以光學共軛斷層掃描測量之視網膜生物標記與老年人認知功能之關聯性研究

Abstract

研究背景: 視網膜是中樞神經系統的延伸，視網膜的變化被認為可以反映阿茲海默氏症的神經退化狀況。光學共軛斷層掃描是一項快速且非侵入性的檢查，藉由測量視神經纖維層厚度及節細胞-內網狀層厚度，可用來評估視網膜節細胞的狀況。而在阿茲海默氏症患者及輕度認知功能缺損者，已有研究發現其視神經纖維層及節細胞-內網狀層厚度均較年齡相符之對照組有變薄的情況。因此，這些以光學共軛斷層掃描測量之視網膜生物標記被認為有潛力可應用在未來阿茲海默氏症之早期偵測上。然而，過去並沒有研究探討老年人其詳細的認知功能和視神經纖維層及節細胞-內網狀層厚度之間的相關性。 研究方法：本研究為橫斷性研究，收案對象為參加台大醫院年度老人健檢、年齡65歲以上之老年人，所有受試者均完成眼睛的光學共軛斷層掃描測量，及詳細的認知功能評估，包括整體認知功能評估(使用台灣版蒙特利爾認知評估)及不同認知領域之功能的評估。本研究使用回歸分析探討經調整重要的變數之後，視神經纖維層及節細胞-內網狀層厚度與認知功能之間的相關性。 研究結果：總共有191位受試者納入分析。雙眼平均節細胞-內網狀層厚度與整體認知功能 (台灣版蒙特利爾認知評估分數)有顯著的非線性關係 (二次項：β=-0.006, 95%信賴區間: -0.009, -0.002)，並且在記憶領域的認知功能也有類似的發現。進一步說明，雙眼平均節細胞-內網狀層厚度越偏離平均值(77.4μm)，無論是變少或變多，整體認知功能及記憶領域之認知功能都可觀察到有較差的趨勢。相對地，本研究並沒有觀察到視神經纖維層厚度與認知功能有顯著的相關性。 結論：在老年人，以光學共軛斷層掃描測量之視網膜節細胞-內網狀層厚度與認知功能有相關性。視網膜節細胞-內網狀層厚度可能可以作為老年人認知功能缺損之早期生物標記。

Background: Retina is regarded as the extension of central nervous system and can reflect the neurodegeneration in Alzheimer’s disease (AD). Optical coherence tomography (OCT) is a quick and non-invasive tool to evaluate the in vivo condition of retinal ganglion cell (RGC) by measuring retinal nerve fiber layer thickness (RNFL) and ganglion cell – inner plexiform layer thickness (GC-IPL). Thinning of RNFL and GC-IPL have been found in AD and mild cognitive impairment (MCI), a preclinical status of AD. Hence it is thought that these retinal biomarkers have a potential in future application of early detection for AD. However, the association between detailed cognitive function and RNFL / GC-IPL in the elderly has not been investigated. Materials and methods: This is a cross-sectional study which recruited community-dwelling elders (≧65 years old) from the annual Elderly Health Checkup at National Taiwan University Hospital. All participants received OCT measurement and detailed cognition assessment, including global cognition (Montreal Cognitive Assessment-Taiwanese version, MoCA-T) and domain-specific cognition. The association between RNFL / GC-IPL and global / domain-specific cognition was investigated by means of regression analyses adjusted for important covariates. Results: A total of 191 participants were included. Mean GC-IPL of bilateral eyes was non-linearly associated with global cognition (i.e., MoCA-T) [quadratic: β=-0.006, 95% confidence interval (CI): -0.009, -0.002]. Similar association was also observed in memory domain cognition. Clearly speaking, global cognition and memory domain decreased as mean GC-IPL of bilateral eyes deviated from the mean value in our population (77.4μm). In contrast, no significant association was observed between mean RNFL of bilateral eyes and cognition in our study. Conclusion: OCT-measured GC-IPL was associated with cognition in elders, indicating that GC-IPL might be an early biomarker for cognitive impairment.