P2‐010: Does variable progression of incidental white matter hyperintensities in Alzheimer's disease relate to venous insufficiency?

Incidental white matter hyperintensities (WMH) in Alzheimer's disease (AD) are usually attributed to small arterial occlusive disease. However, variability in lesion change over time and unpredictable conditions between lesion volumes and cognition raise questions. An intraparenchymal venular disorder or CSF circulation disturbance in perivascular spaces may need to be considered to explain non-lacunar focal WMH in AD. Thirty-two AD (age=74) and 10 healthy elderly(age=72) had two high resolution MRI at 1.3 years apart. After 3D-T1, T2W and PDW images were co-registered, focal WMH were identified, and locations compared with intraparenchymal vascular anatomy (including perivascular spaces), evident as linear hypointense signals on appropriately windowed 3D-T1 images. Vessels or perivascular spaces were considered to be deep intramedullary or transcerebral venous structures if connected to the lateral ventricle (Fig1A), and overlap of focal WMH with these veins was deemed to implicate venous pathology. Change over time (enlargement, shrinkage, new appearance or disappearance) of each focal WMH was carefully analyzed. Total WMH volume and mean focal WMH count did not differ in AD vs controls. Anatomically, 94% of 561 focal WMH at baseline and 94% of 33 new focal WMH at one year overlapped with enlarged intraparenchymal vessels or perivascular spaces (see examples in Fig1B,C,D and Fig2A). Approximately 52% of these lesions overlapped the deep intramedullary or transcerebral veins. Over one year, 30% enlarged concentrically or spread along perivascular spaces (Fig2B), and 6% either shrunk or disappeared (Fig2C) at time. Most incidental WMH (i.e. non-lacunar) were associated with enlarged intraparenchymal vessels or perivascular spaces, likely to be venous-related in both AD and normal aging. Their dynamic change over time, their tendency to spread along the perivascular spaces or to disappear would be compatible with cerebral venular insufficiency (related to venous collagenosis of aging) causing leakage of fluid i.e. edema, which appears as hyperintense in T2W/PDW MRI.We suggest that small vessel disease involving both the venous and arterial sides of the cerebral occlusion may contribute to white matter disease in aging and dementia.