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August 5, 2021Open Access

The longitudinal trajectory of anticholinergic burden was predictive of incident dementia (HR 1.094), with the association holding especially for antidepressants, antiepileptics, and high-ceiling antidiuretics.

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Why the study?

Previous studies on long-term anticholinergic drug use and dementia report heterogeneous results, potentially due to different anticholinergic scales and differential effects across drug classes.

Does higher cumulative anticholinergic burden increase the risk of incident dementia in adults?

Population

171,775 UK Biobank participants with linked GP prescription records

Comparison

13 anticholinergic scales and anticholinergic burden from different drug classes vs dementia risk

Design

Observational cohort study using linked records

Key result

The longitudinal trajectory of anticholinergic burden was predictive of incident dementia (HR 1.094), with the association holding especially for antidepressants, antiepileptics, and high-ceiling antidiuretics.

Authors

JMJure MurTRTom C. RussSCSimon R. Cox

Discussion

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Member takes

Overview

May support risk stratification in older adults; leaves open whether reducing exposure prevents dementia.

Study Design

Type

Cohort (n=171,775)

Structured PICO

Does higher cumulative anticholinergic burden increase the risk of incident dementia in adults?

P
Population
171,775 adults from the UK Biobank, median age 55 years and free of prior neurodegenerative diseases, followed to assess the association between anticholinergic burden and incident dementia.
E
Exposure
Cumulative annual anticholinergic burden (ACB) calculated using 13 different anticholinergic scales based on primary care prescription records, as well as the longitudinal trajectory of ACB.
C
Comparator
Lower anticholinergic burden and general polypharmacy (total yearly drug count minus anticholinergic drugs).
O
Outcome
Incident dementia diagnosis ascertained through primary care and inpatient hospital records.hard clinical

Main Result

Hazard Ratio: 1.094 (95% CI 1.068–1.119)

Higher cumulative anticholinergic burden and its longitudinal increase are associated with an increased risk of incident dementia, particularly for antidepressants, antiepileptics, and high-ceiling diuretics.

Limitations

  • Participants in UK Biobank are healthier and live in less deprived areas than the general UK population
  • Linked data do not include over-the-counter drugs and dietary supplements
  • Relatively few cases of dementia due to the low average age of participants
  • Quantity/volume of medicines was not used in the calculation of the dosage-based anticholinergic burden
  • The assumption of linearity between the predictor and the log hazard was sometimes violated
  • UK Biobank participants are healthier and live in less deprived areas than the UK population
  • Linked data do not include information on over-the-counter drugs and dietary supplements
  • Relatively few cases of dementia due to low average age
  • Quantity/volume of medicines was not used in the calculation of the dosage-based ACB
  • Assumption of linearity between predictor and log hazard was sometimes violated
  • Potential confounding by indication

Cite This Study

Mur et al. (2021) conducted a cohort in Dementia (n=171,775). Anticholinergic burden vs. Lower anticholinergic burden was evaluated on Incident dementia (HR 1.094, 95% CI 1.068-1.119). The longitudinal trajectory of anticholinergic burden was predictive of incident dementia (HR 1.094), with the association holding especially for antidepressants, antiepileptics, and high-ceiling antidiuretics.

synapsesocial.com/papers/6a994bf6b3d4f622baf0e3fdhttps://doi.org/10.1101/2021.08.04.21261330
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