We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Comment & Response |

Anticholinergic Use With Incident Dementia—Reply

Shelly L. Gray, PharmD, MS1; Melissa Anderson, MS2; Rebecca Hubbard, PhD3
[+] Author Affiliations
1School of Pharmacy, University of Washington, Seattle
2Group Health Research Institute, Seattle, Washington
3Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
JAMA Intern Med. 2015;175(9):1577. doi:10.1001/jamainternmed.2015.2574.
Text Size: A A A
Published online


In Reply Residual confounding refers to any bias arising from failure to adequately adjust for confounders: either unobserved covariates that are not included in the analysis or observed covariates that are inadequately included in the analysis due to measurement error or model misspecification. In our study, we controlled for confounding through regression adjustment for covariates associated with dementia that differed by exposure status.1,2 All covariates noted by Fried as differing between individuals with varying anticholinergic exposure levels were included in regression models to account for potential confounding due to these observed covariates. In addition to the results reported in our article, we performed several prespecified sensitivity analyses to further investigate this issue and assess the robustness of our primary results. Analyses that additionally adjusted for the Charlson comorbidity index produced similar results to our primary analyses. The hazard ratios for participants in the highest anticholinergic category (>1095 total standardized daily doses) were 1.56 for dementia (95% CI, 1.22-1.99) and 1.68 for Alzheimer disease (95% CI, 1.28-2.20). As discussed in the limitations section of the article,2 we share the concern expressed by Fried that residual confounding due to unobserved covariates may persist despite adjustment for observed confounders. The potential for bias due to unobserved confounding exists in all observational studies. However, we do not agree with the strategy that Fried proposes to address this issue. Restricting the sample to those without comorbidities at study entry (ie, potential confounders) would lead to a highly select group of healthy older adults (56.5% of the sample would be dropped in our study) and would limit the generalizability of the results. Both stratification and regression adjustment account for confounding by conditioning on observed covariates that may be associated with the outcome and the exposure, but neither address confounding due to unobserved covariates.1 Given the limitations to generalizability posed by a stratified analysis, we believe our analysis using regression adjustment provides a more scientifically valid approach.


Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview





September 1, 2015
Roy Fried, MD, MHS
1Premier Senior Care, Bethesda, Maryland
JAMA Intern Med. 2015;175(9):1577. doi:10.1001/jamainternmed.2015.2565.
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...