Journal List > Dement Neurocogn Disord > v.18(2) > 1128674

Dement Neurocogn Disord. 2019 Jun;18(2):62-68. English.
Published online Jul 03, 2019.  https://doi.org/10.12779/dnd.2019.18.2.62
© 2019 Korean Dementia Association
Effect of Paper-Based Cognitive Training in Early Stage of Alzheimer's Dementia
Min Ju Kang,1 So Min Kim,2 Seo Eun Han,2 Ji Hyun Bae,2 Woo Jin Yu,2 Min Young Park,2 Seongsu Ku,2 and YoungSoon Yang1
1Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Korea.
2Hanam City Public Health Center, Hanam, Korea.

Correspondence to YoungSoon Yang. Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, 53 Jinhwangdo-ro 61-gil, Gangdong-gu, Seoul 05368, Korea. Email: astro76@naver.com
Received Jun 10, 2019; Revised Jun 19, 2019; Accepted Jun 21, 2019.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract

Background and Purpose

Cognitive training refers to a series of standardized tasks with inherent challenges that target specific cognitive domains. Positive outcome of cognitive training in persons with Alzheimer's disease has been reported. In this study, the objective was to design sets of cognitive training program, “Gipum-seo” which is combined cognitive training, consists of different levels of difficulty using predesigned paper-and-pencil exercises. Also, to evaluate the effects of the cognitive training on patients' with early stage of Alzheimer's disease.

Methods

The subjects for this study were forty participants who were diagnosed with early stage of Alzheimer's dementia. To test the efficacy of paper-based cognitive training programs to cognition, all patients were randomly grouped to either an intervention group (n=20) or a control group (n=20). The intervention group regularly received 24 sessions of paper-based cognitive training over a 12-week period. Neuropsychological examinations were conducted before and after this training period.

Results

After the 12 weeks, the intervention group showed a significant change in Korean version of the Mini-Mental State Examination (25.90±3.8), compared to the control group (23.7±2.8) (p=0.042). The training group also showed a significant improvement in language, attention and executive function, as compared with controls.

Conclusions

Paper-based cognitive training might have beneficial effects on the general cognitive functions in the early stage of Alzheimer's dementia.

Keywords: Alzheimer's Disease; Cognitive Behavioral Therapy; Cognition; Neurocognitive Disorders; Neuropsychological Test

INTRODUCTION

Alzheimer's disease (AD) is the most common neurodegenerative disease, which leads to deterioration of cognitive function, functional abilities needed for independent living.1 The overall number of persons with AD is increasing, representing a major public health challenge.2 It is therefore necessary to develop pharmacological and/or non-pharmacological treatments to delay or halt the cognitive and functional decline associated with the diseases. Unfortunately, current pharmacological therapies such as acetylcholinesterase inhibitor have limited efficacy in the prevention of the disease progression.3, 4 Nonpharmacological approaches, such as cognitive training, cognitive stimulation, and cognitive rehabilitation have been studied as potential strategies for prevention and treatment of AD.5 Among various approaches, cognitive training is the most effective approach as compared to cognitive stimulation and cognitive rehabilitation in patients with mild cognitive impairment (MCI) or early AD.6 Cognitive training refers to a series of standardized tasks with inherent challenges that target specific cognitive domains,5, 7 and is based on the principles of neuroplasticity and restoration of cognitive abilities.8, 9 Primary objective of cognitive training is to enhance or at least maintain function in a given cognitive domain.

Accumulating evidence indicate that cognitive training could benefit patients with early AD. Recent systemic analysis reported positive effect of cognitive training among 31 randomized controlled trials in patients with mild and moderate AD.10 The pattern of effects of cognitive training was inconsistent across the studies; positive effects were mostly observed in a single global or a few training. Other small-scaled studies also reported positive effects in separate cognitive domains such as working memory and executive function.11, 12

A traditional cognitive training requires a face-to-face interaction and teaching of new learning strategies using paper-and-pencil approach.10 Computer-based cognitive training programs which are relatively easy to access are also being widely developed and applied.11, 13 However, it is challenging to equip all institutions with the electronic devices for computer-based training. Also, using electronic devices may be hard for elderly and requires special guidance. A recent study by Tsolaki et al.14 reported that both computer-based and paper-based cognitive training (PBCT) are beneficial in MCI patients, however, traditional PBCT had better results in general cognitive function, learning ability, delayed verbal recall, visual memory, verbal fluency and visual selective attention and it also transfers the primary cognitive benefit in real life.

This study designed sets of cognitive training program, “Gipum-seo,” on subskills of memory, language, attention, visuospatial function and calculation, which consists of different levels of difficulty using predesigned paper-and-pencil exercises. The program is offered over 3 months in community-dwelling older persons with mild AD. The main goal was to clarify the effects of the cognitive training on patients' cognitive functioning.

METHODS

Study subjects

Patients with memory deterioration who had visited the Veteran Health Service Medical Center, from January 2015 to October 2016, were selected for this study. Patients were diagnosed with Alzheimer dementia, based on the criteria of the National Institute of Neurologic and Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association standard15; patients with mild (early-stage) symptom [Clinical Dementia Rating Scale16 (CDR) or 0.5 or 1] were enrolled for the study. The dosage of medication for all the selected patients remained unchanged for 3 months. Exclusion criteria were: 1) Brain tumor or encephalitis; 2) Mental illnesses, based on the Diagnostic and Statistical Manual of Mental Disorders criteria, within 2 years before the start of the study; 3) Severe depression (Hamilton Depression Rating Scale score >18); 4) Parkinson's disease, Huntington's disease, or any other neurological disorders of normal pressure hydrocephalus; 5) Cases of medical diseases (liver disease, kidney disease, thyroid disease) that cause other cognitive function decline; 6) Patients with alcohol or drug addiction history within 2 years before the start of the study; 7) A physical disability, that may hinder the completion of a cognitive training program. All patients underwent basic demographic investigation and screening tests using the Korean version of the Mini-Mental State Examination (K-MMSE).17 The severity of Alzheimer's disease of patient was assessed based on the CDR.

Study design

All subjects underwent physical and neurological examinations. All patients conducted neuropsychological test and brain MRI at baseline. A total of 40 patients with early AD were enrolled at the Veteran Health Service Medical Center. The subjects were randomly assigned to either attend the PBCT (20 patients) or in the control group where they received the usual standard clinical care (20 patients). After 12 weeks, a set of PBCT were conducted, and the neuropsychological test was repeated within two weeks of completion. This study was approved by the Medical Research Ethics Committee of the Veteran Health Service Medical Center.

PBCT

The cognitive training program is a step-by-step customized PBCT, which covers a visuospatial, language, attention, memory and calculation. The primary aim of this program was to improve global cognitive function by combined training of subdomains. Each chapter of training entailed 10 to 20 tasks and focused on training of single domain. Skilled occupational therapist was providing the subjects with appropriate instructions of the program in each session. The intervention was carried out at the dementia center of Veteran Health Service Medical Center and performed twice a week (60 minutes per session), for 12 weeks.

Neuropsychological test

The Seoul Neuropsychological Screening Battery was conducted for the neuropsychological assessment of each cognitive function area of the patient.18 For each cognitive domain, concentration ability was investigated using the ‘forward and backward’ of the digit span, language ability was investigated using the Korean version of the Boston Naming Test (K-BNT)19 and spatio-temporal ability was investigated using the tracing drawings score of the Rey Complex Figure test (RCFT).20 Verbal memory and visual memory were assessed using immediate recall scores (total score of 3 trials), delayed recall scores, and recognition test scores of each Seoul Verbal Learning Test (SVLT)18 and RCFT.20 For executive function examination, sum of two (animal and market) semantic word fluency scores and sum of the three (ㄱ, ㅇ, ㅅ) phonemic word fluency score of Controlled Oral Word Association Test,21 and word/color reading score of the Korean-Color Word Stroop Test were used.22 Neuropsychological test was performed before the 12-week of PBCT, and follow-up test was performed 13 to 14 weeks after the baseline examination to confirm immediate effects of PBCT.

Statistical analysis method

All statistical analyses were done using SPSS 18.0 (IBM Corp., Armonk, NY, USA) with the 2-tailed test, with the level of significance 0.05. Mann-Whitney U test was used for the analysis of means for continuous variables. The percentage comparison of categorical data was performed using the chi-square test. Efficacy assessment was based on a pre/post comparison of the evaluations carried out at the baseline, and at 12 weeks. For this test, repeated measure of general linear model was used.

RESULTS

Demographic analysis

No significant difference was observed based on age, sex, education and training, and clinical dementia stage between the experimental and control groups. Also, no significant difference was observed between the groups in terms of K-MMSE, CDR, and Geriatric Depression Scale (Table 1).


Table 1
Demographic data comparing PBCT (−) patients and PBCT (+) patients (mean±standard deviation)
Click for larger imageClick for full tableDownload as Excel file

Overall cognitive assessment

The K-MMSE score showed a significant improvement in the paper-based cognitive program group (25.90±3.8) as compared to the control group (23.7±2.8) (p=0.042). The CDR scores of the computer-based cognitive program group significantly reduced to 0.9±3.9, compared with 0.55±0.5 of the baseline test (p=0.034). Neuropsychological tests also showed significant improvements in various areas as compared to control groups. Digit forward span was 3.60±1.2 and 4.40±1.2, for before and after PBCT, respectively. In addition, digit backward span was 2.60±0.6 and 3.90±1.6, for before and after PBCT, respectively. In the ‘go-no-go’ test, the PBCT group results were 11.80±4.5 and 16.69±4.7, for before and after PBCT, respectively. The K-BNT was 43.20±7.3 and 49.00±6.5 (p=0.043), for before and after the PBCT, and showed significant improvement in PBCT group. The results of the PBCT group for the stroop test showed significant improvement in word reading (102.60±10.7 and 108.80±8.9). No significant change was observed in both verbal and visuospatial memory between two groups (Table 2). Significant improvement in language, attention, and executive function of the PBCT group compared to the control was observed.


Table 2
Comparison of neuropsychological tests between PBCT (−) patients and PBCT (+) patients, at baseline and after 12 weeks follow up (mean±standard deviation)
Click for larger imageClick for full tableDownload as Excel file

DISCUSSION

The present study provided evidence that traditional PBCT improves cognitive functions in various areas. Specifically, this study's results showed that cognitive training had a significant impact on language, attention and executive function. Considering the limited pharmacological therapies available for AD, concurrent cognitive training may be an alternative treatment option due to simple and easy accessibility.

Previous studies reported notable improvement in global cognitive function, visuospatial abilities,23 and executive function11 after intervention by cognitive training. A positive result was often observed in global cognition, and was rarely observed in separate cognitive domains.10 Since global cognitive measures such as MMSE briefly reflects several cognitive functions, common improvement in different cognitive domains after cognitive training may be expected. Although number of previous studies reported beneficial effect of cognitive training for memory function,24 this study did not show tendency of positive effect but there was no significant difference. It is probably because this cognitive training program was not designed as combined cognitive training rather than memory strategy training. A previous study that compared combined cognitive training and pure memory training found combined cognitive training to be less efficient in memory outcome.25 Systemic review of cognitive training showed that studies with more intensive or specific cognitive training programs tend to show better efficacy.10

There are a number of limitations of this present study. First, the training duration was too short to confirm the effect of cognitive training program. Second, the follow-up period was relatively short, and longer follow-up period would be necessary for more robust and accurate results. Third, the study lacked analysis for additional confounders, such as APOE ε4 status, or medical condition of the participants which may affect the neuropsychological performance in AD patient. Finally, the sample size was small, and study with larger number of participants may be needed.

This study evaluated the effects of a PBCT, and the results indicated significant improvement in both global cognitive test and on language, attention and executive domain in the training group. The PBCT can be applied in community care facilities or home-basis, and this study result showed promising result in developing training methods to delay cognitive decline in early-stage AD patients. A further study applied in larger cohort with intensified modality is necessary in the future.

Notes

Conflicts of Interest:The authors have no financial conflicts of interest.

Author Contributions:

  • Conceptualization: Yang Y.

  • Data curation: Kang MJ, Kim SM.

  • Formal analysis: Kang MJ.

  • Investigation: Kang MJ, Han SE.

  • Project administration: Park MY.

  • Resources: Bae JH, Yu WJ, Ku S.

  • Software: Kang MJ.

  • Supervision: Yang Y.

  • Writing - original draft: Kang MJ.

  • Writing - review & editing: Kang MJ, Yang Y.

References
1. Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet 2017;390:2673–2734.
2. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 2013;9:63–75.e2.
3. Karakaya T, Fußer F, Schröder J, Pantel J. Pharmacological treatment of mild cognitive impairment as a prodromal syndrome of Alzheimer's disease. Curr Neuropharmacol 2013;11:102–108.
4. Muayqil T, Camicioli R. Systematic review and meta-analysis of combination therapy with cholinesterase inhibitors and memantine in Alzheimer's disease and other dementias. Dement Geriatr Cogn Dis Extra 2012;2:546–572.
5. Buschert V, Bokde AL, Hampel H. Cognitive intervention in Alzheimer disease. Nat Rev Neurol 2010;6:508–517.
6. García-Casal JA, Loizeau A, Csipke E, Franco-Martín M, Perea-Bartolomé MV, Orrell M. Computer-based cognitive interventions for people living with dementia: a systematic literature review and meta-analysis. Aging Ment Health 2017;21:454–467.
7. Clare L, Woods RT, Moniz Cook ED, Orrell M, Spector A. Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia. Cochrane Database Syst Rev 2003:CD003260
8. Belleville S, Clément F, Mellah S, Gilbert B, Fontaine F, Gauthier S. Training-related brain plasticity in subjects at risk of developing Alzheimer's disease. Brain 2011;134:1623–1634.
9. Spironelli C, Bergamaschi S, Mondini S, Villani D, Angrilli A. Functional plasticity in Alzheimer's disease: effect of cognitive training on language-related ERP components. Neuropsychologia 2013;51:1638–1648.
10. Kallio EL, Öhman H, Kautiainen H, Hietanen M, Pitkälä K. Cognitive training interventions for patients with Alzheimer's disease: a systematic review. J Alzheimers Dis 2017;56:1349–1372.
11. Yang Y, Kwak YT. Improvement of cognitive function after computer-based cognitive training in early stage of Alzheimer's dementia. Dement Neurocogn Disord 2017;16:7–11.
12. Jelcic N, Cagnin A, Meneghello F, Turolla A, Ermani M, Dam M. Effects of lexical-semantic treatment on memory in early Alzheimer disease: an observer-blinded randomized controlled trial. Neurorehabil Neural Repair 2012;26:949–956.
13. Shao YK, Mang J, Li PL, Wang J, Deng T, Xu ZX. Computer-based cognitive programs for improvement of memory, processing speed and executive function during age-related cognitive decline: a meta-analysis. PLoS One 2015;10:e0130831
14. Tsolaki M, Poptsi E, Aggogiatou C, Markou N, Zafeiropoulos S, Kounti F. Computer-based cognitive training versus paper and pencil training: which is more effective? A randomized controlled trial in people with mild cognitive impairment. JSM Alzheimers Dis Relat Dement 2017;4:1032.
15. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939–944.
16. Morris JC. Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psychogeriatr 1997;9 Suppl 1:173–176.
17. Han C, Jo SA, Jo I, Kim E, Park MH, Kang Y. An adaptation of the Korean mini-mental state examination (K-MMSE) in elderly Koreans: demographic influence and population-based norms (the AGE study). Arch Gerontol Geriatr 2008;47:302–310.
18. Kang YW, Na DL. In: Seoul Neuropsychological Screening Battery. Seoul: Human Brain Research & Consulting Co.; 2003.
19. Kim H, Na DL. Normative data on the Korean version of the Boston Naming Test. J Clin Exp Neuropsychol 1999;21:127–133.
20. Fastenau PS, Denburg NL, Hufford BJ. Adult norms for the Rey-Osterrieth Complex Figure Test and for supplemental recognition and matching trials from the Extended Complex Figure Test. Clin Neuropsychol 1999;13:30–47.
21. Kang YW, Chin JH, Na DL, Lee JH, Park JS. A normative study of the Korean version of Controlled Oral Word Association Test (COWAT) in elderly. Korean J Clin Psychol 2000;19:385–392.
22. Lee JH, Kang YW, Na DL. Efficiencies of stroop interference indexes in healthy older adults and dementia patients. Korean J Clin Psychol 2000;19:807–818.
23. Hwang HR, Choi SH, Yoon DH, Yoon BN, Suh YJ, Lee D, et al. The effect of cognitive training in patients with mild cognitive impairment and early Alzheimer’s disease: a preliminary study. J Clin Neurol 2012;8:190–197.
24. Cavallo M, Hunter EM, van der Hiele K, Angilletta C. Computerized structured cognitive training in patients affected by early-stage Alzheimer's disease is feasible and effective: a randomized controlled study. Arch Clin Neuropsychol. 2016
25. Li B, Zhu X, Hou J, Chen T, Wang P, Li J. Combined cognitive training vs. memory strategy training in healthy older adults. Front Psychol 2016;7:834.