The Cumulative Use of Muscle Relaxants and the Risk of Alzheimer’s Disease: A Nationwide Case-Control Study

Abstract

Background:

Use of pharmacological treatments is one possible modifiable risk factor for cognitive disorders.

Objective:

To investigate if the use of muscle relaxants is associated with the risk of Alzheimer’s disease (AD).

Methods:

The study was performed in a nested case-control design. Altogether 70,718 community-dwelling residents of Finland who received AD diagnosis in 2005–2011 were included as cases (the MEDALZ study). Each case was matched with four controls without AD by age, sex, and region of residence (N = 282,858). Data was extracted from Prescription register (1995–2012), Special Reimbursement register (1972–2012), and Hospital Discharge register (1972–2012). Drug use periods were modeled with PRE2DUP-method. Defined daily dose (DDD) was used to quantify the use. Analyses were conducted for any muscle relaxant use, and drug specific analyses were done for orphenadrine and tizanidine. A five-year lag window prior to the diagnosis was used, and results analyzed with conditional logistic regression.

Results:

The use of any muscle relaxant was associated with the risk of AD, aOR (95% CI) 1.04 (1.02–1.07). Stronger associations were observed with longer use (>366 days, aOR 1.12 (1.03–1.21)) than shorter use (1–365 days aOR, 1.04 (1.02–1.06)) compared to non-users. Dose-response was not observed. Tizanidine was not associated with AD, whereas cumulative exposure of orphenadrine (≥101 DDDs) was associated with the risk of AD, aOR 1.19 (1.07–1.32).

Conclusion:

Muscle relaxant use was associated with the risk of AD and higher exposure to orphenadrine showed increased risk. Further studies on higher doses and longer durations of use are warranted.