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Impairment in Narrative Episodic Memory and Increased Cognitive Workload Following Chemotherapy for Breast Cancer
Based on findings reported by Sekeres MJ, et al. Transl Neurosci. 2026.
Background and Study Rationale
Subjective cognitive impairment following chemotherapyโcommonly termed “chemobrain”โis “terrifyingly pervasive,” affecting up to 75% of patients treated for cancer. Although neurotoxic effects on cerebral architecture are established, the specific impact of antineoplastic agents on complex, real-world episodic memory has remained poorly characterized.
Melanie J. Sekeres, PhD, associate professor in the School of Psychology at the University of Ottawa, explained the mechanistic rationale:
โWhat really motivated the study is the known impact of chemotherapy on the brain, particularly in a region of the brain called the hippocampus, which is critical for memory formation and specifically for episodic memory formation.โ
Addressing the gap in clinical literature regarding complex daily memory, Sekeres noted that:
โThereโs really a lack of understanding.โ
Study Cohort and Testing Protocol
Investigators conducted an observational study comparing women who had completed chemotherapy for breast cancer at least 6 months prior with female controls who had no history of breast cancer.
Participants completed two remote cognitive evaluation sessions. The first session administered the Montreal Cognitive Assessment (MoCA). The second session evaluated episodic memoryโdefined as โthe vivid recollection of personal eventsโโand semantic memoryโdefined as โgeneral knowledge and facts.โ Testing included immediate and delayed recall of two Taler stories, the Survey of Autobiographical Memory (SAM), the Verbal Paired Associates (VPA) test across 4 sets of 8 unrelated word pairs (e.g., banana and shoe), and the National Aeronautics and Space Administration Task Load Index (NASA-TLX) to assess cognitive workload across tasks.
Table 1. Cohort Demographics and Assessment Battery
| Parameter | Chemotherapy Cohort (n=45) | Control Cohort (n=43) |
| Mean Age (Years) | 51.22 | 49.88 |
| Race: White (%) | 95.6% | 81.4% |
| Clinical Eligibility | $\ge$6 months post-chemotherapy for breast cancer | No prior breast cancer history |
| Primary Testing Measures | * Montreal Cognitive Assessment (MoCA) * Taler Story Recall (Verbatim, Gist, Distortion) * Verbal Paired Associates (VPA) * Survey of Autobiographical Memory (SAM) * NASA Task Load Index (NASA-TLX) | * Montreal Cognitive Assessment (MoCA) * Taler Story Recall (Verbatim, Gist, Distortion) * Verbal Paired Associates (VPA) * Survey of Autobiographical Memory (SAM) * NASA Task Load Index (NASA-TLX) |
Episodic Memory Outcomes and Cognitive Workload
During the “naturalistic” Taler stories task, recall was scored verbatim (exact phrases, e.g., “went to visit”), as gist (semantic equivalents, e.g., “went to see”), or as distortion (altered information, e.g., “went to pick up”). Breast cancer survivors exhibited significantly lower verbatim recall, lower gist recall, and fewer total recalled details compared with controls. Survivors also produced fewer distortions, which researchers attributed to an overall lack of retained narrative content available for retrieval.
In contrast, performance on the VPA task showed no significant differences between cohorts across any of the 4 test sets. Subjectively, survivors reported significantly greater everyday memory difficulty on the SAM and experienced significantly elevated cognitive effort on the NASA-TLX during narrative recall, but not during paired associates testing.
Table 2. Objective Performance, Subjective Memory, and Workload Metrics
| Assessment / Domain | Chemotherapy Cohort vs Controls | Statistical Significance |
| Taler Stories: Verbatim Recall | Significantly reduced in survivors | P = .02 |
| Taler Stories: Gist Recall | Significantly reduced in survivors | P < .001 |
| Taler Stories: Total Details | Significantly reduced in survivors | P = .02 |
| Taler Stories: Memory Distortions | Significantly fewer in survivors | P = .04 |
| Verbal Paired Associates (VPA) | Equivalent performance across all 4 sets | No significant difference |
| SAM: Subjective Episodic Memory | Significantly greater self-reported deficit | P < .001 |
| SAM: Subjective Semantic Memory | Significantly greater self-reported deficit | P < .001 |
| NASA-TLX: Immediate Story Recall | Significantly higher cognitive effort/workload | P < .001 |
| NASA-TLX: Delayed Story Recall | Significantly higher cognitive effort/workload | P < .001 |
| NASA-TLX: VPA Workload | Comparable cognitive workload between groups | No significant difference |
Diagnostic Limitations of Standardized Tests
The divergence between narrative recall tasks and paired-associate testing suggests that conventional neuropsychological assessments may fail to capture real-world cognitive deficits.
Sekeres observed:
โVerbal Paired Associates is used as a measure of episodic memory. Itโs a gold standard test. But it taps into a different kind of episodic memory.โ
She further elaborated:
โThe standardized measures, while well validated, just may not be picking up on the subtypes of memory where deficits in that kind of everyday memory actually lie.โ
Clinical Guidance and Diagnostic Recommendations
The findings demonstrate the importance of combining ecologically valid assessments with systematic tracking of patient-reported outcomes. Clinicians are urged to actively validate patient accounts of cognitive change:
โListen to what your patients are telling you theyโre experiencing. These standardized tests may not be picking up the objective evidence of their cognitive impairment despite the fact that theyโre experiencing this fuzziness.โ
โAn easy thing that clinicians can do is listen and take the subjective cognitive reports of their patients seriously.โ
Clinicians should also account for cognitive reserve. Highly educated, socially active, or multilingual individuals may score within normal reference ranges on standard tests despite meaningful personal functional decline:
โWhen they do actually exhibit a deficit, it may not be detectable at clinical levels. They feel that theyโve lost a lot compared to their pre-treatment selves.โ
Additionally, the authors advised screening cancer survivors for peripheral hearing impairment, a known dementia risk factor that can exacerbate cognitive fatigue:
โThatโs an easy one. Even if they donโt perceive hearing loss, it may in fact be contributing to their cognitive performance, and even just increasing cognitive workload. If youโre not hearing quite as well as you could be, it does take more cognitive effort.โ
Supported by a Canadian Institutes of Health Research grant, Sekeres and colleagues are currently utilizing functional magnetic resonance imaging (fMRI) to evaluate the structural and functional integrity of hippocampal networks during episodic retrieval:
โWe can actually visualize the brain network activation, as they recall this, and see specifically how the hippocampus is impacted at a structural and functional level.โ
Addressing previous neuroimaging findings that demonstrate mixed hyperactivation and hypoactivation in the hippocampus post-chemotherapy, Sekeres concluded:
โPossibly, the brain is less able to recruit these regions important for memory. Thereโs a lack of clarity specifically of how these brain networks are impacted, so that is something that weโre currently looking at.โ
