Anticholinergic Medication Use and Cognitive Impairment
Anticholinergic Medication Use and Cognitive Impairment
Objectives: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative.
Design: A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993.
Setting: Community-dwelling and institutionalized participants.
Participants: Thirteen thousand four participants aged 65 and older.
Measurements: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years.
Results: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=−0.14–0.11, P=.79). Two-year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics.
Conclusion: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.
Identifying risk factors for cognitive decline may lead researchers to a better understanding of clinical interventions to reduce the risk of developing Alzheimer's disease. Less physical, cognitive, and social activity and the presence of diabetes mellitus, hypertension, and hyperlipidemia have been identified as potentially modifiable risk factors for cognitive decline, including incident dementing illnesses such as Alzheimer's disease. Use of anticholinergic medications has been associated with acute cognitive impairment. Animal models link direct antagonism of the muscarinic cholinergic receptor M1 to decline in cognitive function, but there have been few studies evaluating the long-term exposure to medications as a modifiable risk factor. Progression of Alzheimer's-type pathology may be amplified with M1 blockade, whereas enhancing cholinergic transmission through the M1 receptor may reduce the deposits of Aβ peptides.
A recently published systematic review of the association between the anticholinergic activity of medications and cognitive function found a strong link between acute cognitive impairment and anticholinergic potency of medications as measured according to the serum anticholinergic assay or through consensus opinion, but the review did not identify sufficient studies that examined the long-term cognitive effects of anticholinergics. Therefore, data from an ongoing observational study (Medical Research Council Cognitive Function and Ageing Study; MRC CFAS) were examined to support or refute the hypothesis that the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and death in older people and to determine whether there is a cumulative effect.
Abstract and Introduction
Abstract
Objectives: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative.
Design: A 2-year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993.
Setting: Community-dwelling and institutionalized participants.
Participants: Thirteen thousand four participants aged 65 and older.
Measurements: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini-Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years.
Results: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33-point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=−0.14–0.11, P=.79). Two-year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics.
Conclusion: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.
Introduction
Identifying risk factors for cognitive decline may lead researchers to a better understanding of clinical interventions to reduce the risk of developing Alzheimer's disease. Less physical, cognitive, and social activity and the presence of diabetes mellitus, hypertension, and hyperlipidemia have been identified as potentially modifiable risk factors for cognitive decline, including incident dementing illnesses such as Alzheimer's disease. Use of anticholinergic medications has been associated with acute cognitive impairment. Animal models link direct antagonism of the muscarinic cholinergic receptor M1 to decline in cognitive function, but there have been few studies evaluating the long-term exposure to medications as a modifiable risk factor. Progression of Alzheimer's-type pathology may be amplified with M1 blockade, whereas enhancing cholinergic transmission through the M1 receptor may reduce the deposits of Aβ peptides.
A recently published systematic review of the association between the anticholinergic activity of medications and cognitive function found a strong link between acute cognitive impairment and anticholinergic potency of medications as measured according to the serum anticholinergic assay or through consensus opinion, but the review did not identify sufficient studies that examined the long-term cognitive effects of anticholinergics. Therefore, data from an ongoing observational study (Medical Research Council Cognitive Function and Ageing Study; MRC CFAS) were examined to support or refute the hypothesis that the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and death in older people and to determine whether there is a cumulative effect.
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