title: Polypharmacy Is Associated With Higher Frailty Risk in Older People: An 8-Year Longitudinal Cohort Study.
abstract: OBJECTIVE
  To investigate whether polypharmacy is associated with a higher incidence of frailty in a large cohort of North Americans during 8 years of follow-up.
  
  
  METHODS
  Longitudinal study, follow-up of 8 years.
  
  
  METHODS
  A total of 4402 individuals at high risk or having knee osteoarthritis free from frailty at baseline.
  
  
  METHODS
  Details regarding medication prescription were captured and categorized as 0-3, 4-6, and ≥7. Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 out of (1) weight loss ≥5% between baseline and the subsequent follow-up visit; (2) inability to do 5 chair stands; and (3) low energy level according to the Study of Osteoporotic Fracture definition. Cox's regression models calculating a hazard ratio (HR) with 95% confidence intervals (CIs), adjusted for potential confounders, were undertaken.
  
  
  RESULTS
  During the 8-year follow-up, from 4402 participants at baseline, 361 became frail. Compared with participants taking 0-3 medications, the incidence of frailty was approximately double in those taking 4-6 medications and 6 times higher in people taking ≥7 medications. After adjusting for 11 potential baseline confounders, participants using 4-6 medications had a higher risk of frailty of 55% (HR = 1.55; 95% CI 1.22-1.96; P < .0001), whereas those using more than 7 drugs were at approximately 147% (HR = 2.47; 95% CI 1.78-3.43; P < .0001). Each additional drug used at the baseline increased the risk of frailty at the follow-up of 11% (HR = 1.11; 95% CI 1.07-1.15; P < .0001).
  
  
  CONCLUSIONS
  Polypharmacy is associated with a higher incidence of frailty over 8-year follow-up period. Our data suggest evidence of a dose response relationship. Future research is required to confirm our findings and explore underlying mechanisms.
authors.affiliation: National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy; Institute for clinical Research and Education in Medicine, IREM, Padua, Italy; Department of Geriatric Care, OrthoGeriatrics and Rehabilitation, E.O. Galliera Hospital, Genova, Italy. Electronic address: ilmannato@gmail.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: South London and Maudsley NHS Foundation Trust, Denmark Hill, London, United Kingdom; Faculty of Health, Social care and Education, Anglia Ruskin University, Chelmsford, United Kingdom; Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King's College London, London, United Kingdom.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Noale
authors.affiliation: Institute for clinical Research and Education in Medicine, IREM, Padua, Italy; Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Department of Geriatric Care, OrthoGeriatrics and Rehabilitation, E.O. Galliera Hospital, Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
authors.affiliation: Primary Care Department, Azienda ULSS20 Verona, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Vaona
authors.affiliation: Primary Care Department, Azienda USL Toscana Sud Est, Grosseto, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Demurtas
authors.affiliation: South London and Maudsley NHS Foundation Trust, Denmark Hill, London, United Kingdom; Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King's College London, London, United Kingdom.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueller
authors.affiliation: South London and Maudsley NHS Foundation Trust, Denmark Hill, London, United Kingdom; Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King's College London, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Huntley
authors.affiliation: National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Crepaldi
authors.affiliation: National Research Council, Neuroscience Institute, Aging Branch, Padua, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Maggi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D016330:Frail Elderly / Q000706:statistics & numerical data*; D000073496:Frailty / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D015577:Geriatric Assessment / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D055553:Prescription Drugs / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D055553:Prescription Drugs
keywords: Frailty; frail; medication; older adult; polypharmacy