Highlights from the AAN 2011 Annual Meeting include the relationship between cardiovascular risk factors and cognitive decline, using a cerebrospinal fluid test to determine MS onset of disability, an experimental agent for MS, and overcoming dyskinesia in Parkinson’s.

» Amphetamine Use May Increase Parkinson’s Risk
» Cardiovascular Risk Factors & Cognitive Decline
» Experimental Agent Promising for MS Sufferers
» Overcoming Dyskinesia in Parkinson’s
» CSF Test May Help Predict MS Onset of Disability

Amphetamine Use May Increase Parkinson’s Risk

The Particulars: Amphetamines were once recommended for treating patients with Parkinson’s disease. Recent studies, however, have suggested that this class of drugs may be linked to a higher risk of developing Parkinson’s.

Data Breakdown: Researchers conducted an analysis in 66,438 individuals who did not have Parkinson’s disease at baseline and collected information on exposure to amphetamines. Through a mean follow-up of 38.8 years, 1,154 patients received a Parkinson’s diagnosis. The average age at baseline was 36, and the average age at diagnosis was 70. Individuals who reported often taking amphetamine sulfate or dextroamphetamine sulfate had a 56% greater risk of having a Parkinson’s diagnosis decades later. The magnitude of the relationship was similar for both men and women. Participants who reported taking weight-loss medication at baseline did not have an elevated risk for Parkinson’s disease through follow-up (hazard ratio, 0.95).

Take Home Pearls: The use of amphetamines appears to be associated with an elevated risk for developing Parkinson’s disease later in life. Considering the wide population exposure to both legal and illegal amphetamines, more studies are needed to address this association.

Cardiovascular Risk Factors & Cognitive Decline [back to top]

The Particulars: The heart and brain both receive their blood supply through arteries that have the same vulnerabilities to cardiovascular risk factors. Hypertension and elevated cholesterol may increase the risk of dementia by inducing atherosclerosis and impairing blood flow. Smoking has been linked to increased risk of cognitive decline due to high levels of oxidative stress. These cardiovascular risk factors may also directly induce the neurodegeneration of Alzheimer’s disease.

Data Breakdown: In a study of 3,486 men and 1,341 women, participants underwent cognitive testing three times during a 10-year period. Linear regression analyses were performed to assess the association of cardiovascular risk and cognitive function. Each 10-point increment in risk on the Framingham General Cardiovascular Risk Profile was associated with poorer cognitive performance on tests that assessed thinking, memory, reasoning, phonemic and semantic fluency, and vocabulary. Higher cardiovascular risk also was associated with more rapid decline in cognitive ability.

Take Home Pearls: Cardiovascular risk in middle age appears to be related to lower overall cognitive function. Efforts to improve cardiovascular health in middle-aged individuals may help prevent or delay cognitive decline or dementia.

Experimental Agent Promising for MS Sufferers [back to top]

The Particulars: Laquinimod is an investigational oral immunomodulator that is thought to prevent autoreactive T cells from leaving the lymphatic system in people with multiple sclerosis (MS). These agents have the potential to help protect nerve fibers from autoimmune attacks that underlie MS.

Data Breakdown: A 2-year, phase III study sponsored by the manufacturer of laquinimod (Teva Pharmaceuticals) was conducted, involving 1,106 MS patients. Relapses were 23% less common with laquinimod relative to placebo, and progression of disability was reduced by 36%. The number of new T2 and cumulative gadolinium-enhancing lesions on MRI scans was also reduced for patients receiving laquinimod. Progression of brain atrophy was reduced by 32.8%. All differences from the placebo group were highly significant. Dropout rates were similar with the laquinimod versus placebo (about 20%), and the treatment was well tolerated. Liver transaminase elevations were more frequent with the active drug, but these elevations were temporary, reversible, and did not appear to lead to any signs of liver problems.

Take Home Pearls: Laquinimod, an investigational drug, appears to reduce the relapse rate and disease progression in MS. The agent also appeared to reduce the number of new T2 and cumulative gadolinium-enhancing lesions on MRI scans and reduced progression of brain atrophy. More later-phase trials are warranted.

Overcoming Dyskinesia in Parkinson’s [back to top]

The Particulars: Symptoms of Parkinson’s disease, motor fluctuations, and dyskinesia can greatly affect daily living and quality of life in patients with Parkinson’s. Several investigational drugs, such as safinamide, have shown promise for reducing dyskinesia in patients with mid-to-late stage Parkinson’s disease.

Data Breakdown: A 2-year randomized, placebo-controlled clinical trial was conducted in 669 patients with mid-to-late stage Parkinson’s disease who were already taking levodopa and other dopaminergic treatments. Patients received safinamide 50 mg/day, safinamide 100 mg/day, or placebo. After 2 years, a post-hoc analysis revealed that safinamide 100 mg/day plus levodopa reduced dyskinesia by 24% in the one-third of participants who had scored high on the dyskinesia rating scale at the beginning of the study when compared with those taking placebo. No significant differences were seen in patients who took safinamide 50 mg/day. Side effects were comparable among the three treatment groups.

Take Home Pearls: Using safinamide 100 mg/day in addition to levodopa and other dopaminergic treatments appears to help patients with mid-to-late stage Parkinson’s disease who continue to experience dyskinesia. More research is needed to better understand how safinamide impacts patients with severe Parkinson’s disease.

CSF Test May Help Predict MS Onset of Disability [back to top]

The Particulars: Previous investigations have suggested that many patients with progressive multiple sclerosis (MS) are often concerned about how quickly their disease will progress to disability. Cerebrospinal fluid (CSF) test results are sometimes used to help physicians determine when a diagnosis is uncertain. Determining onset of disability from the disease may enhance counseling of MS patients to reduce the potential for anxiety for these individuals.

Data Breakdown: Researchers examined CSF test results from 281 progressive MS patients from 2002 to 2007. A relationship was detected between a faster disability rate and abnormally high levels of the oligoclonal band and immunoglobulin-G molecule. Patients who had a progressive form of MS with proceeding relapses as well as CSF results demonstrating elevated levels of oligoclonal bands and immunoglobulin-G molecules had a faster rate of disability than others.

Take Home Pearls: Noting the presence of certain markers in CSF tests appears to help clinicians predict whether patients will suffer a faster onset of disability from MS. More research is warranted to confirm these results.

References

For more information on these items and other research that was presented at the meeting, go towww.aan.com/go/am11.