Dementia Research Centre, UCL Institute of Neurology, London, UK.
Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK.
J Neurol Neurosurg Psychiatry. 2020 Apr;91(4):418-425. doi: 10.1136/jnnp-2019-322042. Epub 2020 Feb 20.
Dementia is common in Parkinson's disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD.
We assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson's Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content.
We found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p<0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p<0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures.
Brain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.
痴呆在帕金森病(PD)中很常见,但缺乏跟踪 PD 认知变化的措施。脑组织中铁随年龄增长而积累,并与 PD 痴呆相关的病理蛋白(如淀粉样蛋白)共存。我们使用定量磁化率映射(QSM)来检测与 PD 认知变化相关的变化。
我们评估了 100 名早期至中期 PD 患者和 37 名年龄匹配的对照者,使用蒙特利尔认知评估(MoCA)、一种用于 PD 认知下降风险的验证临床算法、视觉感知功能测量和运动障碍协会统一帕金森病评定量表第 3 部分(UPDRS-III)。我们研究了这些测量值与 QSM 之间的关联,QSM 是一种对脑组织铁含量敏感的 MRI 技术。
与对照组相比,我们发现 PD 患者的 QSM 增加(与脑组织铁含量升高一致),在前额叶皮质和壳核中(p<0.05,经多重比较校正)。PD 组内的全脑回归分析确定了与 QSM 增加相关的因素:(1)在海马体和丘脑,与 MoCA 评分较低相关;(2)在顶叶、额叶和内侧枕叶,与视觉功能较差和痴呆风险评分较高相关;(3)在壳核,与 UPDRS-III 评分较高相关(所有 p<0.05,经多重比较校正)。相比之下,使用基于体素的形态计量学测量的萎缩在组间或与临床测量值均无差异。
使用 QSM 测量的脑组织铁可以跟踪 PD 中的认知参与。这可能有助于检测早期认知变化的迹象,为临床试验分层和监测疾病进展。