Neuroplasticity-Based Cognitive Remediation for Chemotherapy-Related Cognitive Impairment

Advances in cancer treatment are producing a growing number of cancer survivors; therefore, issues surrounding quality of life during and following cancer treatment have become increasingly important. Chemotherapy-related cognitive impairment (CRCI) is one such quality of life issue that is commonly reported following chemotherapy treatment in adults. Although studies reporting cognitive impairments associated with chemotherapy have been reported since the 1980s, the phenomenon commonly referred to as 'chemo brain' or 'chemo fog' is poorly understood, and for some patients becomes the most distressful survivorship issue faced. Studies suggest that while up to up to 75% exhibit cognitive decline during treatment, many patients will return to their pre-chemo level of functioning 1 year after completing treatment. However, for 30-35% of cancer patients, their cognitive issues persist.

Studies suggest that this persistent chemotherapy-related cognitive impairment (pCRCI) can remain for months to years after completing treatment, which may have implications for the trajectory of how both normal cognitive aging occurs, but also the risk of cognitive disorders such as Alzheimer's disease, for the growing number of long-term cancer survivors. These concerns are particularly relevant for older individuals as risk for not only cancer, but cognitive impairment (such as dementia) increases with age. As of January 2016, 62% of cancer survivors (9.61 million) are currently 65 years or older, and this number is expected to increase dramatically over the coming decades. Therefore, as the number of older cancer survivors who have will have to cope with pCRCI is likely to increase, it is crucial that The investigators understand the cognitive impairments, the impact on survivors' functioning, and develop treatments for pCRCI.

The investigators propose to target cognitive deficit in CRCI using a novel cognitive enhancement strategy. Our choice of cognitive focus is informed by clinical, behavioral and neurobiological data suggesting a reliable association between cognitive control deficits (CCD), damage to the cognitive control network (CCN), and decline in cognitive functioning. The CCN is a neural network that supports important cognitive control functions such as alerting and orienting attention, response selection, cognitive flexibility, strategy generation, and inhibition of prepotent responses. The investigators propose to apply neuroplasticity-based computerized cognitive remediation (nCCR) to the treatment of CRCI as it has demonstrated training and transfer effects of enhanced CCN function in a similar, abnormally aging population. The theory guiding neuroplasticity-based cognitive interventions is that network abnormalities associated with negative disease-specific clinical outcomes can be altered through the induction of neuroplasticity (even in the aging brain) resulting in enhanced functioning of the target network, and symptomatic improvements.

• Inclusion Criteria:

All participants will:

• Be between 35 and 80 years of age,
• Have been diagnosed with noninvasive or invasive (Stage 1, 2, or 3A) breast cancer, colon cancer, lymphoma, endometrial cancer or ovarian cancer
• Have undergone treatment with systemic chemotherapy within the last 1-8 years,
• Endorse persistent CRCI subjective complaints (as defined below),
• Have no active cardiac, neurologic, or psychiatric illness,
• Fluent in and able to read English.
• Exclusion Criteria:

Participants will be excluded for:

• Any active neurologic psychiatric disease, clinically significant cognitive impairment or dementia, history of significant head trauma followed by persistent neurologic deficits, or known structural brain abnormalities,
• Current major depression or another major psychiatric disorder as described in DSM-5 (use of CNS active medications (e.g. antidepressants) will be permitted, provided dosing has been stable for at least 3 months),
• Any history of alcohol or substance abuse or dependence within the past 2 years (DSM-5 criteria),
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
• Use of any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening, and
• Use of cholinergic agents will be discouraged but will be reviewed on a case-by-case basis by the PI.
• Red-green color blindness. Other types of color blindness will be reviewed on a case-by-case basis by the PI.