Omics-AD-A multimodal biomarker study on cognitive decline and neuropsychiatric symptoms: Design and cohort characteristics.

Background: Alzheimer's disease (AD) clinically manifests in cognitive decline and frequent neuropsychiatric symptoms (NPS). Objective: The Omics-AD study's scope is to perform an in-depth multi-modal and longitudinal characterization of people with early AD to a) better understand pathophysiological changes of AD and b) identify new biomarkers for AD and AD-related clinical manifestation and progression, with a focus on NPS. Methods: Participants in this prospective study were recruited at four Swiss memory-clinics. Comprehensive cognitive and neuropsychiatric assessments were performed at baseline and follow-up. Paired blood and cerebrospinal fluid (CSF) samples along with structural MRI were obtained at baseline. Established CSF AD biomarkers were analyzed. Untargeted omics and targeted molecular analyses will be performed and integrated in multi-modal, multi-omics data analysis. Results: We included 456 participants (mean age 71.2 years, 55.1% female), of which 48.5% were cognitively unimpaired (with no cognitive complains, NC, or with subjective cognitive decline, SCD) and 51.5% cognitively impaired (mild cognitive impairment, MCI, or mild clinical AD dementia). Half of the participants presented with NPS as measured by the Neuropsychiatric Inventory Questionnaire (48.5%) or the Mild Behavioral Impairment Checklist (52.7%). The most common symptoms were irritability (18%) and depression (17%). In total, 41.0% (n = 155) of participants were amyloid positive (20.6% of CN, 21.7% of SCD, 55.4% of MCI, and 72.4% of clinical AD dementia). Conclusions: This multi-centric well-characterized cohort allows for single- and multi-omics analyses to investigate in depth molecular and biological pathway alterations in AD and their relationships with clinical manifestation and progression, with a particular focus on NPS.