NEURONORMA Cognitive Battery Associations with Cerebrospinal Fluid Amyloid-β and Tau Levels in the Continuum of Alzheimer’s Disease

Article type: Research Article

Authors: García-Escobar, Greta^a | Puig-Pijoan, Albert^{a; b} | Puente-Periz, Víctor^{a; b} | Fernández-Lebrero, Aida^{a; b; c} | María Manero, Rosa^{a; b} | Navalpotro-Gómez, Irene^{a; b; c} | Suárez-Calvet, Marc^{b; c; d; e} | Grau-Rivera, Oriol^{b; c; d; e} | Contador-Muñana, José^{a; b; c} | Cascales-Lahoz, Diego^b | Duran-Jordà, Xavier^d | Boltes, Núncia^f | Pont-Sunyer, Maria Claustre^f | Ortiz-Gil, Jordi^{f; g; h} | Carrillo-Molina, Sara^{f; g} | López-Villegas, María Dolores^{d; i} | Abellán-Vidal, María Teresaⁱ | Martínez-Casamitjana, María Isabelⁱ | Hernández-Sánchez, Juan José^j | Padrós-Fluvià, Anna^j | Peña-Casanova, Jordi^{a; *} | Sánchez-Benavides, Gonzalo^{c; d; e; *}

Affiliations: [a] Integrative Pharmacology and Systems Neurosciences Research Group, Neurosciences Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain | [b] Cognitive Impairment and Movement Disorders Unit, Neurology Department, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain | [c] Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain | [d] IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain | [e] Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain | [f] Neurology Department, Hospital General de Granollers, Granollers, Spain | [g] Psychology Unit, Hospital General de Granollers, Granollers, Spain | [h] Maria Angustias Gimenez Research Foundation (FIDMAG), Sant Boi del Llobregat, Spain | [i] Centre Emili Mira, Institut de Neuropsiquiatria i Addiccions (INAD), Parc de Salut Mar, Santa Coloma de Gramenet, Spain | [j] Laboratori de Referència de Catalunya, Sant Boi del Llobregat, Spain

Correspondence: [*] Correspondence to: Gonzalo Sánchez-Benavides, Barce-lonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Wellington 30, 08005 Barcelona, Spain. Tel.: +34 933160990; Fax: +34 932275783; [email protected] and Jordi Peña-Casanova, Integrative Pharmacology and Systems Neurosciences Research Group, Neurosciences Research Program, Hospital del Mar Medical Research Institute (IMIM), Dr. Aiguader, 88, 08003 Barcelona, Spain. Barcelona, Spain. Tel.: +34 933 16 04 00; Fax: +34 93 3160723; [email protected].

Abstract: Background:Neuropsychological assessments are essential to define the cognitive profile and contribute to the diagnosis of Alzheimer’s disease (AD). The progress in knowledge about the pathophysiological process of the disease has allowed conceptualizing AD through biomarkers as a biological continuum that encompasses different clinical stages. Objective:To explore the association between cerebrospinal fluid (CSF) biomarkers of AD and cognition using the NEURONORMA battery, in a sample of cognitively unimpaired (CU), mild cognitive impaired (MCI), and mild dementia of the Alzheimer type (DAT) subjects, and to characterize the cognitive profiles in MCI subjects classified by A/T/N system. Methods:42 CU, 35 MCI, and 35 mild DAT were assessed using the NEURONORMA battery. Core AD biomarkers [amyloid-β42 (Aβ42) peptide, total tau (t-tau), and phosphorylated tau 181 (p-tau181)] proteins were measured in CSF. Correlation coefficients, multivariate regression, and effect sizes were calculated. We explored the age- and education-adjusted cognitive profiles by A/T/N variants within the MCI group. Results:Cognitive outcomes were directly associated with CSF Aβ42 and inversely with CSF tau measures. We found differences in both biomarkers and cognitive outcomes comparing all pairs except for CSF measures between cognitively impaired groups. The highest effect size was in memory tasks and biomarkers ratios. Lower performances were in memory and executive domains in MCI subjects with AD pathology (A+T+N±) compared to those with normal levels of AD biomarkers (A– T– N). Conclusion:This study provides further evidence of the validity of Spanish NEURONORMA cognitive battery to characterize cognitive impairment in the AD pathological continuum.

Keywords: Alzheimer’s disease, biomarkers, cerebrospinal fluid, cognitively unimpaired, mild cognitive impairment, neuropsychological tests

DOI: 10.3233/JAD-220930

Journal: Journal of Alzheimer's Disease, vol. 92, no. 4, pp. 1303-1321, 2023