The Association Between Plasma Amyloid-β 42/40 and Percentage of Semantic Intrusion Errors in Mild Cognitive Impairment

Article type: Research Article

Authors: Curiel Cid, Rosie E.^{a; b; *} | Ortega, Alexandra^{a; b} | Vaillancourt, David^{a; c} | Asken, Breton^{a; d} | Crocco, Elizabeth A.^{a; b} | Armstrong, Melissa J.^{a; e} | Duara, Ranjan^{a; f} | Crenshaw, Kirsten^b | Adjouadi, Malek^{a; g} | Rosselli, Monica^{a; h} | Wang, Wei-en^{a; c} | Loewenstein, David A.^{a; b}

Affiliations: [a] 1Florida Alzheimer’s Disease Research Center (ADRC), Miami, FL, USA | [b] Center for Cognitive Neuroscience and Aging (CNSA), Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA | [c] Department of Applied Physiology and Kinesiology, Gainesville, FL, USA | [d] Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA | [e] University of Florida College of Medicine, Gainesville, FL, USA | [f] Department of Neurology and The Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA | [g] Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA | [h] Department of Psychology, Florida Atlantic University, Boca Raton, FL, USA

Correspondence: [*] Correspondence to: Rosie E. Curiel Cid, PsyD, Professor of Psychiatry and Behavioral Sciences, Center for Cognitive Neuroscience and Aging (CNSA), University of Miami Miller School of Medicine, 1695 NW 9th Avenue, Suite 3202, Miami, FL 33136, USA. E-mail: [email protected].

Abstract: Background:Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-β (Aβ) burden in older adults with amnestic mild cognitive impairment (aMCI). Objective:Plasma Aβ biomarkers including the Aβ42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer’s disease (AD). Methods:This study included 119 older adults enrolled in the 1Florida Alzheimer’s Disease Research Center (ADRC), 45 aMCI participants scored below the established Aβ42/40 ratio cut-off of 0.160 using the Quest AD-Detect™ assay indicating Aβ positivity (Aβ+), while 50 aMCI participants scored above this cut-off indicating Aβ negative status (Aβ–). Additionally, 24 cognitively unimpaired (CU) persons scored above the cut-off of 0.160 (Aβ–). Results:The aMCI plasma Aβ+ group evidenced the greatest percentage of SIEs, followed by the aMCI Aβ–. The CU Aβ– group exhibited the lowest percentage of SIEs. After adjustment for global cognitive impairment, aMCI plasma Aβ+ continued to demonstrate greater SIEs on tests tapping the failure to recover from proactive semantic interference (frPSI) as compared to the aMCI Aβ–group. Using pre-established cut-offs for frPSI impairment, 8.3% of CU Aβ– participants evidenced deficits, compared to 37.8% of aMCI Aβ–, and 74.0% of aMCI Aβ+. Conclusions:SIEs reflecting frPSI were associated with aMCI Aβ+ status based on the Aβ42/40 ratio. Results suggest the importance of SIEs as salient cognitive markers that map onto underlying AD pathology in the blood.

Keywords: Alzheimer’s disease, amyloid-β, Aβ_42/40, LASSI-L, mild cognitive impairment, plasma biomarkers, semantic intrusion errors

DOI: 10.3233/JAD-240164

Journal: Journal of Alzheimer's Disease, vol. 101, no. 4, pp. 1195-1204, 2024