Anticancer drugs show promise in reducing Alzheimer's dementia risk

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Aug 1 2024

In a recent study published in the journal Scientific Reports, researchers leveraged the knowledge that cancers and specific types of dementia share pathophysiological underpinnings to investigate the potential dementia-risk-reducing effects of anticancer drug interventions. Their retrospective study used data from the Korea National Health Insurance Service database comprising more than 100,000 cancer patients (age = 65+) prescribed anticancer medication between January 2008 and December 2018.

Study: Dementia incidence varied by anticancer drugs and molecular targeted therapy in a population-based cohort study. Image Credit: PopTika / Shutterstock

Their findings reveal that two classes of anticancer drugs – molecular targeted therapies and antimetabolites – were able to reduce the risk of the most common type of dementia (dementia of the Alzheimer's type [DAT]) but showed no risk association with the second most common type (vascular dementia [VaD]). Specific hazard ratios (HR) were reported: HR = 0.91 for antimetabolites and HR = 0.60 for molecular targeted therapies for DAT. These findings suggest that specific anticancer drugs may be repurposed to prevent dementia, but further targeted studies are required to identify which and in what dosages.

Background

'Dementia' is an umbrella term for a cohort of age-associated progressive brain disorders characterized by reduced cognitive ability resulting in impaired memory or daily functioning. Advancements in modern medicine have significantly lengthened the average human lifespan, inadvertently increasing the number of individuals susceptible to the condition. The World Health Organization (WHO) estimates that more than 55 million people are currently living with the disease, with an additional 9.9 million individuals developing dementia each year.

Dementia represents substantial mental, physical, and economic trauma for patients and their families. Predictive models project dementia prevalence at 78 million and 139 million in 2030 and 2050, respectively. Unfortunately, dementia has no cure, emphasizing the need for medical research and public health systems to identify dementia risk factors, as in the case of these conditions, prevention truly is the only option.

Previous research has suggested that certain cancers (lung, colorectal, renal, and lymphoma) and dementia (particularly dementia of the Alzheimer type [DAT]) may be pathophysiologically related, given their shared dysregulated cell cycles, oxidative stress, suppressed autophagy, and neuroinflammatory outcomes. These findings have prompted some researchers to hypothesize that anticancer drugs targeting these properties may elicit neuroprotective effects against dementia. Unfortunately, only a handful of studies have attempted to evaluate this hypothesis systematically.

About the study

The present study aims to contribute to the literature by investigating the association between various classes of anticancer drugs and the two most common types of dementia, namely DAT and vascular dementia (VaD). The retrospective large nationwide cohort study utilized data from the Korean National Health Insurance Service (K-NHIS) database comprising almost the entire population of South Korea.

Participants were included in the study if 1. They were above the age of 65 years, and 2. Were administered anticancer drugs during the study duration (January 1, 2008, through December 31, 2018 [n = 116,506). Participants were excluded if 1. They died within six months of cancer identification, 2. They suffered from a brain tumor, or 3. Were diagnosed with dementia before anticancer interventions.

The Korean Drug and Anatomical Therapeutic Chemical Codes [10] and the International Classification of Diseases, 10th Revision (ICD-10) codes were used to identify dementia (DAT [F00, G30], VaD [F01]) and cancers (V193). Prescription claims data were used to determine the class of anticancer drug used (general [platinum, antimetabolites, antibiotics] and mechanistic [molecular targeted therapy]). Covariates included age, sex, residential area, income, and the Charlson Comorbidity Index score.

Statistical analysis included summarizing population baseline characteristics using frequencies/proportions (categorical variables) and means with standard deviations (SDs) for continuous variables. Between-group differences were elucidated using Kaplan-Meier methodologies. Cox proportional hazard ratios (HRs) were computed to evaluate the association between anticancer drug interventions and subsequent dementia risk.

Study findings

The average age of patients receiving anticancer interventions was 71.64 years, with a majority (64.4%) of included patients being female. The most common general-class anticancer drugs used were Platinum (39.0%), antimetabolites (30.5%), and antibiotics (21.3%). The most common molecular targeted therapies were epidermal growth factor receptor (EGFR) inhibitors (45.6%).

Cox proportional hazards ratio analysis revealed that antimetabolites (HR = 0.93) and molecular targeted therapies (HR = 0.67) significantly reduced the risk of subsequent dementia development. However, these findings were only valid for DAT associations, and no risk reductions could be established for VaD.

Given their significantly improved dementia-protective effects, molecular-targeted therapies were reassessed with a focus on their specific subtypes. This analysis revealed that multikinase inhibitors performed best (HR = 0.50), followed by EGFR inhibitors (HR = 0.66). Similar to overall findings, these results were only significant concerning DAT (0.49 for both subtypes) and remained insignificant concerning VaD.

Conclusions

The present study highlights the potential neuroprotective effects of certain classes of anticancer drugs (antimetabolites, multikinase inhibitors, and EGFR inhibitors) against Alzheimer's disease, the most common form of dementia. While in-depth longitudinal research is required before these drugs can be repurposed to help prevent dementia, these findings may represent the first step in realizing the untapped potential of these interventions in combatting these dreaded age-associated diseases.

Study Limitations

The study acknowledged several limitations, including diagnostic reliance on ICD-10 codes, potential confounders such as treatment combinations, cancer types, and stages, and the lack of detailed clinical data like neuroimaging and fluid biomarkers. These factors could impact the accuracy of dementia diagnosis, and the associations reported. Future research should incorporate broader clinical datasets and more sophisticated analyses to unravel underlying mechanisms.