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Updated: Jun 24, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Association between anticholinergic drugs and apolipoprotein E epsilon4 allele and poorer cognitive function in older
Juho Uusvaara1, Kaisu H Pitkala, Pentti J Tienari
1Unit of General Practice, Helsinki University Hospital, Helsinki, Finland. juho.uusvaara@kauniala.fi
Objectives:
To clarify the association between anticholinergic drugs and apolipoprotein E epsilon4 allele carrier status (APOE4) and cognitive dysfunction.
Design:
Cross-sectional analyses of current drug use and cognitive functioning according to the baseline assessments of the Drugs and Evidence-Based Medicine in the Elderly Study.
Setting:
Helsinki, Finland.
Participants:
Four hundred community-dwelling people aged 75 to 90 without clinical dementia but with a history of stable atherosclerotic disease.
Measurements:
Cognitive function according to the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale (CDR). Participants' use of anticholinergic drugs was estimated using definitions from previous scientific literature. APOE alleles determined from peripheral blood leukocyte deoxyribonucleic acid using standard polymerase chain reaction-based methods.
Results:
There was an association between anticholinergic drugs and lower MMSE scores (P for trend <.001). The higher the number of anticholinergic drugs, the lower the MMSE score. Subjects with the APOE4 allele and using drugs with anticholinergic properties had the lowest median MMSE score (26), whereas those without the APOE4 allele and not using drugs with anticholinergic properties had the highest median MMSE score (28). When adjusted for age, sex, and education, the difference between the groups remained significant. The finding was similar for CDR scores.
Conclusion:
Use of drugs with anticholinergic properties was associated with lower cognitive function irrespective of APOE4 carrier status. Having lower cognitive function as a group, APOE4 carriers may be more vulnerable to this undesirable effect, but a follow-up study is needed to demonstrate this.
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