Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking.

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.

Cohort Profile: The Precipitating Events Project (PEP Study).

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.

Modeling repeated time-to-event health conditions with discontinuous risk intervals. An example of a longitudinal study of functional disability among older persons.

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.

Measuring Sarcopenia Severity in Older Adults and the Value of Effective Interventions.

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.

Data Management for Applications of Patient Reported Outcomes.

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.

The ethanol self-administration context as a reinstatement cue: acute effects of naltrexone.

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.

Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons.

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.

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.

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.

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.

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.

Health, functional, and psychological outcomes among older persons with chronic dizziness.

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.

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.

Two recruitment strategies for a clinical trial of physically frail community-living older persons.

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.

Screening mammography: Is it suitably targeted to older women who are most likely to benefit?

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.

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.

Mismatches between the home environment and physical capabilities among community-living older persons.

OBJECTIVE: To determine whether environmental hazards related to transfers, balance, and gait are any less prevalent in the homes of older persons with specific deficits in physical capabilities than they are in the homes of older persons without the same deficits. DESIGN: Cross-sectional study of a population-based cohort. SETTING: The general community in New Haven, Connecticut. PARTICIPANTS: A total of 1088 persons, aged 72 years and older, who had an environmental assessment of their homes. MEASUREMENTS: Each participant underwent a physical performance assessment and comprehensive interview to document the presence of underlying deficits in physical capabilities. Items from the environmental assessment that were potentially hazardous for participants with specific deficits in transfers, balance, or gait were identified. RESULTS: With the exception of no grab bars in the tub/shower, environmental hazards were as prevalent in the homes of participants with specific deficits in physical capabilities as they were in the homes of participants without the same deficits, and, in many cases, they were actually more prevalent. Among participants with and without observed difficulty standing from a chair, for example, the prevalence of a low lying chair was 24% versus 14% (chi2 = 13.4; P < .001), respectively. Among participants with and without an observed deficit in turning, the prevalence of an obstructed pathway was 47% versus 37% (chi2 = 8.7; P = .003), respectively; and the prevalence of loose throw rugs was 72% in both groups. CONCLUSIONS: If the epidemiologic link between environmental hazards and adverse functional outcomes can be strengthened, then interventions designed to enhance the everyday function of frail, older persons should focus on the environment as well as the individual.

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.

The combined effects of baseline vulnerability and acute hospital events on the development of functional dependence among community-living older persons.

BACKGROUND: Many older persons who are highly vulnerable do not develop functional dependence, whereas some older persons with low vulnerability do develop functional dependence. We conducted this study to determine the combined effects of baseline vulnerability and precipitating events on the development of functional dependence. METHODS: We analyzed data from two prospective, population-based cohort studies. The development cohort included 799 community-living persons, 72 years of age and older, who were independent in their activities of daily living (ADLs). The validation cohort included 1,051 comparable persons. Participants were classified by baseline vulnerability, defined on the basis of physical performance, cognitive status, and age, and by exposure to potential precipitating events, determined from information gathered from acute care hospital admissions. The primary outcome was the onset of functional dependence, defined as a new disability in one or more of the seven ADLs at the 1-year follow-up interview or admission to a skilled nursing facility prior to the 1-year interview. RESULTS: Functional dependence developed in 109 (13.6%) participants in the development cohort and in 100 (9.3%) participants in the validation cohort. The rates of functional dependence for the low, intermediate, and high vulnerability groups were 7.1%, 17.2%, and 40.1% (p<.001) in the development cohort and 4.8%, 15.0%, and 28.0% (p<.001) in the validation cohort. For the four categories (none, mild, moderate, severe) of precipitating events, the rates of functional dependence were 9.0%, 19.4%, 27.3%, and 53.2% (p<.001 ) in the development cohort and 5.1%, 12.0%, 28.2%, and 53.3% (p<.001) in the validation cohort. For both cohorts, when baseline vulnerability and precipitating events were analyzed in cross-stratified format, the rate of functional dependence increased progressively from low-risk to high-risk groups in all directions (double-gradient phenomenon). The contributions of baseline vulnerability and precipitating events to the development of functional dependence were independent and statistically significant. CONCLUSIONS: Among community-living older persons, baseline vulnerability and precipitating hospital events contribute independently to the development of functional dependence and should each be targeted for intervention when developing strategies aimed at forestalling the onset of functional dependence.

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.