Cognitive reserve and memory markers in the dementia continuum

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Parra, Mario A.A. and Thumala, Daniela and Lillo, Patricia and Saguez, Rodrigo and Slachevsky, Andrea (2025) Cognitive reserve and memory markers in the dementia continuum. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 21 (S3). e106715. ISSN 1552-5279 (https://doi.org/10.1002/alz70857_106715)

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Abstract

Background: Cognitive reserve can render neuropsychological assessments for dementia unreliable (Pettigrew & Soldan, 2019). It is commonly measured using proxy variables such as educational attainment, intellectual functioning or social engagement (Stern, 2012). The Visual Short-Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) can inform on the dementia continuum (Forno et al., 2022; Parra et al., 2022). However, the FSCRT (Roe et al., 2008) but not the VSTMBT (Parra et al., 2024) has proved sensitive to CR. We investigated if a more reliable measure of CR (León et al., 2016) could dissociate across these tests. Methods: We involved 414 participants (42 Healthy Controls - CTR, 213 with Subjective Cognitive Decline – SCD, and 159 with major Objective Cognitive Decline - OCD) from the GERO cohort (Slachevsky et al., 2020). We also used the VSTMBT, FCSRT, and the new CR Scale. GLM explored changes in CR across three life periods (youth, adulthood, and maturity), binding abilities, and groups. Adjusted stepwise regression models explored the predictive value of Group and CR changes (youth-adult, adult-maturity) on memory binding. Results: The neuropsychological assessment revealed the pattern ((CTR ≥ SCD) > OCD, all p < 0.05). CR decreased across life periods, with SCD and OCD patients displaying the most significant drop (CR Change p <0.001, Group p <0.001, Interaction p = 0.221) (Figure 1A). Specific binding deficits were confirmed in SCD and OCD [F(2,346)=3.38, p = 0.035, η2 = 0.02, β=63%] (Figure 1B). CR did not predict the cost of binding (VSTMBT), with only Group retained (R2 = 1.8%, F = 5.99, p = 0.015). However, Immediate Free Recall (FCSRT) was best predicted by a model that retained CR, MoCA, Education and Age (R2 = 30.1%, F = 25.83, p <0.001). Conclusions: Binding functions assessed by the VSTMBT and the FCSRT are differentially affected by CR. VSTMB is a low-level visual cognition function less influenced by factors underpinning CR. The FCSRT taps into a broader network that involves language, mnemonic, and executive abilities. Future efforts should be directed to exploring versions of these promising tests that can circumvent the influence of CR and thus provide timely and reliable evidence of dementia risk.

ORCID iDs

Parra, Mario A.A. ORCID logoORCID: https://orcid.org/0000-0002-2412-648X, Thumala, Daniela, Lillo, Patricia, Saguez, Rodrigo and Slachevsky, Andrea;
CORE (COnnecting REpositories)