CEREBROSPINAL FLUID CORRELATES OF NEUROPSYCHIATRIC SYMPTOMS IN PATIENTS WITH ALZHEIMER'S DISEASE/MILD COGNITIVE IMPAIRMENT

Abstract

Introduction Neuropsychiatric symptoms (NPS) are common in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) but their association with disease biomarkers remains unknown. The aim of this systematic review is to identify potential cerebrospinal fluid (CSF) biomarkers of neuropsychiatric symptoms in Alzheimer's disease (AD) and MCI based on a systematic review of the current literature. Methods We developed a pre-defined search strategy focused on the association between CSF biomarkers and NPS in patients with AD/MCI using an extensive list of relevant keywords and controlled vocabulary. The search was then performed on four databases: Pubmed, EMBASE, Cochrane, and PsycINFO. 8838 results were recorded and screened by 2 independent reviewers. Studies were selected for critical appraisal based on our inclusion/exclusion criteria. Inclusion criteria were defined as, (1) Study must be in English (2) at least one AD CSF biomarker has been measured (3) at least one NPS from the neuropsychiatric inventory (NPI) has been assessed (4) study population should at least include patients with AD or MCI (5) some type of statistical analysis has been done in an effort to elaborate the association between an AD CSF biomarker and the status of NPS. Furthermore, Non-English, animal and review studies or studies not including an NPS, AD CSF biomarker or AD/MCI patients were excluded. Eventually, a total of 23 studies qualified for the final systematic review and are presented in the study Results Among all neuropsychiatric symptoms, depression was the most evaluated NPS followed by sleep, psychosis, anxiety, agitation/aggression, eating/appetite, apathy, and irritability. Most studies have reported conflicting results regarding the presence/absence of any significant association between any NPS with any of the AD CSF biomarkers. However, the NPS of agitation/aggression was significantly related to at least one CSF biomarker across all the studies evaluating this NPS. Conclusions Our study has revealed agitation/aggression as the most consistent NPS related to AD CSF pathology based on a review of the current literature. However, multiple studies have also revealed a conflicting relationship between AD CSF biomarkers and other NPS. Future studies are required to clarify these associations. Future studies should also focus on other NPS such as elation/euphoria, motor disturbances, and disinhibition as it seems to be the neglected domains in previous studies. Our study has also revealed a great degree of heterogeneity among studies, hence calling for a more standardized “objective” approach for the evaluation of NPS in dementia. This research was funded by Not Applicable