Long-term retrieval performance is associated with CA1 hippocampal volume in older adults and individuals at risk for dementia

Long-term retrieval (LTR) and accelerated long-term forgetting (ALF) paradigms might help differentiating individuals at increased dementia risk from healthy controls (HC). We investigated the utility of a LTR paradigm in discriminating subjective cognitive decline (SCD) from HC and its relationship to the CA1 body volume, a hippocampal structure pivotal to the memory circuitry. LTR was assessed via recall rates of the ADAS-cog word list and the FCSRT-IR free recall in 59 DELCODE study participants, including individuals with SCD and mild cognitive impairment (MCI), as well as HC, all of them DELCODE study participants. LTR performance was compared between groups and its discriminability between SCD and HC was assessed using ROC curve analysis. 32 SCD and HC participants had FreeSurfer-segmented MRI data, and hippocampal subfield volumes were correlated with LTR rates. Only FCSRT-IR LTR rates sufficiently differentiated SCD from HC (AUC of 0.701; 95% CI 0.537-0.865). Moderate associations of the FCSRT-IR LTR rate with CA1 bodies in both hemispheres (left CA1 body r = 0.419, p = 0.017; right: r = 0.412, p = 0.019), in addition to the left C3 body were observed (r = 0.525, p = 0.002). LTR may constitute a potential indicator of memory circuitry integrity in older adults, which is also mirrored by its association with CA1 volume. Thus, assessment of LTR and associated neural circuits may help to better identify individuals at risk for future cognitive decline today indistinguishable from HC, ultimately paving the way for early intervention.