Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.

Marta Marquié, Fernando García-Gutiérrez, Adelina Orellana, Laura Montrreal, Itziar De Rojas, Pablo García-González, Raquel Puerta, Clàudia Olivé, Amanda Cano, Isabel Hernández, Maitée Rosende-Roca, Liliana Vargas, Juan Pablo Tartari, Esteban-De Ester Antonio, Urszula Bojaryn, Mario Ricciardi, Diana M Ariton, Vanesa Pytel, Montserrat Alegret, Gemma Ortega, Ana Espinosa, Alba Pérez-Cordón, Ángela Sanabria, Nathalia Muñoz, Núria Lleonart, Núria Aguilera, Ainhoa García-Sánchez, Emilio Alarcón-Martín, Lluís Tárraga, Agustín Ruiz, Mercè Boada, Sergi Valero