ROLE OF THE PAIRED ASSOCIATES LEARNING TASK FROM CANTAB IN THE ASSESSMENT OF INDIVIDUALS WITH SUBJECTIVE COGNITIVE DECLINE AND MCI PATIENTS

Abstract

The combination of computerized neuropsychological assessment and cerebrospinal fluid (CSF) biomarkers may improve the early diagnosis of Alzheimer's disease (AD) [Soldan et al., 2016]. Cambridge Neuropsychological Test Automated Battery (CANTAB) represents a computerized advanced tool for an in-depth neuropsychological evaluation. In CANTAB, the Paired Associates Learning (PAL) task (total errors and total errors 6-shapes), measuring visuo-spatial associative learning, is altered early in AD course [Junkkila et al., 2012]. We administered PAL in individuals with Subjective Cognitive Decline (SCD) [Jessen et al 2014] and Mild Cognitive Impairment (MCI) [Petersen et al., 2004] who underwent CSF AD biomarkers evaluation. We also explored the capacity of PAL in predicting cognitive decline over time. Seventy-two consecutive patients who referred to our Memory Clinic from 2012 to 2016 for memory complaints underwent a standard neuropsychological evaluation. Forty-one patients were classified as SCD (normal performance) and 31 as MCI (-1.5 SD in memory tests). The neuropsychological assessment also included CANTAB subtests assessing visual memory (pattern recognition memory, PRM), spatial working memory, SWM, and visuo-spatial associative learning, PAL. All patients underwent lumbar puncture to measure CSF AD biomarkers-Aβ1–42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau). The neuropsychological assessment was repeated after 1 year. Out of 72 patients, 26 patients (39%) showed a CSF AD-like profile (16/31, 58%, MCI, 10/41, 24%, SCD). At follow-up, 8/41 (22%) of SCD progressed to MCI, where all but one showed an AD-like profile; 8/31 (25%) of MCI converted to dementia (5 to AD, 3 to other dementias). In SCD group, PAL-total errors fairly discriminated individuals with AD-like CSF profile with respect to those with normal CSF profile (-1.76±1.59 vs -0.65±1.44, p=0.048). Baseline performance on PAL-6 shapes was significantly associated with cognitive worsening as measured by MMSE. These results suggest that PAL test from CANTAB may be a sensitive and reliable neuropsychological measure to identify subjects with subtle cognitive deficits who may deserve CSF analysis for early AD detection.