The cancer Alzheimer’s disease paradox | npj Aging
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The cancer Alzheimer’s disease paradox
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Subjects
Cancer<br>Computational biology and bioinformatics<br>Diseases
A paradoxical inverse correlation between cancer and Alzheimer’s disease has been repeatedly observed in epidemiological studies. While cancer and Alzheimer’s disease share common risk factors, most notably aging, the risk of Alzheimer’s disease in patients with cancer is significantly reduced, and the risk of cancer in patients with Alzheimer’s disease is halved. The convergence of two distinct disciplines, cancer and Alzheimer’s disease, offers an exciting and untapped opportunity to generate new ideas and to understand the fundamental mechanisms of risk and resilience in both diseases. The curious phenomenon of the inverse correlation between cancer and Alzheimer’s disease has the potential to drive innovation and help to identify actionable targets for novel clinical interventions for both diseases.
My personal tragedy<br>On August 17, 2025, I lost my husband and my best friend of thirteen years to the most aggressive form of primary brain cancer, glioblastoma. He was only 46 years old. Like many patients and their families, we were resolute, fueled by an unwavering optimism that we might just “beat the odds” and be spared if we fought hard enough. Despite receiving the most advanced treatment and being in otherwise excellent health, our battle with glioblastoma ended after just 15 months. Glioblastoma took his life, but before that, it robbed him of his soul. As the cancer gradually took over his brain, he began to lose his memories and everything else that defined him – a process tragically analogous to Alzheimer’s disease.<br>Sadly, our story is not unique. Cancer remains the most devastating diagnosis that nearly 40% of Americans will receive during their lifetime. This equates to an estimated 618,120 deaths in 20251,2. For those who have the privilege of reaching old age, one in three people aged 85 and older will be diagnosed with Alzheimer’s disease (AD). This terrifying disease currently affects seven million Americans, a number that is growing as the population ages.
A lack of cures for both cancer and Alzheimer’s disease<br>Billions of dollars in investment and decades of research later, we now have a better understanding of the underlying mechanisms of both cancer and AD. In recent years, significant progress has been made in the early detection and treatment options for both diseases. For example, immune checkpoint inhibitors have revolutionized the treatment landscape of advanced melanoma, once considered an untreatable disease, as over 50% of patients are now surviving for 10 years or more3. In the field of AD, newly FDA-approved blood-based biomarkers will facilitate early diagnosis, creating an opportunity for early intervention when new disease-modifying therapies, such as anti-amyloid monoclonal antibodies, may be most efficacious. Despite all this, many cancers remain fatal, and patients with AD continue to decline cognitively even with current disease-modifying therapies. Both cancer and AD require paradigm shifts beyond refining existing frameworks.
A curious observation of an inverse correlation<br>A curious inverse correlation between cancer and AD has been reported consistently in epidemiological studies4. While cancer and AD share many risk factors, most notably aging, paradoxically, the risk of AD in patients with cancer is reduced by 25–35%4. Conversely, the risk of cancer in patients with AD is halved5. Studies aimed at examining whether this inverse correlation could be an artifact of methodological biases found that competing risk of death, diagnostic bias, and selective survival were unlikely to explain the observed inverse correlation6. Furthermore, a cancer history is associated with a measurable later onset of AD in a dose-dependent manner, as individuals with a history of two cancers from different origins developed AD later in life than those with one prior cancer or no cancer history7. Interestingly, this inverse correlation appears to be unique to AD, as similar associations are not observed with other age-related neurodegenerative diseases, including vascular dementia and Huntington’s disease8. While Parkinson’s Disease (PD) shows an inverse correlation with certain cancer types, its associations are more complex, with positive associations reported for cancers such as melanoma9. This complex relationship, contrasted with the consistently inverse correlation between cancer and AD, suggests the presence of both shared and...