Active — Not RecruitingNot Applicable

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

United States90 participantsStarted 2020-08-17

Plain-language 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.

Who can participate

Age range

45 Years – 85 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: For the aphasic/atypical AD participants: * Must be between 45-85 years of age. * Must be right-handed. * Must be proficient in English. * Must have a minimum of high-school education. * Must be diagnosed as logopenic variant Primary Progressive Aphasia (PPA) with Alzheimer's Disease (AD) biomarkers. Other possible diagnosis for the 'aphasic AD' variant would be Mild Cognitive Impairment (MCI) or 'possible AD' according to 2011 guidelines with AD biomarkers (CSF or positron emission tomography (PET) amyloid-beta or fluorodeoxyglucose (FDG)-positron emission tomography (PET) with unihemispheric atrophy). * Participants will be diagnosed from PPA and early dementias clinics at Johns Hopkins University or other specialized centers in US using current consensus criteria. Diagnosis will be based on neuropsychological testing, language testing (most commonly the Western Aphasia Battery), MRI and clinical assessment. The investigators will also use two new variant classification tests the investigators have developed at the lab which discriminate PPA variants with great accuracy (above 80%): a spelling test and a speech production test (i.e.,Cookie Theft picture description task). For the amnesic/typical AD participants: * Must be between 45-85 years of age. * Must be right-handed. * Must be proficient in English. * Must have a minimum of high-school education. * Must be diagnosed with 'probable AD' in specialized diagnostic centers with neuropsychological (e…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1This trial uses electrical stimulation to target verbal learning and word recall — can you explain what type of electrical stimulation is involved, and what the known risks or side effects of that stimulation are for someone with my diagnosis?
2The study is actively running but no longer enrolling new participants — does that mean there's a similar or follow-up study I might be eligible for, or is there another way I could access this kind of approach?
3The trial is measuring whether people can better recall both trained word lists and untrained word lists after stimulation — what would it actually mean for my day-to-day life if this approach showed some benefit for word memory?
4This trial specifically includes logopenic progressive aphasia and early-onset Alzheimer's — given my particular diagnosis, would my doctor consider my case more similar to the typical or atypical Alzheimer's group in this study, and does that affect whether this line of research is relevant to me?
5Since this is a Phase N/A study focused on measuring changes in word recall, what do we already know about whether electrical brain stimulation is safe and potentially helpful for people at my stage of Alzheimer's disease before considering it as a real option?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically related - trained word-lists

Timeframe: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

Change in auditory delayed recall accuracy of semantically related - trained word-lists

Timeframe: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - trained word-lists

Timeframe: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

Change in auditory delayed recall accuracy of semantically unrelated - trained word-lists

Timeframe: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

Change in auditory recall accuracy based the sum of words recalled in Trials 1-5 of semantically related - untrained word-lists

Timeframe: Before intervention, immediately after intervention, 1 month and 3 months post intervention, up to 31 weeks

Trial details

NCT IDNCT04122001

SponsorJohns Hopkins University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-12-31

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