Validity of CSF alpha‐synuclein to predict psychosis in prodromal Alzheimer´s disease

Abstract

AbstractBackgroundThe emergence of psychotic symptoms (PS) in Alzheimer´s disease (AD) involves a poor prognosis of the illness and may be related with different genetic, personal, environmental and caregiver factors, as well as unbalances in key neural proteins. In this last group, an alteration in the alpha‐synuclein (AS) metabolism may be included. Aim: To study the diagnostic validity of AS in CSF, to predict the emergence of PS in prodromal AD patients.MethodMild cognitive impairment patients (according to Petersen 2006) from the out‐patient consultation of Alicante University General Hospital (Spain) were recruited between 2010‐2018. All the patients followed NIA‐AA 2018 criteria for AD biomarkers. At inclusion, all of them had MMSE higher than 22, Neuropsychiatric Inventory lower than 10, Lawton‐Brody scale higher than 7, IQCODE lower than 80, Barthel index higher than 95 and a follow‐up higher than 2 years. All patients were treated with anticholinesterasic drugs from the diagnostic was made. The Pittsburgh sleep quality index and the Cummings criteria for psychosis (2020) were applied and the requirement of neuroleptic drugs was necessary to consider the inclusion in the psychosis group. Core AD biomarkers and AS were measured in CSF obtained in the prodromal phase of the illness. Different comparisons were made between the groups and subgroups following the time of emergence of PS.Result130 prodromal AD were included. 50 of them (38.4%) accomplished the psychosis criteria into the 8 years follow‐up. In every comparison made between groups and subgroups, AS was the best CSF biomarker to differentiate psychotic versus non psychotic groups. The level of AS 1257 pg/mL reached at least 80% of sensitivity to differentiate between both groups. A negative predictive value of 80% was found to differentiate between groups.ConclusionThe measurement of AS in CSF is the most valid biomarker used in this study to predict the emergence of PS during the 8 years after the prodromal phase of AD. These results must be confirmed in a larger population but, in our knowledge, is the first time that a CSF biomarker shows a diagnostic validity to predict PS in prodromal AD.