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

Topic: Amyloid, tau and blood-test diagnosis

Use of pharmacological treatments is one possible modifiable risk factor for cognitive disorders. To investigate if the use of muscle relaxants is associated with the risk of Alzheimer's disease (AD). 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. 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). 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.

Key findings

• To investigate if the use of muscle relaxants is associated with the risk of Alzheimer's disease (AD).
• A five-year lag window prior to the diagnosis was used, and results analyzed with conditional logistic regression.
• 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.
• 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).

Why it matters

This Finnish case-control study found that use of any muscle relaxant was associated with a slightly increased risk of Alzheimer's disease, with stronger association for longer use, though no dose-response was observed and tizanidine was not associated. It identifies a possible modifiable risk factor but does not establish that muscle relaxants cause Alzheimer's disease or that avoiding them prevents it.

Study details

• Study designcase-control study
• Participants282,858
• Effect sizeaOR 1.12; aOR 1.19
• Evidence strengthModerate

Read the original

• DOI: 10.3233/JAD-220409
• PubMed: 36641664
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{atte2023-36641664,
  author  = {Atte, Rahkonen and Heidi, Taipale and Marjaana, Koponen and Sirpa, Hartikainen and Anna-Maija, Tolppanen and Antti, Tanskanen and Miia, Tiihonen},
  title   = {{The Cumulative Use of Muscle Relaxants and the Risk of Alzheimer's Disease: A Nationwide Case-Control Study}},
  journal = {Journal of Alzheimer's disease : JAD},
  year    = {2023},
  doi     = {10.3233/JAD-220409},
  pmid    = {36641664},
  url     = {https://doi.org/10.3233/JAD-220409}
}

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