Low serum HDL-cholesterol is associated with increased risk of the subcortical small vessel type of dementia

Abstract

Background: There are conflicting results whether serum lipid pattern is related to the amount of white matter hyperintensities (WMHs) on magnetic resonance imaging. Little is known of the associations between lipid concentrations and the subsequent risk of the subcortical small vessel type of dementia (SSVD), in which WMHs are a prominent manifestation. Here, we determined whether lipid levels are associated with the risk of SSVD, Alzheimer's disease (AD), or mixed dementia (combined AD and SSVD).

Methods: This was a longitudinal, prospective study of 329 patients with subjective or objective mild cognitive impairment at baseline. The statistical analyses included Cox proportional hazards regression with adjustments for age, gender, education, body mass index, current smoking, hypertension, diabetes mellitus, and APOE ε4 genotype.

Results: During the follow-up (mean 4.1 years), 80 patients converted to dementia [SSVD, n = 15 (5 %); AD, n = 39 (12 %); and mixed dementia, n = 26 (8 %)]. Serum high-density lipoprotein cholesterol (HDL, per SD increase) was inversely associated with the risk of SSVD, whereas triglycerides (TG), low-density lipoprotein cholesterol (LDL)/HDL ratio, and TG/HDL ratio were positively associated with SSVD risk. Furthermore, the lowest HDL tertile was associated with a sevenfold, and the highest tertile of TG/HDL ratio with a threefold, increase in SSVD risk. There were no associations with the risk of AD or mixed dementia after adjustment for covariates.

Conclusion: In a memory clinic population, low HDL and high TG/HDL ratio were independent risk factors of SSVD, but not of AD or mixed dementia.

Keywords: Alzheimer's disease; HDL-cholesterol; Lipid pattern; Mixed dementia; Subcortical small vessel type of dementia; Triglycerides.

Fig. 1

Low serum high-density lipoprotein cholesterol (HDL) and high serum triglycerides (TG)/HDL ratio are associated with increased risk of conversion to SSVD in patients with subjective or objective mild cognitive impairment. In terms of HDL, the lowest tertile was compared with the two higher tertiles, whereas for TG/HDL ratio, the highest tertile was compared with the two lower tertiles. Kaplan-Meier survival curves are presented for the risk of SSVD by (A) tertile of serum HDL concentration (log-rank test: p < 0.001 tertile 1 vs. tertiles 2–3) and (B) tertile of serum TG/HDL ratio (log-rank test: p < 0.01 tertile 3 vs. tertiles 1–2). Red, low HDL (tertile 1); blue, higher HDL (tertiles 2–3); green, high TG/HDL ratio (tertile 3); purple, lower TG/HDL ratio (tertiles 1–2).