알츠하이머병 환자에서 반복 경두개자기자극치료와 인지치료의 병합치료 : 초기치료와 추가치료 효과 분석 = Treatment of Alzheimer disease (AD) using repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (CT) : Analysis of initial & booster treatment effect

다국어 초록 (Multilingual Abstract)

Background and Purposes
Repetitive transcranial magnetic stimulation (rTMS) has been examined as a potential treatment for many neurological disorders. High-frequency rTMS in particular improves cognitive functions such as verbal fluency and memory. In the previous study, we reported that rTMS combined with cognitive training (rTMS-CT) showed cognitive improvement with Alzheimer’s disease (AD), especially, in the mild stage of the disease. We analyzed the effect of initial and booster rTMS-CT in patients with AD.
Methods
A prospective, randomized, double-blind, placebo-controlled study was performed with 28 AD patients (21 patients and 7 patients in the treatment and sham groups, respectively. After 2 years, eight of the 28 patients engaged themselves in retreating the rTMS-CT. The rTMS protocols were configured for six cortical areas (both dorsolateral prefrontal and parietal somatosensory associated cortices and Broca’s and Wernicke’s areas; 10 Hz, 90–110% intensity, and 5 days/week for 6 weeks). Neuropsychological assessments were performed using the AD Assessment Scale-cognitive subscale (ADAS-cog), MMSE, clinical dementia rating (CDR), and geriatric depression scale (GDS) in the baseline, just after the rTMS-CT and 6 weeks after the second evaluation.
Results
There was no significant interactive effect of time between the groups at first treatment, although the ADAS-cog scores in the treatment group (from 23.3 at baseline to 17.9 at the end of the study) was much more improved than sham group (from 23.7 at baseline to 21.4 at the end of the study). There was significant improvement of the ADAS-cog score after the rTMS-CT treatment compared with that of the baseline ADAS-cog score in the treatment group (p=0.001). The patients who treated with rTMS-CT showed lesser cognitive decline than who belonged to the sham group (p=0.045) when 8 patients engaged in retreatment with rTMS-CT after 2 years. At the booster treatment with rTMS-CT, the 8 patients showed significant improvement compared to the baseline score (ADAS-cog changed from 25.0 to 22.8, p=0.041).
Conclusions
rTMS-CT shows significant effect on cognitive function in AD, so rTMS-CT might be useful adjuvant therapy of cholinesterase inhibitors in AD. Cognitive function in the rTMS-CT treated group retains in 2 years, so booster rTMS-CT treatment might be useful to maintain cognitive function in AD though the treatment interval has not been determined.

목차 (Table of Contents)

• . 서론 1
• II. 연구대상 및 방법 3
• 1. 연구대상 3
• 2. 연구방법 5
• 2-1. 기본설계 5
• 2-2. 뇌좌표 설정과 자극 방법 6
• 2-3. 인지훈련 8
• 2-4. 치료순서 9
• 2-5. 평가항목 9
• 3. 결과 평가 10
• 3-1. 일차 평가목표 10
• 3-2. 이차 평가목표 10
• 4. 추가치료 11
• 5. 통계방법 11
• III. 결과
• 1. 환자의 임상적 특징 12
• 2. 일차 평가목표 13
• 3. 이차 평가목표 13
• 3-1. 간이정신상태검사 13
• 3-2. 임상치매척도 14
• 3-3. 노인우울척도 14
• 3-4. 임상전반변화척도 14
• 4. 추가치료 15
• IV. 고찰 15
• V. 결론 21
• VI. 참고문헌 32
• Abstract 38