Arnold B. Mitnitski

Accumulation of deficits as a proxy measure of aging.

This paper develops a method for appraising health status in elderly people. A frailty index was defined as the proportion of accumulated deficits (symptoms, signs, functional impairments, and laboratory abnormalities). It serves as an individual state variable, reflecting severity of illness and proximity to death. In a representative database of elderly Canadians we found that deficits accumulated at 3% per year, and show a gamma distribution, typical for systems with redundant components that can be used in case of failure of a given subsystem. Of note, the slope of the index is insensitive to the individual nature of the deficits, and serves as an important prognostic factor for life expectancy. The formula for estimating an individuals life span given the frailty index value is presented. For different patterns of cognitive impairments the average within-group index value increases with the severity of the cognitive impairment, and the relative variability of the index is significantly reduced. Finally, the statistical distribution of the frailty index sharply differs between well groups (gamma distribution) and morbid groups (normal distribution). This pattern reflects an increase in uncompensated deficits in impaired organisms, which would lead to illness of various etiologies, and ultimately to increased mortality. The accumulation of deficits is as an example of a macroscopic variable, i.e., one that reflects general properties of aging at the level of the whole organism rather than any given functional deficiency. In consequence, we propose that it may be used as a proxy measure of aging.

Frailty, fitness and late-life mortality in relation to chronological and biological age

BackgroundPeople age at remarkably different rates, but how to estimate trajectories of senescence is controversial.MethodsIn a secondary analysis of a representative cohort of Canadians aged 65 and over (n = 2914) we estimated a frailty index based on the proportion of 20 deficits observed in a structured clinical examination. The construct validity of the index was examined through its relationship to chronological age (CA). The criterion validity was examined in its ability to predict mortality, and in relation to other predictions about aging. From the frailty index, relative (to CA) fitness and frailty were estimated, as was an individuals biological age.ResultsThe average value of the frailty index increased with age in a log-linear relationship (r = 0.91; p < 0.001). In a Cox regression analysis, biological age was significantly more highly associated with death than chronological age. The average increase in the frailty index (i.e. the average accumulation of deficits) amongst those with no cognitive impairment was 3 per cent per year.ConclusionsThe frailty index is a sensitive predictor of survival. As the index includes items not traditionally related to adverse health outcomes, the finding is compatible with a view of frailty as the failure to integrate the complex responses required to maintain function.

Interjoint coordination dynamics during reaching in stroke

A technique is described that characterizes the dynamics of the interjoint coordination of arm reaching movements in healthy subjects (n=10) and in patients who had sustained a left-sided cerebrovascular accident (n=18). All participants were right-handed. Data from the affected right arm of patients with stroke were compared with those from the right arm of healthy subjects. Seated subjects made 25 pointing movements in a single session. Movements were made from an initial target located ipsilaterally to the right arm beside the body, to a final target located in front of the subject in the contralateral arm workspace. Kinematic data from the finger, wrist, elbow, both shoulders and sternum were recorded in three dimensions at 200xa0Hz with an optical tracking system. Analysis of interjoint coordination was based on the patterns of temporal delay between rotations at two adjacent joints (shoulder and elbow). The data were reduced to a single graph (Temporal Coordination or TC index) integrating the essential temporal characteristics of joint movement (the angular displacements, velocities and timing). TC segments, duration and amplitude, were analysed. The analysis was sensitive to the differences in interjoint coordination between healthy subjects and patients with arm motor deficits. In patients, the temporal coordination between elbow and shoulder movements was disrupted from the middle to the end of the reach. More specifically, in mid-reach, all patients had difficulty coordinating elbow flexion with shoulder horizontal adduction. In addition, patients with severe arm hemiparesis had difficulty changing elbow movement direction from flexion to extension and in coordinating this change with shoulder movement. At the end of the reach, patients with severe hemiparesis had deficits in the execution of elbow extension while all patients had impaired coordination of elbow extension and shoulder horizontal adduction. In addition, active ranges of joint motions were significantly decreased in the stroke compared to the healthy subjects. Finally, TC analysis revealed significant relationships between specific aspects of disrupted interjoint coordination and the level of motor impairment, suggesting that it may be a useful tool in the identification of specific movement coordination deficits in neurological impaired populations that can be targeted in treatment for arm motor recovery.

Superposition of independent units of coordination during pointing movements involving the trunk with and without visual feedback.

Abstract. Previous studies addressing the problem of the control of multiple degrees of freedom have examined the influence of trunk movement on pointing movements within the arms reach. Such movements may be controlled by two functionally independent units of coordination (synergies): one involving only arm joints and producing the hand trajectory to the target (the transport synergy), and the other coordinating trunk and arm movements leaving the hand trajectory unchanged (the compensatory synergy). The question of whether or not this functional subdivision depends on visual feedback was addressed in the present study. We also tested whether or not the motor effects of different synergies are summated as independent components, a control strategy called superposition. Finally, we investigated whether or not the relationship between different degrees of freedom within each synergy could be considered linear resulting in proportional changes in different joint angles. Seated subjects produced fast, uncorrected arm movements to an ipsi- or a contralateral target in the direction of ±45° to the sagittal midline of the trunk. Targets could be reached using the arm alone (control trials) or by combining the arm motion with a forward or backward trunk motion produced by hip flexion or extension (test trials), with and without visual feedback. The shape of the hand trajectory, its direction and tangential velocity, movement precision, joint angles and the sequence of the trunk and hand recruitment and de-recruitment were measured. In both visual conditions, the direction of the hand trajectory observed in control trials was generally preserved in test trials. In terms of sequencing, even in the absence of vision, the trunk movement was initiated before the onset of and outlasted the hand shift, indicating that the potential influence of the trunk on the hand movement was compensated by rotations in the elbow and shoulder joint. The analysis of other variables also implied that the effects of trunk recruitment on the hand trajectory were minor compared to those which could be observed if these effects were not compensated by appropriate changes in the arm joint angles. It was concluded that an arm-trunk compensatory synergy is present in pointing movements regardless of visual feedback. Principal component analysis showed that the relationship between elbow, shoulder and hip joint angles in individual arm and combined arm-trunk movements cannot be considered linear, implying that this relationship is adjusted according to the changing arm geometry. The changes in each arm joint angle (elbow, shoulder) elicited by a forward trunk bending in one block of trials were compared with those elicited by a backward bending in another block, whereas the hand moved to the same target in both blocks. These changes were opposite but of similar magnitude. As a result, for each moment of movement, the mean joint angle obtained by averaging across two directions of trunk motion was practically identical to that in control trials in which the trunk was motionless. It is concluded that the transport and arm-trunk compensatory synergies are combined as independent units, according to the principle of superposition. This principle may simplify the control of the coordination of a redundant number of degrees of freedom.

Coordination between the lumbar spine lordosis and trunk angle during weight lifting

OBJECTIVE: To analyze the coordination of the lumbo-sacral angle (lumbar spine lordosis) and the trunk inclination during lifting of different loads. STUDY DESIGN: Kinematic data of spine motion were analyzed. The parameters characterizing the relationships between the lordosis and the trunk inclination angle were estimated. BACKGROUND: The shape of the spine has been analyzed mostly for static or quasi-static conditions. The parameters relating the lumbar spine lordosis and trunk inclination in dynamics have not been analyzed. METHODS: Healthy subjects performed unconstrained weight lifts from ground to mid-thigh level. Kinematic data were derived from the tracking of markers (light-emitted diodes) placed over the spine and pelvis using an OPTPTRAK system. The relationship between lordosis and trunk inclination was analyzed. RESULTS: The relationship between lumbar spine curvature (lumbo-sacral angle or lordosis) and trunk inclination during weight lifting was described by an exponential function with three parameters. These were the lordosis extremes associated with the horizontal and vertical positions of the trunk and the trunk inclination when lordosis equals zero. The absolute value of the lordosis angle decreases at the onset of the extension phase of lifting when the load increases, implying active reaction of musculosceletal system to increasing load. CONCLUSIONS: The changes in the lordosis and trunk inclination are strictly correlated implying that the nervous system actively coordinates the degrees of freedom of the spine, providing an inter-joint synergy.

Aging as a Process of Deficit Accumulation: Its Utility and Origin

Individuals of the same age differ greatly with respect to their health status and life span. We have suggested that the health status of individuals can be represented by the number of health deficits that they accumulate during their life. We have suggested that this can be measured by a fitness-frailty index (or just a frailty index), which is the ratio of the deficits present in a person to the total number of deficits considered (e.g. available in a given database or experimental procedure). Further, we have proposed that the frailty index represents the biological age of the individual, and suggested an algorithm for its estimation. In investigations by many groups, the frailty index has shown reproducible properties such as: age-specific, nonlinear increase, higher values in women, strong association with mortality and other adverse outcomes, and universal limit to its increase. At the level of individual, the frailty index shows complex stochastic dynamics, reflecting both stochasticity of the environment and the ability to recover from various illnesses. Most recently, we have proposed that the origin of deficit accumulation lies in the interaction between the environment, the organism and its ability to recover. We apply a stochastic dynamics framework to illustrate that the average recovery time increases with age, mimicking the age-associated increase in deficit accumulation.

Symptoms and Signs in Dementia Synergy and Antagonism

This paper addresses the synergy and antagonism between symptoms and signs among 2,914 elderly Canadians diagnosed in 15 categories, including no cognitive impairment, cognitive impairment but no dementia, mild, moderate and severe forms of Alzheimers disease and vascular dementia, 4 subtypes of possible Alzheimers disease, Parkinsons dementia, unspecified other dementias and unclassified dementias Attention is paid to the relationships between symptoms and signs rather than conventional analyses which assume independent signs. We demonstrate that dementia progression and specific aetiologies have characteristic patterns of decline and destruction from the strong synergy that exists between symptoms and signs among the population with no cognitive impairment. These findings have potential implications for the incorporation of new diagnostic criteria into existing databases.

An Algorithmic Approach to the Differential Diagnosis of Dementia

The careful definition of cases is fundamental to diagnosis and to any study of cognitive, behavioural and functional problems in dementia. This paper presents an algorithmic approach which mimics a crucial component of diagnostic decision-making; symptoms and signs do not occur independently, but are conditioned on each other. First, we examine whether the conditioned items can be assembled to yield a differential diagnosis of dementia which corresponds to clinical diagnoses, and second, we explore whether subjects whose algorithmic profiles do not fit the clinical diagnoses form new discernable patterns. Such a technique offers two advantages: it allows for the development of validation protocols which are crucial to epidemiological studies, and it allows for the analysis of new patterns of signs and symptoms for emerging criteria of dementia subtypes. This approach has the potential to refine and enhance criteria for the differential diagnosis of dementia and to have an impact on case identification and assessment, particularly in large epidemiologic studies.