Abstract
PURPOSE: This systematic review aimed to summarize the evidence on the association between multimorbidity and fluid biomarkers of Alzheimer's disease (AD). METHODS: We systematically searched PubMed, Web of Science, and Embase for studies investigating the association between multimorbidity-defined as the co-occurrence of multiple chronic conditions in the same individual-and levels of cerebrospinal fluid (CSF) or blood biomarkers of AD, focusing on the most established AD biomarkers (amyloid-beta, phosphorylated-tau, total-tau, neurofilament light chain, and glial fibrillary acidic protein). Studies were selected following PRISMA guidelines. RESULTS: Out of 3,104 records, we identified 10 cross-sectional studies. Four studies assessed CSF biomarkers in dementia-free participants with mean age between 61.8 and 66.6 years, yielding mixed findings with no consistent association between multimorbidity and CSF biomarkers. Six studies focused on blood biomarkers in participants with mean age ranging from 66.5 to 76.4 years, five of which included individuals with dementia. Most of these studies reported an association between multimorbidity and elevated blood biomarker levels. CONCLUSIONS: This review suggests a significant association between multimorbidity and AD blood biomarkers in older populations, while the results on CSF are mixed and inconsistent. Further research is needed, particularly longitudinal studies assessing both CSF and blood biomarkers within the same populations.