1

Cumulative Use of Strong Anticholinergics and Incident

Dementia
A Prospective Cohort Study

Rationale

Many of the modern day medications that we currently have possess

anticholinergic properties. By its pharmacological definition, anticholinergic

agents block acetylcholine from binding to its acetylcholine receptors in nerve

cells, thereby resulting in the inhibition of parasympathetic nerve impulses.

Anticholinergic agents have been proven to cause mild cognitive impairment

with prolonged use, especially in the elderly. Generally, the effects of

anticholinergic agents on cognitive ability are reversible upon cessation of

anticholinergic therapy. However recent studies have suggested that the use of

anticholinergic agents is linked to the increased risk for dementia, primarily due

to the changes in the PNS that result from its usage.

Methodology

Participants who took place in the study were 65 years and above, all

coming from the Seattle area of the United States. Those individuals who

presented with dementia were excluded from the study for obvious reasons.

Additionally, all eligible participants underwent strict assessment in order to

evaluate their cognitive health, and also for the purpose of collecting

demographics and health history. The researchers developed a standardized

daily dose (SDD) by dividing the total medication dose (product of tablet strength

and number of tablets dispensed) with the minimum effective dose per day

according to the researchers references. Covariants were also taken into

consideration and the necessary adjustments were made to the SDDs of each

participant in order to keep the study unbiased with regards to the physiologic

SGMS
 2

discrepancies. Following a 10 year period of cumulative exposure of varying

degrees, mainly to doxepin, chlorpheniramine, and oxybutynin, researchers

summed up the participants SDDs for all prescription fills during exposure period

to create a cumulative total SDD (TSDD). This in turn was the basis for the

degree of cumulative exposure (TSDD was categorized as: no use, 1 to 90, 91 to

365, 366 to 1095, or greater than 1095 [ie, >3 years]).

Results

Findings of the study provide evidence that higher cumulative exposure to

anticholinergic agents correlate to an increased risk for all-cause dementia and

Alzheimers disease (AD). A mean follow-up after 7.3 years showed that out of

the 3434 participants, 797 (23.2%) of them had developed dementia, while 637

(79.9%) out of the 797 participants were at risk for probable AD. Interestingly,

participants in the highest cumulative exposure level had a significantly higher

chance of developing dementia or AD as compared to those in the second

highest cumulative exposure level, whom exhibited only a slightly higher risk of

developing the aforementioned diseases. Furthermore, there were no significant

interactions with the covariants of each participant. The subtype of

anticholinergic agent also had no significant implications on the risk of

developing dementia or AD.

SGMS