Cholinesterase Inhibitor Use and Age in the General Population

Cholinesterase inhibitors (ChEIs) are the only drugs approved in several countries for the symptomatic treatment of mild to moderate Alzheimer disease (AD), the most common type of dementia. Despite their approval, clinical relevance of ChEIs remains controversial. Some 65 out of 100 patients with AD are 80 years or older,^{1 - 2} the fastest growing segment of the elderly population in western countries.^{1 ,3} This age group is systematically and grossly underrepresented in dementia clinical research.^{1 ,4} Estimates of ChEI use by patients with mild to moderate AD in the general population are very scarce, and to our knowledge, no direct assessment is available from population-based surveys.

An ongoing, population-based, door-to-door study (the Monzino 80-plus Study) on the prevalence and incidence of dementia among all residents aged 80 years or older (n = 1983) in the lower Olona Valley, northern Italy, gave us the opportunity to directly investigate the current use of ChEIs in the age classes with the highest AD prevalence. Diagnosis of AD was based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. As in most clinical trials and guidance on the use of ChEIs, patients with AD with a Mini-Mental Status Examination score greater than 9 were classified with a mild to moderate level of disease severity.

To extend prevalence data also to the younger age classes (60-69, 70-74, and 75-79 years), pooled results of all the available Italian studies were used.¹ Up to the age of 75 years, the extent of variability of prevalence rates among the different studies was negligible.

In Italy, ChEIs are dispensed under the National Health Service at no cost to the patient. Data from our survey were compared with those derived from National Health Service drug prescriptions from the same area and period of the prevalence study to control for possible selection bias.

The study protocol was submitted to and approved by the local research ethics review committee (Azienda Sanitaria Locale of the Varese province). Written informed consent was obtained from all participants.

Information was gathered from 1439 of 1891 contacted subjects. As expected, prevalence rates of mild to moderate AD rise with increasing age (Figure). On the contrary, ChEI use steadily decreases with increasing age. Data derived from the National Health Service gave almost identical results to those from our survey. Prescription data were assessed to estimate the ChEI use in the younger age classes as well (open triangles in the Figure). The largest proportion of patients treated were in the younger age groups, with a steep drop following along with age: from 54.7% (60-69 years) to 18.6% (80-84 years) to 1.6% (≥90 years). Altogether, only 1 out of 5 patients with mild to moderate AD in the general population was treated with ChEIs.

Notwithstanding the suggested benefit from ChEI treatment among older patients with AD,⁵ rate of ChEI use is inversely associated with mild to moderate AD prevalence, and overall, the subjects treated are a small proportion of those affected. Several not mutually exclusive hypotheses could be put forth to interpret these findings: difficulties with the diagnoses of dementia syndrome and type, presence of significant concurrent pathologic abnormalities, frequency of adverse drug reactions, and fatalistic acceptance of the condition are all positively associated with age. The small proportion of the treated patients at any age along with the dramatic drop in ChEI use with increasing age could also indicate a perceived low effectiveness of these drugs by both the caregiver and the physician, a conviction consolidating as the subject ages. Prejudice? Wisdom?

Correspondence: Mr Lucca, Laboratory of Geriatric Neuropsychiatry, Istituto di Ricerche Farmacologiche “Mario Negri,” Via Eritrea 62, 20157 Milano, Italy (lucca@marionegri.it).

Funding/Support: This study was supported by a research grant from the Fondazione Italo Monzino, Milano, Italy. The funding body was not involved in the design or analysis or in the decision to publish this study.

Acknowledgment: We are very grateful to Drs Pierluigi Zeli and Olivia Leoni, Azienda Sanitaria Locale (ASL) of the Varese province, for having provided the National Health Service drug prescription data of the lower Olona Valley ASL district.