RecruitingNot ApplicableNCT04122001

Effects of Electrical Stimulation on Verbal Learning in Typical and Atypical Alzheimer's Disease

Transcranial Direct Current Stimulation in Typical and Atypical Alzheimer's Disease

Sponsor

Johns Hopkins University

Enrollment

90 participants

Start Date

Aug 17, 2020

Study Type

INTERVENTIONAL

Conditions

Alzheimer Disease, Early Onset Atypical Alzheimer's Disease Logopenic Progressive Aphasia

Summary

Alzheimer's disease (AD) is the leading neurodegenerative disease of aging characterized by multiple cognitive impairments. Given the recent failures of disease-modifying drugs, the current focus is on 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. The investigators' previous clinical trial on the effects of tDCS in neurodegenerative disorders has also shown augmented effects of lexical retrieval for tDCS. In the present study the investigators will compare the effects of active vs. sham tDCS over the AG-an area that is part of the default mode network but also a language area, particularly important for semantic integration and event processing-in two predominant AD variants: probable AD with amnesic phenotype (amnesic/typical AD) and probable AD with non-amnesic (language deficit) phenotype also described as logopenic variant PPA with AD pathology (aphasic/atypical AD). The investigators 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; (3) identify changes in the inhibitory neurotransmitter GABA at the stimulation site using magnetic resonance spectroscopy. Furthermore, the investigators need to determine the characteristics of the people that may benefit from the new neuromodulatory approaches. For this reason, the investigators will evaluate neural and cognitive functions as well as physiological characteristics such as sleep, and will analyze the moderating effects on verbal learning outcomes. Study results can help provide treatment alternatives as well as a better understanding of the therapeutic and neuromodulatory effects of tDCS in AD, thus improving patients' and caregivers' quality of life.

Eligibility

Min Age: 45 YearsMax Age: 85 Years

Plain Language Summary

Simplified for easier understanding

This study is testing whether mild electrical brain stimulation (transcranial direct current stimulation, or tDCS) can help improve word-learning and memory in people with Alzheimer's disease — including those with typical memory loss and those with a language-related variant of Alzheimer's called logopenic primary progressive aphasia. **You may be eligible if...** - You are between 45 and 85 years old - You are right-handed and proficient in English - You have at least a high-school education - You have been diagnosed with mild-to-moderate Alzheimer's disease (either typical memory-loss type or a language variant called logopenic PPA with Alzheimer's biomarkers) - You have a close friend or family member who can participate as an observer **You may NOT be eligible if...** - You are 86 years old or older - You have a language or memory impairment so severe you cannot participate in testing - You have conditions that prevent safe brain stimulation Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DEVICEActive, in-person HD-tDCS or active remote tDCS

Stimulation will be delivered by a battery-driven constant current stimulator. The electrical current will be administered to a pre-specified region of the brain (angular gyrus). The stimulation will be delivered at an intensity of 2 milliamperes (mA) (estimated current density 0.04 mA/cm2; estimated total charge 0.048 Coulombs/cm2) in a ramp-like fashion for a maximum of 20 minutes. In the active, in-person HD-tDCS the current is delivered in a ring configuration. In the active remote tDCS current is delivered in one electrode patch.

DEVICESham

Current will be administered in a ramp-like fashion but after the ramping the intensity will drop to 0 mA. Current under the Sham condition will last for a maximum of 30 seconds.

OTHERWord List Learning Intervention (WordLLI)

Participants will receive a word list learning intervention (WordLLI) of semantically related and unrelated word lists. Word lists are presented across 10 trials, with an additional trial after a 10-minute delay to assess delayed recall. Immediately following verbal presentation of word lists during each trial, participants will be instructed to recall as many of the words from the list as possible. Participants may use the written modality as a strategy during recall. Word lists include 12 words matched based on psycholinguistics attributes (e.g., imageability, frequency). This task is designed to help participants improve memory via enhancing list learning capabilities.