Risk factors associated with cancer and metabolic encephalopathy in Alzheimer's disease patients

Alzheimer's disease (AD) frequently coexists with risk factors that modify its clinical course. The combined presence of cancer and metabolic encephalopathy (ME) in AD represents a particularly vulnerable and understudied phenotype. We investigated whether cancer-associated risk profiles differ between AD patients with and without metabolic encephalopathy.

We used multivariate logistic regression to identify clinical, vascular, pulmonary, neurocognitive, psychiatric, and treatment-related factors distinguishing (i) AD patients with metabolic encephalopathy with and without cancer (AD + ME ± C) and (ii) AD patients without metabolic encephalopathy with and without cancer (AD - ME ± C). Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were used to identify risk factors and phenotype-specific associations.

Of the total cohort, 10,516 patients had metabolic encephalopathy, and 118,253 did not. Cancer coexistence was present in 146 AD + ME patients and 1,167 AD - ME patients. Among AD + ME patients, cancer was strongly associated with cerebrovascular accident (OR = 3.47, 95% CI 2.16-5.59), secondary dementia (OR = 9.89, 95% CI 3.26-29.98), mild cognitive impairment (OR = 5.20, 95% CI 1.98-13.27), chronic obstructive pulmonary disease (OR = 7.66, 95% CI 5.20-11.29), and SSRI use (OR = 3.27, 95% CI 2.21-4.87). In contrast, memantine, buspirone, and valproate were associated with AD + ME without cancer. Among AD-ME patients, cancer was associated with dyslipidemia, peripheral vascular disease, congestive heart failure, arteriosclerosis, COPD, and cutaneous ulcers, reflecting chronic systemic illness.

Metabolic encephalopathy was associated with a different clinical profile in cancer-associated AD. Patients with ME exhibited increased systemic and neurologic vulnerability (e.g., vascular comorbidity and frailty indicators) rather than differences in baseline cognitive severity alone.