Cognitive Training and Brain Stimulation in Prodromal Alzheimer's Disease

Not Applicable

Completed

• Conditions: Subjective Cognitive Decline; Mild Cognitive Impairment
• Interventions: Device: anodal tDCS; Behavioral: Intensive cognitive training

• Registration Number: NCT04265378
• Lead Sponsor: University Medicine Greifswald

Brief Summary

The aim of this study is to investigate whether a tDCS-accompanied intensive cognitive training of working memory leads to performance improvement in individuals with prodromal Alzheimer's disease.

Detailed Description

The goal of the present study is to assess behavioral (primary) effects of a multi-session cognitive training combined with transcranial direct current stimulation (tDCS). Many studies to date have found tDCS to be an efficient method to enhance various cognitive functions by modulating cortical excitability in young adults, but its behavioral impact and underlying mechanisms in pathological aging still need to be elucidated. Individuals with prodromal Alzheimer's disease, will participate in a three-week cognitive training with concurrent online tDCS application. Cognitive performance (primary) will be examined before, during and after the intervention, in order to draw conclusions about the effect of tDCS. In addition to cognitive training, a control group, receiving sham stimulation during training, will be assessed. Follow-up sessions to assess long-term effects are planned four weeks and seven months after the post assessment. Furthermore, to assess potential predictors of tDCS effects, functional and structural parameters will be measured with MRI. The results of the study will offer valuable insights into efficacy of combined tDCS and cognitive training, as compared to training alone, in individuals with prodromal stages of Alzheimer's disease. Moreover, improved understanding of tDCS effects on cognitive training performance and underlying neural correlates may help to develop novel approaches for modulating cognitive decline in healthy and pathological aging.

Study Timeline

• Study Start: 2019-05-01
• Study First Submitted: 2020-02-03
• Study First Submitted QC: 2020-02-07
• Study First Posted: 2020-02-11
• Primary Completion: 2022-10-10
• Study Completion: 2022-10-10
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-03
• Last Update Posted: 2022-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Older adults (60 - 80 years);
• Right handedness;
• subjective cognitive decline (SCD) or mild cognitive impairment (MCI)

Exclusion Criteria

• Dementia or other neurodegenerative neurological disorders; epilepsy or history of seizures; close relatives with epilepsy or history of seizures; previous stroke;
• Severe and untreated medical conditions that precludes participation in the training, as determined by responsible physician;
• History of severe alcoholism or use of drugs;
• Severe psychiatric disorders such as depression (if not in remission) or psychosis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stimulation group	Intensive cognitive training	Anodal tDCS + intensive cognitive training
Stimulation group	anodal tDCS	Anodal tDCS + intensive cognitive training
Sham group	Intensive cognitive training	Sham tDCS + intensive cognitive training

Primary Outcome Measures

Name	Time	Method
Working memory training performance (Letter Updating task)	3 weeks	Performance in a memory training task (Letter updating) under anodal tDCS compared to sham condition; operationalized by working Memory Updating performance assessed with number of correctly recalled letter lists in the letter updating task, analyzed immediately after training period (anodal condition versus sham)

Secondary Outcome Measures

Name	Time	Method
Transfer outcomes: Wiener Matrices Test (no. correct)	3 weeks	Comparing performance immediately before and after training period (anodal condition versus sham)
Long-term outcomes: Markov decision making task (% optimal actions)	4 weeks and 7 months after training	Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)
Neural correlates: Structural neural correlates of tDCS effect	before training; 7 months after training	- structural neural correlates; assessed by grey matter volumes, cortical thickness, white matter microstructure (diffusion tensor imaging (DTI) measures: fractional anisotropy, mean diffusivity); before the intervention and at 7-months after training period (correlations in anodal group)
Neural correlates: Functional neural correlates of tDCS effect	before training; 7 months after training	- functional neural correlates; assessed by resting-state fMRI analyses to obtain functional connectivities (seed-based connectivity: correlation of BOLD-timeseries between a seed/ROI and every voxel/location in the brain); before the intervention and at 7-months after training period (correlations in anodal group)
Long-term outcomes: numerical n-back task (% correct)	4 weeks and 7 months after training	Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)
Transfer outcomes: AVLT (auditory verbal learning test) (sum of correctly recalled items trials 1-5)	3 weeks	Comparing performance immediately before and after training period (anodal condition versus sham)
Long-term outcomes: Wiener Matrices Test (no. correct)	4 weeks and 7 months after training	Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)
Working memory training performance (Markov task)	3 weeks	Performance in second memory training task (Markov decision making) under anodal tDCS compared to sham condition, analyzed immediately after training period (anodal condition versus sham)
Transfer outcomes: numerical n-back task (% correct)	3 weeks	Comparing performance immediately before and after training period (anodal condition versus sham)
Long-term outcomes: Letter Updating task (no. of correctly recalled lists)	4 weeks and 7 months after training	Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)
Long-term outcomes: AVLT (auditory verbal learning test) (sum of correctly recalled items trials 1-5)	4 weeks and 7 months after training	Comparing performance immediately before and after training period with performance at 4 weeks and 7-months after training period (anodal condition versus sham)

Trial Locations

Locations (1)

University Medicine Greifswald; 🇩🇪 Greifswald, Germany