For years it has been known that people taking antiepileptic drugs (AED) have a higher risk for suicide. The question has been, what is responsible for this; the disease for which a patient is being treated or the drugs used to treat it? Examples of common illnesses treated with AEDs are chronic pain, depression, and bipolar disorder.

In January 2008, the FDA issued a safety alert on the risk for suicidality in people taking AED medications. The alert stemmed from analysis of 199 placebo-controlled AED trials of 11 AEDs. It found a 2-fold increased risk for suicidal thoughts or actions among AED-treated patients compared with placebo-treated patients and suggested that the risk was increased regardless of AED type and indication for use. However, the assessment of suicidality in analysis was "subject to several limitations such as the lack of systematic or standardized language to define suicidal ideation and behavior across clinical trials." To investigate further, data from The Health Improvement Network database looked at the association between AEDs and "harder" endpoints (attempted and completed suicides) in patients with epilepsy, depression, or bipolar disorder.

A new study in the August 5 issue of The New England Journal of Medicine suggests that it might not be antiepileptic drugs (AEDs) themselves that raise the suicide risk in patients, but the underlying disease for which these drugs are prescribed. This new study analyzed more than 5 million patients, so the validity of the data is quite compelling.

A new report from the Framingham published in the August 2 edition of Circulation shows that decreased cardiac function is correlated with increased risk of dementia.

"Generally speaking, it seems that heart and brain health are related, so proper management of cardiovascular risk factors may have important implications on brain health," says Angela Jefferson, PhD, from the Boston University School of Medicine in Massachusetts.

Using Framingham data, the researchers looked at 1504 participants free of clinical stroke, transient ischemic attack, or dementia. They reviewed brain and cardiac magnetic resonance images and neuropsychological and laboratory data. They found that cardiac index (a measure of heart health) was positively related to total brain volume and information processing speed but was inversely related to lateral ventricular volume. Data revealed that participants with the lowest and middle cardiac indices had significantly lower brain volumes than participants with the best cardiac indices.

In an accompanying editorial, Clinton Wright, MD, and Ralph Sacco, MD, from the University of Miami in Florida, suggest the finding that even intermediate reductions in cardiac index were associated with declines in brain volume is striking.

The mechanism for associations between cardiac index and evidence of brain aging is unknown. However, the study authors suggest reduced systemic blood flow may contribute to subclinical brain injury because of its impact on cerebral blood flow homeostasis. In other words, poor heart function may injure the brain long-term.
"It will take years to know the fate of all 1504 Framingham participants," the editorialists add. "Whether lower cardiac index leads to reduced brain volumes and accelerates neurodegeneration on an eventual path to dementia is not yet clear. What is known is that various vascular risk factors, including decrements in cardiac function, are determinants of dementia — both Alzheimer disease and variants of vascular dementia. This provides opportunities to find interventions that modify the course of these diseases predicted to be of major impact on our aging population."

Bottom line: use that gym membership.

An article in the July 29 issue of the New England Journal of Medicine reviewed evidence for the use of acupuncture for chronic low back pain.
"Acupuncture is a therapeutic intervention characterized by the insertion of fine, solid metallic needles into or through the skin at specific sites," write Brian M. Berman, MD, from the University of Maryland School of Medicine in Baltimore. "The technique is believed to have originated in China, where it has remained a fundamental component of a system of [medicine that] espouses an ancient physiological system (not based on Western scientific empiricism) in which health is seen as the result of harmony among bodily functions and between body and nature. Internal disharmony is believed to cause blockage of the body's vital energy, known as qi, which flows along 12 primary and 8 secondary meridians."

Tenderness on palpation is thought to be evidence of blockage of qi, and inserting acupuncture needles at specific points along the meridians is believed to restore the proper flow of qi. The analgesic effects of acupuncture appear to be based on neural innervation, because they are completely blocked by local anesthesia at needle-insertion sites. Furthermore, acupuncture stimulates the release of endogenous opioids in brainstem, subcortical, and limbic structures, as well as producing mechanical stimulation of connective tissue and other effects on local tissues. Despite these effects, the mechanisms underlying chronic pain relief by acupuncture are not completely understood.

Acupuncture is seldom regarded as the first choice of treatment, in part because randomized controlled clinical trials and large meta-analyses have not proven it to be more effective than sham acupuncture in relieving low back pain. However, it may be useful as part of a multidisciplinary approach to the management of chronic low back pain, along with physical therapy, pain medication, and/or exercise.
"Acupuncture is a regulated discipline, and patients should be referred only to practitioners who are licensed by the state in which they practice," the review authors write. "A diploma from the National Certification Commission for Acupuncture and Oriental Medicine is a requirement for licensure in most states. Physicians may practice acupuncture in the United States after completing one of several medical acupuncture programs."

Contraindications to acupuncture include coagulation and bleeding disorders, use of anticoagulants, severe psychiatric disease, and local skin infections or trauma. Electroacupuncture should not be used at the site of pacemakers or other implanted electrical devices. Pregnant women may undergo acupuncture, but not at specific acupuncture points known to be especially sensitive to needle insertion or at acupuncture points in the abdominal regions.

One treatment is considered to be insufficient, and recent trials of acupuncture for low back pain used at least 12 acupuncture sessions, often starting with 2 sessions a week and tapering off after 4 weeks to once weekly, with booster treatments sometimes used monthly or every other month. Acupuncture should be discontinued if there are no apparent effects after 10 to 12 sessions.
"There is continuing debate in the medical community regarding the role of the placebo effect in acupuncture," the review authors write. "The most recent well-powered clinical trials of acupuncture for chronic low back pain showed that sham acupuncture was as effective as real acupuncture. The simplest explanation of such findings is that the specific therapeutic effects of acupuncture, if present, are small, whereas its clinically relevant benefits are mostly attributable to contextual and psychosocial factors, such as patients' beliefs and expectations, attention from the acupuncturist, and highly focused, spatially directed attention on the part of the patient."

Joint clinical practice guidelines from the American College of Physicians and the American Pain Society recommend that clinicians consider acupuncture as one possible treatment option for patients with chronic low back pain refractory to self-care (level of supporting evidence, fair). According to the North American Spine Society, acupuncture offers better short-term pain relief and functional improvement than no treatment, and adding acupuncture to other treatments is more effective than other treatments alone, but high-quality, randomized controlled trials are still needed comparing acupuncture with no treatment and with sham acupuncture.

A report in the Archives of Neurology suggests that Vitamin E may play a modest role in altering the course of dementia. Compared with participants with the lowest intake, investigators found that those patients with higher vitamin E intake were 25% less likely to develop dementia.

"When beta-amyloid — a hallmark of pathologic Alzheimer disease — accumulates in the brain, an inflammatory response is likely evoked that produces nitric oxide radicals and downstream neurodegenerative effects," report investigators led by Elizabeth Devore, ScD, from the Erasmus Medical Center in Rotterdam, the Netherlands. "Vitamin E is a powerful fat-soluble antioxidant that may help to inhibit the pathogenesis of dementia."

Vitamin E is found in whole-grain foods, eggs, milk, nuts, seeds, avocado, spinach, and unheated vegetable oils. The Rotterdam Study previously found that higher dietary intakes of vitamins E and C were associated with a lower risk for dementia and Alzheimer's disease.

In this new long-term follow-up of the Rotterdam Study, investigators followed participants for 9.6 years. The population-based prospective cohort study included 5395 people free of disease at baseline.
A total of 465 people developed dementia. Of these, 365 were diagnosed with Alzheimer's disease. The investigators found that higher dietary intake of vitamin E, but not vitamin C, beta carotene, or flavonoids, was associated with lower long-term risk for dementia.

These results conflict with previous findings, which suggested a link between vitamin C intake and dementia risk. Probably the bottom line is to eat a healthy diet.

The most common sleep complaint in adults is insomnia and is a significant health concern. The criteria for a diagnosis of primary insomnia include difficulty with falling asleep, difficulty remaining asleep, waking up too early, or failing to achieve restorative sleep for a period of 1 month or more while experiencing significant distress and/or impairment in daily functions. One poll found that 64% of participants reported a sleep problem at least a few nights each week, with 41% reporting problems almost every night. Insomnia is 41% more common in women than in men.

Although there are several different degrees of insomnia, three types of insomnia have been clearly identified: transient, acute, and chronic. Transient insomnia lasts for less than a week. It can be caused by another disorder, by changes in the sleep environment, by the timing of sleep, severe depression, or by stress. Its consequences - sleepiness and impaired psychomotor performance - are similar to those of sleep deprivation. Acute insomnia is the inability to consistently sleep well for a period of less than a month. Chronic insomnia lasts for longer than a month. It can be caused by another disorder, or it can be a primary disorder. Its effects can vary according to its causes. They might include being unable to sleep, muscular fatigue, hallucinations, and/or mental fatigue; but people with chronic insomnia often show increased alertness.

Patterns of insomnia are:
Onset insomnia - difficulty falling asleep at the beginning of the night, often associated with anxiety disorders.
Middle-of-the-Night Insomnia - Insomnia characterized by difficulty returning to sleep after awakening in the middle of the night or waking too early in the morning
Terminal (or late) insomnia - early morning waking. Often a characteristic of clinical depression.

Poor sleep quality can occur as a result of sleep apnea or major depression. Poor sleep quality is caused by the individual not reaching stage 3 or delta sleep which has restorative properties.

A common misperception is that the amount of sleep required decreases as a person ages. The ability to sleep for long periods, rather than the need for sleep, appears to be lost as people get older. Some elderly insomniacs toss and turn in bed and occasionally fall off the bed at night, diminishing the amount of sleep they receive.

Treatment for insomnia varies depending on the cause. This is why a good workup by a sleep specialist is the best way to make a proper diagnosis and lay out a treatment plan.

The July issue of the Archives of Neurology reported a longitudinal study of more than 3,000 subjects in which a link between vitamin D and Parkinson’s disease was found. In the 29-year follow-up period, there were 50 incident cases of Parkinson's disease. The study was carried out in Finland where there is restricted sunlight exposure. It is a population that typically has low vitamin D levels. The mean serum level was about 50% of the suggested optimal level of 75 to 80 nmol/L.
The investigators found that individuals with a serum vitamin D concentration of at least 50 nmol/L had a 65% lower risk for Parkinson's than those with values less than 25 nmol/L after adjustment for several potential confounders. The relative risk between the highest and lowest vitamin D levels was 0.35.

Vitamin D is no longer considered a vitamin, but rather a hormone that has autocrine and paracrine functions well beyond those of regulating calcium absorption and bone health.

The exact mechanisms by which vitamin D may protect against Parkinson's disease are not fully understood. Vitamin D has, however, been shown to exhibit neuroprotective effects through antioxidative mechanisms, neuronal calcium regulation, immunomodulation, enhanced nerve conduction, and detoxification mechanisms.

The association with and possible causal role of insufficient vitamin D in many chronic diseases, such as Multiple Sclerosis, is becoming more widely appreciated yet what constitutes an optimal blood concentration of vitamin D for humans, and specifically for the human nervous system, remains unknown.

Making the news this last week was a gene for Alzheimer’s Disease (AD). This prompted a friend to ask me, “Why would you want to know if you were going to develop the disease?” Good question. One reason is for genetic planning. Another reason is that early diagnosis may lead to earlier treatment, and thus better prognosis. After all, this approach has been successful in preventing diseases such as cervical cancer and heart attacks.

But early treatment requires early diagnosis and not all people with dementia have AD. To this end solid criteria must be developed to identify a “preclinical state.” Put another way, we need to be able to identify AD far in advance of symptoms. Genetic testing will be helpful but in itself is not sufficient.

Okay, so what test might yield such information? Probably it will come from imaging studies (MRI or PET scans) that measure the metabolism and accumulation of amyloid, an insoluble protein. Amyloid accumulates in neurons of AD patients, causing cell death. Microscopically AD patients’ brains show “tombstones,” which are small deposits of amyloid that remain after neurons die. So amyloid accumulation is likely to become one metric for defining preclinical AD, allowing people with positive family histories of the disease to be successfully diagnosed and treated.