Abstract
Background
the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear.
Methods
we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I.
Results
twenty-six studies (including 621,548 participants) met our inclusion criteria. ‘Any’ anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09–1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17–1.29, I2 = 2%; and OR 1.50, 95% CI 1.22–1.85, I2 = 90%). ‘Any’ anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09–0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97–1.59, I2 = 0%).
Conclusions
anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.
the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear.
Methods
we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I.
Results
twenty-six studies (including 621,548 participants) met our inclusion criteria. ‘Any’ anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09–1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17–1.29, I2 = 2%; and OR 1.50, 95% CI 1.22–1.85, I2 = 90%). ‘Any’ anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09–0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97–1.59, I2 = 0%).
Conclusions
anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.
| Original language | English |
|---|---|
| Pages (from-to) | 939-947 |
| Number of pages | 9 |
| Journal | Age and Ageing |
| Volume | 49 |
| Issue number | 6 |
| Early online date | 29 Jun 2020 |
| DOIs | |
| Publication status | Published - 1 Nov 2020 |
Bibliographical note
Funding Sources:This work was supported by the Alzheimer’s Society UK [AS-PG-2013-017]. The study funder played no role in the design, execution, analysis and interpretation of data, or writing of the study.
ACKNOWLEGEMENTS
We would like to acknowledge Mr Barry Plumpton, Mrs Ann McLauchlan, Mrs Barbara di Vita, and Mrs Gloria Swan for providing interpretation and oversight during the study as Alzheimer’s Society UK Research Network Volunteers.
Keywords
- systematic review
- meta-analysis
- anticholinergics
- dementia
- cognition
- older people