Paul Edison, MD, PhD
(Credit: Imperial College London)
A newly presented study involving patients with breast cancer treated with anthracycline-taxane chemotherapy revealed significant differences in deep brain regions among those with chemotherapy-associated cognitive impairment, also known as “chemobrain.” Some of these impacted regions overlap with those implicated in small vessel disease and vascular dementia, including parts of the default mode network, which is also disrupted in Alzheimer disease (AD).1
In the study, researchers enrolled 270 patients with breast cancer who received anthracycline-taxane chemotherapy in the last 12 months, following neurocognitive prescreening tests performed on an artificial intelligence-driven online platform. Among these patients, 18 of them with poorer prescreening scores, along with 19 controls, underwent in-person neurocognitive evaluations and an MRI scan (3-Tesla). Investigators then analyzed the MRI images using region of interest and voxel-based norphometric group-level analysis.
In the region of interest analysis, results showed that patients with chemobrain had significantly lower grey matter volumes (mm³) in the left isthmus cingulate and pars opercularis regions. In addition, this group of patients had reduced grey matter surface areas (mm²) in the same regions, as well as in the left medial orbitofrontal, right isthmus cingulate, lingual, and temporal pole areas. These findings were presented at the 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, by Paul Edison, MD, PhD, professor of neuroscience at the Imperial College London.
For the voxel-based norphometric analysis, investigators reported a statistically significant decrease in the periventricular areas, cingulate gyrus, precuneus, as well as in the parietal and medial frontal lobes, in those treated with chemotherapy. Moreover, in-person neurocognitive assessments displayed significantly poorer semantic and verbal fluency and lower Mini-Mental State Examination scores in patients with chemobrain. Overall, these findings suggest that chemotherapy-induced neuroinflammation may disrupt the neurovascular unit, induce vascular toxicity, and lead to brain morphological changes that contribute to the cognitive impairment observed in the chemobrain phenotype.
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Despite chemotherapy significantly improving cancer survival rates, its mechanism of action can be associated with a range of adverse effects that may impact long-term quality of life.2 For example, chemobrain can impact approximately 33% of patients with breast cancer who have undergone chemotherapy, presenting with different degrees of severity. Although some patients may experience temporary symptoms that can resolve in a year, others could have persistent cognitive issues that could elevate the risk for AD. Thus, understanding the underlying mechanisms and characteristics of chemobrain may support earlier detection, targeted interventions, and the development of preventive approaches for patients.
In a similar study published in Pathophysiology, findings revealed significant reductions in both gray and white matter in patients with breast cancer treated with chemotherapy compared with healthy volunteers when using MR morphometry. This analysis demonstrated the utility of MR morphometry in detecting subtle yet statistically significant neuroanatomical changes associated with cognitive and motor impairments in this patient population.3
The prior study enrolled 86 patients who had breast cancer and age-matched 28 healthy female volunteers. Researchers obtained conventional MR sequences in 3 mutually perpendicular planes to exclude an organ pathology of the brain. In addition, investigators used the MPRAGE sequence to perform MR morphometry and assess brain structure volumes. The evaluation was conducted at 2 follow-up visits 6 months and 3 years following completion of breast cancer treatment. Notably, authors did not observe restoration of brain volume structures over the follow-up period of 3 years in patients.
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