New, 12-month data presented today to the World Congress of Neurology support an earlier, short-term finding that Reminyl(R) (galantamine hydrobromide) -- the most recent medication approved for mild to moderate Alzheimer's disease -- also may be effective in treating dementia in individuals with cerebrovascular disease, such as stroke. This is the first Alzheimer's disease treatment to demonstrate benefit in this population, particularly in the longer term. However, Reminyl is not yet approved for vascular or mixed dementia, and further research is needed to confirm these findings.

The new data -- which are derived from a six-month, placebo-controlled study presented earlier this year and a six-month "open-label" extension in which all patients received Reminyl -- suggest that the medication maintains memory, orientation and language skills for a year in patients with both dementia and cerebrovascular disease.

"If the findings of this study are replicated through further research, physicians can be more confident about treating dementia in individuals in whom vascular damage has occurred," says Roger Bullock, MD, of the Kingshill Research Centre in Swindon, United Kingdom. "Reminyl appears to be effective in treating dementia whether or not cerebrovascular disease is present."

Dementia is a decline in memory and intellectual abilities that results in a significantly impaired ability to function. The most common type of dementia is Alzheimer's disease. However, the second-most-common type is vascular dementia, which often is triggered by one or more strokes and can be caused by uncontrolled hypertension or diabetes. Worldwide incidence of vascular dementia is estimated at six to 12 cases per 1,000 people over 70 years of age. Many other individuals have a mix of Alzheimer's and cerebrovascular disease ("mixed" dementia). In fact, it is estimated that between 10 percent and 50 percent of individuals have either vascular or mixed dementia. Unfortunately, these individuals are often unrecognized or untreated.

Study Design and Results

To research the efficacy of Reminyl in this population, 592 patients diagnosed with vascular or mixed dementia were enrolled in an initial six- month, "double-blind" clinical study and received either 24 mg per day of Reminyl (396) or placebo (196). Of this group, 459 individuals (295 who had taken Reminyl and 164 who had previously received placebo) continued the research for another six months in an "open-label" extension of the study. All participants in the open-label extension took 24 mg of Reminyl daily, in two divided doses.

Several tools were used in the study to assess the effectiveness of Reminyl in both phases of the study. These included:

-- The cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) measures patients' memory, orientation, reasoning and language. At 12 months, the cognitive abilities of patients who had taken Reminyl for the entire study period had stayed relatively stable, with no appreciable decline.

-- The Disability Assessment of Dementia (D.A.D.) scale assesses patients' ability to perform routine, daily-living activities. Over the course of the year, participating patients experienced a deterioration in their ability to do tasks such as bathing, dressing and housework. However, the decline in the group who took placebo for the first six months was more than double that of the group receiving Reminyl for the entire year.

-- The Neuropsychiatric Inventory (NPI) tracks behavioral disturbances, such as hallucinations, delusions, pacing and agitation. Among patients who had taken Reminyl for the full 12 months, no change in behavior -- such as emergence of new symptoms or the worsening of existing disturbances -- was observed.

Safety and Tolerability

The most frequent side effects reported by greater than 5% of patients taking Reminyl in the first, double-blind phase of the study were nausea, vomiting, dizziness, diarrhea and insomnia. In the second, open-label phase of the trial -- in which the patients who had previously received placebo were switched to Reminyl -- side effects reported by greater than 5% of patients were nausea, diarrhea, insomnia, depression, agitation, dizziness, vomiting, fatigue and falls. The majority of side effects occurred in fewer than 10% of patients.

Mechanism of Action

Reminyl is thought to inhibit an enzyme that breaks down acetylcholine -- a critical chemical in the brain that plays a key role in memory and learning. In addition, it is thought that Reminyl modulates the brain's nicotinic receptors, to which acetylcholine binds. Laboratory research suggests that through this modulation, Reminyl stimulates greater release of the chemical. However, the significance of this finding in humans is currently unknown and further research is underway.

Reminyl received marketing approval from the US Food and Drug Administration in February for the treatment of mild to moderate Alzheimer's disease. Reminyl is available in 4 mg, 8 mg or 12 mg tablets and should be taken by patients twice a day, preferably with the morning and evening meals. It is recommended that physicians start by prescribing 8 mg of Reminyl per day (in two divided doses), then increase the dose to 16 mg after at least four weeks. Physicians have the flexibility to increase the daily dose to 24 mg after an additional four weeks.

Reminyl was developed by the Janssen Research Foundation under a co-development and licensing agreement with the UK-based Shire Pharmaceuticals Group plc.