Department of Neurology, National Neuroscience Institute, Singapore; Duke - NUS Graduate Medical School Singapore, Singapore.
Eur J Neurol. 2015 Jan;22(1):150-5. doi: 10.1111/ene.12546. Epub 2014 Aug 21.
Whilst there is evidence implicating small vessel cerebrovascular disease in the pathogenesis of Alzheimer's disease (AD), its specific contribution to the pathophysiology of AD remains unclear. The burden of small vessel cerebrovascular disease visualized as white matter hyperintensity (WMH) and its association with medial temporal atrophy (MTA) at different stages of AD was studied.
One hundred and sixty-five cognitively normal (CN) community controls, 103 mild cognitive impairment (MCI) patients, 141 mild AD patients and 68 moderate-severe AD patients were studied. Clinical, cognitive and risk factor data were collected, and WMH and MTA were quantified by trained raters. The Jonckheere-Terpstra test for ordered alternatives was used to study the association between WMH and MTA in different stages of AD.
The burden of total WMH increased significantly with increasing severity of AD, even after correcting for confounders. The proportion of CN, MCI, mild AD and moderate-severe AD subjects with severe burden of WMH was 6.7%, 9.7%, 28.4%, and 39.7%, respectively. A strong positive association between WMH severity and MTA was evident amongst MCI (P = 0.011) and mild AD (P = 0.003) subjects, but not in CN (P = 0.953) and moderate-severe AD subjects (P = 0.301).
The burden of WMH increased significantly from the stage of CN to MCI to AD. The association between WMH and MTA was greatest at the stage of MCI and mild AD. This has implications on the strategy to slow the progression of AD, where measures to reduce WMH, including control of vascular risk factors, need to be optimized at the stage of MCI and mild AD.
虽然有证据表明小血管脑血管疾病与阿尔茨海默病（AD）的发病机制有关，但它对 AD 病理生理学的确切贡献仍不清楚。本研究旨在研究小血管脑血管疾病（以脑白质高信号（WMH）为表现）的负担及其与 AD 不同阶段内侧颞叶萎缩（MTA）的关系。
共纳入 165 例认知正常（CN）社区对照者、103 例轻度认知障碍（MCI）患者、141 例轻度 AD 患者和 68 例中重度 AD 患者。收集临床、认知和危险因素数据，并由经过培训的评分者对 WMH 和 MTA 进行量化。采用 Jonckheere-Terpstra 检验对不同 AD 阶段的 WMH 和 MTA 之间的关系进行研究。
即使在校正混杂因素后，随着 AD 严重程度的增加，总 WMH 的负担也显著增加。WMH 负担严重的 CN、MCI、轻度 AD 和中重度 AD 患者的比例分别为 6.7%、9.7%、28.4%和 39.7%。在 MCI（P = 0.011）和轻度 AD（P = 0.003）患者中，WMH 严重程度与 MTA 之间存在显著的正相关，而在 CN（P = 0.953）和中重度 AD 患者中则无相关性（P = 0.301）。
WMH 的负担从 CN 期到 MCI 期再到 AD 期显著增加。WMH 与 MTA 的相关性在 MCI 和轻度 AD 期最大。这对减缓 AD 进展的策略具有启示意义，在 MCI 和轻度 AD 期，需要优化包括控制血管危险因素在内的降低 WMH 的措施。
