Alzheimer Center, Department of Neurology, VU University Medical Center, Amsterdam Neuroscience, P.O. Box 7057, 1007, MB, Amsterdam, The Netherlands.
VTT Technical Research Center of Finland Ltd, Tampere, Finland.
Alzheimers Res Ther. 2018 Feb 20;10(1):23. doi: 10.1186/s13195-018-0348-0.
Survival after dementia diagnosis varies considerably. Previous studies were focused mainly on factors related to demographics and comorbidity rather than on Alzheimer's disease (AD)-related determinants. We set out to answer the question whether markers with proven diagnostic value also have prognostic value. We aimed to identify disease-related determinants associated with mortality in patients with AD.
We included 616 patients (50% female; age 67 ± 8 years; mean Mini Mental State Examination score 22 ± 3) with dementia due to AD from the Amsterdam Dementia Cohort. Information on mortality was obtained from the Dutch Municipal Register. We used age- and sex-adjusted Cox proportional hazards analysis to study associations of baseline demographics, comorbidity, neuropsychology, magnetic resonance imaging (MRI) (medial temporal lobe, global cortical and parietal atrophy, and measures of small vessel disease), and cerebrospinal fluid (CSF) (β-amyloid 1-42, total tau, and tau phosphorylated at threonine 181 [p-tau]) with mortality (outcome). In addition, we built a multivariate model using forward selection.
After an average of 4.9 ± 2.0 years, 213 (35%) patients had died. Age- and sex-adjusted Cox models showed that older age (HR 1.29 [95% CI 1.12-1.48]), male sex (HR 1.60 [95% CI 1.22-2.11]), worse scores on cognitive functioning (HR 1.14 [95% CI 1.01-1.30] to 1.31 [95% CI 1.13-1.52]), and more global and hippocampal atrophy on MRI (HR 1.18 [95% CI 1.01-1.37] and HR 1.18 [95% CI 1.02-1.37]) were associated with increased risk of mortality. There were no associations with comorbidity, level of activities of daily living, apolipoprotein E (APOE) ε4 status, or duration of disease. Using forward selection, the multivariate model included a panel of age, sex, cognitive tests, atrophy of the medial temporal lobe, and CSF p-tau.
In this relatively young sample of patients with AD, disease-related determinants were associated with an increased risk of mortality, whereas neither comorbidity nor APOE genotype had any prognostic value.
痴呆症诊断后的生存率差异很大。以前的研究主要集中在与人口统计学和合并症相关的因素上，而不是与阿尔茨海默病（AD）相关的决定因素上。我们着手回答这样一个问题，即具有明确诊断价值的标志物是否也具有预后价值。我们的目的是确定与 AD 患者死亡率相关的疾病相关决定因素。
我们纳入了 616 名（50%为女性；年龄 67 ± 8 岁；平均简易精神状态检查评分 22 ± 3）因 AD 导致痴呆的患者，这些患者来自阿姆斯特丹痴呆队列。从荷兰市登记册获取有关死亡率的信息。我们使用年龄和性别调整的 Cox 比例风险分析来研究基线人口统计学、合并症、神经心理学、磁共振成像（MRI）（内侧颞叶、全脑皮质和顶叶萎缩以及小血管疾病测量值）和脑脊液（CSF）（β-淀粉样蛋白 1-42、总 tau 和 tau 磷酸化 threonine 181[p-tau]）与死亡率（结局）之间的关联。此外，我们使用向前选择建立了一个多变量模型。
平均随访 4.9 ± 2.0 年后，213 名（35%）患者死亡。年龄和性别调整的 Cox 模型显示，年龄较大（HR 1.29 [95%CI 1.12-1.48]）、男性（HR 1.60 [95%CI 1.22-2.11]）、认知功能评分较差（HR 1.14 [95%CI 1.01-1.30]至 1.31 [95%CI 1.13-1.52]）以及 MRI 上更广泛的脑萎缩和海马萎缩（HR 1.18 [95%CI 1.01-1.37]和 HR 1.18 [95%CI 1.02-1.37]）与死亡率增加相关。与合并症、日常生活活动水平、载脂蛋白 E（APOE）ε4 状态或疾病持续时间均无关联。使用向前选择，多变量模型包括年龄、性别、认知测试、内侧颞叶萎缩和 CSF p-tau 面板。
在这个相对年轻的 AD 患者样本中，疾病相关决定因素与死亡率增加相关，而合并症或 APOE 基因型均无预后价值。
