On their own, dementia and cancer are grave diagnoses. As comorbidities, they are a disastrous dyad. Previous research has shown that patients with cancer and dementia exhibit worsened survival than those with cancer alone.

Caba Y, Dharmarajan K, Gillezeau C, et al. The impact of dementia on cancer treatment decision-making, cancer treatment, and mortality: a mixed studies review. JNCI Cancer Spectr. 2021;5(3):pkab002.

In the US, the median age of cancer diagnosis is 66 years, whereas that of dementia diagnosis is 83.7 years. Between 2010 and 2030, experts foresee a 67% boost in incidence of cancer in individuals aged 65 years or more. Similarly, the global burden of dementia is expected to heighten from 50 million to 82 million by 2030.

 

Intriguingly, cancer and dementia diagnoses do not synergize—their relationship appears to be inverse. In other words, individuals with dementia exhibit a lower risk of being later diagnosed with cancer, and vice versa. This inverse association has also been noted in other types of neurodegenerative conditions such as Parkinson disease. The inverse correlation between cancer and dementia is not isolated to central nervous system (CNS) cancers, nor to long-term adverse effects of cancer treatments. This association also holds between non-CNS cancers and dementia.

 

A closer look

 

Findings from a population-based study out of Sweden indicated that the risk of dementia in individuals with cancer dropped by 21% compared with controls, and 21 of 35 different cancer types were related to a lower risk of dementia.

Sun M, Wang Y, Sundquist J, et al. The association between cancer and dementia: a National Cohort Study in Sweden. Front Oncol. 2020 Feb 4;10:73.

Decreased dementia risk was also evident before cancer diagnosis, but cancer patients who survived more than 10 years after diagnosis exhibited higher dementia risk. The authors implied the results weren’t accounted for by bias alone.

 

The authors noted that although mechanisms underlying a relationship between cancer and dementia remain to be elucidated, shared underpinnings may be involved.

Other factors that could also play a role include changes secondary to aging, shared risk factors, and impacts of cancer treatment on the brain, with some cancer treatments positively or negatively related to dementia. Importantly, survival bias could play a role, as cancer survivors may die before they develop dementia. The authors even suggested cancer could somehow protect against dementia.

 

The flip side

 

What makes things more complicated is that due to bias and confounders, the direction of the association between cancer and dementia could be flipped, according to the authors of a narrative review published in the European Journal of Clinical Investigation.

van der Willik KD, Schagen SB, Ikram MA. Cancer and dementia: two sides of the same coin? Eur J Clin Invest. 2018 Nov;48(11):e13019.

 

“Based on the high prevalence of cognitive problems among cancer patients, shared genetic traits and the increased risk of cancer in persons with MCI [mild cognitive impairment],” the authors stated, “the existence of a true inverse link between cancer and dementia can be questioned; in fact, it is reasonable to explore the existence of a positive association which may be more plausible from a mechanistic point of view.”

The involvement of inflammation, oxidative stress, and angiogenesis all point to a positive link between cancer and dementia, according to the authors. Fibrinogen and interleukin-6 are inflammatory biomarkers tied to decreased cognitive functioning, with proteins such as amyloid beta (Aβ) peptide also involved in this cognitive decline.

Genetic polymorphisms related to a lower capacity to repair damaged DNA can predict cancer and dementia. DNA damage secondary to oxidative stress and faulty DNA repair mechanisms can also contribute to the pathogenesis of cancer and dementia.

 

Caring for these comorbidities

 

No guidelines currently exist to follow in such cases.

Results from a mixed studies review published in JNCI Cancer Spectrum suggested patients with dementia and cancer were more likely to receive no curative treatment and less likely to be administered chemotherapy, radiation, or surgery.

Caba Y, Dharmarajan K, Gillezeau C, et al. The Impact of Dementia on Cancer Treatment Decision-Making, Cancer Treatment, and Mortality: A Mixed Studies Review. JNCI Cancer Spect. 2021;5(3):pkab002.

 

Clinicians, caregivers, and patients seemed to value quality of life and less-aggressive care over extended life expectancy for patients with dementia.

The authors noted that dementia complicated cancer treatment via impaired decision-making capacity, impaired ability to provide consent, and difficult communication.

“Recognizing the coexistence of cancer and dementia will improve earlier recognition of symptom burden and future development of diagnostic and/or therapeutic interventions,” the authors wrote.

They also suggested that caregivers for patients with dementia and cancer consider seeking a referral to a generic oncologist.

“Taken together,” the authors wrote, “we recommend incorporating a multidisciplinary geriatric oncology team from the beginning and additional training on geriatric conditions for oncologists may help with the processing, planning, and delivery of care and treatment.”