Age-dependent associations of peripheral inflammatory biomarkers with cognition and brain structural abnormalities in patients with Alzheimer's disease and Alzheimer's disease-related mild cognitive impairment.

BACKGROUND: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative conditions. Chronic peripheral inflammation has been implicated in the pathophysiology of AD. Given their accessibility and cost-effectiveness, peripheral inflammatory biomarkers hold promise as potential indicators for AD. However, their associations with cognitive function and brain structural abnormalities may vary across patients and age groups. METHODS: Patients diagnosed with AD or AD-related mild cognitive impairment (AD-MCI) were included. Peripheral inflammatory biomarkers, including white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), and monocyte count (MONO), were obtained from complete blood count (CBC). Composite inflammatory biomarkers were calculated from the aforementioned parameters and included the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-platelet ratio (NPR), neutrophil-monocyte-to-lymphocyte ratio (NMLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). We examined the associations of peripheral blood inflammatory biomarkers and calculated composite inflammatory biomarkers with cognitive function, global cortical atrophy, and hippocampal atrophy. Interaction and stratified analyses were employed to investigate the modifying effects of age and sex on these associations. RESULTS: The study included a total of 395 patients. Within the overall sample, almost all inflammatory biomarkers did not exhibit significant associations with cognitive function, global cortical atrophy, or hippocampal atrophy. Interaction analyses revealed significant interactions between age and several inflammatory biomarkers, while no significant interactions were detected concerning sex. Stratified analyses indicated that among patients younger than 75 years, several composite inflammatory biomarkers were significantly associated with cognitive function, global cortical atrophy, and hippocampal atrophy, whereas no significant associations were observed in patients aged 75 years or older. CONCLUSION: In patients with AD and AD-MCI, the associations between peripheral inflammatory biomarkers and both cognitive impairment and structural brain abnormalities were found to be age-dependent, with stronger associations observed in patients younger than 75 years. Several composite inflammatory biomarkers showed more consistent associations and may help characterize heterogeneity within this clinical population, although their prognostic and diagnostic value requires further validation.