Accepted Manuscript Title: Methamphetamine/amphetamine abuse and risk of Parkinson’s disease in Utah: A population-based assessment Author: Karen Curtin Annette E. Fleckenstein Reid J. Robison Michael J. Crookston Ken R. Smith Glen R. Hanson PII: DOI: Reference:
S0376-8716(14)01894-8 http://dx.doi.org/doi:10.1016/j.drugalcdep.2014.10.027 DAD 5349
To appear in:
Drug and Alcohol Dependence
Received date: Revised date: Accepted date:
9-4-2014 21-10-2014 21-10-2014
Please cite this article as: Curtin, K., Fleckenstein, A.E., Robison, R.J., Crookston, M.J., Smith, K.R., Hanson, G.R.,Methamphetamine/amphetamine abuse and risk of Parkinson’s disease in Utah: a population-based assessment, Drug and Alcohol Dependence (2014), http://dx.doi.org/10.1016/j.drugalcdep.2014.10.027 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Methamphetamine/amphetamine abuse and risk of Parkinson’s disease in Utah: a population‐based assessment
ip t
Karen Curtina,b*, Annette E. Fleckensteinc, Reid J. Robisond,e, Michael J. Crookstond, Ken R. Smithb,f, Glen R. Hansonc,g a
Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112, United States Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT 84112, United States c Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, United States d Intermountain Healthcare, Salt Lake City, UT 84111, United States e Utah Foundation for Biomedical Research, Provo, UT 84601, United States f Department of Family and Consumer Studies, University of Utah, Salt Lake City, UT 84112, United States g School of Dentistry, University of Utah, Salt Lake City, UT 84112, United States
M
an
us
cr
b
Ac ce p
te
d
Word Count: 4673 *Corresponding author at: Pedigree & Population Resource, Huntsman Cancer Institute and The University of Utah, 675 Arapeen Way Ste. 200, Salt Lake City, UT 84112, United States. Tel.: +1 801 585 5320; fax: +1 801 585 7404. E‐mail address:
[email protected] (K. Curtin).
1
Page 1 of 32
ABSTRACT
Background: Despite widespread use of methamphetamine and other amphetamine‐type
ip t
stimulants (METH/AMPH), little is known about the long‐term medical consequences of
cr
METH/AMPH abuse and dependence. Preclinical neurotoxicity findings raise public health
concerns that these stimulants may damage dopamine neurons, resulting in dopamine‐related
us
disorders such as Parkinson’s disease (PD). Methods: A retrospective design was used to
an
examine statewide medical records (1996 through 2011) linked to the Utah Population Database. Individuals 30y or older on December 31, 2011 were assigned to a METH/AMPH
M
cohort (ICD‐9‐CM 304.4, 305.7, 969.7, E854.2; N=4,935), a cocaine cohort (ICD‐9‐CM 304.2, 305.6, 968.5, E855.2; N=1,867) or a population cohort unexposed to drugs or alcohol for control
d
selection. A competing‐risks, proportional hazards model was used to determine whether the
te
METH/AMPH or cocaine cohorts were at increased risk of developing PD (ICD‐9‐CM 332.0) or
Ac ce p
PD/parkinsonism/essential tremor (PD/PT; ICD‐9‐CM 332.0, 332.1, 333.0, 333.1) compared to individually sex‐ and age‐matched controls (5:1 control to case ratio; N=34,010). Results: In METH/AMPH users, we observed an increased risk of PD and PD/PT (HRPD=2.8, 95%CI 1.6‐4.8, P0 event time PD/PT>0 event time
M
METH/AMPH Females Males Females vs. Males
8 7
6 21 ― 49
ip t
Females Males Females vs. Males
Controls 27
30
Cocaine vs. METH/AMPH METH/AMPH vs. Case‐only (sex, birth year) cocaine METH/AMPH
Cases 15
(see above)
PD/PT
Cocaine
d
d
3a.
Number of outcomes a
te
Outcome
Case‐only (sex, birth year)
Exposure
Ac ce p
cr
Figures (covariates) Individual matching (sex, 1a. birth year) Case‐only (birth year) Individual matching (sex, 1b. birth year) Case‐only (birth year) Individual matching (sex, 2. birth year)
us
Competing risks model
an
PD/PT
PD/PT
18 12 4
18 31 ― 22
4 vs. 30
―
30 vs. 4
―
12
27
8 4
6 21 ― 49
(see above)
(see above)
22 15 7 (see above)
PD: ICD‐9‐CM 332.0 primary Parkinson's disease; PD/PT: ICD‐9‐CM 332.0, 332.1, 333.0 333.1. All exposed cases had event times > 0; only one case had PD ICD‐9 332.0. c Includes 3 female cases and one male case, 8 female and 14 male matched controls. d Figure is provided in an online supplement. b
18 31 ―
29
Page 29 of 32
Ac
ce
pt
ed
M
an
us
cr
i
Figure 1a. METH/AMPH and risk of PD
Page 30 of 32
Ac
ce
pt
ed
M
an
us
cr
i
Figure 1b. METH/AMPH and risk of PD/PT
Page 31 of 32
Ac
ce
pt
ed
M
an
us
cr
i
Figure 2 Cocaine risk of PD
Page 32 of 32
