Letter to the Editor: “Dyslipidemia and cerebral atrophy among health check-up individuals: A cross-sectional study”

Dear Editor,

We read with interest the article by He et al. entitled “Dyslipidemia and cerebral atrophy among health check-up individuals: A cross-sectional study,” which presents an important association between metabolic dysregulation and brain structural decline in asymptomatic populations [1]. The study opens new dialogue on the potential utility of routine metabolic screening as a neuropreventive tool. However, several considerations could deepen the interpretation.

First, while the association between dyslipidemia and cerebral atrophy is compelling, it is essential to consider that dyslipidemia particularly elevated triglycerides and low HDL-C is associated not only with vascular pathology but also with impaired neuronal membrane integrity and synaptic plasticity. Longitudinal data from the ARIC-Neurocognitive Study have shown that midlife triglyceride levels are significantly associated with hippocampal and entorhinal cortex volume loss two decades later, independent of overt cerebrovascular disease [2].

Second, global measures of cerebral atrophy may obscure important regional susceptibilities. For example, frontal and temporal lobe atrophy have been more closely linked to metabolic syndrome components and are early indicators of cognitive decline and Alzheimer's pathology [3]. Stratified regional analyses would help delineate which brain structures are most metabolically vulnerable.

Third, the role of systemic inflammation as a key mechanistic link between lipid dysregulation and neurodegeneration warrants deeper exploration. Dyslipidemia is usually associated with a chronic pro-inflammatory state characterized by increased circulating cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP). Studies have shown that higher CRP and IL-6 levels correlate with cortical thinning in frontal and temporal regions, as well as with increased white matter hyperintensities, which are structural markers of small vessel disease and cognitive decline [4,5].

We commend the authors for highlighting the subtle yet significant relationship between dyslipidemia and early brain structural changes in a general population. These findings should encourage clinicians and researchers to regard lipid abnormalities not merely as cardiovascular risk factors but as potential harbingers of neurodegeneration.

CRediT authorship contribution statement

Parth Aphale: Conceptualization, Supervision, Writing – original draft, Writing – review & editing. Shashank Dokania: Writing – original draft, Writing – review & editing. Himanshu Shekhar: Writing – original draft, Writing – review & editing.

Data availability

No data was used for the research described in the article.

Ethics statement

This manuscript is a letter to the editor, hence ethical approval is not applicable.

Funding

This manuscript did not receive any funding from any source.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Handling editor: D Levy