Alzheimer Disease: Whalen E

Gauthier S, Feldman H, Hecker J, Vellas B, Ames D, Subbiah P, Whalen E, Emir B, Anonymous00001. · Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, Verdun, Quebec, Canada. · Int Psychogeriatr. · Pubmed #12670060 No free full text.

Abstract: OBJECTIVE: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. METHODS: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5-17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiatric Inventory (NPI). RESULTS: Baseline demographics were similar between the treatment groups. Least squares mean (+/- SE) baseline NPI 12-item total scores were 19.55 +/- 1.48 and 19.30 +/- 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI (continued) 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). CONCLUSIONS: Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.

Tariot PN, Cummings JL, Katz IR, Mintzer J, Perdomo CA, Schwam EM, Whalen E. · Department of Psychiatry, University of Rochester Medical Center, Monroe Community Hospital, Rochester, New York 14620, USA. · J Am Geriatr Soc. · Pubmed #11843990 No free full text.

Abstract: OBJECTIVES: To evaluate the safety and efficacy of donepezil in the management of patients with Alzheimer's disease (AD) residing in nursing home facilities. DESIGN: Twenty-four-week, randomized, multicenter, parallel-group, double-blind, placebo-controlled trial. SETTING: Twenty-seven nursing homes across the United States. PARTICIPANTS: Two hundred eight nursing home patients with a diagnosis of probable or possible AD, or AD with cerebrovascular disease; mean Mini-Mental State Examination (MMSE) score 14.4; mean age 85.7. MEASUREMENTS: The primary outcome measure was the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). Secondary efficacy measures were the Clinical Dementia Rating (Nursing Home Version)-Sum of the Boxes (CDR-SB), MMSE, and the Physical Self-Maintenance Scale (PSMS). Safety was monitored by physical examinations, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and treatment-emergent adverse events (AEs). RESULTS: Eighty-two percent of donepezil- and 74% of placebo-treated patients completed the trial. Eleven percent of donepezil- and 18% of placebo-treated patients withdrew because of AEs. Mean NPI-NH 12-item total scores improved relative to baseline for both groups, with no significant differences observed between the groups at any assessment. Mean change from baseline CDR-SB total score improved significantly with donepezil compared with placebo at Week 24 (P < .05). The change in CDR-SB total score was not influenced by age. Differences in mean change from baseline on the MMSE favored donepezil over placebo at Weeks 8, 16, and 20 (P < .05). No significant differences were observed between the groups on the PSMS. Overall rates of occurrence and severity of AEs were similar between the two groups (97% placebo, 96% donepezil). Gastrointestinal AEs occurred more frequently in donepezil-treated patients. In general, AEs were similar in older and younger donepezil-treated patients, with the majority of patients experiencing only AEs that were transient and mild or moderate in severity. Weight loss was reported as an AE more frequently in older patients, although a loss at last visit of >or=7% of screening weight occurred at the same rate in older and younger patients (9% of donepezil- and 6% of placebo-treated patients). No significant differences between groups in vital sign changes, bradycardia, or rates of clinically significant laboratory or ECG abnormalities were observed. CONCLUSION: Patients treated with donepezil maintained or improved in cognition and overall dementia severity in contrast to placebo-treated patients who declined during the 6-month treatment period. The safety and tolerability profile was comparable with that reported in outpatient studies of donepezil. These findings also suggest that advanced age, comorbid illnesses, and high concomitant medication usage should not be barriers to donepezil treatment. Given the apparent improvement in behavior in the placebo group, and the high use of concomitant medications in both groups, the impact of donepezil on behavior in the nursing home setting is unresolved and merits further investigation. In summary, effects on cognition, overall dementia severity, and safety and tolerability findings are consistent with previous findings in outpatients and support the use of donepezil in patients with AD who reside in nursing homes.

Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E, Anonymous00206. · Division of Neurology, UBC Hospital, Clinic for Alzheimer's Disease and Related Disorders, Vancouver, BC, Canada. · Neurology. · Pubmed #11524468 No free full text.

Abstract: OBJECTIVE: To investigate the efficacy and safety of donepezil in patients with moderate to severe AD (standardized Mini-Mental State Examination [sMMSE] scores of 5 to 17; Functional Assessment Staging score < or =6 at baseline). METHODS: Two-hundred ninety patients were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil 5 mg/day for the first 28 days and 10 mg/day thereafter as per the clinician's judgment (n = 144) or placebo (n = 146). The primary outcome measure was the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+). RESULTS: Patients' mean age was 73.6 years (range 48 to 92 years). Baseline demographics were similar between the treatment groups. Least squares (LS) mean +/- SE sMMSE scores at baseline were 11.7 +/- 0.35 for the donepezil group and 12.0 +/- 0.34 for the placebo group. Patients receiving donepezil showed benefits on the CIBIC+, compared with placebo, at all visits up to week 24 (p < 0.001) and at week 24 last observation carried forward (LOCF) (p < 0.0001). All other secondary measures (including sMMSE, Severe Impairment Battery, Disability Assessment for Dementia, Functional Rating Scale, and Neuropsychiatric Inventory) showed significant differences between the groups in favor of donepezil at week 24 LOCF. Eighty-four percent of donepezil- and 86% of placebo-treated patients completed the trial. Adverse events (AE) were experienced by 83% of donepezil- and 80% of placebo-treated patients, the majority of which were rated mild in severity; 8% of donepezil- and 6% of placebo-treated patients discontinued because of AE. Laboratory and vital sign abnormalities were similar between the treatment groups. CONCLUSION: These data suggest that donepezil's benefits extend into more advanced stages of AD than those previously investigated, with very good tolerability.