알츠하이머병 환자의 전반적 피질 위축, 내측두엽 위축, 백질 고강도 신호와 인지기능의 연관성
Association between Global Cortical Atrophy, Medial Temporal Atrophy, White Matter Hyperintensities and Cognitive Functions in Korean Alzheimer’s Disease Patients
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초록
현대 고령화 사회에서 치매 인구는 증가하는 추세이며, 이에 따라 치매의 원인과 증상, 그리고 치료에 대한 관심도가높아지고 있다. 치매의 가장 흔한 유형인 알츠하이머병(Alzheimer’s disease)은 기억력뿐 아니라 주의집중력, 언어능력,시공간능력, 계산능력과 집행기능 등 여러 인지기능의 저하가 나타나는 다양한 증상의 집합체로,1)2) 일상생활에 대한 병력 청취, 신경심리검사와 뇌영상검사 등을 통한 종합적인 평가 후 진단이 내려진다. 알츠하이머병 환자의 뇌영상검사에서 초기에 그리고 흔히발견되는 내측두엽 위축(medial temporal atrophy, 이하 MTA) 은 알츠하이머병의 민감한 진단적 표지자이며,3) 경도 인지장애(mild cognitive impairment, MCI)에서 치매로의 진행을예측하는 기능을 하기도 한다.4) 알츠하이머병 환자의 인지기능과 뇌의 변화를 조사한 과거 여러 연구에서 내측두엽 위축, 특히 해마(hippocampus)의 위축은 언어적 기억(verbal memory), 삽화적 기억(episodic memory)과 일반적 인지 상태(general cognitive status)의 저하와 연관이 있다는 일관된 결과를 보여 왔다.5-7) 또한 전반적 피질 위축(global cortical atrophy, 이하 GCA)은 인지기능 저하의 심각도와 연관이 있다는 연구 결과가 있었고,8)9) 최근에는 백질 고강도 신호(white matter hyperintensities, WMH)와 인지기능 사이의 관계에대한 연구가 이루어지고 있으나, 일부 연구에서는 시공간능력(visuospatial function), 실행능력 및 인지 처리 속도의 저하와연관이 있다는 결과를 보인 데 반해, 일부에서는 인지기능과의 연관성이 떨어진다는 등 상반된 결과들을 보이고 있다.10-12) 이렇듯 뇌에서 나타나는 퇴행성 변화의 양상에 따라 연관된 인지기능이 다를 것이며, 뇌영상검사를 통하여 치매 환자의 인지기능 중 어떤 특정 영역에서 어느 수준의 저하가 나타날 것인지를 예측하고 상호연관성을 확인하는 것은 중요한임상적 의의가 있을 것이다. 최근 화소 기반 형태계측술(voxel-based morphometry, 이하 VBM)13)이나 용적측정 자기공명영상(volumetric MRI)14)을 이용해 뇌영역과 인지기능과의 연관성을 알아보는 연구들이 진행되었으나, 보다 간편하게 이용할 수 있는 뇌자기공명영상의 시각적 평가 척도와 세부적인 인지영역별 기능 사이의 연관성에 대한 연구는 특히국내에서 부족한 상태이다. 따라서 본 연구에서는 한국 노인 인구를 대상으로 과거의연구 결과를 확인할 뿐 아니라, 임상에서 보다 용이하고 표준화된 뇌자기공명영상의 시각적 평가 척도와 치매 환자의 인지기능을 포괄적이면서도 간편하게 평가할 수 있는 Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease(이하 CERAD-K)를 이용하여, 알츠하이머병 환자의 전반적 피질 위축, 내측두엽 위축, 백질 고강도 신호와 인지영역별 기능 사이의 상관관계를 알아보고자 한다.
Abstract
Objectives : The aim of this study is to investigate the correlation between degenerative changes in brain [i.e., global cortical atrophy (GCA), medial temporal atrophy (MTA), white matter hyperintensities (WMH)] and neurocognitive dysfunction in Korean patients with Alzheimer’s disease. Methods : A total of 62 elderly subjects diagnosed with Alzheimer’s disease were included in this study. The degenerative changes in brain MRI were rated with standardized visual rating scales (GCA or global cortical atrophy, MTA or medial temporal atrophy, and Fazekas scales) and the subjects were divided into two groups according to the degree of degeneration for each scale. Cognitive function was evaluated with Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-K) and several clinical features, including apolipoprotein E ε4 status, lipid profile and thyroid hormones, were also examined. Chi-square test and Fisher’s exact test were performed to analyze the relationship between the degree of cerebral degeneration and neurocognitive functions. Results : Demographic and clinical features, except for the age, did not show any significant difference between the two groups divided according to the degree of cerebral degenerative changes. However, higher degree of GCA was shown to be associated with poorer performance in verbal fluency test, word list recall test, and word list recognition test. Higher degree of MTA was shown to be associated with poorer performance in Mini-Mental State Examination in the Korean Version of CERAD Assessment Packet (MMSE-KC), word list recognition test and construction praxis recall test. Higher degree of white matter hyperintensities was shown to be associated with poorer performance in MMSE-KC. Conclusions : Our results suggest that severe brain degeneration shown in MRI is associated with significantly poorer performance in neurocognitive tests in patients with Alzheimer’s disease. Moreover, the degree of GCA, MTA and white matter hyperintensities, represented by scores from different visual rating scales, seems to affect certain neurocognitive domains each, which would provide useful information in clinical settings.
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