Components and Indicators of Frailty Measures: A Literature Review.

BACKGROUND: Frailty is a debilitating condition in older adults that is associated with increased risks for adverse outcomes. However, the issue of quantifying frailty remains elusive. There is a lack of consistency in the frailty components and the corresponding indicators used to quantify these components. OBJECTIVE: 1) to describe the components of frailty and examine the existing measures of frailty; and 2) to identify current gaps in knowledge of frailty measures. METHODS: The PubMed, CINAHL, and Web of Science databases were searched. Each study was reviewed to determine its fit with inclusion/exclusion criteria. RESULTS: A total of 49 studies were identified and comprised the sample. Each study described one unique measure of frailty. The frailty components and corresponding indicators within three domains (physical, psychological, and social) were described. The most frequently reported components of frailty were mobility and balance, nutrition, and cognitive function. Fifteen of 49 frailty measures included components across all three domains. Current frailty measures were critiqued and important areas for future study are identified. CONCLUSIONS: The frailty components and corresponding indicators vary considerably across different frailty measures. Future studies are needed to address inconsistences in frailty measures and models.

CNTRICS final animal model task selection: control of attention.

Schizophrenia is associated with impaired attention. The top-down control of attention, defined as the ability to guide and refocus attention in accordance with internal goals and representations, was identified by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative as an important construct for task development and research. A recent CNTRICS meeting identified three tasks commonly used with rodent models as having high construct validity and promise for further development: The 5-choice serial reaction time task, the 5-choice continuous performance task, and the distractor condition sustained attention task. Here we describe their current status, including data on their neural substrates, evidence for sensitivity to neuropharmacological manipulations and genetic influences, and data from animal models of the cognitive deficits of schizophrenia. A common strength is the development of parallel human tasks to facilitate connections to the neural circuitry and drug development research done in these animal models. We conclude with recommendations for the steps needed to improve testing so that it better represents the complex biological and behavioral picture presented by schizophrenia.

Implicit memory is vulnerable to proactive interference.

We investigated the possibility that implicit memory, like explicit memory, can be disrupted by proactive interference. Participants first viewed a list of words, with nontargets in the first half of the list and targets in the second. Nontargets were either similar in structure (e.g., "ANALOGY") or unrelated (e.g., "URGENCY") to the targets (e.g., "ALLERGY"). After several filler tasks, participants completed an implicit fragment-completion test (e.g., "A_L_ _ GY") for the target items. Participants who viewed similar nontargets completed fewer fragments with target items and made more intrusions than did participants who viewed unrelated nontargets. Together with previous findings, these results suggest that similar nontargets can compete with target items to produce interference in implicit memory.

Implicit memory is not immune to interference.

Does interference, a primary source of forgetting in explicit memory, also affect implicit memory? Several early and highly influential studies have suggested that implicit memory is immune to interference. In contrast, a number of subsequent investigations have reported evidence for interference. As well, amnesic patients, whose performance relies primarily on implicit memory, often show interference effects. A review of methods, materials, and findings suggests that interference occurs on implicit tests when targets and nontargets are similar and so compete as potential responses to the memory cue. Further, there is some evidence that the degree of interference on implicit tasks is affected by the number of competing items and their strength relative to the target. Interference effects in implicit memory seem to parallel those in explicit memory, and the authors consider the implications of this conclusion for theoretical concepts of memory and the brain.

Working memory span and the role of proactive interference.

The authors investigated the possibility that working memory span tasks are influenced by interference and that interference contributes to the correlation between span and other measures. Younger and older adults received the span task either in the standard format or one designed to reduce the impact of interference with no impact on capacity demands. Participants then read and recalled a short prose passage. Reducing the amount of interference in the span task raised span scores, replicating previous results (C. P. May, L. Hasher, & M. J. Kane, 1999). The same interference-reducing manipulations that raised span substantially altered the relation between span and prose recall. These results suggest that span is influenced by interference, that age differences in span may be due to differences in the ability to overcome interference rather than to differences in capacity, and that interference plays an important role in the relation between span and other tasks.

Paying attention to time as one gets older.

Age-related changes in attention and interval timing as a function of time of day were examined using a temporal bisection task with single and compound auditory and visual stimuli. Half of the participants in each age group were tested in the morning, and half were tested in the afternoon. Duration judgments were found to be shorter for visual signals than for auditory signals. This discrepancy was greater in the morning than in the afternoon and larger for the older than for the younger adults. Young adults showed equal sensitivity to signal duration for single and compound trials and higher sensitivity in the afternoon than in the morning for both signal modalities. In contrast, older adults showed impaired sensitivity on compound trials and the greatest sensitivity overall to single visual trials in the morning. These results suggest that age-related reductions in attentional resources may cause older adults to focus on signals that require controlled attention during specific phases of the circadian cycle.

Sequencing of behaviors in Aplysia fasciata: integration of feeding, reproduction, and locomotion.

To begin studying the neural basis of higher-order decision-making in Aplysia fasciata, we examined individual bouts of behavior in various conditions of access to food and/or mates. We then determined rules governing transitions between bouts. The data indicate that a single intermediate condition, moving in place, may be centrally related to transitions between behaviors. In all conditions, over 85% of all transitions between behaviors were via moving in place. Moving in place tended to precede and follow other categories of activity (crawling, swimming, immobile), and feeding. Also, moving in place apparently represents a fixed proportion of all bouts of behavior. In each condition, moving in place represented approximately 40% of all bouts, while the number of bouts of other behaviors varied markedly. After a bout of moving in place there was a strong tendency for the animal to return to the behavior performed before moving in place. Additional preferred sequences of behavior were also seen. Courtship tended to precede mating, and crawling preceded swimming.

Effects of food and mates on time budget in Aplysia fasciata: integration of feeding, reproduction, and locomotion.

This study examines the time budgeted to different behaviors in Aplysia fasciata under three conditions: (1) animals have constant access to food and mates: (2) there is access to food, but not to mates; (3) neither food nor mates are present. The data suggest a number of rules underlying behavioral integration: (1) Feeding, reproductive behaviors, and activity seem to be natural categories for behavioral choice. Feeding and reproductive behaviors are controlled in tandem by a common arousal mechanism, while time left over after animals feed and reproduce is distributed in a fixed ratio between locomotion (crawling and swimming) and inactivity (immobility and movement in place). (2) Relative distribution between different forms of locomotion and inactivity is modified by changes in motivational state. More time is spent swimming than crawling when feeding and/or mating is prevented, while more time is spent moving in place than immobile when the arousal level is increased. (3) Feedback control of feeding and reproduction is asymmetric. Satiation of feeding inhibits the common arousal. In the absence of food, time spent on reproductive behaviors increases due to disinhibition of the common arousal. By contrast, positive feedback arising from sexual behavior excites the common arousal. When mating is prevented by removing potential mates, time spent feeding decreases. (4) Generally, animals choose between performing the three main categories of behavior. Although Aplysia simultaneously can feed and mate, or locomote and mate, they do so infrequently. By contrast, different types of reproductive behaviors (male mating, female mating, egg-laying) are commonly performed simultaneously.

Daily variation of multiple behaviors in Aplysia fasciata: integration of feeding, reproduction, and locomotion.

Daily variations in feeding, reproductive behaviors, and activity level were examined under three conditions: (1) animals had access to food and mates; (2) there was access only to food; (3) neither food nor mates were present. Behaviors differed in amplitude of variations from their daily mean value. Egg-laying had the strongest tendency to be clustered. Amplitude of variations in courtship and swimming was larger than those of immobility, crawling, and feeding, while moving in place was the least clustered behavior. Changes in state affected the tendency to be clustered. When food and mates were present, amplitude of variations became progressively larger for immobility, moving in place, crawling, and swimming. Behaviors differed in the degree to which variations were patterned as a 1/day oscillation. Relatively little of the variability in crawling, moving in place, courtship, and egg-laying was due to a 1/day oscillation under any condition. By contrast, a large proportion of the variability of immobility, swimming, mating, and eating was modulated by a 1/day oscillation in at least one condition. The contribution of a 1/day oscillation to variability differed in the conditions examined. For immobility and swimming, when food and mates were present, the 1/day component of variability became smaller. By contrast, presence of mates led to an increase in the 1/day component of variability modulating feeding. Daily peaks of swimming and feeding were in phase with one another, and out of phase with mating and feeding. The ratio of locomotion to inactivity is constant, independent of change in external conditions. However, this ratio varied throughout the day. When food and mates were absent, variations of immobility and swimming were strongly related to variations in the inactivity ratio. When food and mates were added, this tendency decreased. The data suggest that daily variations in occurrence of behaviors can be accounted for by interactions between oscillators affecting Aplysia behavior and motivational variables. A 1/day oscillator has strong effects on mating, swimming, and immobility. The effect of the oscillator is modified by changes in motivational state.

Release kinetics as a tool to describe drug effects on neurotransmitter release.

A procedure is developed wherein the time course of neurotransmitter release is used to discern the mechanism of effects of drugs on the release process. It is shown, in agreement with experiments, that the time course of release is insensitive to the temporal distribution of intracellular Ca2+ concentration. The time course is also invariant to the steps in the release process that are Ca2+ dependent. The most influential events in determining the time course of release are shown to be the steps associated with the slowest forward rate constant and all the backward steps. The procedure was examined for its ability to explain the effects on release of the poison curare and those of temperature. It appears that curare probably blocks release by lowering the rate constant associated with the rate limiting step in release. Increasing temperature is predicted to increase both the forward and the backward rate constants, but not to the same extent.

Neurotransmitter release: development of a theory for total release based on kinetics.

According to the calcium-voltage hypothesis for the control of neurotransmitter release, a molecule (or molecular complex) must be activated by membrane depolarization, after which the activated molecule can bind calcium and initiate release. In this study, we have examined properties of the kinetics of phasic release resulting from a set of differential equations that characterize the calcium-voltage hypothesis. It was found that, in accord with experiments, an important feature is the approximate constancy of the shape of the graph for the kinetics of phasic release at various depolarizations and extracellular calcium concentrations. The shape constancy allowed us to obtain an explicit and relatively simple analytical formula for the total transmitter release (quantal content) by approximating the differential equations of the model. This formula shows a saturating sigmoidal dependence on both intracellular and extracellular calcium concentrations. The formula thus agrees with various experiments. Moreover, it agrees with, and provides meaning to, earlier phenomenological expressions for the dependence of release on calcium concentration. In particular, the formula provides an expression for the maximal release in terms of kinetic parameters from the calcium-voltage model, and thereby allows one to supplement earlier kinetic tests of the calcium-voltage hypothesis with further tests focused upon the dependence of total release on depolarization.

On the quantal hypothesis of neurotransmitter release: an explanation for the calcium dependence of the binomial parameters.

Results for quantal neurotransmitter release can be explained by assuming a binomial distribution with a population of N elements each with a probability p to release a quantum in a given trial. The binomial parameter N was unexpectedly observed to depend on external calcium concentration and (to a lesser extent) on the frequency of stimulation. This observation is explained here by the hypothesis that the release population is not homogeneous. It is shown that the same hypothesis can also account for other experimental findings. A possible cause for this inhomogeneity is suggested.

High-resolution magnetic field measurement system for recording heads and disks.

A high-resolution system for measuring the magnetic fields near recording heads and disks has been built. The perpendicular field components close to the head and disk surfaces are measured with an InSb Hall probe which is moved point-by-point under computer control. The computer also records the magnetic field strength as a function of position in a plane parallel to the head or disk surface. The active area of the probe is 2x2 microm and a roughly 1-microm separation between the probe and the surfaces being measured can be obtained. Measurements of the fields near transitions on a particulate disk and near the gap in in a ferrite recording head are presented and compared with calculated field distributions.