VANCOUVER—New pharmaceuticals and a recently developed nutritional product are among the strategies being explored for the treatment of Alzheimer’s disease, according to research presented at the 2012 Alzheimer’s Association International Conference. Investigators described clinical trials of three drugs and a medical food product designed to reduce various symptoms of the neurodegenerative disease.
EVP-6124 May Have Cognitive and Clinical Benefits
EVP-6124, a selective alpha-7 partial agonist, had cognitive and clinical benefits for patients with mild to moderate Alzheimer’s disease, according to Dana C. Hilt, MD, Senior Vice President of Clinical Development and Chief Medical Officer of EnVivo Pharmaceuticals in Watertown, Massachusetts. The drug had statistically significant effects on patients’ Alzheimer’s Disease Assessment Scale (ADAS)-Cog 13 scores, ADAS-Cog 11 scores, and Clinical Dementia Rating Scale sum of boxes (CDR-SB).
Dr. Hilt and colleagues enrolled 409 patients in a double-blind, placebo-controlled phase IIb trial. Eligible patients had a Mini-Mental State Examination (MMSE) score between 14 and 24 and a CDR-SB score greater than 2. The study population included patients who were taking acetylcholinesterase inhibitors and patients who were not. Participants were assigned to placebo, 0.3 mg of drug per day, 1 mg of drug per day, or 2 mg of drug per day for 24 weeks.
EVP-6124 had a highly statistically significant effect on the primary end points, ADAS-Cog 13 and CDR-SB. The drug was associated with fewer adverse events than acetylcholinesterase inhibitors, according to Dr. Hilt. Typical adverse events were mild constipation and mild nausea. “The drug is well tolerated and safe, and it has a relatively mild adverse event profile,” concluded Dr. Hilt.
Citicoline May Preserve Cognition
MMSE score increased by 0.5 points for patients who took citicoline for nine months, according to Pietro Gareri, MD, PhD, Head of Research at the Ambulatory Center for Dementia in Catanzaro, Italy. MMSE score declined by approximately two points for untreated patients.
Citicoline had no effect on activities of daily living (ADL) or instrumental activities of daily living (IADL),
however.
Dr. Gareri and colleagues enrolled 387 patients with vascular mild cognitive impairment in the IDEALE study—an open, multicentric project to assess the effectiveness and safety of oral citicoline. Eligible patients were 65 or older, had an MMSE score of 21 or higher, and underwent a CT or MRI scan of the brain to confirm vascular lesions. Patients with probable Alzheimer’s disease were excluded. Investigators evaluated patients with the ADL and IADL scales and gauged their mood with the Geriatric Depression Scale (GDS).
A total of 265 patients received 500 mg of citicoline twice per day for nine months. A second group of 84 patients received no treatment. Patients were evaluated at baseline, three months, and nine months. The investigators found a slight difference in GDS between treated and untreated patients. “This was not a surprise, because citicoline increases noradrenaline and dopamine levels in the CNS,” said Dr. Gareri. The researchers observed no adverse events during the course of the study.
Souvenaid May Improve Memory
Memory improved significantly for patients who took Souvenaid for 24 weeks, according to Philip Scheltens, MD, Professor of Cognitive Neurology at the VU University Medical Center in Amsterdam. Memory improved further during a 24-week open-label extension. Souvenaid is a once-per-day nutrient drink formulated to build synapse membrane that contains choline, phospholipids, B vitamins, and several antioxidants.It may also help to supplement the dietary needs of Alzhiemer’s patients, which are shown to be deficient in uridine and DHA.
Dr. Scheltens and colleagues enrolled 259 patients in the Souvenir II study, a six-month trial to examine Souvenaid’s effect on memory. Eligible patients had mild Alzheimer’s disease and were randomized to Souvenaid or a control drink. Patients who completed the study were enrolled in a six-month open-label extension. Memory, the primary outcome, was assessed as part of a neuropsychologic test battery. Secondary outcomes included executive dysfunction.
Composite neuropsychologic test battery scores improved during the study, but the change was not statistically significant. The dropout rate of the double-blind phase was 8%, and the dropout rate for the open-label phase was 7.5%, “which is very small for this type of study in this population,” said Dr. Scheltens. Overall compliance in the study and the open-label extension was more than 90%, “so people really liked [Souvenaid] and stayed on the product for a long time,” he added. “[Souvenaid] may also help to supplement the dietary needs of patients with Alzheimer’s disease who are deficient in uridine and DHA,” Dr. Scheltens told Neurology Reviews. “The product is intended to be used under medical supervision.”
Methylphenidate May Reduce Apathy
After six weeks of treatment, apathy decreased significantly in patients with Alzheimer’s disease who took methylphenidate. In contrast, apathy increased slightly in patients who took placebo, according to Jacobo Mintzer, MD, MBA, Professor of Neurosciences and Psychiatry at the Medical University of South Carolina and Staff Physician at the Ralph H. Johnson VA Medical Center in Charleston.