To the best of our knowledge, this study was the first to report on the AC prescription among Thai patients with AD including the prevalence of AC prescription, the concomitant use with AChEIs and the association with adverse effects on cognition among elderly Thais with AD.
The authors found a high rate of AC drugs among patients with AD (31.6%) even though this was lower than that in other studies ranging from 46.83% to 65.8 [25, 26]. The reason could be that our participants were collected from tertiary care, a university hospital of northern Thailand. This group of patients had concomitant medications from other secondary care centers, in which we have not yet had an effective accessible system among hospitals and other health care providers. This gap may have allowed unnecessary and unthoughtful prescription of ACs to take place.
The present study showed adverse effects on cognition among the elderly with AD. TMSE score was lower with statistical significance among patients that were AC concomitant even though they received AChEIs. The study confirmed the negative predictors of TMSE score that could be predicted by advanced age and AC use. These were in line with a 2-year longitudinal study of the elderly in that the use of AC medication with definite anticholinergic effects was associated with a greater decline in MMSE score than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline . Advancing age was, as expected, another predictor for longitudinal outcome of cognition, as found in related research . Notably, not only did the anticholinergic effect have a direct impact on cognition, a pharmacodynamic drug interaction between AChEIs and AC also nullified the benefit of AChEI at the neuronal level. However, we are not yet able to conclude that any pair of combinations of AC and AChEIs has the same effect on cognition. Verifying this may require a large sample size. Despite that, clinicians should be more aware of using ACs among patients receiving AChEIs because it may not only worsen cognition but also become a huge loss regarding economic aspects.
One important point to be note is that the most common AC drug used was quetiapine, which is mostly related to remedy behavioral and psychological symptoms of dementia (BPSD). This finding was in line with related studies in that quetiapine was the most used drug among patients with dementia and was harmful to cognitive outcome [27, 28]. For what reason, quetiapine has become commonly prescribed for clinicians remains unclear and may not be an easy answer to find using this type of research design. Several atypical antipsychotic drugs can be used among patients with disturbed symptoms of dementia. Aripiprazole and risperidone may be better than quetiapine in terms of anticholinergic effects, but provide more risk of extrapyramidal side effects. In complicated situations of the patient, clinicians should individualize the assessment of safety risks against expected benefits when prescribing atypical antipsychotics. Therefore, it may be difficult to simply suggest not using quetiapine with this situation. Consistent with the recent network meta-analysis, the study revealed a trade-off between the effectiveness and safety of atypical antipsychotics in the treatment of BPSD and assures that a single most effective and safe treatment option does not exist .
Regarding BZD, the present study showed that only a small percent of the patients received a combination between both ACs and BZD, which was lower than a related study in a large population (approximately 6%) . A recent cohort study suggested that ACs or BZDs could increase dementia risk at 10-year follow-up. By that an ACB score of 3 was found, but neither BZDs nor ACB score 1 or 2 medications was associated with dementia, particularly in those with good baseline cognitive function . According to a related study, our result demonstrated that BZDs use was not associated with a negative predictor of TMSE score. This finding was also supported by a longitudinal study in that MMSE was not associated with BZD use in the models . Considering a relatively small sample size, we cannot conclude that t no long-term effect exists of BZD concerning cognition, on the contrary, prescribing long term BZDs among the elderly regardless concomitant with AC or no AC should be cautious, as it remains potentially inappropriate due to other harmful effects of BZD .
In conclusion, despite the fact that AC medication should be avoided among patients with dementia, it may not be easy to avoid using medication with anticholinergic effects especially atypical antipsychotic to deal with BPSD. AC drugs and age were the strong predictors of negative cognitive outcomes in the long run. Awareness of potential anticholinergic risk of medication seems to be the best policy. In a setting where a geriatric physician or nurse is lacking, the incidence of prescribing such medication is relative high. Therefore, maintaining awareness and monitoring whenever these anticholinergic drugs are used is important regardless of what use they are for.
The main limitation of the present study is the small sample size which may have an impact on statistical power. A larger sample is required, particularly for subgroup analysis of the combinatorial effects of AC and AChEIs on cognition. The method used made information regarding the patients accessed in other health care centers unavailable. In addition, over-the-counter medications were unreported. Moreover, being prescribed a medication does not mean that the patients have actually taken them. Finally, further prospective studies with larger populations should be warranted to demonstrate proportion and the impact of AC use.