Cognitive training and brain stimulation in prodromal Alzheimer's disease (AD-Stim)-study protocol for a double-blind randomized controlled phase IIb (monocenter) trial

TY - JOUR

T1 - Cognitive training and brain stimulation in prodromal Alzheimer's disease (AD-Stim)-study protocol for a double-blind randomized controlled phase IIb (monocenter) trial

AU - Thams, Friederike

AU - Kuzmina, Anna

AU - Backhaus, Malte

AU - Li, Shu-Chen

AU - Grittner, Ulrike

AU - Antonenko, Daria

AU - Flöel, Agnes

PY - 2020/11/7

Y1 - 2020/11/7

N2 - BACKGROUND: Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer's disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stimulation (tDCS) to be an effective method to boost cognitive performance, especially when applied in combination with cognitive training in healthy older adults. So far, no studies combining tDCS concurrent with an intense multi-session cognitive training in prodromal AD populations have been conducted.METHODS: The AD-Stim trial is a monocentric, randomized, double-blind, placebo-controlled study, including a 3-week tDCS-assisted cognitive training with anodal tDCS over left DLPFC (target intervention), compared to cognitive training plus sham (control intervention). The cognitive training encompasses a letter updating task and a three-stage Markov decision-making task. Forty-six participants with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) will be randomized block-wise to either target or control intervention group and participate in nine interventional visits with additional pre- and post-intervention assessments. Performance in the letter updating task after training and anodal tDCS compared to sham stimulation will be analyzed as primary outcome. Further, performance on the second training task and transfer tasks will be investigated. Two follow-up visits (at 1 and 7 months post-training) will be performed to assess possible maintenance effects. Structural and functional magnetic resonance imaging (MRI) will be applied before the intervention and at the 7-month follow-up to identify possible neural predictors for successful intervention.SIGNIFICANCE: With this trial, we aim to provide evidence for tDCS-induced improvements of multi-session cognitive training in participants with SCD and MCI. An improved understanding of tDCS effects on cognitive training performance and neural predictors may help to develop novel approaches to counteract cognitive decline in participants with prodromal AD.TRIAL REGISTRATION: ClinicalTrials.gov , NCT04265378 . Registered on 07 February 2020. Retrospectively registered. Protocol version: Based on BB 004/18 version 1.2 (May 17, 2019).SPONSOR: University Medicine Greifswald.

AB - BACKGROUND: Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer's disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stimulation (tDCS) to be an effective method to boost cognitive performance, especially when applied in combination with cognitive training in healthy older adults. So far, no studies combining tDCS concurrent with an intense multi-session cognitive training in prodromal AD populations have been conducted.METHODS: The AD-Stim trial is a monocentric, randomized, double-blind, placebo-controlled study, including a 3-week tDCS-assisted cognitive training with anodal tDCS over left DLPFC (target intervention), compared to cognitive training plus sham (control intervention). The cognitive training encompasses a letter updating task and a three-stage Markov decision-making task. Forty-six participants with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) will be randomized block-wise to either target or control intervention group and participate in nine interventional visits with additional pre- and post-intervention assessments. Performance in the letter updating task after training and anodal tDCS compared to sham stimulation will be analyzed as primary outcome. Further, performance on the second training task and transfer tasks will be investigated. Two follow-up visits (at 1 and 7 months post-training) will be performed to assess possible maintenance effects. Structural and functional magnetic resonance imaging (MRI) will be applied before the intervention and at the 7-month follow-up to identify possible neural predictors for successful intervention.SIGNIFICANCE: With this trial, we aim to provide evidence for tDCS-induced improvements of multi-session cognitive training in participants with SCD and MCI. An improved understanding of tDCS effects on cognitive training performance and neural predictors may help to develop novel approaches to counteract cognitive decline in participants with prodromal AD.TRIAL REGISTRATION: ClinicalTrials.gov , NCT04265378 . Registered on 07 February 2020. Retrospectively registered. Protocol version: Based on BB 004/18 version 1.2 (May 17, 2019).SPONSOR: University Medicine Greifswald.

KW - Aged

KW - Alzheimer Disease/therapy

KW - Cognition

KW - Cognitive Dysfunction/therapy

KW - Double-Blind Method

KW - Humans

KW - Prefrontal Cortex

KW - Randomized Controlled Trials as Topic

KW - Transcranial Direct Current Stimulation

U2 - 10.1186/s13195-020-00692-5

DO - 10.1186/s13195-020-00692-5

M3 - SCORING: Journal article

C2 - 33160420

VL - 12

JO - ALZHEIMERS RES THER

JF - ALZHEIMERS RES THER

SN - 1758-9193

IS - 1

M1 - 142

ER -