The Role of Lipoprotein (a) on the Structural Integrity of the Human Hippocampus

Abstract

Introduction

Obesity's broader implications, especially for neurocognitive functions, have recently captured significant scientific interest. Here the influence of obesity on the hippocampus, a brain area critically involved in cognitive function, is investigated.

Obesity, classified as a global epidemic, is defined as an increase in fat mass affecting health [1]. Each year, it is estimated that at least 2.8 million people die as a result of being overweight or obese. Of the health complications associated with obesity, the implications for hippocampal structural integrity are of special interest.

The hippocampus is a common target of investigation in cognitive science for its crucial role in learning and memory, which has been described since at least 1957 [2]. Additionally, the hippocampus plays an important role in cognitive tasks including pattern separation, pattern completion, regulation of emotion, fear, anxiety, and stress. As a site of increased adult neurogenesis and neuroplasticity, it is especially vulnerable to external influences [3], such as obesity-related changes in inflammation markers and metabolism. The impact of these changes on the hippocampus can be different for each subfield, thus presenting different cognitive consequences.

Method

Here the complex interplay between obesity, chronic inflammation, Lipoprotein(a) (Lp(a)), and hippocampal volume is investigated. Using high-resolution magnetic resonance imaging (MRI), hippocampal volumes in 94 obese and non-obese individuals were measured and checked for correlations with essential metabolic and inflammatory biomarkers, including insulin, interleukin 6 (IL6), C-reactive protein (CRP), and Lp(a), a genetically determined protein linked to inflammatory processes, as well as data on lifestyle, collected using a standardised questionnaire. Neuroscientific methods and methods of nutritional sciences are used to investigate the medical, neuroscientific, psychological and nutritional implications of hippocampal alterations resulting from obesity-related changes and genetics.

 Results

In this study, higher levels of lipoprotein(a) have been observed to correspond to lower volumes in the left and bilateral CA1. This could point to genetically determined processes impacting hippocampal subvolumes, affecting brain structures crucial for long-term memory, related behaviour and spatial tasks. The CA1, a key output node of the whole hippocampal memory circuit, has a major role in transferring excitatory information via the deep layers of the EC or subiculum. Impact on the CA1 could influence cognitive function related to memory and spatial tasks. Degenerative effects on the CA1 have been observed in mice and linked to Alzheimer’s in humans as well. Adding to that, a direct influence of lipoprotein (a) has been observed in Vascular Alzheimer’s disease.

These findings underscore the necessity for a multifaceted approach to studying how obesity impacts cognitive health, highlighting complex interactions between metabolic dysfunctions, inflammation, and brain architecture.

References

[1] Word Health Organization, International Classification of Diseases, Eleventh Revision (ICD-11), https://icd.who.int/browse11, 2019/2021 (accessed May 2, 2024). 

[2] W. B. Scoville and B. Milner, “Loss of recent memory after bilateral hippocampal lesions,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 20, no. 1, pp. 11–21, Feb. 1957. doi:10.1136/jnnp.20.1.11 

[3] T. Bartsch and P. Wulff, “The hippocampus in aging and disease: From plasticity to vulnerability,” Neuroscience, vol. 309, pp. 1–16, 2015. doi:https://doi.org/10.1016/ j.neuroscience.2015.07.084