Alzheimer Disease in People With Cancer: What’s the Risk?

Individuals diagnosed with cancer have a significantly lower risk of developing Alzheimer disease and related dementias (ADRD), according to the findings of a large population-based cohort study published in The Journal of Prevention of Alzheimer’s Disease.

To investigate the association between cancer and dementia, researchers conducted a retrospective cohort analysis using data from the UK Clinical Practice Research Datalink (CPRD). The study included 3,021,508 individuals aged 60 years and older, with a median follow-up period of 7.9 years (mean, 9.3 years). Additionally, a 2-sample Mendelian randomization (MR)-analysis was performed using genome-wide association study data to explore potential causal links between cancer and ADRD.

The researchers categorized participants into 3 groups: those with no history of cancer at study entry (n=2,895,842; mean age, 65.7; women, 53.9%), those with prevalent cancer (diagnosed before study entry, n=125,666; mean age, 68; women, 60.8%), and those with incident cancer (diagnosed during follow-up, n=287,237). Baseline characteristics revealed that, compared with individuals without cancer, those with cancer were slightly older, more likely to have cardiovascular disease (23.4% vs 14.8%), and had a higher prevalence of diabetes (8.7% vs 6%).

Over the study period, 230,558 participants developed dementia. After adjusting for confounders such as age, sex, socioeconomic status, smoking status, body mass index, diabetes, and cardiovascular disease, cancer survivors had a 25% lower risk of developing dementia (hazard ratio [HR], 0.75; 95% CI, 0.74 -0.76).

The inverse association was stronger for incident cancer cases (HR, 0.72; 95% CI, 0.71-0.73) compared with prevalent cancer cases (HR, 0.84; 95% CI, 0.82-0.85).

To account for the competing risk of death, the researchers conducted a Fine and Gray competing risk analysis, which further confirmed the inverse association (sub-distribution HR, 0.56; 95% CI, 0.55-0.56). This pattern was consistent across multiple common cancer types, including:

• breast (HR, 0.80; 95% CI, 0.77-0.82),
• prostate (HR, 0.68; 95% CI, 0.65-0.70),
• lung (HR, 0.64; 95% CI, 0.59-0.69),
• colorectal (HR, 0.70; 95% CI, 0.67-0.72), and
• melanoma (HR, 0.77; 95% CI, 0.73-0.81).

Using 357 cancer-related genetic variants as instrumental variables, MR-analysis identified a significant inverse relationship between genetically predicted cancer risk and the likelihood of developing ADRD. The results showed an odds ratio (OR) of 0.97 (95% CI, 0.95–0.99; P =.003), supported by evidence of vertical pleiotropy.  The strongest genetic associations were observed for breast cancer (OR, 0.94; 95% CI, 0.90-0.98) and lung cancer (OR, 0.90; 95% CI, 0.84-0.96). No significant associations were found for prostate, colorectal, or melanoma cancers. No evidence of horizontal pleiotropy was found, as indicated by MR–Egger intercept tests (P >.10).

“These findings allude to a potential neuro-protective effect of biological processes implicated in cancer or an unforeseen neuro-protective effect of cancer chemotherapies as plausible drivers for the observed associations,” the researchers concluded.

This research was supported by Imperial College London. One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.