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

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $753,120

## Abstract

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 intervent...

## Key facts

- **NIH application ID:** 10447136
- **Project number:** 5R01AG068881-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kyrana Tsapkini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $753,120
- **Award type:** 5
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447136

## Citation

> US National Institutes of Health, RePORTER application 10447136, Transcranial direct current stimulation in typical and atypical Alzheimer's disease (5R01AG068881-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10447136. Licensed CC0.

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