Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036 Graz, Austria.
Stroke. 2010 May;41(5):e402-8. doi: 10.1161/STROKEAHA.109.576629. Epub 2010 Mar 4.
The mechanisms by which leukoariosis impacts on clinical and cognitive functions are not yet fully understood. We hypothesized that ultrastructural abnormalities of the normal-appearing brain tissue (NABT) assessed by diffusion-weighted imaging played a major and independent role.
In addition to a comprehensive clinical, neuropsychologic, and imaging work-up, diffusion-weighted imaging was performed in 340 participants of the multicenter leukoariosis and disability study examining the impact of white matter hyperintensities (WMH) on 65- to 85-year old individuals without previous disability. WMH severity was rated according to the Fazekas score. Multivariate regression analysis served to assess correlations of histogram metrics of the apparent diffusion coefficient (ADC) of whole-brain tissue, NABT, and of the mean ADC of WMH with cognitive functions.
Increasing WMH scores were associated with a higher frequency of hypertension, a greater WMH volume, more brain atrophy, worse overall cognitive performance, and changes in ADC. We found strong associations between the peak height of the ADC histogram of whole-brain tissue and NABT with memory performance, executive dysfunction, and speed, which remained after adjustment for WMH lesion volume and brain atrophy and were consistent among centers. No such association was seen with the mean ADC of WMH.
Ultrastructural abnormalities of NABT increase with WMH severity and have a strong and independent effect on cognitive functions, whereas diffusion-weighted imaging metrics within WMH have no direct impact. This should be considered when defining outcome measures for trials that attempt to ameliorate the consequences of WMH progression.
白质疏松症影响临床和认知功能的机制尚不完全清楚。我们假设，通过弥散加权成像评估的正常外观脑组织（NABT）的超微结构异常起着主要和独立的作用。
除了进行全面的临床、神经心理学和影像学检查外，还对多中心白质疏松症和残疾研究中的 340 名参与者进行了弥散加权成像检查，该研究旨在检查白质高信号（WMH）对无既往残疾的 65-85 岁个体的影响。WMH 严重程度根据 Fazekas 评分进行评定。多元回归分析用于评估全脑组织、NABT 和 WMH 平均 ADC 的表观扩散系数（ADC）直方图指标与认知功能的相关性。
WMH 评分的增加与高血压的频率增加、WMH 体积增大、脑萎缩更严重、整体认知表现更差以及 ADC 变化有关。我们发现全脑组织和 NABT 的 ADC 直方图峰高与记忆功能、执行功能和速度之间存在很强的相关性，这些相关性在调整 WMH 病变体积和脑萎缩后仍然存在，并且在各中心之间是一致的。而 WMH 的平均 ADC 则没有这种相关性。
NABT 的超微结构异常随 WMH 严重程度的增加而增加，对认知功能有强烈和独立的影响，而 WMH 内的弥散加权成像指标对认知功能没有直接影响。在定义试图改善 WMH 进展后果的试验的结果衡量标准时，应考虑这一点。
