Cerebral hemodynamics and cognitive impairment: baseline data from the RECON trial.

OBJECTIVE: To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke-sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON). METHODS: Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio >1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or ≤1.13, stratifying by TIA vs. stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests. RESULTS: There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was -1.45 for the PET-positive and -1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score = -1.41 vs. -0.76, p = 0.040). Older age and right ICA side were also significant in this model. CONCLUSION: Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested.

Role of feedforward control of movement stability in reducing slip-related balance loss and falls among older adults.

Human upright posture is inherently unstable. To counter the mechanical effect of a large-scale perturbation such as a slip, the CNS can make adaptive adjustments in advance to improve the stability of the body center-of-mass (COM) state (i.e., its velocity and position). Such feedforward control relies on an accurate internal representation of stability limits, which must be a function of anatomical, physiological, and environmental constraints and thus should be computationally deducible based on physical laws of motion. We combined an empirical approach with mathematical modeling to verify the hypothesis that an adaptive improvement in feedforward control of COM stability correlated with a subsequent reduction in balance loss. Forty-one older adults experienced a slip during a sit-to-stand task in a block of slip trials, followed by a block of nonslip trials and a re-slip trial. Their feedforward control of COM stability was quantified as the shortest distance between its state measured at seat-off (slip onset) and the mathematically predicted feasible stability region boundary. With adaptation to repeated slips, older adults were able to exponentially reduce their incidence of falls and backward balance loss, attributable significantly to their improvement in feedforward control of stability. With exposure to slip and nonslip conditions, subjects began to select "optimal" movements that improved stability under both conditions, reducing the reliance on prior knowledge of forthcoming perturbations. These results can be fully accounted for when we assume that an internal representation of the COM stability limits guides the adaptive improvements in the feedforward control of stability.

Lower extremity muscle strength does not independently predict proximal femur bone mineral density in healthy older adults.

The relationship described in the published literature between muscle strength and bone mineral density of older adults is not entirely certain. It is possible that the direct relationship reported in some studies is biased by failing to mathematically account for the biological influence of body weight and body height on both bone mineral density and muscle strength. This study sought to determine if the relationships between measures of lower extremity muscle strength and bone mineral density of the proximal femur are independent of body size (i.e., body height and body weight) in healthy older adults. We recruited 50 older women and 29 older men, all of whom were healthy community dwellers and not involved in resistance training. Quantitative analysis of the isometric strength of the bilateral ankle, knee, and hip joints and assessment of bone mineral density of the proximal femur were conducted. Muscle strength values were adjusted for the influence of body height and body weight using an allometric scaling procedure. The correlations between proximal femur bone mineral density and the unadjusted strength values were weak but statistically significant. After adjusting muscle strength to account for the influence of body height and body weight, the magnitudes of the correlations between bone mineral density and muscle strength diminished substantially and were not significantly different from zero. The results reveal that, for a typical sample of healthy older adults not involved in resistance training, the relationship between maximal isometric muscle strength of lower extremity joints and proximal femur bone mineral density is reliant on body size.

Response time is more important than walking speed for the ability of older adults to avoid a fall after a trip.

We previously reported that the probability of an older adult recovering from a forward trip and using a "lowering" strategy increases with decreased walking velocity and faster response time. To determine the within-subject interaction of these variables we asked three questions: (1) Is the body orientation at the time that the recovery foot is lowered to the ground ("tilt angle") critical for successful recovery? (2) Can a simple inverted pendulum model, using subject-specific walking velocity and response time as input variables, predict this body orientation, and thus success of recovery? (3) Is slower walking velocity or faster response time more effective in preventing a fall after a trip? Tilt angle was a perfect predictor of a successful recovery step, indicating that the recovery foot placement must occur before the tilt angle exceeds a critical value of between 23 degrees and 26 degrees from vertical. The inverted pendulum model predicted the tilt angle from walking velocity and response time with an error of 0.4+/-2.2 degrees and a correlation coefficient of 0.93. The model predicted that faster response time was more important than slower walking velocity for successful recovery. In a typical individual who is at risk for falling, we predicted that a reduction of response time to a normal value allows a 77% increase in safe walking velocity. The mathematical model produced patient-specific recommendations for fall prevention, and suggested the importance of directing therapeutic interventions toward improving the response time of older adults.

Mechanisms of failed recovery following postural perturbations on a motorized treadmill mimic those associated with an actual forward trip.

OBJECTIVE: To examine the recovery strategies employed during a treadmill acceleration task, to determine if mechanisms that contributed to failed recoveries on a motorized treadmill are the same general biomechanical mechanisms that contributed to falls from a trip, and to determine if failed recovery responses could be modified to allow for successful recoveries on subsequent trials. DESIGN: A motorized treadmill was used to induce postural perturbations in healthy older adults. BACKGROUND: Previously, we induced trips in older adults to identify the mechanisms of failed recovery. However, inducing trips is not a clinically practical test for identifying older adults who are predisposed to falling. METHODS: Safety-harnessed older adults stood on a treadmill that was accelerated from 0 to 0.89 m/s to impose a postural perturbation. Recoveries were classified as successful (n=42) or failed (n=23). Selected biomechanical variables were calculated using motion analysis methods. RESULTS: Initial failed recoveries had slower reaction times, shorter step lengths, and greater trunk flexion angles and velocities. Subjects who failed on the initial attempt modified their recovery strategy to successfully recover. The biomechanics of these recoveries resembled those used by subjects who successfully recovered on their initial attempt. CONCLUSIONS: The biomechanical mechanisms involved with a failed treadmill recovery mimic those responsible for failed recoveries from an induced trip. Subjects who failed on their initial recovery response made modifications allowing successful recoveries on subsequent attempts. RELEVANCE: This protocol may be useful as a testing and rehabilitation tool for fall recovery.

Mechanisms leading to a fall from an induced trip in healthy older adults.

BACKGROUND: Tripping is a leading cause of falls in older adults, often resulting in serious injury. Although the requirements for recovery from a trip are well characterized, the mechanisms whereby trips by older adults actually result in falls are not known. This study sought to identify such mechanisms. METHODS: Trips were induced during gait in 79 healthy, community-dwelling, safety-harnessed, older adults (50 women) using a concealed, mechanical obstacle. Kinematic and kinetic variables describing the recovery attempts were compared between those who fell and those who recovered. Subjects were analyzed according to the recovery strategy employed (lowering vs elevating) and the time of the "fall" (during step vs after step). RESULTS: Three apparent mechanisms of falling were identified. For a lowering strategy, during-step falls were associated with a faster walking speed at the time of the trip (91% +/- 8% vs 68% +/- 11% body height [bh] per second; p <.001) and delayed support limb loading (267 +/- 49 milliseconds vs 160 +/- 39 milliseconds; p <.001). After-step falls were associated with a more anterior head-arms-torso center of mass at the time of the trip (6.2 +/- 1.3 degrees vs 0.2 +/- 4.4 degrees; p <.01), followed by excessive lumbar flexion and buckling of the recovery limb. The elevating strategy fall was associated with a faster walking speed (93% vs 68% +/- 11% bh per second; p <.001) followed by excessive lumbar flexion. CONCLUSIONS: Walking quickly may be the greatest cause of falling following a trip in healthy older adults. An anterior body mass carriage, accompanied by back and knee extensor weakness, may also lead to falls following a trip. Deficient stepping responses did not contribute to the falls.

Does the intracarotid amobarbital procedure predict global amnesia after temporal lobectomy?

PURPOSE: The intracarotid amobarbital procedure (IAP) is widely used to help predict who might be at risk for postoperative amnesia after unilateral temporal lobectomy for intractable seizures. We describe the memory outcome in 10 patients who underwent standard temporal lobectomy, including mesial temporal structures, despite failing the memory portion of the IAP after injections both ipsilateral and contralateral to the resected seizure focus. METHODS: Data for seven of the study subjects were obtained through a retrospective review of patients assessed on a surgical epilepsy unit during a 15-year period who failed the Montreal Neurological Institute IAP memory protocol after both ipsilateral and contralateral injections and subsequently underwent unilateral temporal lobectomy. More recently, we have studied temporal lobectomy patients who failed the Medical College of Georgia memory protocol after both ipsilateral and contralateral injections (n = 3). Preoperative and postoperative memory test scores were compared, and data regarding seizure outcome and self-perception of postoperative memory were collected. RESULTS: At follow-up, none of the patients presented with a pattern indicative of a global amnesia, and 80% demonstrated >90% improvement in their seizure disorder or were seizure-free. CONCLUSIONS: These findings indicate that bilateral memory failure on the IAP does not preclude the removal of an epileptogenic temporal lobe or a successful surgical outcome. In addition, the findings raise questions regarding the validity of the IAP and the possibility that memory may be reorganized in patients with a long history of temporal lobe epilepsy.

Foot displacement but not velocity predicts the outcome of a slip induced in young subjects while walking.

The purpose of the present study was to induce slips in healthy subjects as a means to determine if recovery from an induced slip is possible under conditions in which the displacements and velocities of the slipping foot exceed the generally accepted limits of 10cm and 50cm/s, respectively, and to determine if there are gait-related variables that predispose an individual to falling after a slip. Thirty-three young and barefoot adults, protected by an instrumented safety harness, were subjected to a single slipping trial following a series of unperturbed walking trials. The slip was induced when the bare foot contacted a vinyl sheet coated with mineral oil. Lower extremity kinematics were acquired using a video-based motion capture system. Fourteen and 12 subjects could be unambiguously categorized as having fallen or recovered, respectively. Four variables demonstrated significant between-group differences and two were used to compute the probability of the slip outcome using logistic regression. The variables were the displacement of the foot during the slip and the angle of the shank relative to the ground at the instant of ground contact just prior to the slip. Separate univariate logistic regressions using each variable were significant and correctly classified about 70% of the slip outcomes. The results demonstrated that previously published values for the displacement and velocity of the slipping foot, 10cm and 50cm/s, respectively, may not accurately represent the upper limits beyond which recovery is not possible. The results also demonstrated that heel-strike angle, reflective of stride length, exerts a significant influence on the outcome of a slip.

Knee strength variability between individuals across ranges of motion and hip angles.

PURPOSE: Isokinetic strength is normally measured for a single range of motion and body position. This study quantified the variability, between individuals, in the relationships between a single peak knee extension moment and the isokinetic extension moments measured for different hip angles and ranges of knee motion. Effects of hip angle, and of the starting knee angle of the range of motion, on isokinetic knee extension strength were also determined. METHODS: The isokinetic knee extension strength of 10 subjects was measured at 30 degrees x s(-1) to a knee flexion angle of 10 degrees from starting knee angles of 90, 75, 60, 45, and 30 degrees, in both the seated and supine positions. Moments were normalized to the peak moment from a reference contraction. RESULTS: Peak moments and moments at larger knee flexion angles were greater in the seated than in the supine position. The starting knee angle affected the peak moment, the angle of peak moment, and the moments over the initial and final portions of the range of motion. Peak moments were highly correlated between all hip angle-starting knee angle combinations. However, the normalized peak moments, the angles of peak moment, and the normalized angle-specific moments all varied considerably between subjects. The pooled standard deviation and average coefficient of variation of the normalized angle-specific moments between subjects were 10.5% of the normalizing moment and 15.7%, respectively. Excluding the reference contraction, between-subject variability was unaffected by hip angle or starting knee angle. CONCLUSIONS: Influences of hip angle, starting knee angle, and individual differences on isokinetic knee extension strength must be considered to ensure that the moments obtained from isokinetic testing adequately reflect the general strength capabilities of an individual.

Measures of postural stability are not predictors of recovery from large postural disturbances in healthy older adults.

OBJECTIVES: To determine, in healthy older adults, the relationship between postural steadiness, stability limits, and the ability to recover balance from three postural disturbances requiring anteriorly directed stepping responses. DESIGN: Analysis of multiple motor tasks in a cross-sectional sample of healthy older adults. SETTING: A biomechanics research laboratory. PARTICIPANTS: Fifty women and 29 men aged 65 or older, all healthy, living in the community, participated in this study. Subjects were examined by a geriatrician to identify the presence of exclusionary factors. MEASUREMENTS: Anterior-posterior and medial-lateral excursion distances of the center of pressure during quiet standing (postural steadiness), static leaning (static stability limits), and dynamic swaying (dynamic stability limits) were determined from ground reaction forces measured by a strain gauge forceplate. Within the same group of subjects, the maximum angle of forward lean from which a subject could recover with a single step, the ability to recover balance in response to an accelerated support surface, and the ability to recover balance after being tripped were determined. RESULTS: Recovery from the three types of postural disturbances were found to be statistically independent. The postural steadiness and the stability limit variables were only weakly correlated. Postural steadiness and stability limits were not related to the maximum recoverable angle of lean. The average medial-lateral center of pressure speed during the postural steadiness test was significantly slower for those who failed to recover after tripping than for the subjects who recovered successfully. However, a logistic regression model failed to achieve statistical significance, suggesting that the difference may not be functionally important. The anterior-posterior static stability limits were significantly larger for subjects who recovered successfully than for those who failed to recover during the accelerated support surface test. Although logistic regression suggested that a reduced anterior-posterior stability limit represents a risk factor for failure to recover during this task, only nine of 28 failures could be properly classified, thus diminishing the functional importance of this finding. CONCLUSIONS: Because recovery following postural disturbances could not generally be predicted from measures of postural stability, these findings suggest that these measures of postural stability are of limited utility in identifying potential anteriorly directed fallers in healthy older adults.

The sex and age of older adults influence the outcome of induced trips.

BACKGROUND: Falls are a significant source of morbidity and mortality in older adults, with up to 53% of these falls due to tripping. To aid in fall prevention, there is a need to identify the factors that determine whether a trip is recoverable and those factors that increase an older adult's risk of falling. METHODS: Trips were induced during gait in 79 healthy, community-dwelling, safety-harnessed older adults (50 women) using a concealed, mechanical obstacle. Trip outcomes were graded as recoveries, falls, rope-assists, or misses. Kinematics were recorded during normal gait, without and with the safety harness. Selected gait parameters were compared to determine whether the experimental conditions affected gait at the time of the trip. RESULTS: Thirty-nine trip outcomes were classified as recoveries, 10 as falls, 12 as rope-assists, and 18 as misses. Women fell more than four times as frequently as men. Women younger than 70 years fell more than three times as frequently as those older. Trip outcomes in the men were essentially unaffected by age. The foot obstructed to induce the trip did not affect the trip outcome. The presence of the safety harness had almost no effect on gait. The length of the stride preceding the trip did not differ from normal. CONCLUSIONS: The majority of trips in healthy older adults did not result in falls. Older women were more likely than men to fall following a trip. The likelihood of falling from a trip was greatest in the youngest older women.

Maximum grip strength is not related to bone mineral density of the proximal femur in older adults.

In the past decade there have been numerous publications reporting a significant and direct relationship between handgrip strength and bone mineral density (BMD) of the proximal femur in older adults. The present report challenges the appropriateness of the methods, and thus the conclusions used in these studies. Specifically, these studies failed to control for the concomitant influence of body weight on both BMD and muscle strength. In the present study, maximum handgrip strength was measured using a conventional hand-held hydraulic dynamometer. Bone mineral density of the proximal femur was measured using dual-energy X-ray absorptiometry (DXA). Using allometric scaling, the influence of body weight on the value of maximum handgrip strength was removed for the data of the women. A small, but significant relationship between BMD of the proximal femur and maximum handgrip strength was found that accounted for about 6% of the total variation. The relationship between BMD of the proximal femur and unscaled maximum handgrip strength was not significant for the men. The findings diminish the confidence in a protective effect of skeletal muscle on some nonadjacent skeletal structures and suggest that these relationships may benefit from being revisited. The results highlight the utility of allometric scaling in analyses in which the relationship between a physiological variable and a body dimension variable can be nonlinearly and simultaneously influenced by other body dimension variables that are not considered in the analysis and therefore are statistically uncontrolled.

Gait characteristics as risk factors for falling from trips induced in older adults.

BACKGROUND: Falls are a significant source of morbidity and mortality in older adults, with up to 53% of these falls due to tripping. To aid in preventing trip-related falls, the factors that increase an individual's risk of falling following a trip must be identified. This study investigated whether an older adult's gait influences their risk of failing following a trip. METHODS: Trips were induced during gait in 79 healthy, safety-harnessed, community-dwelling older adults using a concealed, mechanical obstacle. Associations between selected gait kinematic characteristics, recorded during normal walking, and the likelihood of falling following the trip were determined using logistic regression. RESULTS: Older adults who walked faster, took more rapid steps, or took longer steps relative to their body height had a significantly increased likelihood of falling following the trip. Step width, average trunk flexion during gait, and the phase of gait in which the trip occurred did not affect the likelihood of falling. A multivariable logistic regression model correctly classified 89.8% of trip outcomes based on two gait characteristics: step time and step length. As predicted from their gait characteristics, the subjects, as a group, had a low likelihood of falling following a trip, but selected individuals had a high likelihood of falling. CONCLUSIONS: The incidence of trip-related falls in healthy older adults is determined primarily by the frequency of tripping and not the ability to recover from a trip. Older adults can reduce their likelihood of falling following a trip by not hurrying while walking.

Klüver-Bucy syndrome after bilateral selective damage of amygdala and its cortical connections.

Isolated symmetric damage to the amygdala and their cortical connections occurred in an individual following cancer treatment. The lesions were imaged after reversal of hyponatremia. The patient displayed marked behavioral changes including visual agnosia, hypersexuality, hyperorality, a tendency to react to every visual stimulus, and memory deficits. The cluster of neurobehavioral symptoms is similar to previously reported accounts of Klüver-Bucy syndrome and suggests the importance of bilateral amygdala involvement in these behavioral changes.

Three-dimensional knee joint kinetics during a golf swing. Influences of skill level and footwear.

This study characterized knee joint kinetics during a golf swing and determined the influence of shoe type and golfer skill on the peak knee joint loads. Thirteen golfers each hit a golf ball using a five iron under two footware conditions: spiked and spikeless golf shoes. Data from a video-based motion capture system and force plates were used to compute the knee joint kinetics. Mean peak forces and moments differed significantly between the lead and trail knees, but these peak loads were not significantly affected by shoe type. Only the lead knee flexion and internal rotation moments were significantly correlated to skill level. The magnitude of some of the peak loads at the knee during the golf swing approached those reached during activities prohibited until late-stage knee rehabilitation. We concluded the following: The type of shoe worn and the skill level of the golfer need not be considered in deciding time to return to golfing; however, the leg that is recovering from surgery or injury should be considered. The most stressful phase of the golf swing, relative to the knee, is the downswing. There is probably no "normal" swing; each golfer seems to possess consistent, characteristic, patterns of knee loading.

Pattern of neurobehavioral deficits associated with interferon alfa therapy for leukemia.

We evaluated the neuropsychological and personality profiles of 25 patients with chronic myelogenous leukemia treated with interferon alfa (IFN-alpha). This group of persons performed well below expectation on tests of cognitive speed, verbal memory, and executive functions. Personality changes included depression, increased somatic concern, and stress reactions. A control group of leukemia patients not treated with IFN-alpha had significantly better cognitive speed and mood. The pattern of cognitive and personality changes in patients receiving IFN-alpha is highly suggestive of frontal-subcortical brain dysfunction.

Prospective studies of cerebral perfusion and cognitive testing among elderly normal volunteers and patients with ischemic vascular dementia and Alzheimer's disease.

To compare longitudinal changes of cerebral perfusion (CBF) and cognitive status in two common forms of dementia in the elderly, 42 patients with ischemic vascular dementia (IVD), 44 patients with dementia of the Alzheimer type (DAT), and 120 elderly normal volunteers were evaluated prospectively over a mean interval of 3.35 years. Subjects were at least age sixty, (mean age 71.1). Mean bihemispheric cerebral blood flow and cognitive test scores of control subjects were significantly higher than those of both demented groups at entry and remained so. After adjustment for initial CBF, course over time was similar for all groups. Group variability was similar for CBF but not for cognition. Both IVD and DAT patients were more variable than controls but similar to each other. Throughout, DAT patients showed greater cognitive impairments than IVD patients. Cognitive impairments stabilized among IVD patients treated by control of risk factors, antiplatelet or anticoagulant therapy but declined progressively among DAT patients.

Analysis of familial and individual risk factors among patients with ischemic vascular dementia and Alzheimer's disease.

UNLABELLED: The purpose of this study was to determine relative contributions of first-degree familial and individual risk factors to clinical manifestations of two major age-related dementias. The authors interviewed 183 patients with dementia of the Alzheimer's type (DAT) and 137 patients with ischemic vascular dementia (IVD) together with family members and caregivers. Information was also obtained from medical records and collateral sources as required. Risk factor data within a predictive model for differentiating the two dementias were evaluated. There was a greater incidence of family history of degenerative and dementing neurologic disorders in DAT than in IVD. Both groups were equivalent for family histories of cerebrovascular disease. Despite familial equivalence, patients with IVD had a greater individual incidence of risk factors for cerebrovascular disease. Analysis by gender revealed three observations. Among DAT patients, family history for degenerative and dementing neurologic disorders proved to be significantly greater among women than among men. This risk factor did not, however, predict individual diagnoses for DAT. Women with IVD were more likely to have a family history of cancer than men. Multiple regression analyses revealed that reduced educational levels in women predicted greater liability for IVD than for DAT. Hypertension, heart disease, and diabetes mellitus were all risk factors for IVD, but not for DAT. CONCLUSIONS: Individual and familial historical data provide useful information concerning identification, pathogenesis, prevention, and treatments for vascular dementia but little predictive information for identifying patients with Alzheimer's disease.

Leuko-araiosis and cerebral perfusion in normal aging.

To clarify the incidence, age relationships and pathogenesis of white matter lesions of unknown origin (leuko-araiosis) detected by neuroimaging among normal elderly volunteers, we measured the severity of leuko-araiosis using computerized tomographic (CT) densitometry among 42 healthy self-supporting men and women of different ages, all with normal neurological and cognitive test performance. Results were correlated with local cerebral perfusion using xenon-contrasted CT. The 42 volunteers, who are followed in this laboratory for studies of normal aging, were divided into two groups in order to determine aging effects by an extremes design. One group consisted of 19 adults below age 60 (M = 53.3, SD = 6.0). The index group comprised 23 individuals all over the age of 60 (M = 71.6, SD = 8.7). Leuko-araiosis around the anterior horns of the lateral ventricles (frontal leuko-araiosis) was more severe (p < .01) among the older group, however, occipital leuko-araiosis did not significantly differ between older and younger groups. Cerebral perfusion in frontal, temporal, and parietal cortex was decreased among older compared with younger volunteers (ps < .001, .01, and .05, respectively). Multiple regression analyses disclosed significant and direct relationships between severity of frontal leuko-araiosis and (a) frontal cortical atrophy and (b) reductions of cerebral perfusion within frontal white matter and caudate nucleus. We conclude that cortical atrophy with hypoperfusion and ischemia of frontal white matter play a part in the pathogenesis of frontal leuko-araiosis associated with normal aging and this may be a predictor for later cognitive declines.