Hydroxychloroquine, Chloroquine Use for CTD Not Linked to Alzheimer Disease Risk

Alzheimer's brain scan
Alzheimer’s brain scan
Patients who have been chronically exposed to hydroxychloroquine/chloroquine were not at increased risk for Alzheimer disease.

Patients with connective tissue diseases who have been chronically exposed to hydroxychloroquine/chloroquine are not at increased risk for Alzheimer disease, according to the results of a population-based cohort study published in Annals of the Rheumatic Diseases.1

The investigators sought to examine whether chronic exposure to hydroxychloroquine/chloroquine increases a person’s risk for Alzheimer disease. Data from The Health Improvement Network, a primary care database in the United Kingdom that includes >12 million individuals, were used in the analysis. Researchers included individuals in the study if they had been prescribed hydroxychloroquine/chloroquine for ≥1 year at a mean dose of ≥50 mg/d for chloroquine and ≥100 mg/d for hydroxychloroquine. The first control group comprised individuals who were treated with hydroxychloroquine for <1 year for the same underlying condition as the exposed individuals. In these 2 groups, the beginning of the at-risk period was defined as the first day of the first prescription for hydroxychloroquine/chloroquine.

The second control group comprised individuals who had never been exposed to chloroquine, hydroxychloroquine, quinine, quinacrine, or mefloquine, but had the same connective tissue disease as the exposed patients. A randomly selected start of the at-risk period was defined for all unexposed individuals.. For every chronically exposed patient, ≥3 unexposed and briefly exposed patients were selected. For all persons included in the analysis, the researchers identified cases of Alzheimer disease, vascular dementia, and other unspecified dementias, and symptoms that could be linked to dementia and death.  

Overall, a total of 11,550 patients were exposed to hydroxychloroquine/chloroquine for

≥1 year, 4873 patients were exposed to hydroxychloroquine for <1 year, and 30,930 patients were not exposed to either of these agents. Compared with the control groups, individuals who had been chronically exposed to hydroxychloroquine/chloroquine were not at a higher risk for Alzheimer disease. In patients with chronic exposure to hydroxychloroquine/chloroquine, neither the duration of exposure (adjusted sub-distribution hazard ratio [sHR], 1.03; 95% CI, 0.98-1.09 per each year of exposure; P =.24) nor the mean hydroxychloroquine/chloroquine dosage (adjusted sHR, 1.01; 95% CI, 0.90-1.13 per each 50-mg/d increase; P =.90) were associated with the risk for Alzheimer disease.

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The investigators concluded that along with no increased risk for Alzheimer disease observed in chronically exposed individuals, chronic exposure to hydroxychloroquine/chloroquine lowered the risk for death in patients with a connective tissue disease. It remains to be determined whether this latter finding can be explained by metabolic and cardiovascular profile improvement.2

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  1. Fardet L, Nazareth I, Petersen I. Chronic hydroxychloroquine/chloroquine exposure for connective tissue diseases and risk of Alzheimer’s disease: a population-based cohort study [published online September 5, 2018].Ann Rheum Dis. doi:10.1136/annrheumdis-2018-214016
  2. Rempenault C, Combe B, Barnetche T, et al. Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis.Ann Rheum Dis. 2018;77(1):98-103.