High-Density Lipoprotein (HDL) Subtypes Adversely Alter Brain Structure in Mild Cognitive Impairment: A Tensor-Based Morphometry Analysis

High-density lipoprotein (HDL) cholesterol is typically protective for cognitive function due to its anti-inflammatory, antioxidant, and vascular health benefits. However, recent studies indicated that certain HDL subtypes might be associated with adverse brain structural changes, commonly seen in mild cognitive impairment (MCI). Thus, further research is needed to understand the intricate relationship between HDL levels and brain structure, potentially leading to more effective therapeutic strategies. The current study aimed to investigate the impact of HDL subtypes, such as XL_HDL_P, M_HDL_FC_PCT, M_HDL_P, M_HDL_C, and M_HDL_CE, as well as APOA1, on brain structure in individuals with MCI using tensor-based morphometry (TBM). The study analyzed ADNI data from subjects with at least two serial MRI scans, processed using the Mayo TBM-Symmetric Normalization (SyN) pipeline and SyN for longitudinal measures. The CDR and ADAS scores were used to assess the severity of cognitive impairment and disease progression in our study participants. Significant ROIs were identified from a Mayo Clinic training set, and TBM-SyN scores were computed. The significant correlation was considered with p-values less than 0.05. The study found significant negative effects of several lipoproteins on TBM scores in individuals with MCI. Specifically, XL_HDL_P, with an effect size of - 0.00145 (p=0.029), and M_HDL_FC_PCT, with an effect size of -0.00199 (p=0.0016), were linked to lower TBM scores. Similarly, M_HDL_P (-0.00138, p=0.028), M_HDL_C (-0.00140, p=0.025), M_HDL_CE (-0.00136, p=0.031), and APOA1 (-0.00149, p=0.017) also showed significant associations. These findings indicate that higher levels of HDL subtype cholesterol are significantly associated with reduced TBM scores, suggesting that elevated levels are linked to adverse structural brain changes, such as atrophy, in individuals with MCI, potentially contributing to cognitive decline.