Neuropsychiatric Symptoms and In Vivo Alzheimer’s Biomarkers in Mild Cognitive Impairment

Article type: Research Article

Authors: Spampinato, Maria Vittoria^{a; *} | Ulber, Jenny L.^b | Fayyaz, Habiba^b | Sullivan, Allison^b | Collins, Heather R.^a | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Radiology and Radiological Science Department, Medical University of South Carolina, Charleston, SC, USA | [b] College of Medicine, Medical University of South Carolina, Charleston, SC, USA

Correspondence: [*] Correspondence to: Maria V. Spampinato, MD, Department of Radiology and Radiological Science, Medical University of South Carolina, 96 Jonathan Lucas Street, MSC 323, Charleston, SC 29425, USA. Tel.: +1 843 792 0209; Fax: +1 843 792 1889; E-mail: spampin@musc.edu; Twitter handle: @mvspampinato.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background:Neuropsychiatric symptoms (NPS) carry an increased risk of progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). There is a need to understand how to integrate NPS into the paradigm outlined in the 2018 NIA-AA Research Framework. Objective:To evaluate a prediction model of MCI-AD progression using a collection of variables, including NPS, cognitive testing, apolipoprotein E4 status (APOE4), imaging and laboratory AD biomarkers. Methods:Of 300 elderly subjects, 219 had stable MCI and 81 MCI-AD progression over a 5-year follow-up. NPS were measured using the Neuropsychiatric Inventory (NPI). A multivariate Cox Proportional Hazards Regression Analysis assessed the effects of APOE4, baseline NPI, baseline CSF amyloid-β, phosphorylated and total tau, baseline AD-signature MRI biomarker, baseline memory and executive function on MCI-AD progression. Results:27% progressed to dementia (median follow-up = 43 months). NPS were found in stable MCI (62.6%) and MCI-AD converters (70.3%). The Cox model exhibited a good fit (p < 0.001), and NPS (HR = 1.033, p = 0.027), phosphorylated tau (HR = 1.011, p = 0.025), total tau (HR = 1.005, p = 0.024), AD-signature MRI biomarker (HR = 0.111, p = 0.002), executive function (HR = 0.727, p = 0.045), and memory performance (HR = 0.387, p < 0.001) were significantly associated with dementia. Conclusions:NPS may inform dementia risk assessment in conjunction with cognitive testing and imaging and laboratory AD biomarkers. NPS is independently associated with the risk of MCI-dementia progression, over and beyond the contributions of CSF biomarkers.

Keywords: Alzheimer’s disease, amyloid, cerebrospinal fluid, cognitive dysfunction, magnetic resonance imaging, neuropsychiatric symptoms

DOI: 10.3233/JAD-220835

Journal: Journal of Alzheimer's Disease, vol. 96, no. 4, pp. 1827-1836, 2023