Accelerated long-term forgetting as an objective marker of subjective memory impairment in multiple sclerosis

Accelerated long-term forgetting (ALF), defined as an increased rate of memory loss over extended intervals, has so far been detected in a pilot study of patients with mild multiple sclerosis (MS). This study aimed to (I) confirm the presence of ALF in a larger, heterogeneous MS sample, (II) explore associations with patient-reported outcomes, and (III) assess the diagnostic performance of ALF tests for subjective memory impairment.

This study compared 62 MS patients and 65 age-, sex-, and education-matched healthy controls using standardized memory tests (RAVLT, WMS-IV Logical Memory subtest). Recall was assessed immediately, after 30 min, and after 7 days. Seven-day/30-minute recall ratios (Q_RAVLT, Q_WMS) served as primary outcomes. Self-report measures included memory complaints, fatigue, depression, and sleep disturbances. Spearman correlations and Receiver operating characteristic (ROC) analyses assessed associations and diagnostic accuracy.

ALF was observed in multiple sclerosis since Q_RAVLT was lower in patients than in controls (0.64 [95% CI 0.59-0.69] vs. 0.78 [0.73-0.82], p < 0.001), as was Q_WMS (0.79 [95% CI 0.74-0.84] vs. 0.95 [0.90-1.00], p < 0.001), despite comparable initial learning. Greater fatigue, higher memory complaints, sleep disturbances, older age, and greater disability were associated with lower ALF scores. The combined ALF score moderately discriminated subjective memory impairment (AUC 0.74; sensitivity 0.73; specificity 0.73).

MS patients showed ALF despite normal initial learning, indicating a specific memory deficit undetected by standard tests. Long-delay recall using RAVLT and WMS-IV Logical Memory subtest may improve cognitive impairment detection in MS.

German Clinical Trials Register (DRKS00035204), registered 17 April 2025.