Associations between Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers in People with Mild Cognitive Impairment

Giulia Arenare; Riccardo Manca; Paolo Caffarra; Annalena Venneri; On Behalf Of The Alzheimer's Disease Neuroimaging Initiative

doi:10.3390/brainsci13081195

Associations between Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers in People with Mild Cognitive Impairment

Brain Sci. 2023 Aug 12;13(8):1195. doi: 10.3390/brainsci13081195.

Authors

Giulia Arenare¹, Riccardo Manca^{1

2}, Paolo Caffarra¹, Annalena Venneri^{1

2}, On Behalf Of The Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy.
² Department of Life Sciences, Brunel University London, Uxbridge UB8 3BH, UK.

Abstract

Background: Neuropsychiatric symptoms (NPS) are associated with faster decline in mild cognitive impairment (MCI). This study aimed to investigate the association between NPS severity and Alzheimer's disease (AD) biomarkers, i.e., amyloid-β (Aβ), phosphorylated tau protein (p-tau) and hippocampal volume ratio (HR), to characterise in more detail MCI patients with a poor prognosis.

Methods: A total of 506 individuals with MCI and 99 cognitively unimpaired older adults were selected from the ADNI dataset. The patients were divided into three different groups based on their NPI-Q total scores: no NPS (n = 198), mild NPS (n = 160) and severe NPS (n = 148). Regression models were used to assess the association between the severity of NPS and each biomarker level and positivity status.

Results: Cerebrospinal fluid Aβ levels were positively associated with older age and lower MMSE scores, while higher p-tau levels were associated with female sex and lower MMSE scores. Only patients with severe NPS had a lower HR (β = -0.18, p = 0.050), i.e., more pronounced medio-temporal atrophy, than those without NPS.

Discussion: Only HR was associated with the presence of NPS, partially in line with previous evidence showing that severe NPS may be explained primarily by greater grey matter loss. Future longitudinal studies will be needed to ascertain the relevance of this finding.

Keywords: amyloid; biomarkers; mild cognitive impairment; neurodegeneration; neuropsychiatric symptoms; tau.

Grants and funding

The data collection and sharing for this project were funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense, award number W81XWH-12-2-0012). The ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosi-ty; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org (accessed on 10 July 2023)). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. R.M. acknowledges the support received through a research fellowship from the Alzheimer’s Association.