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

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-β 42 (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 the 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.

Neuropsychological Assessment for Early Detection and Diagnosis of Dementia: Current Knowledge and New Insights

“…The IWGMCI consensus provided a flexible framework for MCI diagnosis and agreed that biomarkers could help elucidate clinical progression [ 12 ]. Given that access to biomarkers is usually very limited in diverse community settings (e.g., low-income countries) [ 13 ], neuropsychological assessment may play an important role in identifying cognitive risk profiles in the prodromal stages of neurodegenerative diseases and dementia diagnosis [ 14 , 15 , 16 ].…”

“…The IWGMCI consensus provided a flexible framework for MCI diagnosis and agreed that biomarkers could help elucidate clinical progression [12]. Given that access to biomarkers is usually very limited in diverse community settings (e.g., low-income countries) [13], neuropsychological assessment may play an important role in identifying cognitive risk profiles in the prodromal stages of neurodegenerative diseases and dementia diagnosis [14][15][16]. Notes: O, optional; X, mandatory; -, not specified or not considered; a social cognition: cognitive processes involved in interacting with and understanding other people (e.g., emotion perception, theory of mind, social knowledge of rules and roles) [19].…”