High serum high-density lipoprotein-cholesterol is associated with memory function and gyrification of insular and frontal opercular cortex in an elderly memory-clinic population

Abstract

The issue of whether serum lipid marker values are cognitively and neurologically significant for elderly individuals attending a memory clinic has been controversial. We investigated the associations of serum lipid markers with the memory function and cortical structure in 52 patients aged ≥75 years who had attended our memory clinic based on their subjective memory complaints. None had a history of medication for hyperlipidemia. The Wechsler Memory Scale-Revised (WMS-R) was administered to all patients for the assessment of their memory function. Serum low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDLC), and triglyceride (TG) were measured for each patient. Surface-based morphometry (SBM) was performed for the calculation of each patient's cortical thickness and gyrification index based on structural MRI data. Our analyses revealed that the serum HDLC level was positively and significantly correlated with the WMS-R subtests of visual paired associates I/II and logical memory I (p < 0.05). The serum TG level was negatively correlated with the logical memory I subtest. The SBM results showed positive correlations between the serum HDLC level and the gyrification indices of the bilateral insular and frontal opercular cortices, and those two gyrification indices were positively correlated with the logical memory I and visual paired associates I/II. These results suggest that in these elderly patients, a high serum HDLC level was associated with not only preserved memory function but also gyrification of the insular and frontal opercular cortex. We conclude that elderly individuals' serum lipid markers should be carefully assessed in memory clinic settings, because serum HDLC may be a biomarker for memory function and cortical structure.

Low Cholesterol Level Linked to Reduced Semantic Fluency Performance and Reduced Gray Matter Volume in the Medial Temporal Lobe

“…Underlying neural mechanism of the relationship between cholesterol levels and cognitive performance/decline has not been well established. While studies have generally agreed that high HDL levels might be beneficial to brain health (Wolf et al, 2004;Ward et al, 2010;Armstrong et al, 2019;Kinno et al, 2019), the relationship between hTC/LDL levels and brain function/structure remains controversial; both negative (Whalley et al, 2003;Reiman et al, 2010;Qiu et al, 2012;Williams et al, 2013) and positive (Leritz et al, 2011;Aine et al, 2014;Coutinho et al, 2017;Chung et al, 2018) relationships have been identified, even in the same sample (Zhang et al, 2016). In the present study, we provided evidence suggesting low-normal TC (TC < 160 mg/dl) is associated with reduced GMv in medial temporal regions (including bilateral anterior HIP).…”

“…In another study involving healthy older controls and individuals with mild cognitive impairment (MCI) or AD, low HDL was associated with low hippocampal volume (Wolf et al, 2004). In a very recent study with older adults (75 years old or older) who had subjective memory complaints, HDL was positively correlated with memory performance and gyrification indices of bilateral insular and frontal opercular cortices (Kinno et al, 2019). In a large longitudinal cohort study, higher HDL levels were associated with less steep GMv decline in the entorhinal cortex and parahippocampal gyrus, as well as a lower risk of future cognitive impairment (Armstrong et al, 2019).…”

Large-Scale Internetwork Functional Connectivity Mediates the Relationship between Serum Triglyceride and Working Memory in Young Adulthood

“…A recent structural MRI study demonstrated that gray matter reduction in the parietal, occipital, and cerebellar areas associated with increased serum TG and LDL-C in subjects with obesity [ 14 ]. Using surface-based morphometry analysis, Kinno et al identified positive correlations between serum HDL-C level and gyrification indices of the insular and frontal opercular cortices in an elderly memory-clinic population [ 5 ]. Collectively, these prior reports point towards a negative effect of serum TC, TG, and LDL-C yet a protective effect of HDL-C on brain function and structure.…”

“…Evidence is now emerging that serum lipid profile is linked to many aspects of human cognition. A large number of cross-sectional studies have established that higher serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) are associated with poorer cognitive performance in multiple domains (e.g., working memory, recognition memory, executive control, sustained attention, and inhibitory processing) [ 1 – 5 ], whereas higher serum high-density lipoprotein cholesterol (HDL-C) level is related to better cognitive functions such as verbal learning, memory, and executive function [ 5 – 7 ]. These associations are also confirmed by longitudinal studies consistently suggesting that elevated TC, TG, and LDL-C in midlife are predictive of greater cognitive decline in late life while higher HDL-C predicts better maintenance of cognitive function [ 8 – 10 ].…”

“…There have been several neuroimaging studies attempting to clarify the associations between serum lipids and the brain in both normal and disease-affected populations. As a consequence, previous findings consistently suggest a negative effect of serum TC, TG, and LDL-C yet a protective effect of HDL-C on brain structure and function, by using structural magnetic resonance imaging (MRI) to evaluate gray matter morphology [ 5 , 12 – 14 ] and using functional MRI (fMRI) to measure task-induced brain activation [ 15 ] and resting-state functional connectivity [ 4 , 16 , 17 ]. Nevertheless, whether and how differences in serum lipid parameters relate to variations in neuroimaging phenotypes in healthy young adults is still an open question.…”