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1.
J Nutr Health Aging ; 24(4): 438-444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32242212

RESUMO

The Precipitating Events Project (PEP Study) is an ongoing longitudinal study of 754 nondisabled community-living persons age 70 years or older who were members of a large health plan in greater New Haven, Connecticut, USA. The study was established to rigorously evaluate the epidemiology of disability in older persons and to elucidate the role of intervening illnesses and injuries on the disabling process. Of the eligible members, 75.2% agreed to participate and were enrolled between March 1998 and October 1999. Participants have completed comprehensive home-based assessments at 18-month intervals and have been interviewed monthly over the phone with a completion rate of 99%. Detailed participant-level data on health care utilization are obtained annually through linkages with Medicare claims. Through June 2019, 702 (93.1%) participants have died after a median of 109 months, while 43 (5.7%) have dropped out of the study after a median of 27 months. Death certificates are available for all decedents. To date, 117 original reports have been published using data from the PEP Study, including many focusing on other high priority areas such as end of life, frailty, depressive symptoms, aging stereotypes, pain, sleep, and methodologic research. The PEP Study welcomes proposals to access data for meritorious analyses from qualified investigators.


Assuntos
Atividades Cotidianas/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos
2.
J Nutr Health Aging ; 22(10): 1253-1258, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498834

RESUMO

OBJECTIVES: Little is known about the severity and long-term health and economic consequences of sarcopenia. We developed a sarcopenia index to measure severity in older Americans and estimated the long-term societal benefits generated by effective interventions to mitigate severity. DESIGN: Using a micro-simulation model, we quantified the potential societal value generated in the US in 2010-2040 by reductions in sarcopenia severity in older adults. All analyses were performed in Stata and SAS. SETTING AND PARTICIPANTS: Secondary data from the National Health and Nutrition Examination Survey (NHANES) (N = 1634) and Health and Retirement Study (HRS) (N = 952) were used to develop a sarcopenia severity index in older adults. MEASUREMENTS: Multi-trait multi-method and factor analyses were used to validate and calibrate the sarcopenia severity index, which was modeled as a function of gait speed, walking without an assistive device, and moderate physical activity. RESULTS: In representative elderly populations, reducing sarcopenia severity by improving gait speed by 0.1 m/s in those with gait speed under 0.8 m/s generated a cumulative benefit of $65B by 2040 (2015 dollars). Improving walking ability in those with walking difficulty generated cumulative social benefit of $787B by 2040. CONCLUSIONS: Reducing sarcopenia severity would generate significant health and economic benefits to society-almost $800B in the most optimistic scenarios.


Assuntos
Sarcopenia/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Humanos , Masculino , Limitação da Mobilidade
3.
EGEMS (Wash DC) ; 6(1): 5, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29881763

RESUMO

CONTEXT: Patient reported outcomes (PROs) are one means of systematically gathering meaningful subjective information for patient care, population health, and patient centered outcomes research. However, optimal data management for effective PRO applications is unclear. CASE DESCRIPTION: Delivery systems associated with the Health Care Systems Research Network (HCSRN) have implemented PRO data collection as part of the Medicare annual Health Risk Assessment (HRA). A questionnaire assessed data content, collection, storage, and extractability in HCSRN delivery systems. FINDINGS: Responses were received from 15 (83.3 percent) of 18 sites. The proportion of Medicare beneficiaries completing an HRA ranged from less than 10 to 42 percent. Most sites collected core HRA elements and 10 collected information on additional domains such as social support. Measures for core domains varied across sites. Data were collected at and prior to visits. Modes included paper, clinician entry, patient portals, and interactive voice response. Data were stored in the electronic health record (EHR) in scanned documents, free text, and discrete fields, and in summary databases. MAJOR THEMES: PRO implementation requires effectively collecting, storing, extracting, and applying patient-reported data. Standardizing PRO measures and storing data in extractable formats can facilitate multi-site uses for PRO data, while access to individual PROs in the EHR may be sufficient for use at the point of care. CONCLUSION: Collecting comparable PRO data elements, storing data in extractable fields, and collecting data from a higher proportion of eligible respondents represents an optimal approach to support multi-site applications of PRO information.

4.
5.
Cell Death Dis ; 6: e1725, 2015 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-25880092

RESUMO

Disrupting particular mitochondrial fission and fusion proteins leads to the death of specific neuronal populations; however, the normal functions of mitochondrial fission in neurons are poorly understood, especially in vivo, which limits the understanding of mitochondrial changes in disease. Altered activity of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) may contribute to the pathophysiology of several neurologic diseases. To study Drp1 in a neuronal population affected by Alzheimer's disease (AD), stroke, and seizure disorders, we postnatally deleted Drp1 from CA1 and other forebrain neurons in mice (CamKII-Cre, Drp1lox/lox (Drp1cKO)). Although most CA1 neurons survived for more than 1 year, their synaptic transmission was impaired, and Drp1cKO mice had impaired memory. In Drp1cKO cell bodies, we observed marked mitochondrial swelling but no change in the number of mitochondria in individual synaptic terminals. Using ATP FRET sensors, we found that cultured neurons lacking Drp1 (Drp1KO) could not maintain normal levels of mitochondrial-derived ATP when energy consumption was increased by neural activity. These deficits occurred specifically at the nerve terminal, but not the cell body, and were sufficient to impair synaptic vesicle cycling. Although Drp1KO increased the distance between axonal mitochondria, mitochondrial-derived ATP still decreased similarly in Drp1KO boutons with and without mitochondria. This indicates that mitochondrial-derived ATP is rapidly dispersed in Drp1KO axons, and that the deficits in axonal bioenergetics and function are not caused by regional energy gradients. Instead, loss of Drp1 compromises the intrinsic bioenergetic function of axonal mitochondria, thus revealing a mechanism by which disrupting mitochondrial dynamics can cause dysfunction of axons.


Assuntos
Região CA1 Hipocampal/fisiologia , Dinaminas/fisiologia , Mitocôndrias/metabolismo , Neurônios/fisiologia , Animais , Axônios/fisiologia , Região CA1 Hipocampal/metabolismo , Dinaminas/deficiência , Dinaminas/genética , Dinaminas/metabolismo , Metabolismo Energético , Feminino , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Sinapses/fisiologia
6.
Intensive Care Med ; 40(3): 370-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24257969

RESUMO

PURPOSE: Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. METHODS: We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%). RESULTS: Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up. CONCLUSIONS: This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Disfunção Cognitiva/terapia , Estado Terminal/reabilitação , Terapia por Exercício/métodos , Unidades de Terapia Intensiva/estatística & dados numéricos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Ocupacional/métodos , Projetos Piloto , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento
7.
Eur J Neurosci ; 38(5): 2751-61, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23758059

RESUMO

Environmental contexts associated with drug use promote craving in humans and drug-seeking in animals. We hypothesized that the basolateral amygdala (BLA) itself as well as serial connectivity between the BLA and nucleus accumbens core (NAC core) were required for context-induced renewal of Pavlovian-conditioned alcohol-seeking. Male Long-Evans rats were trained to discriminate between two conditioned stimuli (CS): a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2 mL/CS+, 3.2 mL per session) and a CS- that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS- without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using a solution of GABA receptor agonists (0.1 mm muscimol and 1.0 mm baclofen; M/B; 0.3 µL per side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6 µg per side) or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context.


Assuntos
Consumo de Bebidas Alcoólicas , Tonsila do Cerebelo/fisiologia , Condicionamento Clássico/fisiologia , Comportamento de Procura de Droga/fisiologia , Animais , Extinção Psicológica/fisiologia , Masculino , Núcleo Accumbens/fisiologia , Ratos , Ratos Long-Evans
8.
J Gerontol A Biol Sci Med Sci ; 66(1): 109-14, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21030467

RESUMO

BACKGROUND: Longitudinal studies in gerontology are characterized by termination of measurement from death. Death is related to many important gerontological outcomes, such as functional disability, and may, over time, change the composition of an older study population. For these reasons, treating death as noninformative censoring of a longitudinal outcome may result in biased estimates of regression coefficients related to that outcome. METHODS: In a longitudinal study of community-living older persons, we analytically and graphically illustrate the dependence between death and functional disability. Relative to survivors, decedents display a rapid decline of functional ability in the months preceding death. Death's strong relationship with functional disability demonstrates that death is not independent of this outcome and, hence, leads to informative censoring. We also demonstrate the "healthy survivor effect" that results from death's selection effect, with respect to functional disability, on the longitudinal makeup of an older study population. RESULTS: We briefly survey commonly used approaches for longitudinal modeling of gerontological outcomes, with special emphasis on their treatment of death. Most common methods treat death as noninformative censoring. However, joint modeling methods are described that take into account any dependency between death and a longitudinal outcome. CONCLUSIONS: In longitudinal studies of older persons, death is often related to gerontological outcomes and, therefore, cannot be safely assumed to represent noninformative censoring. Such analyzes must account for the dependence between outcomes and death as well as the changing nature of the cohort.


Assuntos
Atividades Cotidianas , Morte , Geriatria , Idoso , Avaliação da Deficiência , Humanos , Estudos Longitudinais , Modelos de Riscos Proporcionais
9.
Methods Inf Med ; 47(2): 107-16, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18338081

RESUMO

OBJECTIVES: Researchers have often used rather simple approaches to analyze repeated time-to-event health conditions that either examine time to the first event or treat multiple events as independent. More sophisticated models have been developed, although previous applications have focused largely on such outcomes having continuous risk intervals. Limitations of applying these models include their difficulty in implementation without careful attention to forming the data structures. METHODS: We first review time-to-event models for repeated events that are extensions of the Cox model and frailty models. Next, we develop a way to efficiently set up the data structures with discontinuous risk intervals for such models, which are more appropriate for many applications than the continuous alternatives. Finally, we apply these models to a real dataset to investigate the effect of gender on functional disability in a cohort of older persons. For comparison, we demonstrate modeling time to the first event. RESULTS: The GEE Poisson, the Cox counting process, and the frailty models provided similar parameter estimates of gender effect on functional disability, that is, women had increased risk of bathing disability and other disability (disability in walking, dressing, or transferring) as compared to men. These results, especially for other disabilities, were quite different from those provided by an analysis of the first-event outcomes. However, the effect of gender was no longer significant in the counting process model fully adjusted for covariates. CONCLUSION: Modeling time to only the first event may not be adequate. After properly setting up the data structures, repeated event models that account for the correlation between multiple events within subjects can be easily implemented with common statistical software packages.


Assuntos
Técnicas e Procedimentos Diagnósticos/estatística & dados numéricos , Modelos Estatísticos , Idoso , Avaliação da Deficiência , Feminino , Humanos , Estudos Longitudinais , Masculino , Limitação da Mobilidade , Periodicidade , Recidiva , Risco
10.
Neuroscience ; 139(3): 877-87, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16516392

RESUMO

A major difficulty in treating alcohol addiction is the high rate of relapse even after prolonged abstinence. Relapse can be triggered by several factors, including stress, re-exposure to the drug, conditioned discrete stimuli and exposure to the context in which alcohol consumption occurred. The present study investigated the role played by the environmental context on ethanol relapse using an extinction/reinstatement animal model: rats were trained to self-administer ethanol in a distinctive context, and extinction occurred in a setting that differed by visual, tactile and olfactory properties; reinstatement was tested by placing the animals into the ethanol-associated context in the absence of ethanol. We found that re-exposure to the ethanol-associated context significantly increased responses on the ethanol-paired lever. The increase in responding required the presence of the complete configuration of the multimodal context. The non-selective opioid receptor antagonist naltrexone (0.3 mg/kg) administered 20 min prior to the reinstatement test significantly attenuated context-induced reinstatement of lever press responding, compared with saline-treated subjects. These data indicate that the environmental context associated with ethanol availability influences ethanol-seeking behavior in the rat, and that endogenous opioids are involved in this process. Our findings are in accordance with clinical reports demonstrating naltrexone efficacy in the treatment of alcohol relapse in humans, and indicate that the context-induced reinstatement model described here may be useful to investigate the biological mechanisms underlying alcohol relapse.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Extinção Psicológica/efeitos dos fármacos , Animais , Aprendizagem por Associação/efeitos dos fármacos , Masculino , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Long-Evans , Recidiva , Autoadministração , Edulcorantes/administração & dosagem
11.
Ann Intern Med ; 135(5): 313-21, 2001 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-11529694

RESUMO

BACKGROUND: Restricted activity is a potentially important indicator of health and functional status. Yet, relatively little is known about the incidence, precipitants, or health care utilization associated with restricted activity among older persons. OBJECTIVE: To more accurately estimate the rate of restricted activity among community-living older persons, to identify the health-related and non-health-related problems that lead to restricted activity, and to determine whether restricted activity is associated with increased health care utilization. DESIGN: Prospective cohort study. SETTING: New Haven, Connecticut. PARTICIPANTS: 754 nondisabled members of a large health plan, 70 years of age or older, who were categorized according to their risk for disability (low, intermediate, or high). MEASUREMENTS: Occurrence of restricted activity (defined as having stayed in bed for at least half a day or having cut down on one's usual activities because of an illness, injury, or another problem), problems leading to restricted activity, and health care utilization were ascertained during monthly telephone interviews for up to 2 years. RESULTS: In median follow-up of 15 months, 76.6% of participants reported restricted activity during at least 1 month and 39.3% reported restricted activity during 2 consecutive months. The rates of restricted activity per 100 person-months were 19.0 episodes for all participants and 16.9, 27.3, and 22.7 episodes for participants at low, intermediate, and high risk for disability, respectively. Of the 24 prespecified health-related and non-health-related problems, the rates per 100 person-months of restricted activity ranged from 0.1 episode for "problem with alcohol" to 65.5 episodes for "been fatigued." On average, participants identified 4.5 different problems as a cause for their restricted activity. Health care utilization was substantially greater during months with restricted activity than months without restricted activity. The corresponding rates per 100 person-months were 63.8 and 45.1 for physician office visits, 12.5 and 1.0 for emergency department visits, 14.1 and 0.3 for hospital admissions, and 67.6 and 45.1 for any health care utilization (P < 0.001 for each pairwise comparison). CONCLUSIONS: Restricted activity is common among community-living older persons, regardless of risk for disability, and it is usually attributable to several concurrent health-related problems. Although restricted activity is associated with a substantial increase in health care utilization, older persons with restricted activity often do not seek medical attention.


Assuntos
Atividades Cotidianas , Pessoas com Deficiência/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Medição de Risco , Fatores de Risco
12.
J Am Geriatr Soc ; 49(8): 1039-45, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11555064

RESUMO

OBJECTIVES: To compare the efficiency and cost of two distinct but complementary recruitment strategies for a clinical trial of physically frail, community-living persons, age 75 and older. DESIGN: In the first recruitment strategy, potential participants were identified and screened for physical frailty during office visits to their primary care physicians; in the second, potential participants were identified from the patient rosters of primary care physicians and were screened for physical frailty in their home. Physical frailty was defined on the basis of slow gait speed and inability to stand from a chair with one's arms folded. SETTING: General community in greater Bridgeport, Connecticut. PARTICIPANTS: Community-living persons, age 75 and older, who met criteria for physical frailty. MEASUREMENTS: Measures of efficiency included the number of persons screened for each participant randomized, the number of persons eligible for each participant randomized, and the refusal rate. Costs were calculated per randomized participant. RESULTS: One hundred eighty-eight participants, with a mean age of 83.2 years, were enrolled over 22 months. One hundred and one participants were enrolled via the office-based strategy; 87 were enrolled via the roster-based strategy. Participants in each group had considerable quadriceps weakness and performed poorly on objective measures of gait and upper- and lower-extremity function. For each participant randomized, the number of persons screened, number of persons eligible, and cost were 15.2, 1.2, and $868, respectively, for the office-based strategy and 11.6, 1.1, and $764, respectively, for the roster-based strategy. The corresponding refusal rates for the two strategies were 14.9% and 10.1%, respectively (P < .001). CONCLUSIONS: Although each recruitment strategy successfully identified older persons who were physically frail, the roster-based strategy was less expensive and performed modestly better on each measure of efficiency than the office-based strategy.


Assuntos
Ensaios Clínicos como Assunto , Idoso Fragilizado , Avaliação Geriátrica , Seleção de Pacientes , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto/economia , Connecticut , Análise Custo-Benefício , Eficiência Organizacional , Feminino , Humanos , Masculino
13.
J Am Geriatr Soc ; 49(8): 1101-4, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11555074

RESUMO

OBJECTIVES: To determine whether screening mammography is suitably targeted to older women who are most likely to benefit. DESIGN: Prospective cohort study. SETTING: New Haven County, Connecticut. PARTICIPANTS: Eight hundred forty-four community-dwelling older women were interviewed as part of the 1990 New Haven Established Populations for the Epidemiologic Study of the Elderly (EPESE) program. MEASUREMENTS: Mammography use was ascertained from Medicare Part B claims data. A four-level prognostic mortality index was developed using items previously shown to be predictive of mortality. Mammography use and all-cause mortality were evaluated by prognostic stage over a 5-year period, January 1, 1991, to December 31, 1995. RESULTS: Five-year mortality increased steadily with each prognostic stage (12% to 68%, P = .001), whereas the 5-year mammography use rate declined (48% to 7%, P = .001). Over half the women (53%) in the most favorable prognostic group did not receive a mammogram, whereas 13% in the two worst prognostic groups received at least one mammogram. CONCLUSION: Screening mammography may be underutilized among older women who are the most likely to benefit and overutilized among those who are unlikely to benefit.


Assuntos
Neoplasias da Mama/prevenção & controle , Serviços de Saúde para Idosos/organização & administração , Mamografia/estatística & dados numéricos , Saúde da Mulher , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Connecticut/epidemiologia , Feminino , Humanos , Medicare/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Prospectivos , Encaminhamento e Consulta , Fatores de Risco , Estados Unidos
15.
Proc AMIA Symp ; : 136-40, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11079860

RESUMO

The determination of physical therapy treatment protocols, based on an in-home evaluation of a patient, is a complex task. The specific rules for treatment indications are individually simple, but numerous and hence time-consuming and prone to error using pencil-and-paper methods. This paper describes PTEVAL, a computerized Point-of-Care instrument designed to support the intervention protocols of an ongoing clinical trial. With appropriate modifications and extensions, PTEVAL can be a model for instruments used in clinical practice.


Assuntos
Serviços de Assistência Domiciliar , Modalidades de Fisioterapia , Sistemas Automatizados de Assistência Junto ao Leito , Atividades Cotidianas , Idoso , Protocolos Clínicos , Periféricos de Computador , Estudos de Avaliação como Assunto , Idoso Fragilizado , Serviços de Saúde para Idosos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Interface Usuário-Computador
16.
JAMA ; 284(3): 342-9, 2000 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-10891966

RESUMO

While the benefits of physical activity and exercise among older persons are becoming increasingly clear, the role of exercise stress testing and safety monitoring for older persons who want to start an exercise program is unclear. Current guidelines regarding exercise stress testing likely are not applicable to the majority of persons aged 75 years or older who are interested in restoring or enhancing their physical function through a program of physical activity and exercise. In addition to being expensive and of unproven benefit, the current policy of routine exercise stress testing potentially could deter many older persons from participating in an exercise program. Research is needed to investigate current physician practices, evaluate the risk of adverse cardiac events, determine the role of pharmacological stress testing, and measure and compare absolute and relative exercise intensities. To assist clinicians, we offer a set of recommendations regarding precautions that can be taken to minimize the risk of adverse cardiac events among previously sedentary older persons who do not have symptomatic cardiovascular disease and are interested in starting an exercise program. JAMA. 2000;284:342-349


Assuntos
Teste de Esforço , Exercício Físico , Infarto do Miocárdio , Aptidão Física , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço/normas , Feminino , Humanos , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Guias de Prática Clínica como Assunto , Risco , Segurança
17.
J Neurosci ; 20(12): 4745-57, 2000 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-10844044

RESUMO

Cortical cholinergic inputs are hypothesized to mediate attentional functions. The present experiment was designed to determine the single unit activity of neurons within the medial prefrontal cortex (mPFC) of rats performing a sustained visual attention task. Demands on attentional performance were varied by the presentation of a visual distractor. The contribution of cholinergic afferents of the mPFC to performance-associated unit activity within this area was determined by recording neuronal activity before and after unilateral cholinergic deafferentation using intracortical infusion of the immunotoxin 192 IgG-saporin. Presentation of the visual distractor resulted in a decrease in the detection of brief, unpredictable visual signals. As predicted, the unilateral loss of cholinergic inputs within the recording area of the mPFC did not affect sustained attentional performance. Cholinergic deafferentation, however, resulted in a decrease in the overall firing rate of medial prefrontal neurons and a substantial reduction in the proportion of neurons whose firing patterns correlated with specific aspects of behavioral performance. Furthermore, cholinergic deafferentation attenuated the frequency and amplitude of increased mPFC neuronal firing rates that were associated with the presentation of the visual distractor. The main findings from this experiment suggest that cholinergic inputs to the mPFC strongly influence spontaneous and behaviorally correlated single unit activity and mediate increases in neuronal activity associated with enhanced demands for attentional processing, all of which may be fundamental aspects in the maintenance of attentional performance.


Assuntos
Atenção/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Percepção Visual/fisiologia , Vias Aferentes/fisiologia , Animais , Anticorpos Monoclonais/toxicidade , Colinérgicos/toxicidade , Condicionamento Operante/fisiologia , Imunotoxinas/toxicidade , Masculino , N-Glicosil Hidrolases , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Long-Evans , Recompensa , Proteínas Inativadoras de Ribossomos Tipo 1 , Saporinas
18.
J Am Geriatr Soc ; 48(4): 417-21, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10798469

RESUMO

OBJECTIVE: The recommended clinical strategy for a health condition should depend both on the known causes of and outcomes associated with the condition. The aim of this study was to determine the range of adverse outcomes associated with chronic dizziness. DESIGN: Population-based prospective cohort study. SETTING AND PARTICIPANTS: A probability sample of 1087 persons, age 72 and older, living in the community. MEASUREMENTS: The following were measured: chronic dizziness, death, hospitalizations, falls, syncope, basic and instrumental activities of daily living, depressive symptoms, self-rated health, falls self-efficacy, and social activities. RESULTS: Of the 1087 participants, 261 (24%) reported chronic dizziness. Over 1 year of follow-up, chronic dizziness was not associated with mortality, hospitalization for any reason, or change in basic or instrumental activities of daily living, but was associated with risk of falling (unadjusted relative risk [RR] 1.35; 95% confidence interval [CI] 1.06-1.72) and with experiencing syncope (RR 2.31; 95% CI 1.24-4.30). After adjustment for baseline level, chronic dizziness also was associated with worsening of depressive symptoms, self-rated health, falls efficacy, and social activities. The relationship remained significant, after adjustment for potential confounding factors, for self-rated health (T-statistic -2.95, P = .003) and falls efficacy (T-statistic -2.68; P = .008), and was of marginal significance for depressive symptoms (T-statistic -1.73; P = .085). CONCLUSIONS: These results suggest that the goals of care for older persons with chronic dizziness should be redirected from solely identifying and treating discrete diseases--an often expensive and unrewarding task--toward reducing the symptoms of chronic dizziness and alleviating the resulting physical, psychological, and social disability.


Assuntos
Tontura/complicações , Avaliação Geriátrica , Vigilância da População , Acidentes por Quedas/estatística & dados numéricos , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Doença Crônica , Tontura/epidemiologia , Tontura/psicologia , Feminino , Hospitalização , Humanos , Masculino , Prevalência , Estudos Prospectivos
19.
Hippocampus ; 10(1): 111-21, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10706222

RESUMO

Ethanol affects behavior by interacting with synaptic sites at many levels of the nervous system. However, it targets most readily and at the lowest concentrations those sites mediating higher cognitive functions such as attention and memory. The memory-impairing effects of ethanol are thought to involve the hippocampus, a structure particularly vulnerable to the effects ethanol at low concentrations and early in the rising phase of the blood ethanol concentration curve. One of the early, low-dose effects of ethanol is an interruption of the normal physiological regulation of the hippocampus by the ascending septohippocampal pathway originating in the medial septal area (MSA). Ethanol enhances GABAergic transmission in the MSA, thereby reducing the regularity and vigor with which rhythmically bursting neurons of the MSA drive the hippocampal theta rhythm. Disruption of septohippocampal activity also has consequences on the response of the hippocampus to cortical inputs. Ethanol produces a loss of hippocampal responsivity that reduces the ability of the hippocampus to encode and retrieve relevant stimulus information necessary for accurate memory. This paper examines the behavioral and neural evidence for hippocampal vulnerability to ethanol and explores the hypothesis that these effects are due to ethanol disrupting septohippocampal modulation of the hippocampus, resulting in impairments of memory.


Assuntos
Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Núcleos Septais/efeitos dos fármacos , Animais , Hipocampo/citologia , Hipocampo/fisiologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Núcleos Septais/citologia , Núcleos Septais/fisiologia , Ritmo Teta
20.
Ann Intern Med ; 132(5): 337-44, 2000 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-10691583

RESUMO

BACKGROUND: In previous studies of dizziness, the prevalence of specific causes has varied widely and either no or multiple causes have been identified. Dizziness might be better considered a geriatric syndrome that results from impairment or disease in multiple systems. OBJECTIVE: To determine the predisposing characteristics and situational factors associated with dizziness. DESIGN: Population-based, cross-sectional study. SETTING: Community. PARTICIPANTS: Probability sample of 1087 community-living persons in New Haven, Connecticut, who were at least 72 years of age. MEASUREMENTS: Episodes of dizziness that occurred for at least 1 month; manifestations of dizziness; and predisposing demographic, medical, neurologic, sensory, and psychological characteristics. RESULTS: 261 participants (24%) reported dizziness; 56% of dizzy persons described several sensations and 74% reported several triggering activities. The adjusted relative risks for characteristics associated with dizziness were 1.69 (95% CI, 1.24 to 2.30) for anxiety, 1.36 (CI, 1.02 to 1.80) for depressive symptoms, 1.27 (CI, 0.99 to 1.63) for impaired hearing, 1.30 (CI, 1.01 to 1.68) for five or more medications, 1.31 (CI, 0.92 to 1.87) for postural hypotension, 1.34 (CI, 0.95 to 1.90) for impaired balance, and 1.31 (CI, 1.00 to 1.71) for past myocardial infarction. The adjusted relative risk for dizziness was 1.38 (CI, 1.27 to 1.49) for each additional characteristic. CONCLUSIONS: The association among characteristics in multiple domains (cardiovascular, neurologic, sensory, psychological, and medication-related) and dizziness, coupled with the multiplicity of sensations and triggering activities, suggests that dizziness may be a geriatric syndrome, similar to delirium and falling. If so, an impairment reduction strategy, proven effective for other geriatric syndromes, may be effective in reducing the symptoms and disabilities associated with dizziness.


Assuntos
Tontura/etiologia , Idoso , Idoso de 80 Anos ou mais , Ansiedade/complicações , Connecticut/epidemiologia , Estudos Transversais , Depressão/complicações , Tontura/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Transtornos da Audição/complicações , Humanos , Hipotensão Ortostática/complicações , Masculino , Infarto do Miocárdio/complicações , Equilíbrio Postural , Prevalência , Fatores de Risco , Transtornos de Sensação/complicações , Estatística como Assunto , Síndrome
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