Longitudinal decrements in the sensitivity of cueing in the Free and Cued Selective Reminding Test predict A+T+ status in cognitively unimpaired individuals

Abstract

AbstractBackgroundThe Index of Sensitivity of Cueing (ISC) from the Free and Cued Selective Reminding Test (FCSRT) memory test evaluates the efficacy of the semantic cues to facilitate retrieval from stored information. Although the ISC has been extensively studied in individuals with prodromal Alzheimer’s disease (AD), its association with AD core pathology, amyloid‐β (A) and p‐tau (T), in cognitively unimpaired (CU) individuals remains unknown. The aim of the present study was to explore the cross‐sectional and longitudinal differences in ISC scores among cerebrospinal fluid (CSF)‐defined AT groups in CU individuals.MethodsWe studied 341 CU participants from the ALFA+ study with available baseline CSF and longitudinal data for the word‐FCSRT‐without‐immediate‐recall version after 3 years. The ISC was computed as: (“total recall”‐“free recall”)/(48‐“free recall”). We defined AT groups (A‐T‐, A+T‐, and A+T+) using baseline CSF levels (Table1) using the cut‐offs defined in Milà‐Alomà et al., 2020. We set independent ANCOVAs to explore the associations between AT status and cross‐sectional and longitudinal (delta) ISC and main FCSRT variables (Table 1). All models were adjusted for age, education and sex, and longitudinal analyses were further adjusted for inter‐visit time and baseline scores. Nominal and FDR‐adjusted p‐values are reported.ResultsNo differences among AT groups were found for baseline FCSRT variables (Table 2). At nominal p‐value levels We observed differences in total recall (TR) and ISC both at visit2 and delta in association with AT status at nominal p‐value levels (Table2), but only the ISC change survived FDR corrections (pFDR = 0.03). Associations were driven by the A+T+ group (Figure1). No differences between A‐T‐ and A+T‐ were found (p>0.05). TR delta was still significant after adjusting for free recall (nominal p = 0.011), suggesting ISC as the main driver of TR decrements.ConclusionDecrements in sensitivity of cueing after 3 years, that in turn diminish FCSRT total recall, were related to concurrent CSF Aβ and p‐tau abnormal levels in CU individuals. No differences between AT groups were observed in free recall, in contrast with other studies using other FCSRT versions that include immediate recall during learning. Further research on secondary memory variables may elucidate the subtle changes related to early AD pathology.