Potentially Inappropriate Medication Use in Individuals with Mild Cognitive Impairment: Results from the K erala E instein S tudy

Potentially inappropriate medication (PIM) use is a major safety concern, especially in cognitively impaired elderly adults. Despite the availability of guidelines for identifying PIM,1 a high proportion of older adults (8–21%) continue to receive PIM.2-4 Studies in developed countries suggest that individuals with mild cognitive impairment syndrome (MCI) are at higher risk than the general population of receiving PIM,5 but little is known about PIM usage in older adults, especially those with MCI, in developing countries. Elderly adults in developing countries have limited access to health care, and PIM may not only unnecessarily expend resources, but also the adverse side effects may not be readily recognized. Twenty-seven individuals with MCI (mean age 70.9, 40.7% women) attending neurology clinics at Baby Memorial Hospital, Kozhikode, India, between October 2008 and October 2010 were identified as part of the Kerala Einstein Study (KES).6 The goal of the KES is to identify risk factors for dementia in the southern Indian state of Kerala. Cases were frequency matched according to age and sex to 79 cognitively normal adults (mean age 70.4, 35.4% women) recruited from relatives of clinic attendees (70%) and from individuals referred for noncognitive complaints such as headaches, back pain, and peripheral neuropathies (30%). Inclusion criteria for KES were aged 60 and older and willingness to complete study procedures. Exclusion criteria were severe audiovisual loss or presence of active medical or psychiatric illness that, in the judgment of the study clinician, would interfere with completion of study procedures. Informed consent was obtained from all participants, and study evaluations followed protocols approved by the local institutional review board. A neurologist (MN) experienced in dementia evaluation obtained medical history and recorded medication use, by reviewing medication bottles, medical records, and verified information with informants. Another clinician (BJ) with behavioral neurology expertise administered a battery of cognitive tests in the local language (Malayalam) and validated in the Kerala elderly population. The cognitive battery assessed general cognition Addenbrooke Cognitive Examination (ACE), memory (Rey Auditory Verbal Learning Test), attention and executive function (Digit Span Test), and mood (15-item Geriatric Depression Scale). The ACE incorporates the Mini-Mental State Examination (MMSE). MCI was diagnosed in individuals without dementia with cognitive complaints and objective impairment (1.5 standard deviations or more below age and sex appropriate means) on tests of memory, attention and executive function, or language at consensus diagnostic conferences attended by two or more study clinicians. An independent clinician (RT) who did not perform study evaluations or diagnosis reviewed medications blinded to cognitive status to identify PIM usage according to the updated 2003 Beer's criteria1 with the addition of benzodiazepines.5 Descriptive statistics were used to test group differences according to MCI status. Logistic regression analysis adjusted for cognitive status (MMSE), Charlson Comorbidity Index, and depressive symptoms was used to further examine the association between MCI and PIM. Seven participants were prescribed PIM (5.6%). They had higher Charlson Comorbidity Index scores (1.43) than those not on PIM (0.70, P = .03). There were no significant group differences in age, education, depressive symptoms, cognitive scores, or prescription medication count. Table 1 shows baseline and cognitive test characteristics according to MCI status. The 27 participants with MCI (20 amnestic, 7 nonamnestic) had higher PIM usage (18.5%) than the 79 controls (2.5%, P = .01). Among MCI cases, PIMs included two medications with anticholinergic properties, two benzodiazepines. and one cardiac glycoside. In the controls, PIMs consisted of one tricyclic antidepressant and one nonsteroidal anti-inflammatory drug. Individuals with MCI were at higher risk of being on a PIM (adjusted odds ratio = 8.75, 95% confidence interval = 1.58–48.23). Higher PIM use (18.5%) was seen in individuals with MCI in a clinic-based population from Kerala, India. Individuals with MCI had an eight times greater risk of being on PIM than cognitively normal adults. A U.S.-based study of 689 individuals with MCI reported PIM usage in 20.8%, with anticholinergics and benzodiazepines being the most common.5 U.S.-based studies have reported that higher prescription medication count increases risk of PIM usage,2, 4, 5 but this was not the case in the current study. The lower PIM usage (5.6%) in the overall sample may be a result of cultural differences in medical or social practices as well as resource availability but is still of concern in individuals with MCI. The high prevalence of medications with anticholinergic effects is troubling, because they may negatively affect cognition.7 Furthermore, concomitant use of cholinesterase inhibitors and anticholinergics diminishes the effectiveness of dementia medications.8 Although limited by sample size, the results serve as a reminder that extra care should be taken when managing medications for individuals with MCI in developing countries. Conflict of Interest: Drs. Noone, Johnson, Pradeep, and Verghese have received research support from National Institutes of Health (NIH) Grants 1 R21 AGO25119 and 1R01 AG039330–01. Dr. Verghese has reviewed for NIH and received funding from National Institute on Aging Grants PO1 AG03949 and R01AG036921–01A1. Author Contributions: Richard Tsai: study concept, data acquisition, data analysis, data interpretation, and drafting manuscript. Mohan Noone, Beena Johnson, and VG Pradeep: study design, data acquisition, data interpretation, drafting manuscript. Joe Verghese: study design and concept, obtained grant support, data analysis, data interpretation, drafting manuscript. Sponsor's Role: The funding sources had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.