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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.
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