Associations between placental growth factor, white matter lesions, and vascular risk factors in non‐demented elderly individuals

Abstract

AbstractBackgroundPlacental growth factor (PlGF) is a pro‐inflammatory marker of angiogenesis, which may play a role in cardiovascular disease and is upregulated by hyperglycemia. In non‐demented elderly, cerebrospinal fluid (CSF) PlGF is strongly associated with white matter lesions (WML), a commonly used measure of cerebrovascular disease. However, it is unclear to what degree CSF PlGF and WML provide overlapping or complementary information about pathological processes in the brain. To investigate this, we tested associations for different vascular risk factors with CSF PlGF and WML.Methods495 cognitively unimpaired (CU) elderly and 247 patients with mild cognitive impairment (MCI) from the Swedish BIOFINDER study were included. CSF samples were analyzed for PlGF, Aβ40 and Aβ42. Information about the vascular risk factors stroke (present in 8%), hypertension (35%), diabetes (9%), and ischemic heart disease (IHD) (10%) was collected. Associations between WML and PlGF as well as their associations with these risk factors were tested with linear regression models. Analyses were adjusted for age, gender, Aβ status, and intracranial volume.ResultsPlGF was associated with WML in the whole group (β = 0.18; CI 0.14‐0.22), and in diagnostic subgroups CU (β = 0.16; CI 0.10‐0.21) and MCI (β = 0.17; CI 0.11‐0.24). Stroke (β = 0.44; CI 0.29‐0.59) and hypertension (β = 0.12; CI 0.03‐0.20) were associated with WML, whereas diabetes (β = 0.37; CI 0.15‐0.60) was associated with PlGF. There was also a nominally significant association between WML and IHD (β = 0.15; CI 0.017‐0.29). In diagnostic subgroups, associations between stroke and WML were significant in CU (β = 0.35; CI 0.12‐0.59), and MCI (β = 0.38; CI 0.20‐0.57) after correction for multiple comparison.ConclusionWe confirmed that PlGF is strongly associated with WML. However, PlGF and WML were differentially associated with vascular risk factors. PlGF was strongly associated with diabetes, which could indicate alterations in endothelial function, frequently seen in diabetes complications. In contrast, WML was associated with stroke and hypertension, both associated with cerebrovascular disease. This suggests that WML and PlGF contribute complementary information about vascular disease processes in the brain.