Working Memory Training in Amnestic and Non-amnestic Patients With Mild Cognitive Impairment: Preliminary Findings From Genotype Variants on Training Effects.

Susanne S Hernes,Jon Skranes,Linda Chang,Xin Zhang,Andreas Engvig,Haakon R Hol,Bengt-Ove Madsen,Are Pripp,Trine Lona,Anne-Brita Knapskog,Marianne M Flak,Gro C C Løhaugen,Ingun Ulstein

doi:10.3389/fnagi.2021.624253

Abstract

Working memory training (WMT) effects may be modulated by mild cognitive impairment (MCI) subtypes, and variations in APOE-epsilon (APOE-ε) and LMX1A genotypes. Sixty-one individuals (41 men/20 women, mean age 66 years) diagnosed with MCI (31 amnestic/30 non-amnestic) and genotyped for APOE-ε and LMX1A completed 4 weeks/20–25 sessions of WMT. Cognitive functions were assessed before, 4 weeks and 16 weeks after WMT. Except for Processing Speed, the non-amnestic MCI group (naMCI) outperformed the amnestic MCI (aMCI) group in all cognitive domains across all time-points. At 4 weeks, working memory function improved in both groups (p < 0.0001), but at 16 weeks the effects only remained in the naMCI group. Better performance was found after training for the naMCI patients with LMX1A-AA genotype and for the APOE-ε4 carriers. Only the naMCI-APOE-ε4 group showed improved Executive Function at 16 weeks. WMT improved working memory and some non-trained cognitive functions in individuals with MCI. The naMCI group had greater training gain than aMCI group, especially in those with LMX1A-AA genotype and among APOE-ε4-carriers. Further research with larger sample sizes for the subgroups and longer follow-up evaluations is warranted.

Highlights

As many as 15% of individuals with mild cognitive impairment (MCI) transition into dementia (Huang et al, 2016)
We explored the modulatory effects of allelic variations in APOEε and Lim homeobox transcription factor 1 alpha (LMX1A) on the Working memory (WM) training outcomes
Blood samples were collected from 63 individuals who provided the additional consents required for the genotyping, but usable genetic data were available only from 61 of these individuals (Figure 1)

Summary

Introduction

As many as 15% of individuals with mild cognitive impairment (MCI) transition into dementia (Huang et al, 2016). Working memory (WM) deficits are often found in aging individuals, especially in those with MCI or early stages of Alzheimer’s disease (Huntley and Howard, 2010; Saunders and Summers, 2010). Randomized controlled trials indicate that computerized working memory training (WMT) may improve performance on WM tasks with similar processing demands (Simons et al, 2016). Studies on computerized cognitive training programs in MCI individuals showed mixed results, only some studies showed benefits on cognition, and the transfer effects to non-trained tasks were inconclusive (Belleville et al, 2006; Rozzini et al, 2007; Talassi et al, 2007). The heterogeneity within the MCI population, due to various underlying brain pathology or co-morbid conditions, might have contributed to the diverse findings on training effects of cognitive interventions in MCI patients

Results

Discussion

Conclusion