Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Department of Epidemiology and Biostatistics, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
J Alzheimers Dis. 2018;65(3):1029-1039. doi: 10.3233/JAD-171088.
Alzheimer's disease (AD) is a heterogeneous disorder.
To investigate whether cognitive AD subtypes are associated with different rates of disease progression.
We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative (n = 268), Dementia Competence Network (n = 226), and University of California, San Francisco (n = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n = 663) and one with most prominent non-memory impairment (n = 403). We examined associations between cognitive subtype and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses.
Patients were 71±9 years old; 541 (51%) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p < 0.001; CDR sob 4.1±0.1; p < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (-2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE - 1.9±0.1; pinteraction<0.001; CDR sob 1.3±0.1; pinteraction<0.001). Furthermore, the non-memory subtype was associated with an increased risk of mortality compared with the memory subtype at trend level (HR = 1.36, CI = 1.00-1.85, p = 0.05).
AD patients with most prominently non-memory impairment show faster disease progression and higher risk of mortality than patients with most prominently memory impairment.
阿尔茨海默病（AD）是一种异质性疾病。
研究认知 AD 亚型是否与不同的疾病进展速度有关。
我们纳入了来自阿姆斯特丹痴呆队列（n=290）、阿尔茨海默病神经影像学倡议（n=268）、痴呆能力网络（n=226）和加利福尼亚大学旧金山分校（n=282）的 1066 例可能的 AD 患者，这些患者都有随访数据。根据神经心理学测试结果，患者之前被分为两个亚型：以记忆障碍为主（n=663）和以非记忆障碍为主（n=403）。我们使用线性混合模型检查认知亚型与疾病进展（以重复的简易精神状态检查（MMSE）和临床痴呆评定量表总和（CDR sob）测量）之间的关联。此外，我们使用 Cox 比例风险分析研究了与亚型相关的死亡率风险。
患者年龄为 71±9 岁；541 名（51%）为女性。基线时，混合型非记忆患者的 MMSE 评分（23.1±0.1）和 CDR sob（4.4±0.1）略差于记忆型患者（MMSE 24.0±0.1；p<0.001；CDR sob 4.1±0.1；p<0.001）。在随访期间，混合型非记忆患者的 MMSE 年下降幅度（-2.8±0.1）和 CDR sob 年上升幅度（1.8±0.1）均大于记忆型患者（MMSE -1.9±0.1；p 交互<0.001；CDR sob 1.3±0.1；p 交互<0.001）。此外，非记忆亚型与记忆亚型相比，死亡风险增加趋势（HR=1.36，CI=1.00-1.85，p=0.05）。
以非记忆障碍为主的 AD 患者比以记忆障碍为主的患者疾病进展更快，死亡风险更高。
