Can You Outrun Cognitive Impairment?

Unfortunately, the short answer is no. Some studies have shown that physical activity is associated with better cognition and reduced risk of dementia. A new study involved 900 subjects. Cardiorespiratory fitness was measured. Patients with the best fitness and lower weight had most benefit on cognition.

Other studies have shown different results. A study of 1600 sedentary persons measured the benefit of moderate physical activity on cognition. The intervention group did not perform better. Perhaps, a broader lifestyle intervention, including but not only exercise, is needed to promote brain health.

See Neurology, 2016, page 408-409.

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Airplane Headache

Airplane Headache
Airplane Headache

“The Case of the Woman Who Did Never Dare to Fly” is the title of a case report in Headache, February 2016, page 389. Oliver Sacks would have enjoyed this. It describes a woman who consistently developed headache during rapid descent by car from mountain elevations of about 6000 feet.

“Headache attributed to airplane travel” is now an established diagnosis in International Classification of Headache Disorders. It is typically severe, unilateral, stabbing or throbbing, usually occurring just prior to landing and lasting 20 to 30 minutes. Yawning may improve it. It is thought to be an imbalance between intrasinusal and external air pressure. This assumption, however, does not explain why it occurs only occasionally and not consistently in an individual. Perhaps the change in pressure is not the direct cause but rather a “trigger,” analogous to that seen in cold pressor (ice cream) headache and other primary headache disorders, such as cough, sexual, exertional headache.

Add this to the many indignities of air travel. Perhaps, pretreating with a low dose of indomethacin may block the headache.

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Bad News For The Dairy Council?

Dairy Products and Parkinson’s desease risk.
Dairy Products and Parkinson’s desease risk.

So, are there bad news for the dairy council? Probably not. Increasingly, risk factors for Parkinson’s are being defined. Cigarette smoking is associated with a 50% lower risk, and exposure to pesticides, such as rotenone and paraquat, doubles the risk. Higher concentrations of serum urate lower the risk.

A new study found that higher consumption of dairy products or milk alone was associated with a higher risk for Parkinson’s in the Honolulu-Asia Aging Study. Drinking more than 2 cups of milk per day in midlife was now found in another report to lead to 40% fewer brain cells in areas affected by Parkinson’s. This association was seen only among nonsmokers.

The initial milk study concluded that contamination with heptachlor was the culprit for the risk rather than milk consumption alone. Possibly, however, in that milk consumption lowers plasma urate, that may lead to a higher risk. It is too soon to hope that limiting milk consumption will lower the risk of Parkinson’s.

See Neurology, 2016, page 496-497.

Nobody Should Have An Excuse To Still Use The Old Animal Models

neurology center
Fullerton Neurology and Headache Center

“Nobody Should Have An Excuse To Still Use The Old Animal Models” says Professor Thomas Hartung. His team at ‎Johns Hopkins University has created mini-brains from human stem cells that grow into little balls of neurons about the size of a fly’s eye. He notes that there is no output or input and the electrical activity is meaningless, but the neurons are trying to communicate with each other.

Ninety-five percent of drugs that look promising in animal studies fail when tested in humans. Other researches have produced larger mini-brains, but the advantage of the ‎Johns Hopkins research is that each is identical and they can be produced by the hundreds.

It is dazzling to consider the potential. Skin cells from patients with diseases with genetic predisposition, such as Alzheimer’s, Parkinson’s, autism, can be used to create mini-brains. Prospective treatments can then be applied rapidly and cheaply to these brains.

Update On Progressive MS

Progress Update on MS
progressive multiple sclerosis

Why some patients continue with a relapsing and remitting course in multiple sclerosis and others develop progressive MS is unclear. Possible neurodegenerative mechanisms include chronic “smoldering” inflammation, microglial activation with oxidative damage, ion channel dysfunction and failure of energy in demyelinated axons, hypoxic injury, glutamate excess, mitochondrial failure, and accumulation of iron. It is unclear which of these are key. There are increasingly powerful medications, such as alemtuzumab and ocrelizumab, that are very effective against relapsing and remitting MS. They may have approached parity with stem cell transplants, and some researchers believe that we may have reached the limits of effectiveness of this class of medications.

Obviously, patients with progressive MS constitute an unmet need. A summary of completed and ongoing trials for this disorder follows.

Fingolimod (Gilenya) in phase III trials in patients with relapsing and remitting MS demonstrated an effect on brain atrophy. A class I trial termed INFORMS targeted primary progressive MS. It included almost 1000 patients. The primary endpoint was not met.

Ocrelizumab is not yet indicated by the FDA for multiple sclerosis, but approval is likely for use in 2017. It is a monoclonal antibody targeting CD20, a receptor on B-cells, and mechanism of action is similar to that of rituximab, which is off-label for MS though indicated for rheumatoid arthritis, and to ofatumumab, which is beginning phase III trials. Rituximab was of no benefit in disease progression in a phase III trial with PPMS, but a subgroup of patients younger than 51 years and those who had gadolinium-enhancing lesions at baseline seemed to benefit. A phase III trial of ocrelizumab called ORATORIO in PPMS was recently completed and reported. It showed a reduction of about 25% in clinical disability and less brain volume loss.

Biotin is a widely used supplement thought to improve hair and nail growth. It also activates an enzyme involved in synthesis of myelin. A phase III trial in patients with primary or secondary progressive MS was recently completed. A dose of 300 mg daily was used. Keep in mind that biotin is widely available, but highest capsule dose is 10 mg. Thus, a patient would need to take 30 pills daily. Thirteen percent of patients treated with biotin and none with placebo had improvement in a disability scale termed EDSS. Even though this was a low proportion of responders, the differences were statistically significant. There were no imaging data, and effects on atrophy are not known. Further trials are likely to proceed.

Ibudilast has potential neuroprotective properties and has been tested in Parkinson’s, without statistically significant benefit. In a phase II study in patients with relapsing MS, a dose of 30 or 60 mg a day had no effect on MRI or clinical relapses, but the 60 mg dose seemed to have protective effects on brain atrophy. These results led to an ongoing phase II trial termed SPRINT-MS. Results may be available in 2017.

Statins have been studied for years. Some trials have demonstrated an effect on new MRI lesions and brain atrophy. In one trial, however, adding simvastatin 80 mg a day to an interferon seemed to have deleterious effects on MRI for unclear reasons. A recent trial showed reduced atrophy by 43% compared to placebo. The medication is off patent, and there is thus no incentive for the pharmaceutical industry to fund a large phase III trial.

Natalizumab (Tysabri) was studied in a recently completed phase III placebo-controlled trial termed ASCEND in secondary progressive MS. Almost 1000 patients were studied. Results did not achieve statistical significance on the primary measure, but there seemed to be benefit on one of the components, termed the nine-hole pegboard test, which evaluates function of the upper extremities.

Lastly, an ongoing phase IIb multicenter trial in the UK termed MS-SMART is evaluating patients with secondary progressive MS. There are 4 treatment arms: placebo, amiloride 5 mg b.i.d. (widely used to treat hypertension), riluzole 50 mg b.i.d. (indicated and currently used to treat ALS), or fluoxetine (Prozac) 20 mg b.i.d., the first SSRI approved to treat major depression and still widely used. It is a 2-year study and the primary endpoint is change in brain volume. Of interest, the study involves potential neuroprotective rather than immunomodulating agents. Completion is expected in 2017.

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Does This Explain The “Second Impact” Phenomenon?

Concussions Second Impact effects
Concussions and “Second Impact” Effects

Concussions affect millions of people each year and are especially prevalent in contact sports like football. Only motor vehicle accidents lead to more cases of traumatic brain injury in people ages 15 to 24. Some studies have shown that concussed athletes who have a second concussion before they recover fully may have permanent brain injuries. The reason for this has been elusive. So, Does This Explain The “Second Impact” Phenomenon?

A new study used arterial spin labeling, an advanced MRI technique that detects blood flow in the brain. It found that there was a reduction in cerebral blood flow at 24 hours post concussion, and this persisted at 8 days, even if the athletes seemed clinically improved. Reduced blood flow is likely a marker of neurons under continued physiological stress, and this measure supports efforts to reduce the risk of a second injury. It remains unclear at what point athletes should be returned to contact sports. Would blood flow be normal at 14 days? At 30 days? Obviously, more studies are needed, but erring on the side of caution seems prudent.

Presented at annual meeting of The Radiological Society of North America, lead author Y. Wang.

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