Older people with impaired mobility have specific loci of periventricular abnormality on MRI.

BACKGROUND: Recent investigations using MRI suggest that older persons with mobility impairment have a greater volume of abnormal cerebral white matter compared with persons with normal mobility, thus raising the possibility that those with impairment have lesions in areas critical for the control of mobility. OBJECTIVE: To utilize automated image analysis methods to localize the specific regions of abnormal white matter that distinguish subjects with lower mobility from subjects with higher mobility. METHODS: Tissue classification was performed on subjects' dual-echo long repetition time spin-echo MRI using computer algorithms operating on intensity criteria integrated with anatomic information. Statistical analysis of group differences was obtained after spatially normalizing each brain to a standard reference brain. RESULTS: Four discrete periventricular regions, including bilaterally symmetric frontal and bilateral occipitoparietal regions, were identified as being sensitive (frontal) or specific (occipitoparietal) in discriminating the subjects with lower mobility from subjects with higher mobility. The symmetry of these lesions in individual subjects suggested pathology other than arteriolar infarction. CONCLUSIONS: These results suggest that damage to discrete frontal and occipitoparietal periventricular white matter locations may be associated with a mobility disorder of aging.

Lower standing systolic blood pressure as a predictor of falls in the elderly: a community-based prospective study.

OBJECTIVES: We investigated prospectively the relationships among falls, physical balance, and standing and supine blood pressure (BP) in elderly persons. BACKGROUND: Falls occur often and adversely affect the activities of daily living in the elderly; however, their relationship to BP has not been clarified thoroughly. METHODS: A total of 266 community-dwelling elderly persons age 65 years or over (123 men and 143 women, mean age of 76 years) were selected from among residents of Coop City, Bronx, New York. Balance was evaluated at baseline using computerized dynamic posturography (DPG). During a one-year follow-up, we collected information on subsequent falls on a monthly basis by postcard and telephone follow-up. RESULTS: One or more falls occurred in 60 subjects (22%) during the one-year follow-up. Women fell more frequently than men (28% vs. 16%, p < 0.03), and fallers were younger than nonfallers. Fallers (n = 60) had lower systolic BP (SBP) levels when compared with nonfallers (n = 206) (128 +/- 17 vs. 137 +/- 22 mm Hg for standing, p < 0.006; 137 +/- 16 vs. 144 +/- 22 mm Hg for lying, p < 0.02), whereas diastolic BP was not related to falls. Falls occurred 2.8 times more often in the lower BP subgroup (<140 mm Hg for standing SBP) than in the higher BP subgroup (> or =140 mm Hg, p < 0.0003), and gender-related differences were observed (p = 0.006): 3.4 times for women (p < 0.0001) versus 1.9 times for men (p = 0.30). Loss of balance, as detected by DPG, did not predict future falls and was also not associated with baseline BP levels. Multiple logistic regression analysis demonstrated that female gender (relative risk [RR] = 2.1, p = 0.02), history of falls (RR = 2.5, p = 0.008) and lower standing SBP level (RR = 0.78 for 10 mm Hg increase, p = 0.005) were independent predictors of falls during one year of follow-up. CONCLUSIONS: Lower standing SBP, even within normotensive ranges, was an independent predictor of falls in the community-dwelling elderly. Elderly women with a history of falls and with lower SBP levels should have more attention paid to the prevention of falls and related accidents.

Attrition in an exercise intervention: a comparison of early and later dropouts.

OBJECTIVE: To identify reasons for dropout and factors that may predict dropout from an exercise intervention aimed at improving physical function in frail older persons. DESIGN/SETTING: An 18-month randomized controlled intervention in a community setting. The intervention comprised 2 groups: class-based and self-paced exercise. PARTICIPANTS: 155 community-dwelling older persons, mean age 77.4, with mildly to moderately compromised mobility. MEASUREMENTS: The primary outcome measure was dropout. Dropouts were grouped as: D0, dropout between baseline and 3-month assessment, and D3, dropout after 3-month assessment. MEASUREMENTS: Measurements of demographics, health, and physical performance included self-rated health, SF-36, disease burden, adverse events, PPT-8, MacArthur battery, 6-minute walk, and gait velocity. RESULTS: There were 56 dropouts (36%), 31 in first 3 months. Compared with retained subjects (R), the D0 group had greater disease burden (P = .011), worse self-perceived physical health (P = .014), slower usual gait speed (P = .001), and walked a shorter distance over 6 minutes (P<.001). No differences were found between R and D3. Multinomial logistic regression showed 6-minute walk (P<.001) and usual gait velocity (P<.001) were the strongest independent predictors of dropout. Controlling for all other variables, adverse events after randomization and 6-minute walk distance were the strongest independent predictors of dropout, and self-paced exercise assignment increased the risk of dropout. CONCLUSIONS: We observed baseline differences between early dropouts and retained subjects in disease burden, physical function, and endurance, suggesting that these factors at baseline may predict dropout. Improved understanding of factors that lead to and predict dropout could allow researchers to identify subjects at risk of dropout before randomization. Assigning targeted retention techniques in accordance with these factors could result in decreased attrition in future studies. Therefore, the results of selective attrition of frailer subjects, such as decreased heterogeneity, restricted generalizability of study findings, and limited understanding of exercise effects in this population, would be avoided.

Childhood-onset spinocerebellar syndrome associated with massive polyglucosan body deposition.

INTRODUCTION: Polyglucosan body disease (PBD) is a progressive neurological disorder beginning in adult life and associated pathologically with widespread accumulation of polyglucosan bodies (PB) in neuronal and astrocytic processes. We report the unique clinicopathological findings in an early onset spinocerebellar syndrome associated with massive PB deposition. PATIENT & METHODS: A 14-month-old male developed a slowly progressive neurological disorder characterized by distally predominant weakness and sensory loss, urinary bladder incontinence, and cerebellar signs. He died at age 62 years from pneumonia. We report the clinical and autopsy findings. RESULTS: The autopsy findings were remarkable for diffuse cortical and cerebellar atrophy, diffuse neuronal loss and gliosis, and massive accumulations of PB within neuronal and astrocytic processes. CONCLUSION: PBD may begin in childhood.

A cross-sectional validation study of the FICSIT common data base static balance measures. Frailty and Injuries: Cooperative Studies of Intervention Techniques.

BACKGROUND: Two simple balance scales comprising three or four familiar tests of static balance were developed, and their validity and reliability are described. The scales were such that the relative difficulties of the basic tests were taken into consideration. METHODS: Using FICSIT data, Fisher's method was used to construct scales combining ability to maintain balance in parallel, semi-tandem, tandem, and one-legged stances. Reliability was inferred from the stability of the measure over 3-4 months. Construct validity was assessed by cross-sectional correlations. RESULTS: Test-retest reliability (over 3-4 months) was good (r = .66). Validity of the FICSIT-3 scale was suggested by its low correlation with age, its moderate to high correlations with physical function measures, and three balance assessment systems. The FICSIT-4 scale discriminated balance over a wide range of health status; the three-test scale had a substantial ceiling effect in community samples. CONCLUSION: A balance scale was developed that appears to have acceptable reliability, validity, and discriminant ability.

Dynamic balance in older persons: effects of reduced visual and proprioceptive input.

BACKGROUND: Understanding the motor and sensory contributions to balance function in older persons is important in order to design effective interventions to prevent falls and loss of mobility. We tested the contributions of visual and proprioceptive input, muscle strength, and age to balance performance in 110 subjects free of clinical evidence of neurologic disease (mean age 80 years). METHODS: The EquiTest Sensory Organization Test was used to present sequential conditions that altered sensory input in a 2 (tactile/proprioceptive input) x 3 (visual input) design. Center of force and shear force data were recorded from the platform; the primary outcomes were loss of balance (LOB) and anterior-posterior center of force (COF) displacement as a proportion of foot length (COFD). RESULTS: Subjects had 3.5 +/- 2.7 LOB during testing. Reduction of vision input increased the odds ratio of a LOB 5.7 fold (3.9, 8.4, 95% CI) in unstable surface conditions, but adaptation with repeated trials was substantial. The adjusted odds ratio of a LOB was 0.65 and 0.45 in the second and third trials, respectively, compared to the first. Muscle strength and age were independent predictors of LOB. Gait velocity, single stance balance, and reported difficulty with ambulation, mobility, and instrumental activities of daily living were also associated with LOB. CONCLUSIONS: Performance on clinical tests of strength, balance, and gait was associated with performance on a challenging balance test which reduced sensory input and effectiveness of motor responses. Adaptation to challenging balance conditions was substantial in this group of older subjects, but was diminished in the oldest subjects.

Effects of resistive and balance exercises on isokinetic strength in older persons.

OBJECTIVE: To determine the safety and efficacy of 3 months of resistive training of multiple lower extremity muscle groups compared with balance training in persons over 75 years. DESIGN: Randomized 3-month clinical trial. Subjects (n = 110, mean age 80) were randomized to 4 groups in a 2 x 2 design (control, resistive, balance, combined resistive/balance). INTERVENTIONS: Resistive training involved knee extension and flexion, hip abduction and extension, and plantar and dorsiflexion using simple resistive machines and sandbags. Balance training consisted of exercises to improve postural control. The control group attended 5 health-related discussion sessions. MEASUREMENTS: Summed isokinetic moments (N m) of 8 leg movements: hip, knee and ankle flexion/extension, and hip abduction/adduction. Secondary outcomes were gait velocity and chair rise time. MAIN RESULTS: Summed peak moment increased in both resistive exercise-trained groups (13% increase in the resistive group and 21% in the combined training group, P < 0.001). The effect of resistance training was significant (MANOVA F = 21.1, P < 0.001), but balance training did not improve strength, and there was no interaction (positive or negative) between balance and resistive training. Maximal gait velocity and chair rise time did not improve. Eleven subjects (20%) had musculoskeletal complaints related to resistive training, but all were able to complete the program with modifications. CONCLUSION: Resistive training using simple equipment is an effective and acceptable method to increase overall leg strength in older persons. Resistive or balance training did not improve maximal gait velocity or chair rise time in this sample of relatively healthy older persons.

Antemortem diagnosis of diffuse Lewy body disease.

Using the presence of widespread cortical Lewy bodies (LB) as the pathologic criteria of diffuse Lewy body disease (DLBD), we describe serial neurologic and mental status examinations in 6 patients with DLBD, 3 patients with Alzheimer's disease (AD), and 1 patient with Parkinson's disease (PD). The 6 patients with DLBD included 3 with neocortical neurofibrillary tangles (NFT) consistent with coincident AD. Most patients with DLBD had gait impairment concurrent with mild to moderate dementia. Abnormalities of tone or resting tremor were also prominent early symptoms in the subjects with DLBD, but not AD. Patients with DLBD frequently had abnormal EEGs with background posterior slowing and a frontally dominant burst pattern at the time of mild to moderate dementia. Agitation, hallucinations, and delusions were frequent early symptoms in DLBD patients. Patients with DLBD without concomitant AD had numerous Alz-50 negative cortical plaques. Patients with DLBD have a distinct clinical syndrome that can be differentiated from AD. Pathologic features, including the absence of Alz-50 immunoreactivity, also differentiate DLBD from AD.

Functional neuroanatomic mapping of the rat striatum: regional differences in glucose utilization in normal controls and after treatment with apomorphine.

Glucose utilization was measured in 5 regions of rat striatum within four anterior-posterior levels. Areas of minimal and maximal glucose utilization were identified. Density-window image analysis was used to quantify areas of minimal and maximal glucose utilization, which were also apparent upon close visual inspection. In a normal control group, there were substantial regional variations in striatal glucose utilization (e.g. dorsal vs ventral; dorsomedial vs dorsolateral), revealing a detailed pattern, previously unavailable, which served as a baseline to study the effect of systemic apomorphine. The highest levels of glucose utilization were in small islands 0.01-0.25 mm2, and in what appeared to be dense clusters of islands that formed larger zones. Apomorphine treatment decreased glucose utilization in dorsomedial regions, increased it in a ventromedial region, and did not change it in others. The findings emphasize the importance of regional analysis of striatum in functional and physiological studies, and provide a new baseline for analyses of striatal glucose utilization in studies of development and aging, drug effects, external stimuli, and rat models of movement disorders.

The relationship of knee and ankle weakness to falls in nursing home residents: an isokinetic study.

The strength of the knees and ankles of a group of nursing home residents with a history of falls was compared to age-matched controls. Peak torque (PT) and power (POW) were recorded at two limb velocities (60 degrees/s and 120 degrees/s) on a Cybex II Isokinetic dynamometer for four muscle groups: knee extensors, knee flexors, ankle plantar flexors and ankle dorsiflexors. The PT and POW of fallers were significantly decreased for all four muscle groups in comparison to controls, with the ankles showing the greatest decrements. Although POW in fallers was significantly lower at the higher velocity in both joints, the decrease was most prominent in the ankles. Dorsiflexion POW production in fallers was the most affected of all the motions (7.5 times less than the control value). At the higher, more functional limb velocities, ankle weakness particularly involving the dorsiflexors appears to be an important factor underlying poor balance.

Stressing the postural response. A quantitative method for testing balance.

Using a series of graded destabilizing forces, we have developed a simple quantitative test of the postural response: the Postural Stress Test (PST). Suitable for widespread testing of elderly subjects, the test evaluates the subject's ability to avoid a fall as well as the appropriateness of the response. We have determined that by comparison with young subjects, the elderly controls have compromised although functionally effective balance. On the other hand, the balance response was severely compromised in half of the individuals with a history of falls. Experience with the Postural Stress Test suggests it will predict those elderly individuals with a tendency to fall as well as provide a simple mechanism for studying the balance response in the elderly.

Serotonin models of myoclonus in the guinea pig and rat.

Myoclonus could not be induced in rats with either L-5-HTP alone or hypoxia. Following amine depletion or destruction of the serotonin neurons with 5,7-DHT, myoclonus appeared as part of a complex serotonergic behavioral syndrome induced by serotonin agonists. On the other hand, in the guinea pig, L-5-HTP induces a pure myoclonic syndrome in a dose-dependent fashion. Myoclonus also was induced by injection of serotonin into the dorsal pons of the guinea pig. This is additional evidence confirming the importance of the brainstem structures in the L-5-HTP guinea pig model of myoclonus. Deoxyglucose (DG) autoradiography in guinea pigs following systemic L-5-HTP administration demonstrated increased glucose metabolism within thalamic and third nerve nuclei, with decreased metabolism in the cortex, and the molecular layer of the hippocampus. Since serotonin is an inhibitory transmitter, we hypothesize that the decreases observed in cortex may be the result of direct serotonergic inhibition, whereas the increases observed in the thalamus probably represent indirect effects via polysynaptic pathways.

Alterations of regional cerebral blood flow and oxygen metabolism in Parkinson's disease.

Regional cerebral blood flow (rCBF) and oxygen metabolism (rCMRO2) were determined in six normals, six unilateral Parkinson's disease (PD) patients, and eight bilateral PD patients. In the unilateral patients, rCBF and rCMRO2 in the basal ganglia contralateral to the symptomatic limbs was 13% higher than on the other side (p less than 0.01); in the frontal cortex it was 8% lower than the other side, suggesting abnormal neuronal function in both regions. The bilateral PD patients had a widespread decrease (20%) in rCBF unaccompanied by comparable changes in rCMRO2, suggesting vasoconstriction due to loss of dopaminergic innervation of blood vessels in more advanced PD patients.

Gait and balance in the elderly. Two functional capacities that link sensory and motor ability to falls.

Neuromuscular function, which underlies efficient gait and balance, deteriorates with age and disease. A review of the literature and of data from the current study suggests the presence of poor gait and balance in elderly individuals who have a history of multiple falls. The tests of gait and balance are simple to perform and therefore may be widely applicable in evaluating individuals at risk of falls. Quantitative studies of motor and sensory function, vibratory sensation, and electrophysiologic studies of nerve integrity are discussed. Deteriorating motor and sensory control mechanisms appear to play an important role in falling.

Decreased ventricular fluid norepinephrine metabolite in childhood-onset dystonia.

3-methoxy-4-hydroxyphenylglycol (MHPG), the primary brain metabolite of norepinephrine (NE), was measured in ventricular fluid from 51 patients with dystonia, other movement disorders, or hydrocephalus. The dystonic patients were divided into three categories: childhood-onset form with early limb dystonia and rapid progression to generalized symptoms, more localized and benign adult-onset dystonia, and symptomatic dystonia. Patients with the childhood form had significantly lower ventricular fluid MHPG levels (8.7 +/- 0.6 ng per milliliter) than other dystonic patients (11.4 +/- 1 ng per milliliter), age-matched controls with neurologic disease (11.7 +/- 1.1 ng per milliliter), or other movement disorders (11.8 +/- 0.7 ng per milliliter). Decreased ventricular fluid MHPG levels suggest a possible abnormality of brain NE function in childhood dystonia.

A dopamine-sensitive striatal efferent system mapped with [14C]deoxyglucose in the rat.

Rats which had exhibited contralateral rotation following unilateral injection of dopamine (DA) through a striatal cannula were given 0.5 - 50 micrograms DA intrastriatally and then were injected with [14C]deoxyglucose peripherally to measure glucose utilization in the striatum and its projection nuclei. Quantitative autoradiographic techniques were used to measure glucose utilization. Brain areas which showed L-R asymmetries and changes in glucose utilization different from vehicle-injected animals were: the substantia nigra (pars compacta and pars reticulata), the subthalamic n., entopeduncular n., lateral habenula, and deep layers of the superior colliculus. The globus pallidus was affected also, but only in one group for which the injected DA may have spread and affected it directly. Each of these areas receives projections from the striatum or is one additional synapse away. Intrastriatal injections of norepinephrine, isoproterenol, and procaine did not produce changes in glucose utilization in the striatal projection nuclei. The results support the existence of a DA-sensitive strionigral system to both the reticulata and compacta regions of the nigra, and suggest that this activity is paralleled by a strio-subthalamic and strio-entopeduncular-habenular system. The onset of changes in glucose utilization in the entopeduncular-habenular system was later than in the strio-subthalamic and strionigral systems and correlated with the onset of rotation. However, data from 4 animals which did not rotate suggest that each of these systems is necessary but not sufficient for rotation. It is concluded that DA receptors in the striatum play a significant role in the effects of peripherally administered DA agonists on other nuclei, even though most of these other nuclei also have their own DA receptors.