Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Alzheimers Dis. 2019;70(4):965-981. doi: 10.3233/JAD-181210.
Recently, the field of Alzheimer's disease (AD) research has adopted a new framework that places the progression of AD along a continuum consisting of a preclinical stage, followed by conversion to mild cognitive impairment, and ultimately dementia. Important neuropathological changes occur in the preclinical phase, necessitating the identification of metrics that can detect such early changes. While cerebrospinal fluid (CSF) measures of amyloid and tau are generally accepted as biomarkers of AD pathology, neuroimaging measures used to index white matter alterations throughout the brain remain less widely endorsed as candidate biomarkers. To explore the relationship between white matter alterations and AD pathology, we review the literature on multimodal studies that assessed both CSF markers and white matter indices, derived from diffusion tensor imaging (DTI) methods, across cohorts primarily in the early phases of AD. Our review indicates that abnormal CSF measures of Aβ42 and tau are associated with widespread alterations in white matter microstructure throughout the brain. Furthermore, white matter variability is related to individual differences in behavior and can aid in tracking longitudinal changes in cognition. Our review advocates for the utilization of DTI metrics in investigations of early AD and suggests that the combined use of DTI and CSF markers may better explain individual differences in cognition and disease progression. However, further research is needed to resolve certain mixed findings.
最近,阿尔茨海默病(AD)研究领域采用了一种新的框架,将 AD 的进展沿着一个连续体进行划分,包括临床前阶段、随后转化为轻度认知障碍,最终发展为痴呆。在临床前阶段会发生重要的神经病理学变化,因此需要确定能够检测到这些早期变化的指标。虽然脑脊液(CSF)中淀粉样蛋白和 tau 的测量通常被认为是 AD 病理学的生物标志物,但用于标记整个大脑白质变化的神经影像学测量作为候选生物标志物的接受程度仍较低。为了探讨白质改变与 AD 病理学之间的关系,我们回顾了有关多模态研究的文献,这些研究评估了 CSF 标志物和源自弥散张量成像(DTI)方法的白质指数,这些研究主要在 AD 的早期阶段在队列中进行。我们的综述表明,异常的 CSF Aβ42 和 tau 测量值与大脑白质微观结构的广泛改变有关。此外,白质变异性与行为上的个体差异有关,有助于追踪认知的纵向变化。我们的综述主张在早期 AD 的研究中使用 DTI 指标,并表明 DTI 和 CSF 标志物的联合使用可能更好地解释认知和疾病进展的个体差异。然而,仍需要进一步的研究来解决某些混杂的发现。