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Chronic hydroxychloroquine/chloroquine exposure for connective tissue diseases and risk of Alzheimer’s disease: a population-based cohort study
  1. Laurence Fardet1,2,3,
  2. Irwin Nazareth1,
  3. Irene Petersen1
  1. 1 Department of Primary Care and Population Health, University College London, London, UK
  2. 2 Department of Dermatology, AP-HP, Henri Mondor Hospital, Créteil, France
  3. 3 EA 7379 EpiDermE, Université Paris Est Créteil, Créteil, France
  1. Correspondence to Professor Laurence Fardet, Department of Dermatology, AP-HP, Henri Mondor Hospital, Créteil F-94000, France; laurence.fardet{at}sat.aphp.fr

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Autophagy is an intracellular pathway by which cells generate energy and metabolites by recycling their own non-essential, redundant or damaged components.1 Pathophysiological studies have demonstrated that the impairment of autophagy contributes to protein aggregate accumulation that occurs during Alzheimer’s disease and experiments have shown that autophagy inhibitors, such as chloroquine and hydroxychloroquine, block amyloid plaque degradation.1 2 Further, a recent case–control study found that patients with rheumatoid arthritis who used hydroxychloroquine were at increased risk of dementia.3 We investigated whether chronic exposure to chloroquine/hydroxychloroquine increases the risk of Alzheimer’s disease.

Data from The Health Improvement Network (THIN) were used (January 1990–December 2016). THIN is a UK primary care database on >12 million people. Participating general practitioners prospectively enter clinical information on individuals so that the database provides a longitudinal medical record for each individual. THIN is representative of the UK population. …

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