Subtle cognitive deficits assessed by means of CANTAB in a cohort of subjects with CSF AD profile

Abstract Background In order to make successful disease‐modifying treatments, it is needed to shift Alzheimer’s disease (AD) diagnosis toward individuals with subtle cognitive deficits not yet fulfilling MCI criteria (pre‐MCI), entity associated with AD biomarkers positivity and increased risk of progression (Parnetti et al.,2019). This might allow to identify the individuals candidate to biomarker assessment. The detection of subtle cognitive impairment is limited by the sensitivity of standard neuropsychological measures (Wolfsgruber et al.,2020; Chipi et al.,2019). Cambridge Neuropsychological Test Automated Battery (CANTAB) represents an advanced computerized tool for the assessment of non‐verbal frontal‐subcortical functioning (Robbins et al.,1994). We aimed to explore the frequency of cerebrospinal fluid (CSF) AD‐like profile in pre‐MCI subjects defined as those obtaining low scores (≥‐1 SD) in at least one CANTAB test. Method We retrospectively analyzed 64 consecutive subjects (31 males, 33 females, mean age = 67±7.9) referring to our Memory Clinic for subjective cognitive complaints. All participants performed a comprehensive standard neuropsychological battery, reporting normal scores, and tests from CANTAB (Paired Associated Learning‐PAL; Pattern Recognition Memory‐PRM; Spatial Working Memory‐SWM). Pathological performance at CANTAB (CANTAB+) was defined as scores ≥‐1 SD in at least one task. All of them underwent lumbar puncture for the analysis of CSF core AD biomarkers (Aβ42/Aβ40 ratio, total tau, phospho‐tau). By applying the A/T/(N) classification scheme (Jack et al.,2018), AD CSF profile was defined as A+/T+. As A biomarker, we considered the Aβ42/40 ratio. Result Out of 64 subjects, 43 performed ≥‐1SD in at least one test from CANTAB. In those 43 CANTAB+ subjects, 10 (23%) were A+/T+, 4 (9%) A+, and 22 (51%) A‐/T‐. Among CANTAB‐ (N = 21), 3 (14%) were A+/T+; 3 (14%) A+; 13 (61%) A‐/T‐. Among CANTAB+ subjects with A+/T+ (N = 10), 8 (80%) showed deficit in PAL, 4 at SWM and none of them showed altered scores at PRM. Conclusion Consistent proportion (23%) of pre‐MCI subjects with at least one altered score at CANTAB showed a CSF pattern compatible with AD. Since PAL test was altered in 80% of these subjects, if confirmed in independent cohorts, it might represent a sensitive neuropsychological measure to identify subjects with subtle cognitive deficits who may deserve CSF analysis for detecting preclinical AD.