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. 2018 Sep 8;89(10):1107–1115. doi: 10.1136/jnnp-2018-318190

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.