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Reduction of behavioral disturbances and caregiver distress by galantamine in patients with Alzheimer's disease.

Memantine, the fifth Alzheimer's drug, is an NMDA (N-methyl-D-aspartate) receptor antagonist, which works by regulating the activity of glutamate, an important neurotransmitter in the brain involved in learning and memory.

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The basal thresholds from P11 to P18, even after cessation of donepezil treatments, were similar to the naive level ().

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The prespecified primary efficacy variables were the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) global score (New York University version) at 28 weeks and the change from base line to week 28 in the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) modified for more severe dementia (ADCS-ADLsev).

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We thank the trial steering committee: Cornelius Katona (chair), Ken Wilson (independent psychiatrist for the elderly), Robert Hills (independent statistician), and Victoria Morgan and Angela Clayton-Turner (patient and caregiver representatives from the Alzheimer's Society); the independent data monitoring and ethics committee: Brian Lawlor (chair), Tony Bayer (independent physician), and Deborah Ashby (independent statistician); local collaborators: Paul Koranteng (Northamptonshire) and Stephen Pearson (Plymouth); Elaine Bygrave, Hannah Mason, and Jacky Pullen (Joint Clinical Trials Office, King's College London); Debbie Johnson and Sue Tebbs (Medical Research Council Clinical Trials Unit); Graham Cadwallader (Medical Research Council); the Dementia and Neurodegenerative Diseases Research Network; the participating patients and their caregivers; and our National Health Service colleagues who supported recruitment for the trial.

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Zhang and colleagues 1 conducted a prospective randomized controlled study of donepezil in brain-injured patients in which significant improvements were achieved during the treatment phases on both memory and concentration measures.

Seventy-one of the patients (42 of the 126 assigned to placebo and 29 of the 126 assigned to memantine) discontinued their assigned treatment before week 28, and the remaining 181 completed the double-blind portion of the study.

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Clinicians recorded the presence or absence of any adverse events (including abnormal laboratory parameters) that occurred after donepezil administration: the name of the event, the date of onset, severity, use of donepezil, regimen, date of outcome determined, outcome, and causal relationship with donepezil.

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The absence of recurrence of syncope after pacemaker insertion during a follow-up of over 18 months in each patient may be further evidence of this causal relationship.

Once at steady state, plasma donepezil hydrochloride concentrations and the related pharmacodynamic activity show little variability over the course of the day.

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