台灣老年人視網膜血管碎形維度與認知功能相關性研究

Abstract

研究背景：在認知功能異常，包含輕度認知功能障礙及失智症的病理機轉中，腦部血管因素的角色愈趨重要。因為生理及結構上的相似性，視網膜血管的型態可以反映腦部血管的狀態。視網膜血管碎形維度是視網膜血管的複雜程度的指標，代表著視網膜血管的整體狀態。視網膜的血管型態是否可以因為反映了腦部的血管狀態而和認知功能有關係缺乏一致性、長期追蹤的證據。本研究即為探討在社區老人之中，視網膜血管碎形維度和認知功能異常的關係。 研究方法：本研究為台灣老年流行病學研究世代追蹤的一部份（2011年迄今），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，並於四年追蹤（2015-2017）時完成眼睛的眼底照相，收集四年及六年追蹤（2017-2019）時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。 本研究將視網膜血管碎形維度分作連續變項及三切後以最小三分之一與否這兩種形式納入回歸分析。認知功能首先以六年及四年追蹤時的分數差做線性迴歸分析；再以兩年的追蹤後下降與否做羅吉斯回歸分析。經調整重要的變數之後，探討視網膜血管碎形維度與認知功能之間的相關性。 研究結果：總共有177位受試者納入分析。其中右眼視網膜血管碎形維度較低的三分之一者，和其他三分之二相比，邏輯記憶測試-主題二在追蹤兩年後下降的機會顯著上升（勝算比=2.35, 95%信賴區間=1.09-5.04）。右眼視網膜血管碎形維度每下降0.1單位，兩年後邏輯記憶測試-回憶一下降的機會顯著上升（勝算比=2.76, 95%信賴區間=1.03-7.38）。而左眼視網膜血管碎形維度較低的三分之一者，和其他三分之二相比，執行功能（路徑描繪測驗A）在追蹤兩年後下降的機會顯著上升（勝算比=2.87, 95%信賴區間= 1.24-6.65）。 結論：視網膜血管碎形維度可能可以做為認知功能異常臨床前期的早期指標。

Background: Cerebral vascular factor plays an important role in the pathogenesis of cognitive dysfunction, including mild cognitive impairment (MCI) and dementia. The small retinal vessels reflect cerebral microcirculation and its fractal dimension (Df) representing the complexity of the retinal microcirculation. However, the connection between the retinal circulation and cognitive function lacked consistent and longitudinal evidence. This study aimed to explore the association between the retinal vascular Df and cognitive dysfunction in the community-dwelling older adults. Materials and methods: This study is part of the prospective cohort “Taiwan Initiative for Geriatric Epidemiological Research” (TIGER, 2011 to present). Participants from the 4-year (2015–2017) and 6-year (2017-2019) follow-ups were included. All participants were aged ≥ 65 years old at baseline and received retinal fundus examination at 4-year follow-up. We segmented the retinal vessels by Coyefilter of MATLAB from fundus photography. Skeletonization and fractal analyses of the segmented images were then performed by ImageJ. Cognition assessment, including global cognition (Montreal Cognitive Assessment-Taiwanese version, MoCA-T) and domain-specific cognition were performed at 4- and 6- year follow-up. Multivariable linear regression models were used to estimate the association of global or domain-specific cognitive function change from 4- to 6-year follow up with relative low Df (T1) compared with those with higher Df (T2+T3) and by every 0.1 unit decrement of retinal vascular Df. Multivariable logistic regression analyses were performed to estimate the risk of decline in global or domain-specific cognitive function for eyes with low Df (the lowest tertile, T1) compared with those with higher Df (T2+T3) and by every 0.1 unit decrement of retinal vascular Df over 2 years. Results: A total of 177 participants were included. Participants with low right vascular complexity were associated with decline of logical memory theme-II over 2 years [odds ratio (OR)=2.35, 95% confidence interval (CI)=1.09-5.04], compared with participants with higher right vascular complexity (T1 vs. T2+T3 of Df). A 0.1 unit decrease of right vascular Df was associated with the decline of logical memory recall-I over 2 years (OR=2.76, 95% CI=1.03-7.38). For left eye, lower vascular complexity was associated with significant decline of executive function (Trail making test A) over 2 years (OR=2.87, 95% CI= 1.24-6.65). Conclusion: Retinal vascular fractal dimension may be used for screening cognitive decline in the preclinical stage.