Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
Alzheimers Res Ther. 2017 Dec 29;9(1):101. doi: 10.1186/s13195-017-0328-9.
Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia.
We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Aβ and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics.
MTA and t-tau were elevated in the Aβ - WMH+, Aβ + WMH-, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline.
In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.
脑血管疾病（CVD）和淀粉样蛋白-β（Aβ）常同时存在，但它们在痴呆前期对神经退行性变和认知的影响尚不清楚。我们研究了无痴呆的患者中 CVD 和 Aβ 与神经退行性标志物和认知的关系。
我们纳入了来自生物银行阿尔茨海默病中心林堡队列（n=99）、LeARN（n=50）和 DESCRIPA（n=122）多中心研究的 271 名有主观或客观认知障碍但无痴呆的记忆诊所患者。脑脊液 Aβ和磁共振成像（MRI）上的脑白质高信号（WMH）分别作为 Aβ和 CVD 的测量指标。根据 Aβ 和 WMH 的存在（+）或不存在（-），将个体分为四组。我们使用一般线性模型比较各组之间磷酸化 tau、总 tau（t-tau）和内侧颞叶萎缩（MTA）的差异。我们使用线性混合模型和 Cox 比例风险模型检查认知下降和向痴呆的进展。所有分析均根据研究和人口统计学进行调整。
在 Aβ- WMH+、Aβ+ WMH-和 Aβ+ WMH+组中，MTA 和 t-tau 升高。与具有单一病变的组相比，Aβ+ WMH+组的 MTA 最严重。WMH 和 Aβ 均与认知下降相关，但同时存在两种病变与下降速度加快无关。
在本研究中，我们发现 Aβ 和 CVD 病理与基线 MTA 有附加关联，但与认知下降无关。由于我们的发现可能对记忆诊所患者的诊断和预后以及未来的科学研究有影响，因此应在具有更长随访时间的更大样本中进行验证。
