Pinheiro Adlin, Ekenze Oluchi, Aparicio Hugo J, Beiser Alexa S, Decarli Charles S, Demissie Serkalem, Seshadri Sudha, Romero Jose Rafael
Department of Biostatistics, Boston University School of Public Health, MA.
Framingham Heart Study, MA.
Neurology. 2025 Oct 7;105(7):e214113. doi: 10.1212/WNL.0000000000214113. Epub 2025 Sep 15.
Individual MRI markers of cerebral small vessel disease (CSVD) are associated with impaired cognition and dementia but may not reflect the overall burden of CSVD. In addition, it is unclear whether these markers provide additional value in dementia risk assessment beyond vascular risk factors alone. Thus, we studied the association between the additive burden of multiple CSVD markers and incident dementia and determined whether this relationship remains independent of the Framingham Stroke Risk Profile (FSRP), a tool used commonly used for stroke risk prediction.
A total of 1,152 MRI scans from participants in the Original and Offspring cohorts of the Framingham Heart Study, a large observational cohort study, were included. Participants were older than 55 years and free of prevalent dementia, stroke, or other neurologic conditions at the time of MRI. A multimarker score capturing CSVD burden was defined as the sum of CSVD features detected in the MRI: cerebral microbleeds, covert brain infarcts, extensive white matter hyperintensities, high-burden perivascular spaces, and cortical superficial siderosis. Multivariate Cox regression models examined the association between the multimarker CSVD score and incident all-cause dementia, Alzheimer dementia (AD), and vascular dementia.
The mean age was 70.9 years (SD 8.7) (527 [46%] were male), and 211 (18%) had a CSVD score of ≥2. Over a median follow-up time of 7.4 years (interquartile range 4.6-11.3), participants with a score ≥2 had significantly elevated risk of all-cause dementia compared with those with no CSVD markers after adjustment for the FSRP (hazard ratio [HR] 1.67; 95% CI 1.05-2.66) and vascular risk factors (HR 1.76; 95% CI 1.10-2.81). The multimarker CSVD score demonstrated similar model performance metrics to the FSRP (Harrell -statistics 0.82-0.83).
We found a significant association between all-cause dementia and multimarker CSVD scores, which was independent of the FSRP as well as its individual components. Our results support the use of a multimarker CSVD score as an indicator for incident all-cause dementia risk and suggest that it may be as robust as the FSRP. Further studies are necessary to validate the use of a multimarker CSVD score in dementia risk prediction.
脑小血管病（CSVD）的个体磁共振成像（MRI）标志物与认知功能受损及痴呆相关，但可能无法反映CSVD的总体负担。此外，尚不清楚这些标志物在痴呆风险评估中是否能提供超出血管危险因素本身的额外价值。因此，我们研究了多种CSVD标志物的累积负担与新发痴呆之间的关联，并确定这种关系是否独立于常用的中风风险预测工具弗雷明汉姆中风风险评估量表（FSRP）。
纳入了弗雷明汉姆心脏研究的原队列和子代队列参与者的1152份MRI扫描数据，该研究是一项大型观察性队列研究。参与者年龄大于55岁，在进行MRI检查时无现患痴呆、中风或其他神经系统疾病。一个反映CSVD负担的多标志物评分被定义为MRI中检测到的CSVD特征的总和：脑微出血、隐匿性脑梗死、广泛的白质高信号、高负担的血管周围间隙和皮质表面铁沉积。多变量Cox回归模型检验了多标志物CSVD评分与新发全因性痴呆、阿尔茨海默病（AD）和血管性痴呆之间的关联。
平均年龄为70.9岁（标准差8.7）（527名[46%]为男性），211名（18%）的CSVD评分为≥2。在中位随访时间7.4年（四分位间距4.6 - 11.3）内，在对FSRP（风险比[HR] 1.67；95%置信区间1.05 - 2.66）和血管危险因素（HR 1.76；95%置信区间1.10 - 2.81）进行调整后，评分≥2的参与者与无CSVD标志物的参与者相比，全因性痴呆风险显著升高。多标志物CSVD评分显示出与FSRP相似的模型性能指标（Harrell统计量0.82 - 0.83）。
我们发现全因性痴呆与多标志物CSVD评分之间存在显著关联，这独立于FSRP及其各个组成部分。我们的结果支持将多标志物CSVD评分用作新发全因性痴呆风险的指标，并表明它可能与FSRP一样可靠。需要进一步研究来验证多标志物CSVD评分在痴呆风险预测中的应用。
