Cancer Patients Have Better Memory, Despite Dip at Diagnosis

Pam Harrison

June 25, 2019

Amid the devastation of a cancer diagnosis, there may be one glimmer of relief — the biological processes that lead to cancer seem to work in opposite ways to those for memory loss, a new study suggests.

It found that middle-aged and older adults in the United States had a better functional memory before being diagnosed with cancer and experienced a slower decline in memory after their cancer diagnosis than similarly-aged adults with no history of cancer.

"These findings support the possibility of a common pathologic process working in opposite directions in cancer and Alzheimer disease," say the researchers.

The study was published online June 21 in JAMA Network Open

Maria Glymour, ScD, MS, University of California, San Francisco, and colleagues conducted an analysis of data from 14,583 participants in the Health and Retirement Study (HRS). They all had no cancer history on study enrolment.

Participants (58% female, 42% male) were born before 1949 and the target population consisted of adults 50 years of age and older living in the US. The mean age of the cohort was 66.4 years.

"Information on participants was collected by telephone or in-person biennial interviews or proxy interviews for participants who were too impaired to answer," the authors explain.

Memory function in the cohort was evaluated using immediate and delayed recall of a 10-word list.

For participants too impaired to participate directly in memory assessments, proxies — typically spouses — assessed participants' memory based on a Likert scale as well as the Informant Questionnaire for Cognitive Decline.

Researchers then used a composite memory score they had previously developed that combined both direct memory assessments and proxy assessments to analyze the longitudinal data.

At each biennial assessment, patients were asked if they had ever been told by their physician if they have any type of cancer (excluding minor skin cancers).

"The prediagnosis memory assessments were assigned negative time (in years) until the diagnosis...[whereas] the postdiagnosis memory assessments were assigned positive time (in years) since diagnosis," investigators explain. Both of these assessments were then used to describe the pre- and postcancer memory trajectories in the years before and after participants had received a cancer diagnosis.

Findings at Follow-Up

Over a mean follow-up of 11.5 years, 2250 individuals (15.4%) from the HRS cohort were diagnosed with cancer whereas the remaining 12,333 participants remained cancer-free during the study interval.

"Before diagnosis, participants who were subsequently diagnosed with cancer had higher memory scores than those who were not diagnosed," Glymour and colleagues report.

For example, at the age of 75, mean memory function for individuals who were not diagnosed with cancer during the study was -0.251 standard deviation (SD) units compared with a mean memory function of -0.155 SD units for those who had received a cancer diagnosis at the same point in time.

In other words, prior to receiving a cancer diagnosis, those diagnosed with cancer had a decline in memory that was 10.5% slower than similarly-aged participants who did not receive a cancer diagnosis, the investigators point out.

Moreover, those diagnosed with cancer had a 3.9% slower rate of memory decline after they had received a cancer diagnosis compared with similarly-aged individuals who remained cancer-free, they add.

"Mean memory function was better among individuals with a cancer diagnosis at all time points during follow-up, even in the immediate short-term period after diagnosis, compared with otherwise similar individuals who remained free of a cancer diagnosis," the authors comment.

However, participants diagnosed with cancer did experience a short-term decline in memory immediately after their diagnosis, so the gap in memory function between the two groups narrowed during this brief interval.

Genetic Risk Factors

Common genetic risk factors for both cancer and Alzheimer's disease might help explain the inverse association between cancer diagnosis and slower memory decline observed in this study, the authors suggest.

For example, the cellular environment is critical in the pathogenesis of both cancer and Alzheimer's disease, "and local or systematic signals that promote tumor cell growth in peripheral cells could translate into antiapoptotic signals in neurons," they comment.

The authors also suggest that a better understanding of the observed association between cancer diagnosis and rate of memory decline might help contribute to the development of preventive/treatment strategies for neurodegenerative diseases such as Alzheimer's disease.

"To our knowledge, this is the first study to evaluate long-term cognitive trajectories before and after a cancer diagnosis," Glymour and colleagues state.

Accompanying Editorial

In an accompanying editorial, editorialists Olivia Okereke, MD, Massachusetts General Hospital in Boston, and Mary-Ellen Meadows, PhD, Brigham and Women's Hospital, Boston, point out that the routine biennial memory assessments done over a mean follow-up of 11.5 years in the Glymour et al study ensured that individuals with or without cancer had an equal opportunity to be assessed for memory function — thus mitigating against surveillance or detection bias.

As the authors themselves explain, the inverse association observed between cancer and Alzheimer's disease could be explained by the fact that people who live long enough to develop cancer may simply be a healthy group of individuals — and the same factors that help them survive their cancer may also protect them against Alzheimer's disease.

Selective survival of such individuals then could lead to a spurious association between a history of cancer and the incidence of Alzheimer's disease, Okereke and Meadows note.

Repeated measurements of memory decline over time are also likely to pick up patients with the earliest stages of Alzheimer's disease and are less susceptible to detection and survival bias compared with other approaches, as the authors also point out.

"Overall, the study results support prior reports of the negative effects on memory that cancer or cancer treatment may have in the acute phase, and patients who survive indeed appear to have better memory outcomes over the long term," Okereke and Meadows write.

"[These] compelling results speak to the need for further work to address the origins of the inverse association between cancer and AD, with a view toward identifying new paths to prevention and treatment of both diseases," the editorialists reaffirm.

The study was supported by the National Institute on Aging, the National Cancer Institute, and the American Cancer Society. The Health and Retirement Study is a longitudinal project sponsored by the National Institute on Aging and the Social Security Administration. Glymour reports receiving grants from the National Institute on Aging during the conduct of the study. Okereke and Meadows have disclosed no relevant financial relationships.

JAMA Network Open. Published online June 21, 2019. Full text, Editorial

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