Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3–2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

Sergi Valero, Marta Marquié, Itziar De Rojas, Ana Espinosa, Sonia Moreno-Grau, Adelina Orellana, Laura Montreal, Isabel Hernández, Ana Mauleón, Maitée Rosende-Roca, Montse Alegret, Alba Pérez-Cordón, Gemma Ortega, Natalia Roberto, Angela Sanabria, Carla Abdelnour, Silvia Gil, Juan Pablo Tartari, Liliana Vargas, Ester Esteban-De Antonio, Alba Benaque, Lluís Tárraga, Mercè Boada, Agustín Ruíz