AD and the dosage od Donepezil

In a recently read article I found that the doses of Donepezil are being reconsidered in moderate to severe AD.
The article says that an immediate-release formulation of donepezil has been available at an approved dose of 5-10 mg/d for the past decade. Recently, the United States Food and Drug Administration approved a higher-dose (23 mg/d) donepezil formulation, which provides more gradual systemic absorption, a longer time to maximum concentration (8 hours) versus the immediate-release formulation (3 hours), and higher daily concentrations.
The research evidence indicates that cholinergic deficits correlate with the cognitive defects of AD. As AD symptoms increase in severity over time, there are progressive declines in markers of cholinergic activity. Inhibition of AChE increases cholinergic function, which is theorized to result in dose-dependent improvements in cognition.

Patients with AD continue to decline even when treated with the highest currently approved doses of AChEIs, and patients with advanced disease demonstrate the most profound impairment in cholinergic function. Imaging studies have demonstrated that, with the currently used doses of AChEIs, inhibition of brain AChE is suboptimal. Data from a recently published 24-week clinical trial in patients with moderate to severe AD demonstrate that treatment with a 23 mg formulation of donepezil results in significant benefits in cognition compared with standard doses, with an acceptable tolerability profile that is consistent with the AChEI class. Donepezil 23 mg did not differ from the 10 mg dose in terms of the incidence of serious side effects and differences in discontinuation rates between the two doses were not evident after the first month of treatment. Once-daily donepezil 23 mg, therefore, represents an additional treatment choice for patients with advanced AD.

below is the link to the article.
http://www.biomedcentral.com/1471-2377/11/21

Important Article. Good post by Psychinmymind

Few more important facts from article:
- Of the estimated 5.3 million people with Alzheimer's disease in the United States, more than half would be classified as having moderate or severe disease.
- These advanced stages are often the most challenging for both patients and their caregivers/families.
- Progressive symptomatic decline is nevertheless inevitable even with the available therapies, and therefore additional treatment options are urgently needed for this segment of the Alzheimer's disease population.
- Appreciable loss of cortically projecting cholinergic neurons occurs as a hallmark of the disease, particularly in brain areas associated with memory and learning (ie, the hippocampus, nucleus basalis of Meynert, and cortex).