ABNORMALITY OF GAIT MAY PREDICT DEMENTIA

Gait abnormalities in the elderly may be a predictor of non-Alzheimer’s dementia, according to a study in the November 28 New England Journal of Medicine. While researchers often employ cognitive tests to identify persons at high risk for Alzheimer’s disease, predictors of non-Alzheimer’s dementia have been less well categorized. The investigators in this study hypothesized that gait abnormalities may precede and predict the diagnosis of non-Alzheimer’s dementia.

Researchers recruited 422 participants 75 and older without dementia. At baseline, 85 of the participants had neurologic abnormalities affecting gait, which were subclassified as unsteady, ataxic, frontal, parkinsonian, neuropathic, hemiparetic, or spastic. Neuropsychologic tests were administered to assess general cognitive status, attention, executive function, memory, visual-perceptual processing, motor skills, language skills, and mood. Participants had follow-up visits every 12 to 18 months.

During a median follow-up of 6.6 years, 125 patients developed dementia. Seventy of these cases were classified as Alzheimer’s disease, and 55 were classified as non-Alzheimer’s disease (47 as vascular dementia, eight as other). Investigators observed that specific subtypes of gait abnormalities (hemiparetic, unsteady, and frontal) were associated with an increased risk of dementia. They determined that individuals who presented with abnormal gaits at baseline were more likely to have non-Alzheimer’s dementia; there was no significant correlation between Alzheimer’s disease and gait status. In addition, researchers were surprised to find that “the presence of abnormal gaits predicted the risk of non-Alzheimer’s dementia well into the future,” suggesting a long prodrome that only later progresses to dementia.

Suggested Reading
Verghese J, Lipton RB, Hall, CB, et al. Abnormality of gait as a predictor of non-Alzheimer’s dementia. N Engl J Med. 2002;347:1761-1768.

BORDERLINE HYPERTENSION LINKED WITH INCREASED STROKE RISK

Borderline isolated systolic hypertension is associated with an increased risk of stroke, ischemic stroke, and intracerebral hemorrhage, similar to that observed in patients with isolated systolic hypertension and diastolic hypertension, concluded a report in the December Stroke. Because the risk was also noted in the younger group of participants (those ages 45 to 64) who had systolic hypertension, researchers recommended that future clinical trials should evaluate the effect of antihypertensive treatment in younger persons with borderline isolated systolic hypertension and isolated systolic hypertension.

“Our analysis showed that each category of hypertension represented in this study confers an increased risk for stroke, including both ischemic stroke and intracerebral hemorrhage,” reported Adnan I. Qureshi, MD, of the Department of Neurosurgery, State University of New York at Buffalo, and colleagues. “Isolated systolic hypertension appeared to pose the highest risk for both types of stroke events.”

Dr. Qureshi’s team sought to evaluate the long-term risks of stroke, type of stroke, and predictors of stroke associated with isolated systolic hypertension and borderline isolated systolic hypertension and how this risk compared with that for persons with diastolic hypertension and normotension. They analyzed 20-year follow-up data from 12,344 adults, ages 25 to 74, who participated in the First National Health and Nutrition Examination Survey Follow-Up Study. Blood pressure was measured at baseline evaluation for each participant, and the incidence of overall stroke and of ischemic stroke and intracerebral hemorrhage were determined by reviewing hospital records and death certificates. The relative risk of stroke and stroke type in association with each hypertensive category was determined by Cox proportional hazards analysis after adjusting for potential confounding variables.

The researchers found isolated systolic hypertension in 493 subjects, borderline isolated systolic hypertension in 1,241 participants, diastolic hypertension in 3,954 patients, and normotension in 6,656 participants. After adjusting for age, sex, education, serum cholesterol level, body mass index, diabetes mellitus, and cigarette smoking, the investigators found a significantly higher relative risk for all strokes in patients with isolated systolic hypertension and borderline isolated systolic hypertension than in those with normotension.

“Among the 1,734 persons with either isolated systolic hypertension or borderline isolated systolic hypertension, the risk of stroke was independently associated with older age, diabetes mellitus, and systolic [blood pressure] greater than or equal to 180 mm Hg,” the researchers reported.

Suggested Reading
Qureshi AI, Suri FK, Mohammad Y, et al. Isolated and borderline isolated systolic hypertension relative to long-term risk and type of stroke—a 20-year follow-up of the National Health and Nutrition Survey. Stroke. 2002;33:2781-2788.

RATE VERSUS RHYTHM CONTROL IN PATIENTS WITH ATRIAL FIBRILLATION

Managing atrial fibrillation with the rhythm control strategy offers no survival advantage compared with the rate control strategy, according to a report in the December 5 New England Journal of Medicine. In addition, the study found that rate control offers other potential advantages, including a lower risk of adverse drug effects.

“The implication is that rate control should be considered a primary approach to therapy and that rhythm control, if used, may be abandoned early if it is not fully satisfactory,” concluded the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) investigators. “Our data also suggest that continuous anticoagulation is warranted in all patients with atrial fibrillation and risk factors for stroke, even when sinus rhythm appears to be restored and maintained.”

The researchers conducted a randomized, multicenter comparison of the rhythm control and rate control treatment strategies in patients with atrial fibrillation and a high risk of stroke or death in which the primary end point was overall mortality. A total of 4,060 patients were enrolled in the trial, with 70.8% having a history of hypertension and 38.2% having coronary artery disease. Among the 2,033 patients receiving rhythm control therapy, 356 deaths occurred. Among the 2,027 subjects assigned to rate-control therapy, there were 310 deaths. More patients were hospitalized, and more adverse drug effects were noted in, the rhythm control group compared with the rate control group. The researchers also found that the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic.

In an accompanying editorial, Rodney H. Falk, MD, of the Boston University School of Medicine, advised, “There remains a substantial proportion of patients in whom atrial fibrillation causes symptoms despite pharmacologic attempts to control heart rate. Younger patients with structurally normal hearts and paroxysmal arrhythmia may be disproportionately represented in this group. For them, the goal is still the maintenance of sinus rhythm, and the quest for better drugs and techniques to achieve this goal will, and should, continue.”

Suggested Reading
The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347:1825-1833.

USUAL BLOOD PRESSURE AND MORTALITY—AN AGE-RELATED CORRELATION

A study of individual data for nearly one million adults has revealed that through middle and old age, usual blood pressure “is strongly and directly related to vascular (and overall) mortality.” The results, published in the December 14 Lancet, were drawn from an analysis of 958,074 participants in 61 prospective observational studies of blood pressure and mortality. Seventy percent of the studies were conducted in Europe, 20% in North America or Australia, and 10% in Japan or China. The Prospective Studies Collaboration analyzed data on systolic and diastolic blood pressure in an age-specific fashion for cause-specific death rates during the five decades of age at risk period—ages 40 through 89. During the 12.7 million person-years at risk (mean of 12 years to death), there were 11,960 deaths attributed to stroke, 34,283 attributed to ischemic heart disease, 10,092 attributed to other vascular causes, and 60,797 attributed to non-vascular causes.

The relationship between usual blood pressure (down to a threshold of 115/75 mm Hg) and stroke mortality, ischemic heart disease mortality, and other vascular mortality was strong and direct across all age groups, the researchers reported. Between the ages of 60 and 69, each difference of 20 mm Hg usual systolic blood pressure (or approximately, equivalently 10 mm Hg usual diastolic blood pressure) was associated with a more than twofold increase in the rate of death from stroke, ischemic heart disease, and other vascular causes. While the proportional differences in vascular morbidity were about half as extreme at ages 80 to 89 as at ages 40 to 49, the researchers found that the annual absolute differences in risk were greater in old age. The age-specific associations were similar for men and women, and for cerebral hemorrhage and cerebral ischemia.

Additionally, the researchers observed that for participants with no previous vascular disease, the relationship between usual blood pressure and risk of death was not only found among individuals who were hypertensive, but among those who would be considered normotensive. They asserted that “the absolute benefits of a lower blood pressure are likely to be greatest for those at greatest absolute risk of vascular disease,” but nonetheless opined that “blood pressure–lowering treatment should be considered for a wide range of patients with evidence of occlusive vascular disease, largely irrespective of their current blood pressure or the use of other medication.”

Suggested Reading
Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903-1913.

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