Chemotherapy Linked to Brain Atrophy in Breast

Patients with breast cancer who undergo chemotherapy may face an increased risk for brain atrophy and cognitive decline, new findings from a pilot study suggested.

Memory problems in patients with cancer may not stem solely from stress or anxiety related to their diagnosis but could reflect underlying changes in brain structure, study investigator Paul Edison, PhD, MPhil, professor of neuroscience and clinical professor of neurology at Imperial College London, London, England, told Medscape Medical News.

While the findings suggest that chemotherapy may contribute to neuronal damage, the researchers noted that many aspects of the relationship between treatment and brain changes remain unclear.

Edison highlighted three key areas that require further investigation — uncovering the mechanisms driving brain atrophy, determining the proportion of patients affected, and identifying effective prevention strategies.

Another investigator on the study, Laura Kenny, MD, PhD, associate professor and consultant medical oncologist at Imperial College London, noted that the issue has received limited attention to date but expressed hope that the findings will raise awareness and encourage further research, given its clinical importance.

The findings were presented on July 29 at the Alzheimer’s Association International Conference (AAIC) 2025.

Investigating Cognitive Impact

Advances in chemotherapeutic agents have improved survival rates in patients with cancer. However, challenges persist regarding the long-term impact of these drugs.

Chemotherapy-associated cognitive impairment, often referred to as “brain fog” or “chemobrain,” affects approximately one third of patients with breast cancer following treatment.

While cognitive decline resolves within 12 months for some patients, others experience persistent effects that may elevate the risk for neurodegenerative conditions, Edison explained.

To evaluate the impact of chemotherapy on the brain, investigators studied 328 women with nonmetastatic breast cancer who had undergone chemotherapy within the past 12 months.

Patients received either anthracycline — a drug derived from the Streptomyces peucetius bacterium — or taxanes such as docetaxel and paclitaxel, both commonly used in breast cancer treatment, or a combination of these agents. In addition, some patients may also have had hormone therapy at some point during treatment, said Kenny.

Participants completed neurocognitive prescreening tests every 3 months using a specialized artificial intelligence-driven platform, allowing them to take detailed memory assessments online from home.

Among those prescreened, 18 individuals with lower neurocognitive scores (mean age, approximately 55 years) and 19 cognitively normal control individuals without breast cancer (mean age, approximately 67 years) underwent comprehensive, in-person, neurocognitive evaluations and MRI scans.

Researchers analyzed the scans using region of interest (ROI) and voxel-based morphometry (VBM), which uses sophisticated computer software, to assess grey matter volumes and surface areas.

The ROI analysis revealed significant reductions in gray matter volume (measured in mm³) and surface area (measured in mm²) among patients experiencing chemobrain, particularly affecting the isthmus cingulate and pars opercularis, with changes extending into the orbitofrontal and temporal regions.

Significant Atrophy

The VBM analysis confirmed significant atrophy in the frontal, parietal, and cingulate regions of patients with chemobrain compared with control individuals (P < .05). Edison noted that this pattern overlaps with brain changes typically observed in Alzheimer’s disease and vascular cognitive impairment.

For both analyses, “we demonstrated there is some amount of shrinkage in the brain among patients with chemobrain.” he said. “The fact that controls are older means the results are even more significant as there’s more brain atrophy as people age.”

Some of the affected brain regions may be linked to impaired memory, a hallmark of Alzheimer’s disease, but Edison cautioned that given the small sample size this finding should be interpreted with caution.

While the analysis demonstrated overall lower brain volumes in patients with “chemobrain” compared with controls, Edison emphasized that this finding reflects a single time point and does not indicate brain shrinkage over time.

Other events, including stroke — can also cause brain changes.

Edison highlighted the importance of determining the significance of these brain changes, how they affect patients and whether they can be prevented.

In-person neurocognitive testing revealed significantly reduced semantic and verbal fluency, as well as lower Mini-Mental State Examination scores in patients with chemobrain. Edison noted that these results support the MRI findings.

The team plans to follow patients to track brain changes and memory recovery, Kenny said. While patients with breast cancer are a common focus, the researchers intend to expand the study to other cancers in both men and women, said Kenny. Anecdotally, many patients report memory problems during chemotherapy, she added.

Based on discussions with her oncology colleagues, Kenny noted that many patients anecdotally report experiencing memory problems during chemotherapy.

More Research Needed

Commenting for Medscape Medical News, Rebecca M. Edelmayer, PhD, vice president, Scientific Engagement, at the Alzheimer’s Association, said the research may help shed light on why women are more likely to develop dementia than men.

For years now, experts have been trying to figure out what puts women at higher risk for AD and other dementias, said Edelmayer.

“We still don’t understand whether this involves biologically driven risk factors or socially driven risk factors.”

Research linking treatments for other health conditions to increased memory problems may offer some clues, she noted, suggesting a potential avenue for further investigation into the intersection of chemotherapy and neurodegenerative diseases such as Alzheimer’s.

However, Edelmayer emphasized that this line of research is still in its infancy. Much more work is needed to determine whether there is a direct cause-and-effect relationship with specific chemotherapy drugs, and whether some patients may already be predisposed or at higher risk for cognitive decline, she said.

Also commenting for Medscape Medical News, Eric Brown, MD, associate scientist and associate chief of geriatric psychiatry at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada, raised concerns about the study’s design.

One issue, he noted, is that the researchers did not image all patients who received chemotherapy but instead selected those with the most significant cognitive impairment. As a result, the findings may not have reflected outcomes in the average post-chemotherapy patients but rather represent the most severely affected subgroup.

Brown also pointed out that the study did not clarify whether this subgroup had comorbid conditions. It’s possible, he said, that some individuals may have had Alzheimer’s disease or other forms of dementia unrelated to chemotherapy.

He agreed that tracking longitudinal changes in both cognitive scores and neuroimaging — comparing patients who receive chemotherapy with those who do not — would be a valuable next step.

The investigators, Edelmayer and Brown, reported no relevant conflicts of interest.