Ng Yi Lin, Tan Chuen Seng, Egle Marco, Gyanwali Bibek, Tozer Daniel J, Markus Hugh S, Chen Christopher, Hilal Saima
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Department of Clinical Neurosciences, Stroke Research Group, University of Cambridge, Cambridge, United Kingdom.
Cereb Circ Cogn Behav. 2023 Jul 5;5:100174. doi: 10.1016/j.cccb.2023.100174. eCollection 2023.
Median and peak height of fractional anisotropy (FA) and mean diffusivity (MD) are diffusion tensor imaging (DTI) markers used to quantify white matter microstructure changes. We examine the association of DTI histogram-derived measures in global normal appearing white matter (NAWM) and cognitive decline in patients with normal cognition and cognitive impairment no dementia from a memory clinic in Singapore.
A total of 252 patients (mean age: 71.1 ± 7.6 years, 53.2% women) were included. All patients underwent clinical assessments, a brain MRI scan at baseline, and neuropsychological assessments annually for 2 years. DTI scans were processed to obtain MD and FA histogram-derived measures. The National Institute of Neurological Disorders and Stroke and the Canadian Stroke Network harmonization neuropsychological battery were used to assess cognitive function. Linear regression models with generalised estimating equation (GEE) and logistic regression models were used to examine the association between DTI histogram measures and cognitive decline.
When compared to baseline, MD and FA measures at Year 2 were associated with an accelerated worsening in global cognition (all for interaction <0.001; Year 0 vs 2, MD median: -0.29 (95%CI: -0.49, -0.09) vs -0.45 (95%CI: -0.65,-0.25); MD peak height: 0.22 (95%CI: 0.07, 0.37) vs 0.37 (95%CI: 0.21, 0.53); FA median: 0.11 (95%CI: -0.05, 0.26) vs 0.22 (95%CI: 0.07, 0.37); FA peak height: -0.14 (95%CI: -0.28, 0.00) vs -0.24 (95%CI: -0.38, -0.10);). Similar findings were observed for executive function and visuomotor speed while only MD measures predicted worsening in memory domain.
This study shows that DTI histogram measures are associated with accelerated cognitive decline suggesting the utility of DTI as a pre-clinical marker in predicting the worsening of cognition in clinical trials.
分数各向异性（FA）和平均扩散率（MD）的中位数及峰值高度是用于量化白质微观结构变化的扩散张量成像（DTI）标记物。我们在新加坡一家记忆诊所中，研究了DTI直方图衍生指标与认知正常和认知障碍但无痴呆患者的全脑正常表现白质（NAWM）及认知衰退之间的关联。
共纳入252例患者（平均年龄：71.1±7.6岁，53.2%为女性）。所有患者均接受临床评估、基线脑MRI扫描，并在2年中每年进行神经心理学评估。对DTI扫描进行处理以获得MD和FA直方图衍生指标。使用美国国立神经疾病和中风研究所及加拿大中风网络协调神经心理学成套测验来评估认知功能。采用广义估计方程（GEE）的线性回归模型和逻辑回归模型来研究DTI直方图指标与认知衰退之间的关联。
与基线相比，第2年时MD和FA指标与全脑认知加速恶化相关（所有交互作用P<0.001；第0年与第2年相比，MD中位数：-0.29（95%CI：-0.49，-0.09）对-0.45（95%CI：-0.65，-0.25）；MD峰值高度：0.22（95%CI：0.07，0.37）对0.37（95%CI：0.21，0.53）；FA中位数：0.11（95%CI：-0.05，0.26）对0.22（95%CI：0.07，0.37）；FA峰值高度：-0.14（95%CI：-0.28，0.00）对-0.24（95%CI：-0.38，-0.10））。执行功能和视觉运动速度方面也观察到类似结果，而只有MD指标可预测记忆领域的恶化。
本研究表明，DTI直方图指标与认知加速衰退相关，提示DTI作为一种临床前标记物在预测临床试验中认知恶化方面具有实用性。
