What causes ‘chemobrain’? It’s time for neuroscientists to get serious about finding out, experts say

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At some point in their treatment for cancer, somewhere between 17% and 75% of patients with malignancies that don’t affect the central nervous system report the sensation that a mental fog has set in.

For months or years after their hair has grown back, the exhaustion has lifted and the medical appointments taper off, the “new normal” for these patients includes problems with concentration, word-finding, short-term memory and multitasking.

Their doctors nod their heads knowingly: It’s “chemobrain,” they report.

Among the nation’s roughly 15.5 million cancer survivors, the ranks of those who’ve experienced mental fog after cancer treatment are probably increasing as detection and therapies improve, survival rates rise and lives are extended.


But when it comes to cancer’s cognitive aftermath, the medical profession’s expertise ends. Why chemobrain happens, how long it will linger, and what deficits it actually causes — and especially whether it could be treated, or even prevented — are questions for which oncologists have no answers.

But they want them. And three specialists from the National Cancer Institute have issued an appeal to neuroscientists for help.

“We need an infusion of new ideas,” said Todd S. Horowitz, a cognitive psychologist and program director in the institute’s Division of Cancer Control and Population Sciences. “Cognitive neuroscience would help us characterize the deficits people have and allow us to connect them to particular brain systems.”

Writing this week in the journal Trends in Neurosciences, Horowitz and two fellow researchers at the institute drafted a road map toward a better understanding of the condition officially known as cancer-related cognitive impairment, which was first described by breast cancer survivors.

Until now, experts have tried to characterize the phenomenon using standard batteries of neuropsychological tests. The tests gauge problems in a variety of cognitive “domains,” including attention, processing speed, visuospatial skill and several different kinds of memory.

Those clinical measures were typically devised to diagnose or assess the injury wrought by severe brain diseases such as Alzheimer’s, traumatic brain injury or stroke. They are unlikely to detect, measure or explain the often subtle impairments that, for many cancer survivors, make it hard to return to a mentally demanding job, continue driving or lay plans for the future.


That problem is evident in the wide-ranging estimates of how many patients are affected by chemobrain. That the latest prevalence figures stretch from 17% to 75% of cancer patients suggests that existing tests are missing their mark.

Chemobrain sufferers often complain of a mix of impairments across several domains. And, to make matters more complicated, patients with different cancers, or who have been treated with different therapies, lodge different mixes of complaints.

Gaining a better understand of chemobrain’s causes and consequences will require “embracing theories and methods of experimental neuroscience,” the researchers wrote.

That would include thoroughly examining some of the theories researchers have had about chemobrain’s origins.

Among them is the possibility that cancer, and/or its treatment, somehow knocks the immune system off balance and unleashes a toxic flood of inflammatory agents upon the central nervous system. Researchers have also speculated that chemotherapy may inflame the brain and scramble DNA there, or that it acts to accelerate the aging process or disable normal repair mechanisms.

Then again, the explanation could be more simple: Chemotherapies designed to kill certain cells are breaching the blood-brain barrier and attacking neurons directly.


A few studies have offered glimmers of insight.

MRI scans that capture some of the brain’s more elusive structures have shown that even before they are treated, breast cancer patients have reduced volumes of white matter, the brain’s connective tissue. The scans also make clear that paying attention requires more effort, and that these patients’ cortical structures show both early and long-term losses in volume.

In addition, functional MRI studies that capture activation in particular brain regions have shown reduced connectivity in a neural circuit called the default mode network. Given this circuit’s central role in diseases of aging as well those involving inflammation and cell stress, neuroscientists who study it might unravel the mystery of chemobrain, the authors wrote.

“Patients and their families want to know what to expect during and after treatment,” Horowitz said. A better understanding of all aspects of chemobrain will help cancer patients and their families make better decisions, and may help identify treatments or strategies to reduce or prevent it.

“Cancer-related cognitive impairment is real,” he said. “And those of us in the field are intent on figuring it out.”




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