Scheltens P, Barkhof F, Valk J, Algra P R, van der Hoop R G, Nauta J, Wolters E C
Department of Neurology, Free University Hospital, Amsterdam, The Netherlands.
Brain. 1992 Jun;115 ( Pt 3):735-48. doi: 10.1093/brain/115.3.735.
In a prospective magnetic resonance imaging (MRI) study we evaluated the prevalence and severity of white matter changes in 29 patients with Alzheimer's Disease (AD) and 24 age-matched healthy elderly, all without cerebrovascular risk factors. The AD patients were divided into two groups according to age at onset of symptoms, one with presenile onset AD (n = 13) and one with senile onset AD (n = 16), who were matched for dementia severity. Signal hyperintensities were rated using a semiquantitative scoring method, separately in the periventricular region (PVH) and in the lobar white matter (WMH), as well as in the basal ganglia (BGH) and in the infratentorial region (ITFH). Cortical atrophy as a parameter of grey matter involvement was rated on a 0 (absent) to 3 (severe) scale. We found PVH, WMH and BGH scores to be significantly higher in senile onset AD patients than in age-matched controls. By means of multiple linear logistic regression we found that PVH, WMH and BGH scores were significantly dependent on the diagnosis of senile onset AD, while the PVH score also showed a significant age dependency. Cortical atrophy did not differ significantly between presenile onset AD and senile onset AD patients. These results indicate that presenile onset AD and senile onset AD patients differ with respect to white matter involvement, but not with respect to grey matter involvement on MRI. Since cerebrovascular risk factors were excluded these findings may indicate that senile onset AD patients display more small vessel involvement (arteriolosclerosis) than presenile onset AD patients, suggesting additional (microvascular) factors for the dementia syndrome in senile onset AD. Our data lend support to the growing body of evidence that AD is heterogeneous, consisting of at least two types. Based on our findings two forms can be distinguished: (i) a 'pure' form of the disease, usually with early disease onset, and no more white matter changes than normal for age; (ii) a 'mixed' form, usually with disease onset later in life, and showing more white matter changes on MRI than normal for age.
在一项前瞻性磁共振成像（MRI）研究中，我们评估了29例阿尔茨海默病（AD）患者和24名年龄匹配的健康老年人（均无脑血管危险因素）白质改变的患病率和严重程度。根据症状出现时的年龄，将AD患者分为两组，一组为早发性AD（n = 13），另一组为晚发性AD（n = 16），两组在痴呆严重程度上相匹配。使用半定量评分方法分别对脑室周围区域（PVH）、脑叶白质（WMH）、基底节（BGH）和幕下区域（ITFH）的信号高增强进行评分。将皮质萎缩作为灰质受累的参数，按0（无）至3（严重）进行评分。我们发现，晚发性AD患者的PVH、WMH和BGH评分显著高于年龄匹配的对照组。通过多元线性逻辑回归分析，我们发现PVH、WMH和BGH评分显著依赖于晚发性AD的诊断，而PVH评分也显示出显著的年龄依赖性。早发性AD和晚发性AD患者的皮质萎缩无显著差异。这些结果表明，早发性AD和晚发性AD患者在白质受累方面存在差异，但在MRI上的灰质受累方面无差异。由于排除了脑血管危险因素，这些发现可能表明晚发性AD患者比早发性AD患者表现出更多的小血管受累（小动脉硬化），提示晚发性AD痴呆综合征存在其他（微血管）因素。我们的数据支持了越来越多的证据，即AD是异质性的，至少由两种类型组成。根据我们的研究结果，可以区分出两种形式：（i）疾病的“纯”形式，通常发病较早，白质改变不超过同龄人正常水平；（ii）“混合”形式，通常在生命后期发病，MRI显示白质改变超过同龄人正常水平。
