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Quantitative Electroencephalogram Markers for Predicting Cerebral Amyloid Pathology in Non-Demented Older Individuals With Depression: A Preliminary Study

비치매 노인 우울증 환자에서 대뇌 아밀로이드 병리 예측을 위한 정량화 뇌파 지표: 예비연구

  • Park, Seon Young (Department of Neuropsychiatry, Seoul National University Hospital) ;
  • Chae, Soohyun (Department of Psychiatry, Seoul National University College of Medicine) ;
  • Park, Jinsick (Department of Research Planning, Mental Health Research Institute, National Center for Mental Health) ;
  • Lee, Dong Young (Department of Neuropsychiatry, Seoul National University Hospital) ;
  • Park, Jee Eun (Department of Neuropsychiatry, Seoul National University Hospital)
  • 박선영 (서울대학교병원 정신건강의학과) ;
  • 채수현 (서울대학교 의과대학 정신과학교실) ;
  • 박진식 (국립정신건강센터 정신건강연구소 연구기획과) ;
  • 이동영 (서울대학교병원 정신건강의학과) ;
  • 박지은 (서울대학교병원 정신건강의학과)
  • Received : 2021.10.28
  • Accepted : 2021.11.15
  • Published : 2021.12.31

Abstract

Objectives: When elderly patients show depressive symptoms, discrimination between depressive disorder and prodromal phase of Alzheimer's disease is important. We tested whether a quantitative electroencephalogram (qEEG) marker was associated with cerebral amyloid-β (Aβ) deposition in older adults with depression. Methods: Non-demented older individuals (≥ 55years) diagnosed with depression were included in the analyses (n = 63; 76.2% female; mean age ± standard deviation 73.7 ± 6.87 years). The participants were divided into Aβ+ (n = 32) and Aβ- (n = 31) groups based on amyloid PET assessment. EEG was recorded during the 7min eye-closed (EC) phase and 3min eye-open (EO) phase, and all EEG data were analyzed using Fourier transform spectral analysis. We tested interaction effects among Aβ positivity, condition (EC vs. EO), laterality (left, midline, or right), and polarity (frontal, central, or posterior) for EEG alpha band power. Then, the EC-to-EO alpha reactivity index (ARI) was examined as a neurophysiological marker for predicting Aβ+ in depressed older adults. Results: The mean power spectral density of the alpha band in EO phase showed a significant difference between the Aβ+ and Aβ- groups (F = 6.258, p = 0.015). A significant 3-way interaction was observed among Aβ positivity, condition, and laterality on alpha-band power after adjusting for age, sex, educational years, global cognitive function, medication use, and white matter hyperintensities on MRI (F = 3.720, p = 0.030). However, post-hoc analyses showed no significant difference in ARI according to Aβ status in any regions of interest. Conclusion: Among older adults with depression, increased power in EO phase alpha band was associated with Aβ positivity. However, EC-to-EO ARI was not confirmed as a predictor for Aβ+ in depressed older individuals. Future studies with larger samples are needed to confirm our results.

목 적 : 노년기 우울증 환자에서 우울증상이 알츠하이머병의 전구 증상으로 나타났는지를 감별하는 것은 중요한 임상적 과제이다. 본 연구에서는 정량화 뇌파(quantitative EEG) 지표가 노년기 우울증 환자의 알츠하이머병 병리를 예측할 수 있는 바이오마커로 기능할 수 있는지 확인하고자 하였다. 방 법 : 치매로 진단 받지 않은 55세 이상의 우울증 환자 63명이 본 연구에 포함되었다(여성 76.2%; 평균 연령 ± 표준편차 73.7 ± 6.87세). 연구 대상자들은 [18F] florbetabenPET 결과에 따라 아밀로이드 양성(Aβ+, n = 32)과 음성으로(Aβ-, n = 31) 분류하였다. 뇌파는 7분 간의 눈을 감은 상태(eye-closed, EC)와 3분 간의 눈을 뜬 상태(eye-open, EO)로 촬영하였으며, 푸리에 변환(Fourier transform)을 이용하여 스펙트럼 분석을 시행하였다. 선행연구 결과에 따라 안구 개폐 알파파 반응성 지표(EC-to-EO alpha reactivity index)가 노년기 우울증 환자의 아밀로이드 침착을 예측할 수 있는 신경생리학적 마커가 될 수 있는지 검증하였다. 알파 밴드 파워에서 아밀로이드 침착 여부(Aβ+ vs. Aβ-), 안구 개폐 조건(EC vs. EO), 지형학적 요인(laterality, polarity) 간의 상호작용을 확인하고 사후 분석을 시행하였다. 결 과 : Aβ+군과 Aβ-군에서 각 주파수 밴드의 평균 파워 스펙트럼 밀도 중 EO phase의 알파 밴드 파워에서만 유의미한 차이가 관찰되었다(F = 6.258, p = 0.015). 알파 밴드에서의 Group (Aβ+ vs. Aβ-) × Condition (EC vs. EO) × Laterality (Left, midline, or right) 3-way interaction이 연령, 성별, 교육 연수, 전반적 인지 기능, 약물 사용, MRI상 백질 고신호강도를 보정한 뒤에도 유의하였다(F = 3.720, p = 0.030). 하지만 대뇌 관심영역 별로 아밀로이드 침착에 따른 알파파 반응성을 비교한 사후 분석에서는 유의한 수준의 차이가 관찰되지 않았다. 결 론 : 노년기 우울증 환자에서 EO phase의 알파 밴드 파워 증가가 대뇌 아밀로이드 침착과 관련이 있었다. 하지만 본 연구에서 검증하고자 했던 안구개폐 알파파 반응성 지표는 알츠하이머병 병리를 예측하지는 못했다. 보다 많은 대상자를 포함한 추후 연구로 해당 결과를 재검증할 필요가 있다.

Keywords

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