Table 5.

Associations linking cumulative exposure to anticholinergic drugs over a 3-year period and z-scores on cognitive function tests according to anticholinergic class†, adjusted on lifestyle‡ and health status§ variables (n=34 267)

Cumulative AC exposure			Episodic memory				Verbal fluency				Executive functions
			Immediate free recall		Delayed free recall		Semantic fluency		Phonemic fluency		DSST		TMT-A		TMT-B
			Estimate (SE)		Estimate (SE)		Estimate (SE)		Estimate (SE)		Estimate (SE)		Estimate (SE)		Estimate (SE)
Antihistamines	None	26 385	Ref		Ref		Ref		Ref		Ref		Ref		Ref
	<1 year	7298	0.015 (0.014)		0.009 (0.014)		−0.007 (0.014)		0.010 (0.014)		0.015 (0.014)		0.024 (0.014)		0.027 (0.014)	*
	≥1 year	584	0.027 (0.042)		0.058 (0.042)		−0.020 (0.042)		−0.003 (0.042)		0.037 (0.042)		0.011 (0.042)		0.049 (0.042)
Opioids	None	29 284	Ref		Ref		Ref		Ref		Ref		Ref		Ref
	<1 year	4902	−0.040 (0.016)	*	−0.048 (0.016)	**	−0.004 (0.016)		−0.016 (0.016)		−0.013 (0.016)		−0.005 (0.016)		−0.018 (0.016)
	≥1 year	81	−0.161 (0.112)		−0.101 (0.112)		0.094 (0.112)		0.182 (0.112)		0.014 (0.112)		0.094 (0.112)		0.085 (0.112)
Alimentary tract and metabolism drugs	None	29 554	Ref		Ref		Ref		Ref		Ref		Ref		Ref
	<1 year	4635	0.014 (0.016)		0.011 (0.016)		0.006 (0.016)		−0.007 (0.016)		0.015 (0.016)		0.005 (0.016)		−0.019 (0.016)
	≥1 year	78	0.099 (0.114)		−0.082 (0.114)		−0.024 (0.114)		−0.130 (0.114)		−0.154 (0.114)		−0.287 (0.114)	*	−0.344 (0.114)	**
Anxiolytic drugs	None	30 251	Ref		Ref		Ref		Ref		Ref		Ref		Ref
	<1 year	3812	−0.043 (0.018)	*	−0.044 (0.018)	*	−0.007 (0.018)		0.011 (0.018)		−0.005 (0.018)		0.008 (0.018)		−0.014 (0.018)
	≥1 year	204	−0.060 (0.072)		−0.185 (0.072)	*	−0.060 (0.072)		−0.024 (0.072)		−0.197 (0.072)	**	−0.176 (0.072)	*	−0.170 (0.072)	*
Antidepressant drugs	None	32 216	Ref		Ref		Ref		Ref		Ref		Ref		Ref
	<1 year	1427	−0.022 (0.028)		−0.012 (0.028)		−0.030 (0.028)		−0.012 (0.028)		0.006 (0.028)		0.058 (0.028)	*	0.049 (0.028)
	≥1 year	624	0.014 (0.042)		−0.034 (0.042)		0.039 (0.042)		−0.010 (0.042)		0.018 (0.042)		−0.014 (0.042)		−0.017 (0.042)
Cardiovascular system drugs	None	33 317	Ref		Ref		Ref		Ref		Ref		Ref		Ref
	<1 year	537	−0.033 (0.044)		0.003 (0.044)		−0.002 (0.044)		0.006 (0.044)		−0.045 (0.044)		−0.087 (0.044)	*	−0.075 (0.044)
	≥1 year	413	0.052 (0.050)		0.144 (0.050)	**	0.027 (0.050)		−0.001 (0.050)		−0.080 (0.050)		−0.085 (0.050)		−0.028 (0.050)
Antipsychotics	None	33 949	Ref		Ref		Ref		Ref		Ref		Ref		Ref
	<1 year	217	−0.146 (0.069)	*	−0.177 (0.069)	*	−0.183 (0.069)	**	−0.049 (0.069)		−0.347 (0.069)	***	−0.148 (0.069)	*	−0.268 (0.069)	***
	≥1 year	101	−0.433 (0.101)	***	−0.493 (0.101)	***	−0.380 (0.101)	***	−0.262 (0.101)	**	−0.658 (0.101)	***	−0.590 (0.101)	***	−0.511 (0.101)	***
Other AC drugs	None	30 774	Ref		Ref		Ref		Ref		Ref		Ref		Ref
	<1 year	3235	−0.015 (0.019)		−0.038 (0.019)	*	0.017 (0.019)		0.012 (0.019)		−0.022 (0.019)		−0.037 (0.019)	*	−0.001 (0.019)
	≥1 year	258	−0.082 (0.063)		−0.057 (0.063)		−0.054 (0.063)		0.007 (0.063)		−0.086 (0.063)		−0.090 (0.063)		−0.054 (0.063)

Values are given as the adjusted difference between two groups in terms of cognitive z-score.

P values: *0.01–0.05, **0.001–0.01, ***<0.001.

†Drug classes of anticholinergic agents were determined based on the ATC classification level.

‡Lifestyle variables: living with a partner, smoking status, alcohol consumption, physical activity and body mass index.

§Health status variables: self-rated health status, depressive symptoms, diabetes, respiratory diseases, cardiovascular diseases, osteoarticular disease, hypercholesterolaemia and cancer.

AC, anticholinergic drug; ATC, Anatomical Therapeutic Chemical classification system; DSST, Digit Symbol Substitution Test; ref, reference; TMT, A and B, Trail Making Test.