From Sunnybrook Research Institute (W.S., M.M., J.R., N.H., J.D.E., M.S., P.C., D.Y., S.M.N., C.J.M.S., M.F.H., A.K., P.I.O., F.G., B.S., J.K., S.S., R.H.S., K.L.L., D.T.S., S.E.B.), Toronto; University of Toronto (W.S., M.M., N.H., M.S., P.C., D.Y., S.M.N., A.K., P.I.O., S.C.S., F.G., B.S., J.K., S.S., R.H.S., K.L.L., D.T.S., S.E.B.); University Health Network Toronto Rehabilitation Institute (W.S., P.I.O., K.L.L.), Canada; Universidade Federal de São Paulo (H.C.-M.), Brazil; McMaster University (D.J.S., S.C.S.), Hamilton; and Rotman Research Institute (D.T.S.), Baycrest, Toronto, Canada.
Neurology. 2018 Feb 20;90(8):e673-e682. doi: 10.1212/WNL.0000000000004983. Epub 2018 Jan 26.
To determine the relationship between white matter hyperintensities (WMH) presumed to indicate disease of the cerebral small vessels, temporal lobe atrophy, and verbal memory deficits in Alzheimer disease (AD) and other dementias.
We recruited groups of participants with and without AD, including strata with extensive WMH and minimal WMH, into a cross-sectional proof-of-principle study (n = 118). A consecutive case series from a memory clinic was used as an independent validation sample (n = 702; Sunnybrook Dementia Study; NCT01800214). We assessed WMH volume and left temporal lobe atrophy (measured as the brain parenchymal fraction) using structural MRI and verbal memory using the California Verbal Learning Test. Using path modeling with an inferential bootstrapping procedure, we tested an indirect effect of WMH on verbal recall that depends sequentially on temporal lobe atrophy and verbal learning.
In both samples, WMH predicted poorer verbal recall, specifically due to temporal lobe atrophy and poorer verbal learning (proof-of-principle -1.53, 95% bootstrap confidence interval [CI] -2.45 to -0.88; and confirmation -0.66, 95% CI [-0.95 to -0.41] words). This pathway was significant in subgroups with (-0.20, 95% CI [-0.38 to -0.07] words, n = 363) and without (-0.71, 95% CI [-1.12 to -0.37] words, n = 339) AD. Via the identical pathway, WMH contributed to deficits in recognition memory (-1.82%, 95% CI [-2.64% to -1.11%]), a sensitive and specific sign of AD.
Across dementia syndromes, WMH contribute indirectly to verbal memory deficits considered pathognomonic of Alzheimer disease, specifically by contributing to temporal lobe atrophy.
确定脑白质高信号（WMH）与颞叶萎缩和阿尔茨海默病（AD）及其他类型痴呆患者的言语记忆缺陷之间的关系，WMH 被认为与脑小血管疾病相关。
我们纳入了一组伴有或不伴有 AD 的患者，包括存在广泛 WMH 和最小 WMH 的亚组，进行了一项横断面初步原理研究（n=118）。一项来自记忆诊所的连续病例系列研究被用作独立验证样本（n=702；Sunnybrook 痴呆研究；NCT01800214）。我们使用结构 MRI 评估了 WMH 体积和左侧颞叶萎缩（以脑实质分数表示），并使用加利福尼亚语言学习测验评估了言语记忆。通过带有推断性自举程序的路径建模，我们测试了 WMH 通过依次依赖于颞叶萎缩和言语学习对言语回忆产生的间接影响。
在两个样本中，WMH 均预测了较差的言语回忆，这主要是由于颞叶萎缩和较差的言语学习（初步原理 -1.53，95%自举置信区间[CI] -2.45 至-0.88；验证-0.66，95%CI[-0.95 至-0.41]个单词）。在伴有（n=363）和不伴有（n=339）AD 的亚组中，该通路均具有统计学意义（分别为-0.20，95%CI[-0.38 至-0.07]个单词和-0.71，95%CI[-1.12 至-0.37]个单词）。通过相同的途径，WMH 导致了识别记忆缺陷（-1.82%，95%CI[-2.64%至-1.11%]），这是 AD 的一种敏感且特异的标志物。
在各种痴呆综合征中，WMH 通过导致颞叶萎缩，间接地导致被认为是 AD 特征性的言语记忆缺陷。
