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

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.

Diagnostic Performance of Cerebrospinal Fluid Neurofilament Light Chain and Soluble Amyloid-ß Protein Precursor ß in the Subcortical Small Vessel Type of Dementia.

BACKGROUND: The subcortical small vessel type of dementia (SSVD) is a common subtype of vascular dementia, but there is a lack of disease-specific cerebrospinal fluid (CSF) biomarkers. OBJECTIVE: We investigated whether CSF concentrations of neurofilament light chain (NFL), soluble amyloid-ß protein precursor α (sAßPPα), sAßPPß, and CSF/serum albumin ratio could separate SSVD from healthy controls, Alzheimer's disease (AD), and mixed dementia (combined AD and SSVD). METHODS: This was a mono-center study of patients with SSVD (n = 38), AD (n = 121), mixed dementia (n = 62), and controls (n = 96). The CSF biomarkers were measured using immunoassays, and their independent contribution to the separation between groups were evaluated using the Wald test. Then, the area under the receiver operating characteristics curve (AUROC) and 95% confidence intervals (CIs) were calculated. RESULTS: Elevated neurofilament light chain (NFL) and decreased sAßPPß independently separated SSVD from controls, and sAßPPß also distinguished SSVD from AD and mixed dementia. The combination of NFL and sAßPPß discriminated SSVD from controls with high accuracy (AUROC 0.903, 95% CI: 0.834-0.972). Additionally, sAßPPß combined with the core AD biomarkers (amyloid-ß42, total tau, and phosphorylated tau181) had a high ability to separate SSVD from AD (AUROC 0.886, 95% CI: 0.830-0.942) and mixed dementia (AUROC 0.903, 95% CI: 0.838-0.968). CONCLUSIONS: The high accuracy of NFL and sAßPPß to separate SSVD from controls supports that SSVD is a specific diagnostic entity. Moreover, SSVD was distinguished from AD and mixed dementia using sAßPPß in combination with the core AD biomarkers.