Association of Hippocampus volume with normal serum Natrium levels and predictive analyses of cognitive adversities in non-demented middle-aged and older adults

Hallab, Asma; · 2024 · Crossref

DOI: 10.1101/2024.11.01.24316554

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Summary

This study investigates the association between serum natrium (sodium) levels within normal clinical ranges and hippocampal volume in non-demented middle-aged and older adults, specifically examining whether these electrolyte variations predict cognitive adversity. While pathological natrium dysregulation is known to increase morbidity and mortality in older adults, the relationship between normal-range natrium fluctuations and medial temporal brain structures, which are critical for memory and cognition, remains poorly understood. The research aimed to determine if subtle variations in serum natrium correlate with hippocampal atrophy or clinical cognitive decline in individuals with healthy controls (HC) or mild cognitive impairment (MCI). The analysis utilized baseline data from 469 non-demented participants (298 HC and 171 MCI) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI3) cohort. Participants had a median age of 70 years and median serum natrium levels of 141 mmol/L. Hippocampal volumes were segmented using FreeSurfer 6.0 from 3 Tesla MRI scans, and cognitive status was assessed via the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS13). Statistical models included linear and non-linear regressions adjusted for confounders such as age, sex, education, APOE ε4 status, and intracranial volume. The Holm-Bonferroni method was applied to adjust for family-wise error rates. Results indicated a significant linear association between serum natrium levels and hippocampal volume in the total study population and specifically within the MCI subgroup. In the MCI group, each 1 mmol/L increase in serum natrium was associated with a 95 mm³ decrease in hippocampal volume (adjusted β = -95, p = 0.006, q = 0.036), representing a 1.31% reduction relative to the median volume. No significant association was observed in the healthy control group. Conversely, serum natrium levels showed no significant association with ADAS13 total scores or the odds of being diagnosed with MCI at baseline, even after adjusting for confounders. The findings suggest that normal-range serum natrium variations are significantly associated with hippocampal volume loss in individuals with underlying neurodegenerative pathology, such as MCI, but do not predict clinically measurable cognitive deficits or the likelihood of MCI diagnosis. The authors hypothesize that neurodegeneration may increase hippocampal sensitivity to electrolyte fluctuations, potentially through blood-brain barrier disruption or subclinical edema. These results highlight a structural link between electrolyte homeostasis and brain integrity in early cognitive decline, though further longitudinal studies are required to elucidate the underlying mechanisms and clinical implications.

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• cognitive impairment