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T M Gill

Publications and source records attributed to T M Gill.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cognitive correlates of single neuron activity in task-performing animals: application to ethanol research.

The deleterious effects of ethanol on cognitive processes result from an interaction between ethanol and the neural structures that are critical for executing those cognitive functions. Results from studies that employ contemporary behavioral neuroscience techniques are beginning to elucidate the neural circuits that underlie specific cognitive processes, and the stage is set for rigorous investigations into the neural basis for ethanol-induced cognitive impairments. In this article, the application of single neuron recording techniques to the study of the memory and attentional deficits produced by acute exposure to low levels of ethanol are described, with an emphasis on the advantages of combining physiological techniques with operant behavioral procedures in rats. After reviewing background information on the basic neurophysiological and behavioral techniques, empirical results from this laboratory will be used to illustrate how single-unit analysis can be applied to the study of ethanol-induced cognitive impairments.

Alcoholism↗
PubMed1997

Hippocampal N-methyl-D-aspartate and kainate binding in response to entorhinal cortex aspiration or 192 IgG-saporin lesions of the basal forebrain.

Lesion models in the rat were used to examine the effects of removing innervation of the hippocampal formation on glutamate receptor binding in that system. Bilateral aspiration of the entorhinal cortex was used to remove the cortical innervation of the hippocampal formation and the dentate gyrus. The subcortical input to the hippocampus from cholinergic neurons of the basal forebrain was lesioned by microinjection of the immunotoxin 192 IgG-saporin into the medial septum and vertical limb of diagonal band. After a 30-day postlesion survival, the effects of these lesions on N-methyl-D-aspartate-displaceable [3H]glutamate and [3H]kainate binding in the hippocampus were quantified using in vitro autoradiography. The bilateral entorhinal lesion induced a sprouting response in the dentate gyrus, measured by an increase in the width of [3H]kainate binding. It also induced an increase in the density of [3H]kainate binding in CA3 stratum lucidum and an increase in N-methyl-D-aspartate binding throughout the hippocampus proper and the dentate gyrus. The selective lesion of cholinergic septal input did not have any effect on hippocampal [3H]kainate binding and induced only a moderate decrease in N-methyl-D-aspartate binding that was not statistically reliable. The entorhinal and cholinergic lesions were used as in vivo models of the degeneration of hippocampal input that occurs in normal aging and Alzheimer's disease. The results from the present lesion study suggest that some, but not all, of the effects on hippocampal [3H]kainate and N-methyl-D-aspartate binding induced by the lesions are consistent with the status of binding to these receptors in aging and Alzheimer's disease. Consistent with the effects of aging and Alzheimer's disease is an altered topography of [3H]kainate binding after entorhinal cortex lesion and a modest decline in N-methyl-D-aspartate binding after lesions of the cholinergic septal input to the hippocampus.

Acetylcholinesterase↗
PubMed1997

The role of change in physical performance in determining risk for dependence in activities of daily living among nondisabled community-living elderly persons.

Among community-living elderly persons, a single assessment of physical performance is a powerful predictor of dependence in activities of daily living (ADLs). The aim of this study was to determine whether an assessment of change in physical performance provides useful prognostic information beyond that available from a single assessment. Among a large representative cohort of elderly persons, we evaluated the 586 participants who were ADL independent at both the baseline and the one year interviews. For each of the three timed tests, participants who had a large decline in physical performance were significantly more likely to develop ADL dependence at three years than those who improved or showed no change. After adjusting for 1-year scores, however, change in physical performance was no longer associated with ADL dependence. However, among the 775 participants who were ADL independent at the baseline interview, change in physical performance was significantly associated with the onset of ADL dependence at one year, even after adjusting for baseline performance. When determining risk for ADL dependence, an assessment of change in physical performance over one year does not provide useful prognostic information beyond that available from a single assessment. Nevertheless, change in physical performance is independently associated with concurrent ADL dependence and may be useful in predicting future disability if measured over shorter intervals.

Activities of Daily Living↗
PubMed1997

Predictors of recovery in activities of daily living among disabled older persons living in the community.

OBJECTIVE: To identify the factors that predict recovery in activities of daily living (ADLs) among disabled older persons living in the community. DESIGN: Prospective cohort study with 2-year follow-up. SETTING: General community. PARTICIPANTS: 213 men and women 72 years or older, who reported dependence in one or more ADLs. MEASUREMENTS AND MAIN RESULTS: All participants underwent a comprehensive home assessment and were followed for recovery of ADL function, defined as requiring no personal assistance in any of the ADLs within 2 years. Fifty-nine participants (28%) recovered independent ADL function. Compared with those older than 85 years, participants aged 85 years or younger were more than 8 times as likely to recover their ADL function (relative risk [RR] 8.4; 95% confidence interval [CI] 2.7, 26). Several factors besides age were associated with ADL recovery in bivariate analysis, including disability in only one ADL, self-efficacy score greater than 75, Folstein Mini-Mental State Examination (MMSE) score of 28 or better, high mobility, score in the best third of timed physical performance, fewer than five medications, and good nutritional status. In multivariable analysis, four factors were independently associated with ADL recovery-age 85 years or younger (adjusted RR 4.1; 95% CI 1.3, 13), MMSE score of 28 or better (RR 1.7; 95% CI 1.2, 2.3), high mobility (RR 1.7; 95% CI 1.0, 2.9), and good nutritional status (RR 1.6; 95% CI 1.0, 2.5). CONCLUSIONS: Once disabled, few persons older than 85 years recover independent ADL function. Intact cognitive function, high mobility, and good nutritional status each improve the likelihood of ADL recovery and may serve as markers of resiliency in this population.

Activities of Daily Living↗
PubMed1997

A predictive model for ADL dependence in community-living older adults based on a reduced set of cognitive status items.

OBJECTIVE: To develop and validate a simple tool, based on a reduced set of Mini-Mental State Examination (MMSE) items, that can be used to predict the onset of ADL dependence, and to compare the predictive accuracy of this new tool with that of the MMSE. DESIGN: Two prospective, population-based cohort studies, in tandem. The predictive model developed in the initial cohort was subsequently validated in a separate cohort. SETTING: General community in New Haven, Connecticut. PARTICIPANTS: For the development cohort, 775 community-living persons, 72 years of age and older, who were independent at baseline in their ADI, function. For the validation cohort, 1038 comparable subjects. MEASUREMENTS: All subjects underwent a baseline interview and cognitive assessment in their homes by a trained research nurse using standard instrument. Self-reported ADLs were ascertained at 1 year and 3 years for the development cohort and at 1 year and 21/2 years for the validation cohort. RESULTS: ADL dependence developed in 221 (28.5%) subjects in the development cohort. Although the rate of ADL dependence increased within each MMSE domain as the number of incorrect items increased, only orientation and short-term memory remained significantly associated with ADL dependence in multivariable analysis. A predictive model, based on the presence of impairments in these two domains, was developed that stratified subjects into three risk groups. Rates of ADL dependence were 22% (neither domain impaired), 44% (one domain impaired), and 68% (both domains impaired) (P < .001). The corresponding rates in the validation cohort, in which 191 (18.4%) subjects developed ADL dependence, were 15%, 26%, and 45% (P < .001). The area under the ROC curves for the MMSE and the reduced item strategy were nearly identical at 0.63 and 0.62, respectively. CONCLUSIONS: A simple and valid six-item strategy, based on the presence of impairments in orientation and short-term memory, predicts the onset of ADL dependence as effectively as does the 30-item MMSE. This new tool may be useful as part of a more comprehensive assessment when determining an older person's risk for developing ADL dependence.

Activities of Daily Living↗
PubMed1996

Alterations in opiate receptor binding in the hippocampus of aged Long-Evans rats.

Quantitative in vitro autoradiography was used to examine [3H]D-Ala2, MePhe4, Gly-015 enkephalin (DAGO) (mu-agonist) and [3H]diprenorphine (general opiate antagonist) binding sites in the hippocampal formation of young (6-8 months) and aged (25-28 months) Long-Evans rats. Age-related changes in these binding sites were restricted to specific regions but were not generally dependent on the ligand used. No reliable age-related changes in opiate binding were observed in the CA1 field or subicular region. In contrast, a decrease in the density of binding was found in both dorsal and ventral hippocampus within the CA3 field of aged brains. An age-related decrease in opiate binding within the dentate gyrus differed in its topography at dorsal and ventral levels of the hippocampus. A uniform decrease of opiate receptor binding was found throughout the dorsal dentate gyrus, while a more localized decrease of these sites occurred in hilar and granular layers of the ventral dentate gyrus. These results indicate that a decrease of opiate binding in the hippocampal formation is largely localized to the CA3 region and dentate gyrus of aged rats. These findings are discussed with reference to age-related changes in hippocampal pathways containing opioid peptides. The implications for hippocampal opioid function in learning and age-related cognitive decline are also considered.

Age Factors↗
PubMed1996

Impairments in physical performance and cognitive status as predisposing factors for functional dependence among nondisabled older persons.

BACKGROUND: Little is known about the processes underlying the development of functional dependence. We set out to determine whether impairments in physical performance and cognitive status contribute independently to the risk of functional dependence in nondisabled older persons. METHODS: Among a probability sample of 1,103 community-living adults, aged 72 years and older, we evaluated the 945 subjects who reported no disability in the activities of daily living. Subjects underwent a comprehensive assessment, including physical performance and cognitive testing. RESULTS: Among the 775 subjects alive with complete outcomes data, 221 (28.5%) developed dependence in activities of daily living at either the 1- or 3-year follow-up interview. The rates of functional dependence were 18%, 20%, 26%, and 50% (p < .001) and 18%, 23%, 31%, and 47% (p < .001), respectively, across quarters of worsening physical performance and cognitive status. Compared with subjects in the best group, those with the worst physical performance and cognitive status were more than five times as likely to develop functional dependence (67% vs 13%; p < .001). After adjustment for age, gender, number of chronic conditions, and housing stratum, the risk of functional dependence increased across quarters of both worsening physical performance (relative risks [RR] 1.0, 1.1, 1.3, 2.1) and cognitive status (RR 1.0, 1.3, 1.5, 2.0), independent of the effect of the other. Similar results were found for subjects who developed functional dependence at one year, for those who developed functional dependence at three years, and for the combined endpoint of functional dependence or death. CONCLUSIONS: Impairments in physical performance and cognitive status contribute independently to the risk of functional dependence in nondisabled, community-living older adults. A better understanding of the processes underlying functional dependence may facilitate the design of effective and efficient strategies to prevent or slow functional decline.

Activities of Daily Living↗
PubMed1995

Geriatric medicine.

A prospective study of persons older than 70 years provided evidence to contest the association between blood cholesterol level and incidence of CHD or death due to CHD. Drug treatment for mild to moderate hypertension substantially reduced morbidity and mortality from stroke and from CHD.

Geriatrics↗
PubMed1995

Shared risk factors for falls, incontinence, and functional dependence. Unifying the approach to geriatric syndromes.

OBJECTIVE: To determine whether a set of factors representing impairments in multiple areas could be identified that predisposes to falling, incontinence, and functional dependence. DESIGN: Population-based cohort with a 1-year follow-up. SETTING: General community. PARTICIPANTS: A total of 927 New Haven, Conn, residents, aged 72 years and older who completed the baseline and 1-year interviews. MAIN OUTCOME MEASURES: At least one episode of urinary incontinence per week, at least two falls during the follow-up year, and dependence on human help for one or more basic activities of daily living. RESULTS: At 1 year, urinary incontinence was reported by 16%, at least two falls by 10%, and functional dependence by 20% of participants. The four independent predisposing factors for the outcomes of incontinence, falling, and functional dependence included slow timed chair stands (lower extremity impairment), decreased arm strength (upper extremity impairment), decreased vision and hearing (sensory impairment), and either a high anxiety or depression score (affective impairment). There was a significant increase in each of incontinence, falling, and functional dependence as the number of these predisposing factors increased. For example, the proportion of participants experiencing functional dependence doubled (7% to 14% to 28% to 60%) (chi 2 = 119.8; P < .001) as the number of predisposing factors increased from zero to one to two at least three. CONCLUSIONS: Our findings suggest that predisposition to geriatric syndromes and functional dependence may result when impairments in multiple domains compromise compensatory ability. It may be possible to restore compensatory ability and prevent or delay the onset of several geriatric syndromes and, perhaps, functional dependence by modifying a shared set of predisposing factors. Perhaps it is time to take a more unified approach to the geriatric syndromes and functional dependence.

Accidental Falls↗
PubMed1995

Evaluating the efficacy of cancer screening: clinical distinctions and case-control studies.

To evaluate the efficacy of cancer screening, investigators have turned increasingly to the case-control approach as an efficient alternative design to the randomized controlled trial. Overlooked in the design and implementation of screening case-control studies, however, have been important clinical distinctions that are crucial for decisions in patient management and health policy. These distinctions involve the classification of baseline risk factors and prognostic co-morbidity, the enumeration and definition of the intervention, and the choice and timing of the outcome. When investigators neglect the distinctive characteristics of patients and their diseases, screening case-control studies may have reduced validity and impaired utility. To strengthen the validity of these studies, investigators can analyze co-morbidity suitably, report a "clinical" confidence interval as the estimate of screening efficacy, carefully evaluate the attribution of death, and allow sufficient follow-up time for the death of patients diagnosed with cancer. Moreover, to strengthen the generalizability of screening case-control studies, investigators can stratify their findings for pertinent baseline risk factors and can expand the screening definition. If implemented, these guidelines may enhance the capacity of case-control studies to provide clinicians and policy-makers with critically needed information on the efficacy of cancer screening.

Case-Control Studies↗
PubMed1995

Evaluating the risk of dependence in activities of daily living among community-living older adults with mild to moderate cognitive impairment.

BACKGROUND: Although cognitive impairment has been implicated as a risk factor for dependence in activities of daily living (ADLs), little is known about the risk of ADL dependence among older adults with cognitive impairment. METHODS: Among a representative cohort of 1,103 community-living adults aged 72 years and older, we evaluated the 237 subjects with mild to moderate cognitive impairment who were independent in their basic ADLs. All cohort members had undergone a comprehensive assessment, including a battery of qualitative and timed performance tests. RESULTS: ADL dependence developed in 31 (16%) of the 197 subjects who had complete data at the 1-year follow-up. Of the self-reported characteristics, only three--living alone, not being currently married, and having an impairment in IADL function--were significantly associated (p < .05) with the onset of ADL dependence. Several simple tests of physical performance, on the other hand, were strongly associated with the development of ADL dependence. Both timed and qualitative performance tests successfully identified subjects at risk for ADL dependence. A combination of two performance tests--rapid gait and qualitative chair stands--was particularly effective at distinguishing subjects at low (4.7%) and high (34%-39%) risk for ADL dependence. CONCLUSIONS: Among community-living older adults with mild to moderate cognitive impairment, the risk of ADL dependence is high but varies considerably depending on how well and how quickly one can perform simple tasks of everyday function. An assessment strategy based on tests of physical performance may allow clinicians to identify subgroups of cognitively impaired elders at low and high risk for ADL dependence.

Activities of Daily Living↗
PubMed1995

Assessing risk for the onset of functional dependence among older adults: the role of physical performance.

BACKGROUND: Approximately 10% of nondisabled, community-dwelling adults aged 75 years and older lose independence in basic activities of daily living (ADLs) each year. The purpose of this study was to evaluate whether simple tests of physical performance could identify older adults, independent in their basic ADLs, who were at increased risk for the onset of functional dependence. METHODS: Among a representative cohort of 1103 community-dwelling adults aged 72 years and older, we evaluated the 664 subjects who were cognitively intact and independent in their basic ADLs at the baseline interview. All cohort members had undergone a comprehensive assessment, including a battery of qualitative and timed performance tests. The main outcome event was the onset of functional dependence, defined as a new disability in one or more of the seven basic ADLs at the 1-year follow-up. RESULTS: Functional dependence developed in 53 (9%) of the 563 subjects who had complete data at the 1-year follow-up. Eight of the 12 qualitative tests and all six of the timed tests were significantly associated (P < .05) with the onset of functional dependence. Both qualitative and timed performance tests demarcated subjects into groups at low and high risk for functional dependence. Four timed tests--chair stands, rapid gait, 360 degrees turn, and bending over--showed a threshold phenomenon, where the rate of new dependence increased slowly with worsening performance until a critical point (or threshold) was reached, and the rate of dependence increased substantially. For timed chair stands, for example, the rates of functional dependence within quarters of worsening performance were 5.3%, 6.3%, 6.7%, and 16%. The risk of functional dependence was markedly elevated (30%-50%) for subjects who were unable to perform the timed tests. CONCLUSIONS: Several simple tests of physical performance were strongly associated with the onset of functional dependence. These results support the potential use of physical performance tests to develop a risk assessment strategy that could identify subgroups of older persons, independent in all ADLs, who are at increased risk for functional dependence.

Activities of Daily Living↗
PubMed1992

What have I done?

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Cardiopulmonary Resuscitation↗
PubMed1990

Concurrent muscarinic and beta-adrenergic blockade in rats impairs place-learning in a water maze and retention of inhibitory avoidance.

These experiments examined the effects of separate and concurrent muscarinic cholinergic and beta-adrenergic blockade on inhibitory (passive) avoidance performance and spatial learning in the Morris water maze. Pretraining systemic administration of either scopolamine (0.3 or 1.0 mg/kg) or propranolol (3.0 or 10.0 mg/kg) had no significant effect on one-day retention of step-through inhibitory avoidance training. Similarly, pretraining administration of either 0.3 mg/kg scopolamine or 10 mg/kg propranolol did not affect spatial learning in the Morris water maze. However, combined administration of scopolamine and 10.0 mg/kg of propranolol impaired performance on these tasks. These findings further support a role for interactions between norepinephrine and acetylcholine in the modulation of learning and memory and implicate the participation of beta-adrenergic mechanisms in this interaction. Because cholinergic and noradrenergic deterioration is found in aging and Alzheimer's disease, these results also have implications regarding the role of age-related noradrenergic and cholinergic dysfunction in cognitive decline.

Animals↗
PubMed1986

Health insurance claims of petrochemical company employees.

This paper describes a morbidity data base for epidemiologic studies which uses information from health insurance claims. Strengths of the data base include completeness and relatively low cost. A limitation is the length of time needed for all claims to be received and processed: rates generated using current information are lower than they will be after all claims are processed. Nevertheless, internal comparisons can presently be made using such rates. Examples illustrate differences in claims experience according to employees' smoking habits and according to kind of job.

Adult↗
PubMedDate not supplied

Evaluation of muscarinic M2 receptor sites in basal forebrain and brainstem cholinergic systems of behaviorally characterized young and aged Long-Evans rats.

Aged (23-25-month-old) male Long-Evans rats were assessed for deficits in spatial cognition relative to young (4-6-month-old) rats. An in vitro autoradiography study was then conducted for muscarinic M2 sites using [3H]AF-DX 384 to assess binding in basal forebrain and brainstem areas where cholinergic neurons are localized. The analysis of basal forebrain included the medial septal/diagonal band region that provides cholinergic innervation of the hippocampus; the laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus were analyzed in the brainstem. A significant age-related reduction in M2 binding was found in both the basal forebrain and brainstem. Only the reduction in the basal forebrain, however, was correlated with spatial learning impairment. Although the basal forebrain and brainstem cholinergic systems are each vulnerable in normal aging, contributions to the behavioral effects of aging may be distinctive for the two systems.

Aging↗