Cerebrospinal Fluid Correlates of Neuropsychiatric Symptoms in Patients with Alzheimer’s Disease/Mild Cognitive Impairment: A Systematic Review

Article type: Research Article

Authors: Showraki, Alireza^a | Murari, Geetanjali^a | Ismail, Zahinoor^g | Barfett, Joseph J.^{a; j} | Fornazzari, Luis^{a; b} | Munoz, David G.^{a; h; i} | Schweizer, Tom A.^{a; c; d; e; f} | Fischer, Corinne E.^{a; c; k; *}

Affiliations: [a] Keenan Research Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada | [b] Division of Neurology, St. Michaels Hospital, University of Toronto, Toronto, ON, Canada | [c] Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada | [d] Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada | [e] Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Toronto, ON, Canada | [f] Division of Neurosurgery, St. Michael’s Hospital, Toronto, ON, Canada | [g] Departments of Psychiatry and Neurology, Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada | [h] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada | [i] Division of Pathology, St. Michael’s Hospital, Toronto, ON, Canada | [j] Department of Medical Imaging, St. Michael’s Hospital, Toronto, ON, Canada | [k] Faculty of Medicine, Department of Psychiatry, University of Toronto, Toronto, ON, Canada

Correspondence: [*] Correspondence to: Corinne E. Fischer, Faculty of Medicine, Department of Psychiatry, University of Toronto, Canada, M5 S 1A8. Tel.:+1 416 864 5320; E-mail: FischerC@smh.ca.

Abstract: Background:Neuropsychiatric symptoms (NPS) are common, accelerate the conversion to dementia, and are associated with increased caregiver burden in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Objective:The aim of this study is to identify potential associations between the core cerebrospinal fluid (CSF) biomarkers (amyloid/tau) and NPS in AD/MCI. Methods:For this systematic review, four databases, PubMed (1946–2018), Cochrane (2005–2018), EMBASE (1947–2018), and PsycINFO (1806–2018) were searched for relevant observational studies using an extensive list of keywords. English studies were selected for critical appraisal based on our inclusion/exclusion criteria. Inclusion criteria were defined as 1) at least one AD CSF biomarker has been measured; 2) at least one NPS has been assessed; and 3) analysis has been done to examine the association between core AD CSF biomarker and NPS (main outcome). Animal, postmortem, and review studies were excluded. Results:In total, 21 studies qualified for the systematic review. The overall picture regarding the association between NPS and AD CSF biomarkers is conflicting. However, agitation/aggression was significantly and consistently related to core AD CSF biomarkers. Moreover, depression was the only NPS to occasionally be associated with lower core AD CSF pathology. Conclusion:Our study has revealed agitation/aggression as the most consistent NPS related to core AD CSF biomarkers. Future studies are required to focus on other neglected NPS domains such as disinhibition. Moreover, why depression was the only NPS inversely associated with core AD CSF pathology remains to be elucidated. Our study also revealed a great degree of heterogeneity, hence calling for a more standardized “objective” approach for the evaluation of NPS.

Keywords: Alzheimer’s disease, behavioral symptoms, biomarkers, cerebrospinal fluid, neuropsychiatry, systematic review

DOI: 10.3233/JAD-190365

Journal: Journal of Alzheimer's Disease, vol. 71, no. 2, pp. 477-501, 2019