The Reliability of Functional Brain Connectivity as a Biomarker in the Prediction of Suicide Risk in Neurodegenerative Disease Populations: A Literature Review

Abstract

Introduction: Neurodegenerative diseases, typically appearing in middle-to late-adulthood, are characterized by physical and cognitive decline. Alterations in functional connectivity, measured via functional magnetic resonance imaging (fMRI), have been observed in suicidal, Parkinson’s, Huntington’s, and Alzheimer’s disease populations. The review aims to explore the reliability of functional connectivity as a biomarker of suicide risk in several neurodegenerative disease populations. Methods: A literature search of PubMed and Science Direct was conducted on Covidence from January 2000 to October 2023 to investigate the reliability of functional connectivity metrics as biomarkers of suicide risk in people with neurodegenerative diseases. 2,626 articles were yielded, and a total of 68 articles met the inclusion criteria. Results: A variety of network and regional functional connectivity abnormalities were found to be consistent across study populations. Common network-wide alterations include the default mode network (DMN) and salience mode network (SN), and regional alterations include the posterior cingulate cortex (PCC) and anterior cingulate cortex (ACC). Discussion: There is a clear gap in the literature in investigating connectivity signatures in Huntington’s and suicidal populations, yielding two and five articles, respectively. Common functional connectivity signature alterations were found in individuals with Parkinson’s and Alzheimer’s disease. A lack of uniformity across studies, such as a variation in the type of fMRI functional connectivity analyses, measurement of functional connectivity, and a priori regions of interest limited the degree of confidence in the conclusions made from this review. Conclusion: A literature review utilizing four search strategies was conducted to attempt to discover commonalities between the functional connectivity signatures associated with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and suicide risk. Despite discovering common signatures across some study populations, future research is needed to define a clear functional connectivity profile for DMN and SN alterations due to suicidality, independent of normal disease progression, in individuals with a neurodegenerative disease.