Effectiveness and Safety of Donepezil in Hispanic Patients with Alzheimer’s Disease: A 12-Week Open-Label Study

Abstract

Background Hispanics represent 10% of the U.S. population and are the fastest growing group. Studies show a higher prevalence and incidence of Alzheimer’s disease (AD) in Hispanics than in the non-Hispanic white population, with an earlier age of onset. Among the currently estimated 200,000 Hispanics with AD, a significant number remain undiagnosed and untreated, and Hispanic participation in AD clinical trials has been historically low. This study evaluated the efficacy and safety of donepezil hydrochloride (donepezil) in Hispanics with mild-to-moderate AD. Methods In this multicenter, open-label, 12-week study conducted in the United States, subjects were Hispanic men or women aged ≥50 years with a diagnosis of mild-to-moderate AD (DSMV-IV and NINCDS/ADRDA criteria), with Mini-Mental State Examination (MMSE) scores of 10–26 (inclusive) at screening. Subjects were treated with donepezil 5 mg/day for 6 weeks followed by 10 mg/day for 6 weeks. Clinical evaluation was performed at baseline, week 6 and week 12. Cognitive improvement was measured using the MMSE, Fuld Object Memory Evaluation (FOME) and Symbol Digit Modality Test (SDMT). Behavioral symptoms and associated caregiver distress were assessed with the Neuropsychiatric Inventory (NPI). Results One-hundred-six patients with mild-to-moderate AD (mean age 68.6 years) were enrolled (intent to treat, n=97); most chose to have assessments conducted in Spanish. With 12 weeks of treatment, subjects showed statistically significant improvement from baseline on MMSE (P<0.0001), FOME retrieval (P=0.0042), FOME repeated retrieval (P=0.0020) and SDMT correct scores (P<0.0001). The NPI subdomain “apathy/indifference” showed statistically significant improvement (P=0.0010). The NPI Caregiver Distress scale (NPI-D) total score was statistically significantly improved (P=0.0500), suggesting a positive impact on relieving caregivers’ burden associated with patient behavior. Most patients tolerated the treatment well, with only 2 discontinuing because of adverse events. The most common (>5%) adverse events were insomnia (9.5%), dizziness (7.6%), diarrhea (5.7%) and nausea (5.7%). Conclusion The cognitive improvement and safety results from this study were consistent with those reported for donepezil in the general population. Increased awareness of AD in the Hispanic population will help more Hispanics with AD to benefit from early diagnosis and effective treatment.

The Safety, Tolerability, and Efficacy of Once-Daily Memantine (28 mg): A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients with Moderate-to-Severe Alzheimer’s Disease Taking Cholinesterase Inhibitors

“…It should be noted that our study consisted of a large, mostly non-US Hispanic population (69 %), which has not been extensively represented in clinical trials in AD [13]. Although other ADL measures have been successfully validated in Hispanic patients [25–27], to our knowledge the only Spanish validation of the ADCS–ADL scale involves the 23-item instrument in Spanish-speaking Americans [28], and the possibility exists that some items from the 19-item scale may be less applicable to patients with moderate to severe AD from Central or South America.…”

“…Stable use of any cholinesterase inhibitor was required in this study, similar to a previous trial of immediate-release memantine (10 mg, twice daily) in patients with moderate-to-severe AD who were taking the cholinesterase inhibitor donepezil [9]. In addition, the majority of participants in this study were primarily of Hispanic origin (68.9 %), including participants from Argentina, Mexico, and Chile, a patient population that has traditionally been under-represented in trials of memantine and other AD drugs [13]. …”

Racial and Ethnic Disparities Among Individuals with Alzheimer’s Disease in the United States: A Literature Review

“…Specifically, these disparities persisted for blacks and non-Hispanic others, but diminished among Hispanics when these control variables were accounted for (Zuckerman et al, 2008). Although African Americans are often less likely to be prescribed medications, there is evidence that antidementia medications such as donepezil are safe and moderately effective for African-American and Hispanic patients with mild to moderate AD (Griffith, Lichtenberg, Goldman, & Payne-Parrish, 2006;Lopez et al, 2008).…”

A case of probable non-familial early onset Alzheimer dementia in a Hispanic male

“…Early literature suggested that autosomal dominant mutations accounted for 30–50% of all EOAD cases and 10% of all Alzheimer's dementia cases, but recent literature has questioned this previous data, due to a greater awareness of likely autosomal recessive EOAD conditions (5, 6). There are a number of reports describing higher prevalence of late onset Alzheimer's disease in the Hispanic population (7, 8). Additionally, Athan et al first reported a Gly–Ala substitution in codon 206 of the PSEN1 gene in 8 of 19 unrelated Caribbean Hispanic families with early onset familial AD (9).…”