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

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

이동영|박지은|박진식|박선영|채수현
대한수면의학회 (Korean Academy of Sleep Medicine)|2021.12|수면정신생리 (Sleep Medicine and Psychophysiology)|제28권 제2호|pp. 78-85|DOI 10.14401/KASMED.2021.28.2.78

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참고문헌

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노인Depression우울증Alzheimer’s disease알츠하이머병Aged뇌파Electroencephalography
주제분류정신과학

초록

목 적:노년기 우울증 환자에서 우울증상이 알츠하이머병 의 전구 증상으로 나타났는지를 감별하는 것은 중요한 임상 적 과제이다. 본 연구에서는 정량화 뇌파(quantitative EEG) 지표가 노년기 우울증 환자의 알츠하이머병 병리를 예측할 수 있는 바이오마커로 기능할 수 있는지 확인하고자 하였다. 방 법:치매로진단받지않은55세이상의우울증환자 63명이 본 연구에 포함되었다(여성 76.2%; 평균 연령 ± 표 준편차 73.7 ± 6.87세). 연구 대상자들은 [18F] florbetaben PET 결과에 따라 아밀로이드 양성(Aβ+, n = 32)과 음성으 로(Aβ-, n = 31) 분류하였다. 뇌파는 7분 간의 눈을 감은 상 태(eye-closed, EC)와 3분 간의 눈을 뜬 상태(eye-open, EO) 로 촬영하였으며, 푸리에 변환(Fourier transform)을 이용하 여 스펙트럼 분석을 시행하였다. 선행연구 결과에 따라 안구 개폐 알파파 반응성 지표(EC-to-EO alpha reactivity in- dex)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 개 폐 조건(EC vs. EO), 지형학적 요인(laterality, polarity) 간 의 상호작용을 확인하고 사후 분석을 시행하였다. 결 과:Aβ+군과 Aβ-군에서 각 주파수 밴드의 평균 파 워 스펙트럼 밀도 중 EO phase의 알파 밴드 파워에서만 유 의미한 차이가 관찰되었다(F = 6.258, p = 0.015). 알파 밴드 에서의 Group (Aβ+ vs. Aβ-) × Condition (EC vs. EO) × Laterality (Left, midline, or right) 3-way interaction이 연 령, 성별, 교육 연수, 전반적 인지 기능, 약물 사용, MRI상 백 질 고신호강도를 보정한 뒤에도 유의하였다(F = 3.720, p = 0.030). 하지만 대뇌 관심영역 별로 아밀로이드 침착에 따른 알파파 반응성을 비교한 사후 분석에서는 유의한 수준의 차 이가 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 반응성지표 는 알츠하이머병 병리를 예측하지는 못했다. 보다 많은 대상 자를 포함한 추후 연구로 해당 결과를 재검증할 필요가 있다.

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 associ- ated 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 posi- tivity, 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.

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