TOPLINE:

The use of strong anticholinergic drugs, but not the weak ones, was associated with an increased risk for dementia. This association was most pronounced in men, younger patients, and those with vascular or Lewy body dementia.

METHODOLOGY:

• Researchers conducted a nationwide case-control study to comprehensively evaluate the association between cumulative exposure to multiple drugs with anticholinergic properties, known as anticholinergic burden, and the risk for dementia.
• They included 199,526 individuals aged 40 years or older with incident dementia between July 2008 and December 2017 who were matched with an equivalent number of control individuals without dementia.
• Cumulative defined daily doses (DDDs) were calculated using the Anticholinergic Cognitive Burden (ACB) scale for drugs classified as weak (ACB scale score, 1) or strong (ACB scale score, 2-3) anticholinergics prescribed at least 1 year before the onset of dementia.

TAKEAWAY:

• The strength of the association between the use of strong anticholinergics and the risk for all‑cause dementia increased with increasing cumulative exposure: 1-89 DDDs (adjusted odds ratio [aOR], 1.10), 90-364 DDDs (aOR, 1.39), 365-1094 DDDs (aOR, 1.57), and ≥ 1095 DDDs (aOR, 1.66; P < .001 for all). The association was strongest for urinary antispasmodics, antihistamines, and psychotropic drugs.
• These associations were more pronounced in men and younger individuals and stronger among those with vascular or Lewy body dementia than among those with Alzheimer's disease.
• The cumulative use of weak anticholinergics was associated with a subtle increase in the risk for dementia across 1-89 DDDs (aOR, 1.11), 90-364 DDDs (aOR, 1.11), and 365-1094 DDDs (aOR, 1.06; P < .001 for all), except for ≥ 1095 DDDs.

IN PRACTICE:

"[The study] finding suggests that anticholinergic burden may represent a more relevant and modifiable risk factor at the earlier stages of dementia, underscoring the importance of minimizing unnecessary anticholinergic use, especially in younger individuals or those with milder cognitive symptoms," the authors wrote.

SOURCE:

This study was led by Nanbo Zhu, Department of Neurobiology, Division of Clinical Geriatrics, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. It was published online on October 21, 2025, in Alzheimer's Research & Therapy.

LIMITATIONS:

The observational nature of the study prevented potential conclusions on the causal relationship between anticholinergic burden and the risk for dementia. This study lacked data on lifestyle factors, such as smoking and alcohol use, and primary care data, leading to the underdiagnosis of certain comorbidities such as depression. Individuals may not have fully adhered to their prescribed regimens, potentially leading to the underestimation of the true effects.

DISCLOSURES:

Open access funding for this study was provided by Karolinska Institute. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.