The REACT MCI study: a randomized controlled clinical trial on the effect of repeated advanced cognitive training in mild cognitive impairment

S S Hernes; P R Nordnes; H R Hol; G Ringstad; A B Knapskog; P Emhjellen; G Løhaugen; M Emini; T H Edwin

doi:10.1186/s13063-026-09711-6

The REACT MCI study: a randomized controlled clinical trial on the effect of repeated advanced cognitive training in mild cognitive impairment

Trials. 2026 May 7;27(1):363. doi: 10.1186/s13063-026-09711-6.

Authors

S S Hernes^{1

2

3}, P R Nordnes^{4

5}, H R Hol^{4

6}, G Ringstad^{4

7

6

8}, A B Knapskog^{8

9}, P Emhjellen^{8

9}, G Løhaugen¹⁰, M Emini¹¹, T H Edwin^{7

9}

Affiliations

¹ Department of Geriatric and Internal Medicine, Sorlandet Hospital Arendal HF, Arendal, Norway. susanne.sorensen.hernes@sshf.no.
² Department of Clinical Sciences, Faculty of Medicine, University of Bergen, Bergen, Norway. susanne.sorensen.hernes@sshf.no.
³ KG Jebsen Centre for Brain fluid research, Oslo, Norway. susanne.sorensen.hernes@sshf.no.
⁴ Department of Geriatric and Internal Medicine, Sorlandet Hospital Arendal HF, Arendal, Norway.
⁵ Department of Clinical Sciences, Faculty of Medicine, University of Bergen, Bergen, Norway.
⁶ Department of Radiology, Oslo University Hospital, Oslo, Norway.
⁷ KG Jebsen Centre for Brain fluid research, Oslo, Norway.
⁸ University of Oslo, Oslo, Norway.
⁹ Department of Geriatrics, Oslo University Hospital, Oslo, Norway.
¹⁰ Department of Pediatrics, Sorlandet Hospital Arendal, Arendal, Norway.
¹¹ Norwegian Health Association, Oslo, Norway.

Abstract

Background: Mild cognitive impairment (MCI) and its course have multiple determining factors with both detrimental and compensatory processes in the brain. Computerized working memory training can improve cognitive function and individuals with MCI are potential targets. Since more than 1/3 of these individuals develop dementia within 5 years, any intervention postponing the progression will be immensely important. We aim to investigate the efficiency and cost-effectiveness of working memory training in MCI.

Methods: In this blinded randomized controlled trial, 213 participants will be allocated to three groups: (1) one 5-week period of working memory training, (2) two 5-week periods of working memory training, or (3) the active control group. The participants are followed for a period of 48 months (3, 6, 12, 24, and 48 months). Furthermore, we investigate microstructural effects of working memory training on magnetic resonance imaging and seek to identify high responders to training by assessing the association with function in the glymphatic system and genetic variations. Finally, the impact of working memory training on quality of life and relatives' stress, and whether it is a cost-effective approach in MCI, will be assessed.

Discussion: Effective therapy for MCI is lacking. Finding an intervention postponing the progression of MCI is of great importance for patients as well as for the global economy and health care.

Trial registration: ClinicalTrials.gov NCT04792528. Registered on 02.23.2021.

Keywords: Cost-effectiveness; Mild cognitive impairment; Proxy; Quality of life; Working memory training.

Publication types

Clinical Trial Protocol

MeSH terms

Aged
Cognition*
Cognitive Dysfunction* / diagnostic imaging
Cognitive Dysfunction* / physiopathology
Cognitive Dysfunction* / psychology
Cognitive Dysfunction* / therapy
Cognitive Training
Cost-Benefit Analysis
Female
Humans
Magnetic Resonance Imaging
Male
Memory, Short-Term*
Middle Aged
Quality of Life
Randomized Controlled Trials as Topic
Time Factors
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT04792528

Abstract

Publication types

MeSH terms

Associated data

Grants and funding