Cancer Diagnosis Linked to Lower Risk for Dementia Diagnosis

Individuals diagnosed with cancer appear less likely to later receive a dementia diagnosis, according to findings from a large nationwide case-control study published in the Journal of Alzheimer’s Disease.

Researchers in Germany analyzed 10-year prevalence trajectories of 17 different cancer types before dementia onset using statutory health insurance data covering approximately 88% of the German population. The analysis included 1,686,759 individuals with newly diagnosed dementia (mean [SD] age, 82.15 [6.90] years; 61.70% women) and 3,373,518 matched control individuals without dementia, matched 1:2 by age, sex, region, and outpatient visit history. Cancer diagnoses included 15 solid tumors and 2 hematologic malignancies, with primary central nervous system cancers excluded.

Researchers used conditional logistic regression to calculate unadjusted and adjusted odds ratios (ORs) for dementia according to the prevalence of each cancer subtype across 3 time intervals: 1 year, 2 to 4 years, and 5 to 10 years before dementia diagnosis. Adjustments were made for dementia risk factors identified by the Lancet Commission on Dementia Prevention, Intervention, and Care, including hypertension, diabetes, obesity, hearing loss, depression, alcohol abuse, smoking, and traumatic brain injury.

In this large sample, we found a general decrease in the risk of receiving a dementia diagnosis for all types of cancer as the index date approached.

Across nearly all cancer types, the likelihood of receiving a dementia diagnosis declined progressively as the index date approached, with the inverse association strongest for cancers with poorer prognoses. The most pronounced inverse associations were observed for pancreatic (OR, 0.47; 95% CI, 0.43-0.51), lung (OR, 0.67; 95% CI, 0.65-0.70), colon (OR, 0.89; 95% CI, 0.87-0.91), and breast cancers (OR, 0.91; 95% CI, 0.89-0.93) 1 year before the dementia index date. The inverse association persisted after adjustment for comorbidities, with no cancer subtype showing an increased risk for dementia. Only cervical, thyroid, testicular, and prostate cancers demonstrated ORs approaching 1 after adjustment, indicating little to no difference in dementia risk compared with individuals without these cancers.

The researchers suggested several explanations for this association, including selective survival among cancer survivors, diagnostic and surveillance bias, and biological mechanisms. Potential biological explanations include divergent regulation of tumor suppressor and cell cycle genes, such as p53 and PIN1, as well as shared molecular pathways involving apoptosis, inflammation, DNA repair, angiogenesis, and oxidative stress. Genetic influences such as the APOE ε4 allele, which heightens Alzheimer risk but may offer protection against certain malignancies like melanoma, were also cited as potential contributors.

Study limitations include the absence of treatment data, potential misclassification of dementia subtypes, and limited granularity of cancer categorization.

“In this large sample, we found a general decrease in the risk of receiving a dementia diagnosis for all types of cancer as the index date approached,” the study authors concluded.

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. No relevant financial disclosures were reported.