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. 2025 Aug 22;17(1):195.
doi: 10.1186/s13195-025-01833-4.

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

Claudia Bartels  1 , Joy Tzu-Yueh Chen  2 , Michael Belz  1 , Renat Yakupov  3   4 , Emrah Düzel  3   4 , Wenzel Glanz  3 , Falk Lüsebrink  3 , Peter Dechent  5 , Luca Kleineidam  6   7 , Melina Stark  7 , Annika Spottke  6   8 , Marie Coenjaerts  6 , Klaus Fließbach  6   7 , Anja Schneider  6   7 , Ayda Rostamzadeh  9 , Frank Jessen  6   10   11 , Björn H Schott  1   12   11 , Jens Wiltfang  1   12   13 , Ingo Frommann  6   7 , Michael Wagner  6   7 , Roberto Goya-Maldonado  14
Affiliations

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

Claudia Bartels et al. Alzheimers Res Ther. .

Abstract

Background: Long-term retrieval (LTR) and accelerated long-term forgetting (ALF) paradigms might help differentiating individuals at increased dementia risk from healthy controls (HC).

Objective: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Alzheimer’s disease; Consolidation; Dementia; Hippocampus; Long-term retrieval; Memory; Mild cognitive impairment; Subjective cognitive decline.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The DELCODE study protocol was coordinated by the ethical committee of the medical faculty of the University of Bonn and approved by all participating sites ethical committees. All patients provided written informed consent for their clinical data to be used for research purposes. Consent was obtained according to the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: CB received honoraria for lectures from Lilly and Eisai (2024) and as an advisory board member for Lilly and Boehringer Ingelheim (2024). CB also received funding from the German Alzheimer Association (2021–2023). WG served as a paid advisor for Lilly, Roche, and Eisai, and is a co-founder with stock options in the digital health company neotiv. FJ received fees for advice and presentations from AbbVie, AC Immune, Biogen, Eli Lilly, Eisai, GE Healthcare, Grifols, Janssen-Cilag, and Roche. BS collaborated with Roche and Biogen for clinical studies with no personal financial benefit. JW served on scientific advisory boards for Abbott, Biogen, Boehringer Ingelheim, Lilly, Immungenetics, MSD Sharp & Dohme, Noselab, Roboscreen, and Roche. All other co-authors have no conflicts of interest to disclose over the last 36 months.

Figures

Fig. 1
Fig. 1
Quality check. Example of a participant’s FreeSurfer segmentation and 3D reconstruction of the hippocampi and constituent subfields
Fig. 2
Fig. 2
Participants flow. Abbreviations: LTR: long-term retrieval; HC: healthy controls; SCD: subjective cognitive decline; MCI: mild cognitive impairment; GDS: Geriatric Depression scale (15 item-version); MRI: magnetic resonance imaging
Fig. 3
Fig. 3
Long-term retrieval (expressed as LTR rates) differs between diagnostic groups HC, SCD, and MCI. (A) Results of one-way ANOVA with Bonferroni-adjusted post hoc tests for all diagnostic groups. (B) Diagnostic accuracy (discrimination of HC and SCD) by ROC curves. LTR: long-term retrieval; HC: healthy controls; SCD: subjective cognitive decline; MCI: mild cognitive impairment; FCSRT-IR: Free and Cued Selective Reminding Task with Immediate Recall
Fig. 4
Fig. 4
Association of long-term retrieval in FCSRT-IR LTR rate and CA1 volume. (A) Left and (B) right CA1 body volume were correlated with FCSRT LTR rates in SCD and HC (N = 32). Analyses: Spearman-Rho correlations. HC: healthy controls; SCD: subjective cognitive decline; FCSRT-IR: Free and Cued Selective Reminding Task with Immediate Recall
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