Background: Cancer-related cognitive impairment (CRCI) is among the most frequently reported adverse events during and following cancer treatment. Between 17% to 75% of chemotherapy-treated cancer patients evidence long-term cognitive deficits as many as 20 years after treatment. The variability in prevalence and the mechanisms of persistent CRCI are not well understood. Cancer itself is largely considered a disease of older age, and there are significant commonalities between the risk factors and cognitive trajectories associated with CRCI and those associated with age-related neurodegenerative disorders including amnestic mild cognitive impairment (MCI) and Alzheimer’s dementia (AD). Little is known about how CRCI varies in older adults with premorbid cognitive decline, and how a remote cancer diagnosis impacts cognitive aging and brain health. Older adult cancer survivors may experience cognitive decline due to both CRCI, and MCI/AD, and this may account for some variability in CRCI findings. To address these issues, we identified cancer diagnosis and cancer history in a cohort of ~1600 older adults participating in a longitudinal aging and Alzheimer’s dementia research program called the Alzheimer’s disease Neuroimaging Initiative (ADNI). Methods: Subjects were identified through a review of ~96,000 participant records in the ADNI database. Data were manually searched for reference to cancer diagnosis and/or treatment utilizing a comprehensive list at  https://www.cancer.gov. Participants with an AD diagnosis at baseline and those with CNS-cancers were excluded from the analysis. For Analysis-1, 63 participants with study-concurrent cancer and 63 comparison controls absent a cancer diagnosis were identified: 20 with normal cognition and invasive cancer (NC-Cancer), 22 with normal cognition and NMSC (NC-NMSC), 42 with normal cognition and no cancer diagnosis (NC-no-Cancer), 9 with MCI and cancer diagnosis (MCI-Cancer), 12 with MCI and NMSC diagnosis (MCI-NMSC), and 21 with MCI and no cancer diagnosis (MCI-no-Cancer). For Analysis-2, 443 participants with a remote cancer history and 1,125 comparison controls were identified: 120 with normal cognition and cancer history (NC-Cancer-History), 96 with normal cognition and history of NMSC (NC-NMSC-History), 498 with normal cognition and no history of cancer (NC-no-Cancer-History), 147 with MCI and a history of cancer (MCI-Cancer-History), 82 with MCI and history of NMSC (MCI-NMSC-History), and 634 with MCI and no history of cancer (MCI-no-Cancer-History). Linear mixed effects models (LMM), and paired sample t-tests were used to assess performance in structured and unstructured verbal memory, attention, and processing speed. Survival analysis compared age of conversion to AD/MCI among participants with/without cancer history. Results: In Analysis-1, MCI-Cancer participants evidenced verbal memory decline and performed significantly worse than their matched peers in Structured Verbal Memory tasks. MCI participants without invasive cancer showed significant improvement between Time-1 and Time-2, while MCI participants with invasive cancer did not demonstrate improvement. NC-Cancer participants evidenced no cognitive decline following cancer and performed significantly better in Attention/Processing Speed than NC participants without cancer. In Analysis-2 MCI-no-Cancer-History participants performed significantly worse than MCI-Cancer-History participants in Unstructured Verbal Memory tasks including learning, delayed memory, and recognition. Additionally, MCI-no-Cancer-History participants converted to AD at a younger age and were 1.6 times more likely to convert to AD than MCI participants with a cancer history. NC participants with an invasive cancer history performed significantly better than those without an invasive cancer history in Attention/Processing Speed and showed no difference in conversion rates from NC participants without a cancer history. Conclusions: Taken together these results suggest that pre-cancer cognition influences CRCI development in older adults, and cancer history plays an unexpected role in cognitive aging trajectories. Those that are cognitively normal prior to cancer are more likely to maintain normal cognition after cancer. Those with pre-existing MCI prior to cancer experience significant additive deficits in Structural Memory and overall lower cognitive performance in verbal memory. Cognitively normal older adults with a history of cancer may possess higher pre-cancer attention and processing speed reserves that are resistant to cognitive decline associated with CRCI. Older adults with MCI and a cancer history perform better than those without a cancer history in all Unstructured Memory tasks and convert to AD at significantly lower rates. This would suggest that a percentage of MCI-Cancer-History participants may be experiencing long-term CRCI as the source of memory issues rather than rather than AD.

Creator

• Eastman, Jennifer Ann

DOI

• https://doi.org/10.21985/n2-vq8w-sw48

Subject

• Oncology
• Clinical psychology
• Aging

Language

• en

Alternate Identifier

• etdadmin_upload_677366
• http://dissertations.umi.com/northwestern:14756

Keyword

• mild cognitive impairment
• ADNI
• Cancer-related cognitive impairment
• cancer
• Alzheimer's disease
• Aging

Date created

• 2019-01-01

Resource type

• Dissertation

Rights statement

• In Copyright