From the Departments of Neurology (M.I.B., M.A.J., M.C., R.E., A.M.T., F.-E.D.L.), of Medical Psychology (R.P.C.K.), Geriatrics (J.A.C.), and Radboudumc Alzheimer Center (J.A.C., R.P.C.K.), Radboud University Medical Center; Donders Center for Medical Neuroscience (M.I.B., M.A.J., M.C., R.E., A.M.T., F.-E.D.L.), and Donders Institute for Brain (J.A.C., R.P.C.K.), Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands; Department of Neurology (M.C.), Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, China; Department of Cardiovascular Sciences (J.A.C.), University of Leicester, United Kingdom; Vincent van Gogh Institute for Psychiatry (R.P.C.K.), Venray, the Netherlands.
Neurology. 2024 Mar 12;102(5):e209148. doi: 10.1212/WNL.0000000000209148. Epub 2024 Feb 21.
Patients with cerebral small vessel disease (SVD) show a heterogenous clinical course. The aim of the current study was to investigate the longitudinal course of cognitive and motor function in patients who developed parkinsonism, dementia, both, or none.
Participants were from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study, a prospective cohort of patients with SVD. Parkinsonism and dementia were, respectively, diagnosed according to the UK Parkinson's Disease Society brain bank criteria and the criteria for major neurocognitive disorder. Linear and generalized linear mixed-effect analyses were used to study the longitudinal course of motor and cognitive tasks.
After a median follow-up of 12.8 years (interquartile range 10.2-15.3), 132 of 501 (26.3%) participants developed parkinsonism, dementia, or both. Years before diagnosis of these disorders, participants showed distinct clinical trajectories from those who developed none: Participant who developed parkinsonism had an annual percentage of 22% (95% CI 18%-27%) increase in motor part of the Unified Parkinson's Disease Rating Scale score. This was significantly higher than the 16% (95% CI 14%-18%) of controls, mainly because of a steep increase in bradykinesia and posture and gait disturbances. When they developed dementia as well, the increase in Timed Up and Go Test time of 0.73 seconds per year (95% CI 0.58-0.87) was significantly higher than the 0.20 seconds per year increase (95% CI 0.16-0.23) of controls. All groups, including the participants who developed parkinsonism without dementia, showed a faster decline in executive function compared with controls: Annual decline in -score was -0.07 (95% CI -0.10 to -0.05), -0.09 (95% CI -0.11 to -0.08), and -0.11 (95% CI -0.14 to -0.08) for participants who developed, respectively, parkinsonism, dementia, and both parkinsonism and dementia. These declines were all significantly faster than the annual decline in -score of 0.07 (95% CI -0.10 to -0.05) of controls.
A distinct pattern in deterioration of clinical markers is visible in patients with SVD, years before the diagnosis of parkinsonism and dementia. This knowledge aids early identification of patients with a high risk of developing these disorders.
患有脑小血管病（SVD）的患者表现出不同的临床病程。本研究的目的是调查发生帕金森病、痴呆、两者或两者均无的患者认知和运动功能的纵向病程。
参与者来自拉德堡德大学奈梅亨弥散张量和磁共振队列研究，这是一项 SVD 患者的前瞻性队列研究。帕金森病和痴呆症分别根据英国帕金森病协会脑库标准和主要神经认知障碍标准进行诊断。线性和广义线性混合效应分析用于研究运动和认知任务的纵向病程。
中位随访 12.8 年后（四分位间距 10.2-15.3），501 名参与者中有 132 名（26.3%）发生了帕金森病、痴呆症或两者都有。在这些疾病诊断之前的几年里，出现这些疾病的参与者与没有出现这些疾病的参与者表现出明显不同的临床轨迹：发生帕金森病的参与者在统一帕金森病评定量表的运动部分的评分中，每年增加 22%（95%可信区间 18%-27%）。这明显高于对照组的 16%（95%可信区间 14%-18%），主要是因为运动迟缓、姿势和步态障碍急剧增加。当他们也患上痴呆症时，每年的“计时起立行走测试”时间增加 0.73 秒（95%可信区间 0.58-0.87），明显高于对照组的每年增加 0.20 秒（95%可信区间 0.16-0.23）。所有组，包括没有痴呆症但发生帕金森病的参与者，与对照组相比，执行功能的下降速度都更快：-评分的年下降幅度分别为-0.07（95%可信区间-0.10 至-0.05）、-0.09（95%可信区间-0.11 至-0.08）和-0.11（95%可信区间-0.14 至-0.08），分别为发生帕金森病、痴呆症和帕金森病和痴呆症的参与者。这些下降速度都明显快于对照组的每年下降速度 0.07（95%可信区间-0.10 至-0.05）。
在 SVD 患者中，在帕金森病和痴呆症的诊断前数年，可看到临床标志物恶化的明显模式。这些知识有助于早期识别出患有这些疾病的高风险患者。
