LARGER MIDSECTION IN MIDLIFE INCREASES DEMENTIA RISK

Central obesity in midlife coupled with a high BMI can more than triple a person’s risk of dementia in old age, reported Rachel A. Whitmer, PhD, and colleagues in the March 26 online Neurology. They noted that the risk was greatest among those with both high sagittal abdominal diameter (SAD) and BMI, and the increase was independent of diabetes and cardiovascular comorbidities.

Dr. Whitmer, an Investigator at the Division of Research at Kaiser Permanente Northern California in Oakland, and her coresearchers ascertained dementia status of 6,583 continual members of the Kaiser Permanente Medical Care Program for whom SAD, thigh circumference, and BMI were known between 1964 and 1973, when the participants were between the ages of 40 and 45. Central obesity was defined as SAD of 25 cm or greater. “Those with central obesity were more likely to be female; nonwhite; to have less than a high school level of education; to smoke cigarettes; to have hyperlipidemia, hypertension, or diabetes; and to be either overweight or obese,” said the authors.

Between January 1, 1994, and June 16, 2006—when the study participants were ages 73 to 87—1,049 (15.9%) were diagnosed with dementia. There was an increase in risk of dementia by quintiles of SAD, from 214 events per 10,000 person-years in the first quintile to 324 events in the fifth quintile, reported the researchers. In a fully adjusted multivariate mode, SAD increased the risk of dementia in a dose-dependent fashion: Compared with the first quintile, participants in the second, third, fourth, and fifth quintiles were 20%, 49%, 67%, and 272%, respectively, more likely to develop dementia.

SAD remained a significant risk factor after inclusion of BMI into the model, although the effect of high SAD on dementia risk varied significantly across BMI categories. Compared with those with a normal BMI and a low SAD, the hazard ratios (HRs) for dementia were similar among those with a normal BMI and a high SAD, for those overweight and with low SAD, and for those obese and with a low SAD (1.89, 1.82, and 1.81, respectively). However, for those overweight and with high SAD, the HR for dementia was 2.34, and for those obese and with a high SAD, it was 3.60.

“These results contribute to a recent but growing body of evidence that a centralized distribution of adiposity is particularly dangerous, even for those who are not overweight, and that the brain may also be a target organ to the harmful effects of central obesity,” concluded Dr. Whitmer and colleagues. “If these results are replicated, our findings may imply that central obesity may contribute to a degree of cognitive aging.”

Suggested Reading
Whitmer RA, Gustafson DR, Barrett-Connor E, et al. Central obesity and increased risk of dementia more than three decades later. Neurology. 2008 Mar 26; [Epub ahead of print].

SMOKERS WITH HIGH BLOOD PRESSURE AT GREATER HEMORRHAGIC STROKE RISK THAN NONSMOKERS

Cigarette smoking increased the excess risk of hemorrhagic stroke associated with a 10–mm Hg increase in systolic blood pressure by 15%, according to Koshi Nakamura, MD, of the Nutrition and Lifestyle Division at the George Institute for International Health in Sydney, and colleagues. Their findings, based on data from 563,144 participants from 41 cohort studies in the Asia Pacific Cohort Studies Collaboration, were reported in the March 6 online Stroke.

Eighty-two percent of the pooled cohort were Asian, 35% were women, and 37% were present smokers at baseline; the mean age was 47. During the median follow-up of 6.8 years, 4,344 coronary heart disease events were recorded, 76% of which were fatal. There were also 2,001 ischemic and 1,645 hemorrhagic stroke events, which were fatal 30% and 73% of the time, respectively.

Hazard ratios (HRs) for coronary heart disease comparing the highest with the lowest systolic blood pressures were similar for smokers and nonsmokers (2.27 vs 2.20), and a 10–mm Hg increase resulted in comparable HRs in the two groups (1.29 and 1.24, respectively). Smoking status also did not significantly impact ischemic stroke risk. Comparing the highest and the lowest systolic blood pressure, HRs were 3.71 for smokers and 3.82 for nonsmokers; a 10–mm Hg higher systolic blood pressure affected both groups similarly.

The risk for hemorrhagic stroke was significantly higher in smokers than in nonsmokers when comparing the highest to lowest systolic blood pressures, however (HR, 9.32 vs 7.05), and the risk with a 10–mm Hg higher systolic blood pressure was increased from 66% in nonsmokers to 81% in smokers. “Restricting the analysis to fatal hemorrhagic events resulted in a similar pattern: HR for a 10–mm Hg increase in systolic blood pressure was 1.82 for present smokers and 1.67 for nonsmokers,” reported the authors.

“Unlike coronary heart disease and ischemic stroke, the prevailing cause of hemorrhagic stroke is rupture resulting from fragility … of the intracerebral penetrating arteries caused by nonoptimal levels of blood pressure or amyloid angiopathy,” said Dr. Nakamura and colleagues. “We can only speculate that smoking may promote weakening of the intracranial blood vessels caused by high levels of blood pressure or amyloid angiopathy.” They suggested that smoking cessation initiatives be targeted more rigorously for hypertensive patients to prevent hemorrhagic stroke.

Suggested Reading
Nakamura K, Barzi F, Lam TH, et al. Cigarette smoking, systolic blood pressure, and cardiovascular diseases in the Asia-Pacific region. Stroke. 2008 Mar 6; [Epub ahead of print].

WHITE PATIENTS BENEFIT FROM PRESTROKE STATIN USE, WHILE IT MAY HARM BLACK PATIENTS

The beneficial functional effect of statin pretreatment may depend on a patient’s race, according to the results of a study in the March 27 online Stroke. Mathew J. Reeves, PhD, and coinvestigators with the Paul Coverdell National Acute Stroke Registry Michigan Prototype found that not only did black ischemic stroke patients not benefit from statins as whites did, the statin therapy may have had a harmful effect.

A total of 1,360 consecutively admitted black or white ischemic stroke patients were included in the study; 22.7% were using statins before their stroke event. “Subjects 60 to 69 and 70 to 79 years of age were more likely to be on statins at admission, as were subjects with a past medical history of stroke, heart disease, hypertension, dyslipidemia, and diabetes, while nursing home residents were less likely to be on statins at admission,” said Dr. Reeves, an Associate Professor of Epidemiology at Michigan State University in East Lansing, and coauthors.

Overall, poor stroke outcome (modified Rankin Scale score ≥ 4) was less common in subjects taking statins. After adjusting for age, race, gender, nursing home residence, and ambulatory status prestroke, statin use was associated with a 26% reduction in the odds of a poor outcome, although this was not a significant reduction. There was a statistically significant interaction between statin use and race, however: Among black patients, prestroke statin use was associated with a nonstatistically significant increased odds of a poor outcome (odds ratio [OR], 1.82), while among whites, statin use was associated with a significant decrease in the odds of a poor outcome (OR, 0.61). Matched propensity score analyses confirmed the effect estimates.

The researchers said that their findings raise concern that statins may lead to worse poststroke outcomes in black patients; however, they noted that the results should be interpreted with caution, as the number of black subjects in the present study was small, and therefore not powered to reach statistical significance in this group. They also suggested that different statin prescription and adherence patterns between races may have impacted the results (eg, adherence to statin therapy in the elderly has been shown to be especially poor in nonwhites). The authors concluded that “further studies, including randomized trials, [are needed] to explore the possibility of differential effects of statins among whites and blacks with ischemic stroke.”

Suggested Reading
Reeves MJ, Gargano JW, Luo Z, et al. Effect of pretreatment with statins on ischemic stroke outcomes. Stroke. 2008 Mar 27; [Epub ahead of print].

EXTRAPYRAMIDAL SYNDROME CAN RESULT FROM METHCATHINONE USE

The manganese found in methcathinone solution may cause a persistent extrapyramidal syndrome, according to the results of a study in the March 6 New England Journal of Medicine. Ainars Stepens, MD, from the Department of Neurology at Riga Stradins University, Latvia, and colleagues reported on 23 IV methcathinone–using adults (20 men; mean age, 37.5). Average duration of drug use was 6.7 years, and 10 participants were still actively using, with at least one binge occurring within the previous year. All participants were positive for hepatitis C, and 20 were also HIV-positive.

The onset of first neurologic symptoms—gait disturbance in 20 and hypophonia in three—occurred a mean of 5.8 years after the start of methcathinone use. At the time of the study, all patients had gait disturbance and difficulty walking backward, 11 were falling daily, and one used a wheelchair; in addition, 21 had speech disturbances. No patients reported decline in cognitive function. The extrapyramidal disorders seen in the study group were “strikingly stereotyped,” the researchers noted, because the patients “did not have tremors during rest, had particular difficulty with backward motion, had a symmetric motor disorder, fell frequently, walked on the balls of the feet with a typical ‘cock walk,’ had profoundly soft speech, and did not respond to treatment with levodopa.”

Whole-blood manganese levels were elevated in nine active users (mean, 831 nmol/L). “The levels in the 13 patients who reported cessation of methcathinone use were lower than those in the active users (mean, 346 nmol/L), and one of these patients had a normal manganese level,” the researchers reported.

Twenty-one patients showed increased bilateral and symmetric T₁-signal intensity in the globus pallidus on MRI. All active users had hyperintensity of the globus pallidus, as did nine of the former users, although it was “generally less severe than that in active users,” said the authors. Nine active users also had hyperintensity of the substantia nigra and innominata and of the anterior midbrain, and residual changes were seen in the substantia nigra in two former users and in the anterior midbrain in three. Neurologic deficits did not resolve after patients discontinued methcathinone use, however, “implying that permanent neuronal damage remained despite resorption of manganese from the basal ganglia,” the researchers stated.

“Similar signal changes in the global pallidus have been noted in patients with chronic hepatic disease that is associated with increased manganese concentrations in the basal ganglia, changes that can be associated with an extrapyramidal movement disorder,” the investigators wrote. They concluded that the disorder “probably resulted from contaminants resulting from poorly controlled processes of synthesizing the drug,” because all participants prepared the methcathinone under home conditions by potassium permanganate oxidation of ephedrine or pseudoephedrine.

Suggested Reading
Stepens A, Logina I, Liguts V, et al. A parkinsonian syndrome in methcathinone users and the role of manganese. N Engl J Med. 2008;358(10):1009-1017.

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