To the Editor
Antipsychotic drugs have significant risks of side effects, especially increased risk of death, in elderly people with dementia [1]. Emerging research on racial and ethnic disparities in the treatment of Alzheimer’s Disease (AD) and other dementias has further driven the need to identify groups at greater risk of using these medications. We examined patterns of antipsychotic use in African American, Hispanic, and non-Hispanic White patients with dementia, in the National Alzheimer’s Coordinating Center (NACC) [2]. The objectives of this study were to characterize the incident use of antipsychotics participants, overall and by race/ethnicity, and to assess whether differences in time to antipsychotic use across race/ethnic groups persisted after accounting for demographic and clinical variables.
METHODS
We conducted a retrospective review of prescription medication records for community dwelling NACC participants diagnosed with dementia. The study sample consists of NACC participants (2008–2014) who had a diagnosis of dementia and indicated no current use of antipsychotic medications at their index visit. An index visit was determined by the participant’s first available prescription information starting in 2008. A total of 4,741 participants fit this description: African American (n=401), Hispanic (n=337), and Non-Hispanic White (n=3,389). Demographic information included age, gender, education, and race/ethnicity. Clinical information included informant-reported neuropsychiatric symptoms (NPS) measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q) [3, 4] and a clinician assessment of dementia severity using the Clinical Dementia Rating (CDR) [5,6,7]. The primary outcome was the time until either first record of antipsychotic use or censoring (last follow-up visit.) For a full list of medications included in this study please see the NACC Derived Variables documentation [8]. To estimate differences between racial/ethnic groups and to assess the additional effects of other demographic and clinical variables, we fitted Cox proportional hazard regression models. The effects of race/ethnicity were assessed in a series of three multivariate Cox regression models. The first model assessed whether likelihood of use of antipsychotic medications differed by race/ethnicity, taking account of the demographic variables. The second model added the NPI-Q sum of severity scores at index visit to assess the impact of NPS on future antipsychotic use and determine whether differences across race/ethnic groups might be accounted for by differences in NPS. In the third model, the CDR sum of boxes score at baseline was added to the model to assess the impact of dementia severity. For the purpose of these analyses we assumed that time of censoring was non-informative and independent of later antipsychotic use. All reported p-values were those of two-sided tests; significance was defined as p<0.05.
RESULTS
Of 4,741 participants, 614 (12.95%) went on antipsychotics during the study period. For many participants, data collection ended with the end of study period (10%), or death (25%). We compared rates and causes of censoring across race/ethnicities to see if non-Hispanics White and/or African Americans might not be followed as long for reasons related to decisions about antipsychotic medications, and found no significant difference between the three groups..
A series of multivariate Cox regression analyses examined the association of race/ethnicity with likelihood of future antipsychotic use, adjusted for age, education, and gender (Model I) and sequentially adding NPS (Model II) and CDR (Model III), in participants with dementia (Table 1).
Table 1.
Multivariate Cox Proportional Hazard Analysis of Incident Anti-psychotic Drug Use Among Socio-Demographic Factors, Level of Cognitive Impairment as Measured by CDR, and Severity of Neuropsychiatric Symptoms.
| Model I | Model II | Model III | ||||
|---|---|---|---|---|---|---|
| HR | 95% CI | HR | 95% CI | HR | 95% CI | |
| Primary Predictor of Interest | ||||||
| Race/Ethnicity | ||||||
| Hispanic: White | 1.72 | (1.29, 2.29) | 1.58 | (1.18, 2.09) | 1.58 | (1.19, 2.11) |
| African American: White | 1.13 | (0.86, 1.51) | 1.17 | (0.88, 1.55) | 1.20 | (0.90, 1.59) |
| Key Predictors | ||||||
| Sociodemographic | ||||||
| Age from 70 | ||||||
| Effect of 1 year increase | 0.97 | (0.97, 0.98) | 0.98 | (0.97, 0.99) | 0.98 | (0.97, 0.98) |
| Sex | ||||||
| Female compared to male | 0.73 | (0.62, 0.86) | 0.80 | (0.68, 0.94) | 0.73 | (0.62, 0.86) |
| Education | ||||||
| <HS compared to HS | 0.87 | (0.63, 1.20) | 0.89 | (0.65, 1.22) | 0.89 | (0.65, 1.23) |
| College compared to HS | 0.96 | (0.78, 1.19) | 0.95 | (0.77, 1.17) | 0.93 | (0.75, 1.14) |
| Graduate education compared to HS | 1.06 | (0.87, 1.30) | 1.07 | (0.87, 1.3) | 1.04 | (0.85, 1.28) |
| NeuroPsych SymptomsSeverity | ||||||
| NPS Sum of Boxes | 1.08 | (1.06, 1.09) | 1.07 | (1.05, 1.08) | ||
| Clinical Dementia Rating | ||||||
| CDR Sum of Boxes | 1.06 | (1.04, 1.08) | ||||
Results in bold are significant at p<0.05, CI= confidence interval, HS= high school, HR= hazard ratio, NPS = NeuroPsych Symptom Severity, CDR = Clinical Dementia Rating
Hispanics were significantly more likely to go on antipsychotics after adjusting for age, education, and gender (Hazard ratio (HR)=1.72). In Models II and III, the odds for Hispanics of being on antipsychotics continued to be elevated and remained significant with the Hispanic group about 60% more likely to go on antipsychotics (HR=1.58, 95%CI (1.19,2.11)) in the final model.
DISCUSSION
To our knowledge this analysis is the first to study incident use of antipsychotics in a community setting of elderly patients with dementia, across demographics. Hispanics but not African Americans had an increased likelihood of going on antipsychotics in NACC participants with dementia compared to non-Hispanic Whites. This difference is not accounted for by higher dementia severity and NPS in Hispanic participants either at baseline or during follow-up. By analyzing incidence rather than prevalence, our results can better reflect use of antipsychotics following the diagnosis of dementia, and thus likely attributable to dementia-related concerns rather than to prior issues such as a preexisting psychotic disorder. Further studies are needed to clarify ethnic differences on how families and physicians address dementia progression and neuropsychiatric symptoms in community dwelling patients with dementia.
Acknowledgments
NIH Funding: This study was supported by the UC Davis Alzheimer’s Disease Center (funded by the National Institute of Aging, P30 AG10129 and P30 AG01961) and funding from Center for Health Care Policy and Research and Clinical and Translational Science Center. The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI David Teplow, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), and P50 AG005681 (PI John Morris, MD).”
Sponsor’s Role: Sponsor had no part in design, methods, subject recruitment, data collections, analysis and preparation of paper.
Footnotes
Conflict of Interest: There are no financial or personal conflicts of interest to address for all authors.
Author Contributions: Authors Filshtein, Beckett, Hinton, Xiong contributed to the study concept and design, acquisition of subjects and/or data was performed by Filshtein and Xiong and all authors contributed to the analysis, interpretation of data and preparation of manuscript. The corresponding author (Teresa Filshtein) affirms that everyone who has contributed significantly to this work has been listed as an author. There are no contributors who are not authors.
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