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

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

doi:10.3389/fnagi.2021.624253

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

Front Aging Neurosci. 2021 Feb 15:13:624253. doi: 10.3389/fnagi.2021.624253. eCollection 2021.

Authors

Susanne S Hernes^{1

2}, Marianne M Flak^{3

4}, Gro C C Løhaugen⁴, Jon Skranes^{3

4}, Haakon R Hol^{2

5}, Bengt-Ove Madsen¹, Anne-Brita Knapskog⁶, Andreas Engvig⁷, Are Pripp⁸, Ingun Ulstein⁶, Trine Lona⁹, Xin Zhang¹⁰, Linda Chang^{10

11

12}

Affiliations

¹ Department of Geriatric and Internal Medicine, Sørlandet Hospital, Arendal, Norway.
² Department of Clinical Science, University of Bergen, Bergen, Norway.
³ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Department of Pediatrics, Sørlandet Hospital HF, Arendal, Norway.
⁵ Department of Radiology, Sørlandet Hospital HF, Arendal, Norway.
⁶ Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Oslo, Norway.
⁷ Department of Medicine, Diakonhjemmet Hospital, Oslo, Norway.
⁸ Oslo Centre of Biostatistics and Epidemiology Research Support Services, Oslo University Hospital, Oslo, Norway.
⁹ Department of Psychiatry, Age Psychiatry, The Hospital of Telemark, Skien, Norway.
¹⁰ Department of Diagnostic Radiology and Nuclear Medicine, and Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, United States.
¹¹ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
¹² Department of Medicine, John A. Burns School of Medicine, The University of Hawai'i at Mānoa, Honolulu, HI, United States.

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.

Keywords: APOE genotype; Alzheimer; LMX1A; MCI; working memory training.