Data from: White matter lesions: spatial heterogeneity, links to risk factors, cognition, genetics, atrophy

Objectives: To investigate spatial heterogeneity of white matter lesions or hyperintensities (WMH). Methods: MRI scans of 1836 participants (median age 52.2±13.16) encompassing a wide age range (22–84 years) from the cross-sectional Study of Health in Pomerania (SHIP, Germany) were included as discovery set identifying spatially distinct components of WMH using a structural covariance approach. Scans of 307 participants (median age 73.8±10.2, with 747 observations) from the Baltimore Longitudinal Study of Aging (BLSA, USA) were included to examine differences in longitudinal progression of these components. The associations of these components with vascular risk factors, cortical atrophy, Alzheimer’s disease (AD) genetics and cognition were then investigated using linear regression. Results: WMH were found to occur non-uniformly, with higher frequency within spatially heterogeneous patterns encoded by four components, which were consistent with common categorizations of deep and periventricular WMH, while further dividing the latter into posterior, frontal and dorsal components. Temporal trends of the components differed both cross-sectionally and longitudinally. Frontal periventricular WMH were most distinctive as they appeared in the 5th decade of life, whereas the other components appeared later in life during the 6th decade. Furthermore, frontal WMH were associated with systolic blood pressure and with pronounced atrophy including AD-related regions. AD polygenic risk score was associated with the dorsal periventricular component in elderly. Cognitive decline was associated with the dorsal component. Conclusions: These results support the hypothesis that the appearance of WMH follows age and disease-dependent regional distribution patterns, potentially influenced by differential underlying pathophysiological mechanisms, and possibly with a differential link to vascular and neurodegenerative changes.研究目的：探究脑白质病变或高信号（white matter hyperintensities, WMH）的空间异质性。方法：将来自德国波美拉尼亚健康横断面研究（Study of Health in Pomerania, SHIP）的1836名参与者的磁共振成像（magnetic resonance imaging, MRI）扫描数据纳入作为发现队列，采用结构协变分析方法识别WMH的空间差异化组分。该队列参与者年龄跨度为22~84岁，中位年龄为52.2±13.16岁。纳入来自美国巴尔的摩纵向衰老研究（Baltimore Longitudinal Study of Aging, BLSA）的307名参与者的扫描数据（共747次观测，中位年龄73.8±10.2岁），以考察这些组分的纵向进展差异。随后采用线性回归分析这些组分与血管危险因素、皮质萎缩、阿尔茨海默病（Alzheimer’s disease, AD）遗传因素及认知功能的关联。结果：研究发现，WMH的分布并非均匀一致，在四种由不同组分表征的空间异质性模式中其出现频率更高，该模式与公认的深部及脑室周围WMH分类一致，同时可将脑室周围WMH进一步划分为后组、额叶组及背侧组。这些组分的时间变化趋势在横断面及纵向分析中均存在差异。额叶脑室周围WMH最为独特，其首次出现于50岁年龄段，而其余组分则于60岁年龄段才开始出现。此外，额叶WMH与收缩压及包括AD相关脑区在内的显著皮质萎缩相关。AD多基因风险评分与老年群体的背侧脑室周围组分相关。认知功能下降与背侧组分相关。结论：本研究结果支持以下假说：WMH的出现遵循年龄及疾病依赖性的脑区分布模式，其潜在病理生理机制可能存在差异，且与血管及神经退行性改变的关联也可能有所不同。