‘Amazing’ evidence shows lower Alzheimer’s disease risk among people with cancer
Key takeaways:
- Researchers observed an inverse association between cancer and risk for Alzheimer’s disease or related dementias.
- The association persisted across common cancer types.
Older adults with cancer had a lower risk for Alzheimer’s disease and related dementias than cancer-free individuals of the same age, according to results of a longitudinal retrospective study.
The inverse association persisted across multiple common malignancies, including breast, prostate and lung cancers.
“To some extent, I was surprised by the consistency and the strength of the results,” Elio Riboli, MD, MPH, ScM, chair of cancer epidemiology and prevention at Imperial College London, told Healio. “The reduction in risk is amazing.”
Background and methods
Previous research investigating the association between cancer and dementia has yielded mixed results, according to study background. Some studies showed an inverse relationship between cancer incidence and dementia risk, but others did not.
“Some [investigators raised] the hypothesis that the association, when observed, may have been due to selective mortality and competing risk [for] death, as individuals diagnosed with cancer might not live long enough to develop age-related dementia compared [with individuals who are] cancer-free,” researchers wrote.
Riboli and colleagues used the UK Clinical Practice Research Datalink, a database of more than 17 million individuals, to investigate.
Their study included more than3 million adults aged 60 years or older entered in the database between 1988 and 2018.
Of those, 125,666 (mean age, 68 years; 60.8% women) had a cancer diagnosis at baseline and the other 2.89 million (mean age, 65.7 years; 53.9% women) did not.
The relationship between cancer and dementia diagnoses served as the primary endpoint.
Results and next steps
In all, 412,903 people in the cohort either developed or had cancer during the study period, and 230,558 had dementia.
After mean follow-up of 9.3 years, individuals with cancer exhibited significantly lower risk for dementia (proportional HR = 0.75; 95% CI, 0.74-0.76) than the rest of the cohort.
The association could be seen for people who developed cancer after database entry (proportional HR = 0.72; 95% CI, 0.71-0.73) and those who had an existing malignancy (proportional HR = 0.84; 95% CI, 0.82-0.85).
Analyses that accounted for competing risk for death showed lower risk for dementia among those with all cancer (sub-distribution HR = 0.56; 95 CI, 0.55-0.56), incident cancer (sub-distribution HR = 0.48; 95% CI, 0.47-0.49) and prevalent cancer (sub-distribution HR = 0.73; 95% CI, 0.71-0.74).
People who developed breast, prostate, lung or colorectal cancers, as well as those who developed melanoma, all exhibited lower dementia risk (Cox proportional HR range, 0.64-0.8; P < .05).
A two-sample Mendelian randomization analysis of 357 genetic variants known to be associated with certain cancers showed an inverse association between cancer and Alzheimer's disease (OR = 0.97; 95% CI, 0.95-0.99).
“Until recently there was this assumption that chronic diseases, which are typical of older age and Western society, would all go together,” Riboli said. “There is this assumption that where there is more cancer, there is more cardiovascular disease, there is more diabetes, and there are more neurodegenerative diseases in terms of dementia. The results that have accumulated over the past decade, of which our paper is the most recent, actually say all chronic diseases don’t go hand in hand.”
Researchers acknowledged study limitations, including potential underreporting of dementia and classification difficulties with late-onset dementia.
Future research should investigate the biology connecting cancer and dementia, Riboli said.
Riboli and colleagues are conducting a study evaluating proteins in patients who had cancer and developed dementia, and vice versa.
“Proteins obviously come from genes, but they also come from metabolic differences in lifestyle, diet, physical activity and so on,” he said. “We see them as an intermediate biomarker.
“Perhaps we may understand in a more refined and precise way what might be the factors that explain this inverse association between cancer and dementia,” Riboli added. “This is the dream. Refine the personal profile to better understand is anybody who has got cancer, or anybody who hasn’t got cancer, at higher or lower risk for dementia.”
For more information:
Elio Riboli, MD, MPH, ScM, can be reached at e.riboli@imperial.ac.uk.
Collapse