title: Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study.
abstract: BACKGROUND
  Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized.
  
  
  METHODS
  In a 1993-2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25.
  
  
  RESULTS
  Among men 51-98 at baseline, higher patella Pb concentration (IQR: 21μg/g) was associated with -0.13 lower baseline MMSE (95% CI: -0.25, -0.004) and faster longitudinal MMSE decline (-0.016 units/year, 95% CI: -0.032, -0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: -0.026, -0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: -0.027, -0.002). We found weaker associations with tibia Pb.
  
  
  CONCLUSIONS
  Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging.
authors: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors: Zishaan
authors: Z
authors: Farooqui
authors: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors: Kelly M
authors: KM
authors: Bakulski
authors: Department of Epidemiology and Biostatistics, George Washington University Milken Institute of Public Health, Washington, DC, USA.
authors: Melinda C
authors: MC
authors: Power
authors: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors: Marc G
authors: MG
authors: Weisskopf
authors: VA Normative Aging Study, Veterans Affairs Boston Health Care System, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors: David
authors: D
authors: Sparrow
authors: VA Normative Aging Study, Veterans Affairs Boston Health Care System, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors: Avron
authors: A
authors: Spiro
authors: VA Normative Aging Study, Veterans Affairs Boston Health Care System, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors: Pantel S
authors: PS
authors: Vokonas
authors: School of Health Sciences, Purdue University, West Lafayette, IN, USA.
authors: Linda H
authors: LH
authors: Nie
authors: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors: Howard
authors: H
authors: Hu
authors: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA. Electronic address: sungkyun@umich.edu.
authors: Sung Kyun
authors: SK
authors: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000453:epidemiology*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D007854:Lead / Q000378:metabolism* / Q000633:toxicity*; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010329:Patella / Q000737:chemistry; D016016:Proportional Hazards Models; D013977:Tibia / Q000737:chemistry; D055815:Young Adult
chemical_list: D004785:Environmental Pollutants; D007854:Lead
keywords: Aging; Bone lead; Cognitive decline; Longitudinal study; MMSE