Boston University Alzheimer's Disease Center and CTE Center, Boston University School of Medicine, 72 E. Concord Street, Suite B7800, Boston, MA, 02118, USA.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Alzheimers Res Ther. 2019 Jul 27;11(1):64. doi: 10.1186/s13195-019-0521-0.
Longitudinal investigations are needed to improve understanding of the contributions of cerebral small vessel disease to the clinical manifestation of Alzheimer's disease, particularly in the early disease stages. This study leveraged the National Alzheimer's Coordinating Center Uniform Data Set to longitudinally examine the association between white matter hyperintensities and neuropsychological, neuropsychiatric, and functional decline among participants with normal cognition.
The sample included 465 participants from the National Alzheimer's Coordinating Center Uniform Data Set who had quantitated volume of white matter hyperintensities from fluid-attenuated inversion recovery MRI, had normal cognition at the time of their MRI, and were administered the National Alzheimer's Coordinating Center Uniform Data Set neuropsychological test battery within 1 year of study evaluation and had at least two post-MRI time points of clinical data. Neuropsychiatric status was assessed by the Geriatric Depression Scale-15 and Neuropsychiatric Inventory-Questionnaire. Clinical Dementia Rating Sum of Boxes defined functional status. For participants subsequently diagnosed with mild cognitive impairment (MCI) or dementia, their impairment must have been attributed to Alzheimer's disease (AD) to evaluate the relationships between WMH and the clinical presentation of AD.
Of the 465 participants, 56 converted to MCI or AD dementia (average follow-up = 5 years). Among the 465 participants, generalized estimating equations controlling for age, sex, race, education, APOE ε4, and total brain and hippocampal volume showed that higher baseline log-white matter hyperintensities predicted accelerated decline on the following neuropsychological tests in rank order of effect size: Trails B (p < 0.01), Digit Symbol Coding (p < 0.01), Logical Memory Immediate Recall (p = 0.02), Trail Making A (p < 0.01), and Semantic Fluency (p < 0.01). White matter hyperintensities predicted increases in Clinical Dementia Rating Sum of Boxes (p < 0.01) and Geriatric Depression Scale-15 scores (p = 0.01). Effect sizes were comparable to total brain and hippocampal volume. White matter hyperintensities did not predict diagnostic conversion. All effects also remained after including individuals with non-AD suspected etiologies for those who converted to MCI or dementia.
In this baseline cognitively normal sample, greater white matter hyperintensities were associated with accelerated cognitive, neuropsychiatric, and functional decline independent of traditional risk factors and MRI biomarkers for Alzheimer's disease.
为了深入了解脑小血管疾病对阿尔茨海默病临床表现的影响，特别是在疾病早期阶段，需要进行纵向研究。本研究利用国家阿尔茨海默病协调中心统一数据集，纵向研究了正常认知参与者中脑白质高信号与神经心理学、神经精神和功能下降之间的关系。
该样本包括来自国家阿尔茨海默病协调中心统一数据集的 465 名参与者，他们接受了液体衰减反转恢复 MRI 定量的脑白质高信号体积，在 MRI 时认知正常，并且在研究评估后 1 年内接受了国家阿尔茨海默病协调中心统一数据集神经心理学测试，并且至少有两个 MRI 后时间点的临床数据。神经精神状态通过老年抑郁量表-15 和神经精神问卷进行评估。临床痴呆评定总和量表定义了功能状态。对于随后被诊断为轻度认知障碍 (MCI) 或痴呆的参与者，他们的损伤必须归因于阿尔茨海默病 (AD)，以评估 WM H 与 AD 临床表现之间的关系。
在 465 名参与者中，有 56 名转化为 MCI 或 AD 痴呆（平均随访时间为 5 年）。在 465 名参与者中，使用一般估计方程控制年龄、性别、种族、教育程度、APOE ε4 以及总脑和海马体体积后，较高的基线 log 脑白质高信号预测了以下神经心理学测试中按效应大小排序的加速下降：Trails B（p<0.01）、数字符号编码（p<0.01）、逻辑记忆即时回忆（p=0.02）、Trail 制作 A（p<0.01）和语义流畅性（p<0.01）。脑白质高信号预测临床痴呆评定总和量表评分增加（p<0.01）和老年抑郁量表-15 评分增加（p=0.01）。效应大小与总脑和海马体体积相当。脑白质高信号与诊断转换无关。在包括转换为 MCI 或痴呆的个体的非 AD 疑似病因后，所有影响仍然存在。
在本基线认知正常的样本中，脑白质高信号越多，与认知、神经精神和功能下降加速相关，而与传统危险因素和阿尔茨海默病的 MRI 生物标志物无关。
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