Approved Research

Polygenic risk of cognitive impairment in hematologic cancer survivors

Lay summary

Treatment for blood cancer, although life-saving, can come at a price in the form of several side effects, one of which is cognitive impairment, often referred to as "chemo-brain". Patients may have trouble concentrating or remembering details which makes it difficult for patients to complete daily tasks such as managing their medications and could interfere with the patient's ability to return to school or work after treatment. We studied the extent of cognitive impairment in 477 blood cancer patients who received blood or marrow transplant (BMT) and 99 healthy individuals. Study patients underwent comprehensive assessment of cognitive function using a battery of 14 standardized neuropsychological tests at predefined time-points: pre-BMT, 6 months, 1, 2, and 3 years post-BMT. The cognitive battery tests covered eight cognitive domains: executive function, verbal fluency, verbal speed, processing speed, working memory, auditory memory, visual memory, and fine-motor dexterity. Using scores from the individual neuropsychological tests we constructed a Global Deficit Score (GDS) as a summary measure of global cognitive impairment. A higher GDS indicated higher cognitive decline. We also obtained the patients' DNA to determine genetic susceptibility to cognitive impairment after BMT. Three years after BMT, we found that 19% -36% of patients had evidence of global cognitive impairment. Factors strongly associated with cognitive impairment were older age, male gender, lower education, income, and cognitive reserve. We also identified certain markers in the patients' genetic makeup that were associated with cognitive impairment. Our observations identified a critical need to address cognitive impairment in survivors. Our approach is to identify high-risk survivors using patient's clinical and genetic information with the future goal of testing whether those high-risk survivors would benefit the most when targeted with cognitive interventions. We will use well-established publicly available resources from the UKBB to validate a clinical and genetic risk prediction model to identify blood cancer patients at highest risk of having cognitive impairment following treatment. The long-term goal of this research is to improve the outcomes of blood cancer survivors using a patient-centered individualized approach and positively impact the professional and societal reintegration of survivors at highest risk of cognitive impairment. The proposed analysis is expected to take ~3 years.