TESTOSTERONE INJECTIONS IMPROVE SOME SYMPTOMS OF MS

Testosterone treatment was safe and effective in a group of men with relapsing-remitting multiple sclerosis (MS), according to a study in the May Archives of Neurology. The men showed improved cognitive performance, and the rate of brain atrophy decreased with treatment, suggesting a neuroprotective effect that may be applicable to other neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease, according to researchers from the David Geffen School of Medicine at the University of California, Los Angeles.

Nancy L. Sicotte, MD, of the Division of Brain Mapping, and colleagues enrolled 10 men (mean age, 46) with a median 12.5 years of relapsing-remitting MS; participants had had at least one clinical relapse or the appearance of at least one gadolinium-enhancing lesion within the preceding two years. In addition, the participants were instructed to refrain from receiving disease-modifying treatment during the study period. These requirements “likely created a selection bias toward subjects with a relatively milder clinical disease and less inflammatory activity on MRI,” noted the authors.

“At baseline, all subjects had testosterone levels in the lower range of normal, with a mean of 493 ng/dL,” said Dr. Sicotte and colleagues. However, after the men received a daily gel application of 100 mg of testosterone to the upper arm for 12 months, the investigators reported that the levels increased an average of 50%, to the higher range of normal. Lean body mass also increased significantly. Cognitive improvement was measured with the Paced Auditory Serial Addition Task (PASAT) component of the Multiple Sclerosis Functional Composite; a practice effect was observed in the six months of pretreatment testing but stabilized after three trials, before treatment began, reported the researchers. The cohort’s PASAT scores “remained stable during the first six months of treatment, trended upward after nine months, and were significantly improved by month 12 of treatment,” stated Dr. Sicotte’s group.

At baseline, participants’ whole brain volumes were negatively correlated with age and were not related to baseline testosterone levels. The authors noted that the brain volumes decreased at an annual rate of -0.81% during the six months of pretreatment testing and the first three months of the study. “During the subsequent nine months of testosterone treatment, brain atrophy slowed to an annualized rate of -0.26%,” the investigators stated. “This represented a 67% reduction in the rate of brain volume loss compared with the pretreatment period.” Linear regressions indicated annual atrophy rates of -0.79% during the pretreatment period, -0.58% during early treatment, and -0.22% during later treatment.

Suggested Reading
Sicotte NL, Giesser BS, Tandon V, et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007;64:683-688.

HEADACHE MAY PREDICT LINK BETWEEN SUICIDE AND PSYCHIATRIC DISORDERS IN YOUTH

Adolescents with chronic daily headache may have a high comorbidity of psychiatric disorders and suicide risk, according to Shuu-Jiun Wang, MD, and colleagues. Their results, published in the May 1 Neurology, show that the presence of migraine attacks, especially migraine with aura, was the major predictor for the association between psychiatric disorders and risk of suicide.

A total of 121 subjects (ages 12 to 15; 90 females) with chronic daily headache underwent psychiatric interviews. Eighty-one of the participants (67%) had migraine or probable migraine, 67 (55%) had migraine without aura, and 14 (12%) had migraine with and without aura. Fifty-seven of the participants (47%) had at least one depressive or anxiety disorder; major depression (21%) and panic disorder (19%) were the two most prevalent diagnoses. The researchers found that current suicide risk was high in 20% of the participants and that female gender and older age were associated with depressive disorders. Presence of migraine was also associated with psychiatric comorbidities. The association between migraine and psychiatric comorbidities was stronger when migraine included aura than when it did not. Migraine with aura was also an independent predictor of high risk of suicide, and no correlations between chronic daily headache, headache frequencies, or medication overuse with high risk of suicide were observed.

“Intriguingly, migraine with aura has seldom been raised as an issue in patients with chronic daily headache since most headache experts believe that patients with chronic migraine usually have migraine without aura,” Dr. Wang and colleagues noted. “This concept is also demonstrated in the diagnostic criteria of chronic migraine, in which only the frequencies of migraine without aura are counted.... We suggest that the role of migraine with aura should be emphasized in adolescents with chronic daily headache for its high comorbidities.”

The investigators acknowledged that the prediction of suicide among youth is “highly difficult” and that short-term structured suicidal evaluations may be of limited use for clinical applications. However, “[w]ithout exploration of ... psychiatric disorders, adolescents with chronic daily headache may focus more on their physical disability caused by headaches rather than emotional/mental disability,” Dr. Wang’s team stated. “Therefore, psychiatric comorbidity should be carefully explored and managed in each adolescent with chronic daily headache.”

Suggested Reading
Wang S-J, Juang K-D, Fuh J-L, Lu S-R. Psychiatric comorbidity and suicide risk in adolescents with chronic daily headache. Neurology. 2007; 68:1468-1473.

DAY CARE FOR ALZHEIMER'S PATIENTS MAY REDUCE ACCELERATED COGNITIVE DECLINE IN NURSING HOME

Nursing home placement may be associated with accelerated short-term cognitive decline in Alzheimer’s disease, according to results published in the June American Journal of Psychiatry. This association may be lessened, however, with prior experience in adult day care.

Robert S. Wilson, PhD, and colleagues analyzed 432 older persons with Alzheimer’s disease who had at least one valid composite cognitive score at follow-up. The participants lived in health care settings in the Chicago area and were using day care services a mean of 1.7 days per week. The researchers obtained a composite measure of global cognition from nine cognitive tests administered to the participants at six-month intervals for up to four years and found that overall, cognition declined at a gradually increasing rate. Placement in a nursing home was linked to a faster rate of cognitive decline, but in initial analyses, use of day care at baseline was not related to decreased cognition. Furthermore, a higher level of day care use substantially reduced the link between nursing home placement and accelerated cognitive decline. These results “suggest that experience in adult day care may help persons with Alzheimer’s disease make the transition from the community to institutional residence,” the investigators pointed out.

Day care also attenuated the association between a higher level of education and a greater increase in cognitive decline upon nursing home placement. This finding is “further evidence of the robustness of the association between day care experience and cognition during the transition to institutional residence,” the researchers noted.

Dr. Wilson and colleagues concluded that their “findings suggest that the transition from the community to a nursing home is particularly difficult for people with Alzheimer’s disease and that those planning for their care should consider the possibility that experience in adult day care programs may help prepare affected persons for institutional living.” However, the investigators also pointed out that the observational nature of their study does not allow for any definite conclusions regarding a change in the rate of cognitive decline linked to day care or nursing home placement for patients with Alzheimer’s disease.

In an accompanying editorial, James T. Becker, PhD, Luis Tarraga Mestre, MSc, Scott Ziolko, BS, and Oscar L. Lopez, MD, stated, “The day care environment, even those with limited structured programs, may provide increased social contacts, opportunities for cognitive stimulation, and physical exercise. Individually, these different activities may have limited efficacy, but in combination they may have beneficial effects.”

Suggested Reading
Wilson RS, McCann JJ, Li Y, et al. Nursing home placement, day care use, and cognitive decline in Alzheimer’s disease. Am J Psychiatry. 2007;164:910-915.
Becker JT, Mestre LT, Ziolko S, Lopez OL. Gene-environment interactions with cognition in late life and compression of morbidity. Am J Psychiatry. 2007;164:849-852.

PATIENTS WITH NEWLY TREATED DIABETES MAY HAVE HIGH RISK OF STROKE

The risk of stroke within five years of treatment for patients with type 2 diabetes mellitus may be more than double that for the general population, according to Thomas Jeerakathil, MD, MSc, and colleagues. The researchers, who reported their findings in the June Stroke, analyzed data from 12,272 participants with diabetes from the population of Saskatchewan, Canada. During a mean follow-up period of five years, 1,122 patients with diabetes (9.1%) had a stroke; the age-standardized incidence rate for stroke was 642 per 100,000 person-years among patients with diabetes, compared with 313 per 100,000 person-years in the general population of Saskatchewan.

The relative short-term stroke risk for patients with diabetes compared with persons in the general population ranged from 1.8 in persons 75 and older to 5.6 in patients ages 30 to 44. The absolute risk for stroke in older persons with diabetes was 18.7%, compared with 1% in younger persons with diabetes. Hospitalization for stroke occurred in 8.7% of diabetic women and 9.5% of diabetic men, although compared with the general population, diabetic women had a higher relative risk for stroke than diabetic men did.

“To our knowledge, ours is the first study to specifically examine stroke-related outcomes soon after the diagnosis of and initiation of treatment for type 2 diabetes,” the researchers stated. “Given the number of evidence-based treatments available for the prevention of stroke, these data should be useful for both patients with new-onset diabetes and their healthcare providers.”

However, Dr. Jeerakathil and colleagues acknowledged several limitations to their research. The investigators did not include patients with diet-controlled diabetes, because those patients may have a lower risk for stroke during an earlier stage of the disease. In addition, patients who experienced a recent stroke would not have a higher risk for stroke recurrence; these patients were not definitively excluded from the study. Also, the researchers did not have access to risk factor data such as glycosylated hemoglobin levels, blood pressure, cholesterol levels, or BMI.

Dr. Jeerakathil and colleagues concluded, “An understanding of the high level of short-term risk for stroke, a devastating and disabling condition, will help to dispel the notion that the macrovascular consequences of diabetes occur only in the long term and hopefully will improve the motivation of both patients and providers to aggressively control cardiovascular risk factors soon after diagnosis.”    

Suggested Reading
Jeerakathil T, Johnson JA, Simpson SH, Majumdar SR. Short-term risk for stroke is doubled in persons with newly treated type 2 diabetes compared with persons without diabetes. Stroke. 2007;38:1739-1743.

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