ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This observational study assessed the association between metabolic syndrome (MetS) and its components with structural neuroimaging outcomes and cognitive domains in 37,395 dementia-free adults from the UK Biobank. MetS was associated with poorer brain health, characterized by reduced brain volume, increased vascular pathology, and diminished cognitive function.

Comment: MetS is characterized by the cluster of central obesity, hypertension, dyslipidemia, and impaired glucose tolerance. It is well-established that insulin resistance plays a central role in both initiating and perpetuating MetS. Insulin also has critical functions in the brain, such as promoting neuron growth, modulating the release and uptake of catecholamines, and regulating the expression and distribution of gamma-aminobutyric acid (GABA), all of which contribute to maintaining cognitive function.¹ The presence of insulin receptors in the frontal cortex and hippocampus underscores its pivotal role in learning and memory. Therefore, insulin resistance-induced alterations in insulin signaling may accelerate brain aging, affect neural plasticity, and potentially lead to neurodegeneration.

This study performed neuroimaging and cognitive assessments in dementia-free adults with MetS compared to healthy individuals without MetS. Key findings revealed that MetS health was associated with reduced total brain volume and gray matter volume, which are essential for information processing, as well as increased white matter hyperintensities, often linked to aging, cognitive decline, and dementia. Having more MetS components correlated with reduced brain volume and increased white matter hyperintensities. Specifically, waist circumference and higher HbA1c levels were associated with lower total brain and gray matter volumes, while high blood pressure showed the strongest association with increased white matter hyperintensity volume.

Study participants with MetS performed worse on cognitive tests of working memory, information recall, processing speed, verbal and numerical reasoning, nonverbal reasoning, and executive functions related to planning and problem-solving.

These findings are crucial. Previous research showed that managing MetS components can improve brain health outcomes. For example, aggressive blood pressure management has been shown to slow the progression of white matter hyperintensities. Similarly, metformin as been linked to slower cognitive decline and reduced risk of dementia, while physical activity improves cognition in people with diabetes. Additionally, there is evidence that GLP-1R agonists may have neuroprotective effects.

References: 1. Albar NY, Hassaballa H, Shikh H, Albar Y, Ibrahim AS, Mousa AH, Alshanberi AM, Elgebaly A, Bahbah EI. The interaction between insulin resistance and Alzheimer’s disease: a review article. Postgrad Med. 2024 May;136(4):377-395. doi:10.1080/00325481.2024.2360887.