•Cognitive measures: Lure Discrimination Index (LDI) from the MST and the Preclinical Alzheimer’s Cognitive Composite (PACC).

•Imaging: structural MRI processed with FreeSurfer 7.3.1 to derive regional and hippocampal-subfield volumes.

•Analysis: separate linear regression models relating each cognitive measure to brain volumes, adjusting for eTIV, amyloid PET SUVR, age, sex, and education.

•Statistics: Benjamini–Hochberg (BH) procedure controlled the False Discovery Rate; adjusted R 2 , standardized β, and FDR-adjusted p-values were extracted.

 

Results:

Mean age was 72.52 ± 1.67 years and 61% were female (Table 1). PACC was associated with bilateral whole hippocampal (L: β = 0.63; R: β = 0.52) and amygdala volumes (L: β = 0.56; R: β = 0.51), plus multiple hippocampal subfields. LDI showed a more selective hippocampal-subfield profile (Figure 1).

 

Conclusion:

PACC performance associated with broad medial-temporal and limbic atrophy — consistent with global episodic-memory decline.

LDI showed a selective profile, correlating with CA4, dentate gyrus, and subiculum subfields, but not with whole hippocampal or amygdala volumes — indicating sensitivity to hippocampal-circuit integrity.

The MST may therefore provide a sensitive, circuit-specific marker of early hippocampal dysfunction in preclinical and prodromal Alzheimer’s disease.

Acknowledgment:

We thank the participants and investigators of the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study for making the data available.

We gratefully acknowledge funding from NIH/NIA grants U19AG010483, R01AG063689, and R01AG062706