BACTERIAL MENINGITIS SURVIVORS MAY BE AT RISK OF COGNITIVE IMPAIRMENT

Adult survivors of bacterial meningitis may be at high risk of cognitive impairment that consists mainly of cognitive slowness, according to a report published in the October Journal of Neurology, Neurosurgery, and Psychiatry.

Lead investigator Ben Schmand, PhD, of the University of Amsterdam, and colleagues analyzed data from three prospective multicenter studies that involved 155 adults who survived bacterial meningitis and 72 healthy controls. Of the survivors, 79 had pneumococcal meningitis, and 76 had meningococcal meningitis. The investigators found cognitive impairment in 32% of patients, compared with 5.5% of controls.

Thirty-seven percent of pneumococcal meningitis survivors and 28% of meningococcal meningitis survivors had cognitive impairment. Survivors of pneumococcal meningitis performed worse on memory tasks and tended to be cognitively slower than survivors of meningococcal meningitis; pneumococcal meningitis survivors also had higher depression scale scores than did meningococcal meningitis survivors.

“We found a diffuse pattern of cognitive impairment, in which cognitive speed played the most important role,” Dr. Schmand and colleagues stated. “The findings of executive deficits in this study may also have been associated with a decline in cognitive speed.”

Although significant improvement was observed in the study cohort with respect to subjective physical impairment after bacterial meningitis, the loss of cognitive speed was stable over time. In addition, there was no confounding by higher scores on the depression scale.

“Although speculative, this may imply that patients adapt to their cognitive impairments, even if these impairments remain stable,” the researchers stated. “The effect of cognitive impairment after bacterial meningitis on longer term outcome (>10 years) and the potential influence on the development of dementia remains to be elucidated.”

The researchers also found that use of dexamethasone was not linked to cognitive impairment, as the frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar. Male gender with bacterial meningitis and cranial nerve palsy at discharge were both risk factors for cognitive impairment.

“Over the years, patients tended to report fewer complaints, but the cognitive impairment, if present, does not seem to improve once the subacute phase has elapsed,” Dr. Schmand’s team concluded. Given the finding that one third of patients had cognitive impairment, “large numbers of patients will continue to have complaints attributable to their illness after the acute phase of the disease.”

Suggested Reading
Hoogman M, van de Beek D, Weisfelt M, et al. Cognitive outcome in adults after bacterial meningitis. J Neurol Neurosurg Psychiatry. 2007;78(10):1092-1096.

CHRONIC STRESS MAY SHORTEN CAREGIVER LIFESPAN

The chronic stress that caregivers experience while caring for patients with Alzheimer’s disease may shorten their lives by as much as four to eight years, according to a study published in the September 15 Journal of Immunology. The research shows that excessive telomere loss underlies the link between chronic stress and altered T-cell function and accelerated immune cell aging.

Amanda K. Damjanovic, PhD, of the National Institute on Aging in Baltimore, and colleagues compared 41 Alzheimer’s disease caregivers with 41 noncaregivers matched for age and gender. The researchers studied depressive symptoms, peripheral blood mononuclear cell (PBMC) composition, in vitro activation–induced proliferation and cytokine production, and telomere length and telomerase activity. Depressive symptoms were significantly higher in caregivers than in controls. Janice Kiecolt-Glaser, PhD, of Ohio State University in Columbus, a study coauthor, noted that depressive symptoms in caregivers were twice as severe as those apparent in the control group. In addition, caregivers had significantly lower T-cell proliferation but higher production of immune-regulatory cytokines than controls.

The researchers also found that caregivers had significantly shorter telomere lengths in PBMC than did controls (6.2 and 6.4 kb, respectively), with similar shortening in isolated T cells and monocytes. The “telomere attrition in caregivers was not caused by an increase of shorter telomere possessing T-cell subsets in PBMC,” the investigators pointed out. Dr. Damjanovic and colleagues also found that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls, “pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers,” they stated.

“We believe that the changes in these immune cells represent the whole cell population in the body, suggesting that all the body’s cells have aged that same amount,” said coauthor Ronald Glaser, PhD, of Ohio State University. Dr. Glaser also stated that the changes the research team saw amounted to a shortened life span of four to eight years.

Dr. Kiecolt-Glaser noted that there is ample epidemiologic data showing that stressed caregivers die sooner than noncaregivers. “Now we have a good biological reason for why this is the case,” she said. “We now have a mechanistic progression that shows why, in fact, stress is bad for you, how it gets into the body, and how it gets translated into a bad biological outcome.”

Suggested Reading
Damjanovic AK, Yang Y, Glaser R, et al. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer’s disease patients. J Immunol. 2007;179(6):4249-4254.

ADDITIONAL STROKE RISK DETECTABLE IN PATIENTS RECEIVING ANTICOAGULANTS

Clinicians may be able to identify which patients with atrial fibrillation and receiving anticoagulant therapy are at the greatest risk of ischemic stroke, and therefore those who may need more aggressive interventions, reported researchers in the September Stroke. Lawrence Baruch, MD, of the Department of Medicine at Bronx Veterans Affairs Medical Center in New York, and colleagues tested seven recognized classification schemes and found that three of them predicted stroke significantly better than chance.

Data for 7,329 patients with atrial fibrillation at high risk for stroke who had participated in two randomized, multicenter, parallel-group trials that compared fixed-dose oral ximelagatran with adjusted-dose warfarin for the prevention of stroke were run through each of the classification schemes. Most participants were determined to have a high stroke risk by the American College of Chest Physicians (ACCP) 2001 scheme (96%), the ACCP 2004 scheme (97.5%), the van Walraven scheme (99.2%), and the Atrial Fibrillation Investigators scheme (85.1%); in contrast, the Framingham scheme characterized the fewest participants as being at high risk (21.2%). CHADS2 characterized the largest cohort of participants as being at intermediate risk, and the Stroke Prevention in Atrial Fibrillation (SPAF) scheme classified an almost equal number of participants as being at moderate and high risk.

Dr. Baruch and colleagues reported that in 11,245 patient-years of follow-up, 159 participants had an ischemic stroke. “The highest stroke rate occurred in patients identified as being at high risk by the Framingham scheme,” said the authors. No strokes occurred among the 238 patient-years categorized as low risk by the CHADS2 scheme or in the low-risk cohorts defined by the van Walraven (85 patient-years) and ACCP 2004 (29 patient-years) schemes. Concordance statistics indicated that only the Framingham, CHADS2, and SPAF schemes performed better than chance (c = 0.64, 0.65, and 0.61, respectively).

The authors noted that all seven atrial fibrillation stroke schemes were developed and evaluated in patients not receiving anticoagulant therapy. “Although these stratification schemes help identify which patients are above a risk threshold that would lead to a benefit from anticoagulant therapy, they do not identify who remains at a higher level of risk despite the use of anticoagulant therapy,” they stated. The researchers noted that identification of such patients might influence clinical practice, as clinicians may consider newer therapeutic strategies in patients at high risk for stroke.

Suggested Reading
Baruch L, Gage BF, Horrow J, et al. Can patients at elevated risk of stroke treated with anticoagulants be further risk stratified? Stroke. 2007;38(9):2459-2463.

MINOCYCLINE MAY OFFER LARGER WINDOW FOR STROKE TREATMENT

Patients treated with minocycline within six to 24 hours after a stroke may have significantly fewer disablities, according to a study published in the October 2 Neurology.

In an open-label evaluator-blinded study, Yair Lampl, MD, of the Edith Wolfson Medical Center and Tel Aviv University in Israel, and colleagues studied 152 patients who received either an oral dose of minocycline or placebo for five days following a stroke. Participants who received minocycline were treated an average of 13 hours after stroke, compared with 12 hours in the placebo group. The investigators found that patients treated with minocycline had significantly better outcomes than those who received placebo. After three months, the minocycline group performed four times better than the placebo group on the NIH Stroke Scale (1.6 vs 6.5). Dr. Lampl stated that the improvement shown by patients taking minocycline was not due to the drug’s basic antibiotic effect but rather to its anti-inflammatory effect and ability to protect brain cells from destruction. None of the patients experienced serious side effects from taking minocycline.

“The improvement was already apparent within a week of the stroke,” Dr. Lampl said. “This is exciting, because many people who have had stroke cannot be treated if they don’t get to the hospital within three hours after symptoms start, which is the time frame for current available treatments.

“While these are promising results, a much larger, closed-label study is needed to confirm our findings,” she added. “Further research is also needed to look at whether the dosage of the drug taken in this study is optimal and whether giving the drug through an IV would be more effective.”           

Suggested Reading
Lampl Y, Boaz M, Gilad M, et al. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007;69(14):1404-1410.

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