MRS). Furthermore, in order to determine whether the new neuromodulatory approaches are effective in alleviating AD symptoms, we need to determine the characteristics of the people that benefit from it. For this reason, to identify responders, we will evaluate neural (functional and structural connectivity), cognitive (memory, executive and language) functions, and physiological characteristics such as sleep, and we will analyze their moderating effects on verbal learning outcomes. A complementary group of experts in neurorehabilitation, clinical trials methodology, imaging methodology and statistics (rsfMRI and MRS) and sleep who have already published together will be collaborating in this comprehensive study. Study results can help: (i) optimize future intervention in individuals with neurodegenerative disorders by providing treatment alternatives; and (ii) provide better understanding of the therapeutic and neuromodulatory effects of tDCS in AD, to impede neurodegeneration and improve patients' and caregivers’ quality of life.

阿尔茨海默病（AD）是一种主要的老年神经退行性疾病，对所有人都有毁灭性的影响