Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients.

BACKGROUND: Ketoconazole is a well-known CYP17-targeted systemic treatment for castration-resistant prostate cancer (CRPC). However, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. Chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200-300 mg three times daily) had PSA response rate (>50% decline) of 21-62%. We hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the CRPC post-chemotherapy state. METHODS: Men with CRPC and performance status 0-3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA response rate (>50% reduction from baseline) where a rate of 25% was to be considered promising for further study (versus a null rate of <5%); 25 patients were required. Secondary endpoints included PSA response >30% from baseline, progression-free survival (PFS), duration of stable disease and evaluation of adverse events (AEs). RESULTS: Thirty patients were accrued with median age of 72 years (range 55-86) and median pre-treatment PSA of 73 ng ml(-1) (range 7-11,420). Twenty-nine patients were evaluable for response and toxicity. PSA response (>50% reduction) was seen in 48% of patients; PSA response (>30% reduction) was seen in 59%. Median PFS was 138 days; median duration of stable disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 grade 3 AEs, only 3 were attributed to treatment. None of the two grade 4 AEs were considered related to treatment. CONCLUSIONS: In docetaxel pre-treated CRPC patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy.

Clinical-dosimetric relationship between lacrimal gland dose and ocular toxicity after intensity-modulated radiotherapy for sinonasal tumours.

OBJECTIVE: To characterise the relationship between lacrimal gland dose and ocular toxicity among patients treated by intensity-modulated radiotherapy (IMRT) for sinonasal tumours. METHODS: 40 patients with cancers involving the nasal cavity and paranasal sinuses were treated with IMRT to a median dose of 66.0 Gy. Toxicity was scored using the Radiation Therapy Oncology Group morbidity criteria based on conjunctivitis, corneal ulceration and keratitis. The paired lacrimal glands were contoured as organs at risk, and the mean dose, maximum dose, V10, V20 and V30 were determined. Statistical analysis was performed using logistic regression and the Akaike information criterion (AIC). RESULTS: The maximum and mean dose to the ipsilateral lacrimal gland were 19.2 Gy (range, 1.4-75.4 Gy) and 14.5 Gy (range, 11.1-67.8 Gy), respectively. The mean V10, V20 and V30 values were 50%, 25% and 17%, respectively. The incidence of acute and late Grade 3+ toxicities was 23% and 19%, respectively. Based on logistic regression and AIC, the maximum dose to the ipsilateral lacrimal gland was identified as a more significant predictor of acute toxicity (AIC, 53.89) and late toxicity (AIC, 32.94) than the mean dose (AIC, 56.13 and 33.83, respectively). The V20 was identified as the most significant predictor of late toxicity (AIC, 26.81). CONCLUSION: A dose-response relationship between maximum dose to the lacrimal gland and ocular toxicity was established. Our data suggesting a threshold relationship may be useful in establishing dosimetric guidelines for IMRT planning that may decrease the risk of acute and late lacrimal toxicities in the future. ADVANCES IN KNOWLEDGE: A threshold relationship between radiation dose to the lacrimal gland and ocular toxicity was demonstrated, which may aid in treatment planning and reducing the morbidity of radiotherapy for sinonasal tumours.

Quantitation of sentinel node metastatic burden and Her-2/neu over-expression accurately predicts residual axillary nodal involvement and extranodal disease in breast cancer.

BACKGROUND DATA: Recent literature has suggested that completion axillary lymph node dissection (ALND) in breast carcinoma patients with positive SLN may not be necessary. However, a method for determining the risk of non-SLN or extranodal disease remains to be established. AIMS: To determine if pathological variables from primary tumors and sentinel lymph node (SLN) metastases could predict the probability of non-sentinel lymph node (NSLN) metastases and extranodal disease in patients with breast carcinoma and SLN metastases. METHODS: 84 women with T1-3 breast cancer and clinically-negative axillae underwent completion ALND. Maximum diameter and width of SLN metastases were measured to calculate metastatic area. When multiple SLNs contained metastases, areas were summed to calculate the Total Metastatic Area (TMA). Multiple linear regression models were used to identify predictive factors. RESULTS: Her-2/neu over-expression increased the odds of NSLN metastases (OR 4.3, p = 0.01) and extranodal disease (OR 7.9, p < 0.001). Independent SLN predictors were ≥1 positive SLN (OR, 7.35), maximum diameter and area of SLN metastases (OR 2.26, 1.85 respectively) and TMA (OR, 2.12). Maximum metastatic diameter/SLN diameter (OR 3.71, p = 0.04) and the area of metastases/SLN area (OR 3.4, p = 0.04) were predictive. For every 1 mm increase in diameter of SLN metastases, the odds of NSLN extranodal disease increased by 8.5% (p = 0.02). TMA >0.40 cm(2) was an independent predictor for NSLN metastases and extranodal disease. CONCLUSION: Her-2/neu over-expression and parameters assessing metastatic burden in the SLN, particularly TMA, predicted the presence of NSLN involvement and extranodal disease in patients with breast carcinoma and SLN metastases.

ZNF217, a candidate breast cancer oncogene amplified at 20q13, regulates expression of the ErbB3 receptor tyrosine kinase in breast cancer cells.

Understanding the mechanisms underlying ErbB3 overexpression in breast cancer will facilitate the rational design of therapies to disrupt ErbB2-ErbB3 oncogenic function. Although ErbB3 overexpression is frequently observed in breast cancer, the factors mediating its aberrant expression are poorly understood. In particular, the ErbB3 gene is not significantly amplified, raising the question as to how ErbB3 overexpression is achieved. In this study we showed that the ZNF217 transcription factor, amplified at 20q13 in ∼20% of breast tumors, regulates ErbB3 expression. Analysis of a panel of human breast cancer cell lines (n = 50) and primary human breast tumors (n = 15) showed a strong positive correlation between ZNF217 and ErbB3 expression. Ectopic expression of ZNF217 in human mammary epithelial cells induced ErbB3 expression, whereas ZNF217 silencing in breast cancer cells resulted in decreased ErbB3 expression. Although ZNF217 has previously been linked with transcriptional repression because of its close association with C-terminal-binding protein (CtBP)1/2 repressor complexes, our results show that ZNF217 also activates gene expression. We showed that ZNF217 recruitment to the ErbB3 promoter is CtBP1/2-independent and that ZNF217 and CtBP1/2 have opposite roles in regulating ErbB3 expression. In addition, we identify ErbB3 as one of the mechanisms by which ZNF217 augments PI-3K/Akt signaling.

Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization.

BACKGROUND: Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally. OBJECTIVE: To characterize cross-sectionally and longitudinally clinical measures in normal controls, subjects with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment of the utility of neuroimaging and chemical biomarker measures. METHODS: A total of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were enrolled at baseline and followed for 12 months using standard cognitive and functional measures typical of clinical trials. RESULTS: The subjects with MCI were more memory impaired than the cognitively normal subjects but not as impaired as the subjects with AD. Nonmemory cognitive measures were only minimally impaired in the subjects with MCI. The subjects with MCI progressed to dementia in 12 months at a rate of 16.5% per year. Approximately 50% of the subjects with MCI were on antidementia therapies. There was minimal movement on the Alzheimer's Disease Assessment Scale-Cognitive Subscale for the normal control subjects, slight movement for the subjects with MCI of 1.1, and a modest change for the subjects with AD of 4.3. Baseline CSF measures of Abeta-42 separated the 3 groups as expected and successfully predicted the 12-month change in cognitive measures. CONCLUSION: The Alzheimer's Disease Neuroimaging Initiative has successfully recruited cohorts of cognitively normal subjects, subjects with mild cognitive impairment (MCI), and subjects with Alzheimer disease with anticipated baseline characteristics. The 12-month progression rate of MCI was as predicted, and the CSF measures heralded progression of clinical measures over 12 months.

Molecular specific and cell selective cytotoxicity induced by a novel synthetic HLA-DR antibody mimic for lymphoma and leukemia.

Like rituximab, monoclonal antibodies reactive with human leukocyte antigen have potent antilymphoma activity. However, size limits their vascular and tissue penetration. To mimic monoclonal antibody binding, nanomolecules have been synthesized, shown specific for the beta subunit of HLA-DR10, and selective for cells expressing this protein. Selective high affinity ligands (SHALs) containing the 3-(2-([3-chloro-5-trifluoromethyl)-2-pyridinyl]oxy)-anilino)-3-oxopropanionic acid (Ct) ligand residualized and had antilymphoma activity against expressing cells. Herein, we show the extraordinary potency in mice with human lymphoma xenografts of a tridentate SHAL containing this ligand. After titrating antilymphoma activity in cell culture, a randomized preclinical study of a tridentate SHAL containing the Ct ligand was conducted in mice with established and aggressive human lymphoma xenografts. Mice having HLA-DR10 expressing Raji B- or Jurkat's T-lymphoma xenografts were randomly assigned to receive either treatment with SHAL at a dose of 100 ng i.p. weekly for 3 consecutive weeks, or to be untreated. Primary end-points were cure, overall response rates and survival. Toxicity was also evaluated in these mice, and a USFDA general safety study was conducted in healthy Balb/c mice. In Raji cell culture, the threshold and IC50 concentrations for cytotoxic activity were 0.7 and 2.5 nmol (pm/ml media), respectively. When compared to treated Jurkat's xenografts or untreated xenografts, Raji xenografts treated with the SHAL showed an 85% reduction in hazard of death (P=0.014; 95% confidence interval 32-95% reduction). There was no evidence for toxicity even after i.p. doses 2000 times greater than the treatment dose associated with cure of a majority of the mice with Raji xenografts. When compared with control groups, treatment selectively improved response rates and survival in mice with HLA-DR10 expressing human lymphoma xenografts at doses not associated with adverse events and readily achievable in patients.

Multivariate longitudinal models for complex change processes.

Longitudinal studies offer us an opportunity to develop detailed descriptions of the process of growth and development or of the course of progression of chronic diseases. Most longitudinal analyses focus on characterizing change over time in a single outcome variable and identifying predictors of growth or decline. Both growth and degenerative diseases, however, are complex processes with multiple markers of change, so that it may be important to model more than one outcome measure and to understand their relationship over time. We consider random effects models for the association between the trajectories of two outcomes over time, and then compare their properties to approaches based on separate ordinary least-squares estimates of change. We then illustrate with an example from the Religious Orders Study, a longitudinal cohort study of more than 900 members of Catholic religious orders who have had up to eight annual clinical examinations.

Terminal decline in cognitive function.

BACKGROUND: Impending death is thought to be associated with age-related cognitive decline, but this association has not been well studied. METHODS: Participants were 763 older Roman Catholic nuns, priests, and brothers without dementia at baseline. They completed an average of 5.6 annual evaluations (range 2 to 9), with >95% follow-up participation in survivors. Each evaluation included administration of 19 cognitive function tests from which previously established measures of global cognition (mean = 0.108, SD = 0.502) and specific cognitive functions were derived. In a series of change point random effects models, the average point before death when rate of cognitive decline changed was identified, and rates of cognitive decline before and after the optimal change point were estimated, controlling for the effects of age, sex, and education. RESULTS: There were 122 deaths during the observation period. Those who died had lower global cognitive function at baseline than survivors (by 0.103 unit; p = 0.03), and beginning about 43 months before death, their annual rate of global cognitive decline sharply accelerated from an annual loss of 0.026 to 0.173 unit, a more than sixfold increase. Results were comparable in analyses that controlled for baseline health and disability. Terminal cognitive decline was evident in nearly all of those who died, but at highly variable rates. Remarkably little cognitive decline was evident in survivors. Decline in episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability also greatly increased about 3 to 6 years prior to death. CONCLUSION: On average, cognitive decline sharply accelerates in the last years of life.

Depressive symptoms, cognitive decline, and risk of AD in older persons.

BACKGROUND: Cross-sectional and retrospective case-control studies suggest an association of depression symptoms with cognitive impairment and AD, but there have been few prospective studies and their results have been inconsistent. METHODS: Participants are Catholic clergy members who were aged > or =65 years and who did not have clinical evidence of AD. During a 7-year period, they underwent annual clinical evaluations that included clinical classification of AD and detailed cognitive function testing from which global and specific measures of cognition were derived. Number of depressive symptoms was assessed at baseline with a modified, 10-item Center for Epidemiologic Studies Depression Scale (CES-D). The association of CES-D score with incident AD, using proportional hazards models, and cognitive decline, using random effects models, was examined. RESULTS: At baseline, participants reported an average of about one depressive symptom on the CES-D scale (range, 0 to 8). During the 7 years of follow-up, 108 persons developed AD. In analyses that controlled for selected demographic and clinical variables including baseline level of cognitive function, CES-D score was associated with both risk of AD and rate of cognitive decline. For each depressive symptom, risk of developing AD increased by an average of 19%, and annual decline on a global cognitive measure increased by an average of 24%. CONCLUSIONS: The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD.

Natural history of mild cognitive impairment in older persons.

BACKGROUND: Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. METHODS: Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. RESULTS: On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. CONCLUSIONS: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.

Progression of gait disorder and rigidity and risk of death in older persons.

BACKGROUND: Bradykinesia, gait disturbance, rigidity, and tremor are common motor signs in old age. All of these signs are associated with increased morbidity and mortality, but the extent to which they are progressive is unknown. METHODS: Study participants were 787 older Catholic clergy members without clinically diagnosed PD, related conditions, or dementia at baseline. They were evaluated annually for up to 7 years, with >95% follow-up participation by survivors. Evaluations included administration of a modified version of the motor portion of the Unified PD Rating Scale (UPDRS), from which previously established measures of the global UPDRS and four specific motor signs were derived. Scores represent the percent of the total possible UPDRS score obtained. RESULTS: At baseline, the global UPDRS score ranged from 0 to 36.3 (mean +/- SD, 7.3 +/- 6.4). It increased by an average of 0.69 unit per year during follow-up, with more rapid progression in older persons, but there was wide variability with no progression in 21% of subjects and annual increases of up to 8.23 units in the remaining 79%. Of 129 persons who died, 106 had follow-up UPDRS data. In a proportional hazards model, risk of death was associated with both the level of the global UPDRS score at baseline and the annual rate of progression (both p < 0.001). Overall, risk of death in subjects who had some worsening of the global UPDRS score was 2.93 times the rate among those without progression (95% CI, 1.32-6.50). Gait disorder/postural reflex impairment and rigidity worsened, but bradykinesia and tremor did not. Risk of death was associated with worsening of gait/posture but not with the other signs. CONCLUSION: Gait disorder and rigidity, as assessed with the modified UPDRS, are usually progressive in old age. Both the severity of the gait disorder and its rate of progression are strongly associated with risk of death.

MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer's disease.

With high resolution, quantitative magnetic resonance imaging (MRI) techniques, it is now possible to examine alterations in brain anatomy in vivo and to identify regions affected in the earliest stages of Alzheimer's disease (AD). In this study, we compared MRI-derived entorhinal and hippocampal volume in healthy elderly controls, patients who presented at the clinic with cognitive complaints, but did not meet criteria for dementia (non-demented), and patients with very mild AD. The two patient groups differed significantly from controls in entorhinal volume, but not from each other; in contrast, they differed from each other, as well as from controls, in hippocampal volume, with the mild AD cases showing the greatest atrophy. Follow-up clinical evaluations available on 23/28 non-demented patients indicated that 12/23 had converted to AD within 12-77 months from the baseline MRI examination. Converters could be best differentiated from non-converters on the basis of entorhinal, but not hippocampal volume. These data suggest that although both the EC and hippocampal formation degenerate before the onset of overt dementia, EC volume is a better predictor of conversion.

Annual incidence of Alzheimer disease in the United States projected to the years 2000 through 2050.

Alzheimer disease will affect increasing numbers of people as baby boomers (persons born between 1946 and 1964) age. This work reports projections of the incidence of Alzheimer disease(AD) that will occur among older Americans in the future. Education adjusted age-specific incidence rates of clinically diagnosed probable AD were obtained from stratified random samples of residents 65 years of age and older in a geographically defined community. These rates were applied to U.S. Census Bureau projections of the total U.S. population by age and sex to estimate the number of people newly affected each year. The annual number of incident cases is expected to more than double by the midpoint of the twenty-first century: from 377,000 (95% confidence interval = 159,000-595,000) in 1995 to 959,000 (95% confidence interval = 140,000-1,778,000) in 2050. The proportion of new onset cases who are age 85 or older will increase from 40% in 1995 to 62% in 2050 when the youngest of the baby boomers will attain that age. Without progress in preventing or delaying onset of Alzheimer disease, both the number of people with Alzheimer disease and the proportion of the total population affected will increase substantially.

Standardized submaximal exercise testing in never smokers: a normative study.

In a population survey on the south-western coast of Norway, 373 never smokers aged 18-73 years (230 women) without respiratory symptoms performed a standardized, progressive, incremental submaximal bicycle exercise test. All individuals were able to do an exercise involving oxygen uptake of 1.0 l min(-1), 80% of the subjects reached 1.5 l min(-1) and 50% of the subjects reached 2.0 l min(-1). The respiratory frequency (RF), ventilation (VE) and heart rate (HR) for a given oxygen uptake were all higher in women than in men. Significant predictors of failure to reach oxygen uptake of 1.5 and 2.0 l min(-1) were sex, age, body height and weight. Prediction equations are given for respiratory frequency, heart rate and ventilation for an oxygen uptake of 1.0 l min(-1) in women and 1.5 l min(-1) in men; and body height is a strong predictor for all dependent variables. A multiple linear regression analysis in women showed that age was a significant predictor of respiratory frequency (P<0.05), ventilation (P<0.001) and heart rate (P<0.001), while in men age was a significant predictor only of ventilation (P<0.001) during the bicycle exercise protocol.

Tau-66: evidence for a novel tau conformation in Alzheimer's disease.

We have characterized a novel monoclonal antibody, Tau-66, raised against recombinant human tau. Immunohistochemistry using Tau-66 reveals a somatic-neuronal stain in the superior temporal gyrus (STG) that is more intense in Alzheimer's disease (AD) brain than in normal brain. In hippocampus, Tau-66 yields a pattern similar to STG, except that neurofibrillary lesions are preferentially stained if present. In mild AD cases, Tau-66 stains plaques lacking obvious dystrophic neurites (termed herein 'diffuse reticulated plaques') in STG and the hippocampus. Enzyme-linked immunosorbent assay (ELISA) analysis reveals that Tau-66 is specific for tau, as there is no cross-reactivity with MAP2, tubulin, Abeta(1-40), or Abeta(1-42), although Tau-66 fails to react with tau or any other polypeptide on western blots. The epitope of Tau-66, as assessed by ELISA testing of tau deletion mutants, appears discontinuous, requiring residues 155-244 and 305-314. Tau-66 reactivity exhibits buffer and temperature sensitivity in an ELISA format and is readily abolished by SDS treatment. Taken together these lines of evidence indicate that the Tau-66 epitope is conformation-dependent, perhaps involving a close interaction of the proline-rich and the third microtubule-binding regions. This is the first indication that tau can undergo this novel folding event and that this conformation of tau is involved in AD pathology.

Is the risk of developing Alzheimer's disease greater for women than for men?

A large proportion of people with Alzheimer's disease (AD) are women; however, it is not clear whether this is due to higher risk of disease or solely to the larger number of women alive at ages when AD is common. Beginning in 1982, two stratified random samples of people aged > or =65 years in East Boston, Massachusetts underwent detailed, structured clinical evaluation for prevalent (467 people) and incident (642 people from a cohort previously ascertained to be disease-free) probable AD. The prevalence sample was followed for mortality for up to 11 years (through December 1992). The age-specific incidence of AD did not differ significantly by sex (for men vs. women, odds ratio = 0.92; 95% confidence interval (CI): 0.51, 1.67). Controlled for age, prevalence also did not differ significantly by sex (for men vs. women, odds ratio = 1.29; 95% CI: 0.67, 2.48). The increase in risk of mortality due to AD did not vary by sex. The odds ratio for women with AD compared with women without AD was 2.07 (95% CI: 1.21, 3.56). For men, the odds ratio was 2.22 (95% CI: 1.02, 4.81). These findings suggest that the excess number of women with AD is due to the longer life expectancy of women rather than sex-specific risk factors for the disease.

Premorbid reading activity and patterns of cognitive decline in Alzheimer disease.

BACKGROUND: Educational and occupational attainment have been associated with progression of Alzheimer disease in some studies. One hypothesis about this association is that education and occupation are markers for lifelong participation in cognitively stimulating activities like reading. OBJECTIVE: To assess the relation of premorbid reading activity with patterns of cognitive decline in Alzheimer disease. METHODS: During a 4-year period, 410 persons with Alzheimer disease had annual clinical evaluations, which included administration of 17 cognitive function tests from which global, verbal, and nonverbal summary measures were derived. At baseline, a knowledgeable informant was questioned about the affected person's reading frequency and access to reading materials before dementia onset. RESULTS: A composite measure of premorbid reading activity was developed. It had moderately high internal consistency and was positively correlated with education and baseline level of cognitive function. In analyses that controlled for baseline cognitive function, education, and other demographic variables, higher level of premorbid reading activity was associated with more rapid decline on the global cognitive and verbal measures but not on the nonverbal measure. CONCLUSIONS: These results suggest that both the extent and nature of premorbid cognitive experiences may affect how Alzheimer disease pathology is clinically expressed.

Comparison of informal caregiving by black and white older adults in a community population.

OBJECTIVES: To examine the prevalence of informal caregiving and demographic factors associated with caregiving time in older community residents and compare caregiving prevalence and time spent providing care by black and white residents. DESIGN: A cross-sectional, population-based study. SETTING: The study was conducted as part of the Chicago Health and Aging Project (CHAP) in a geographically defined community of black and white residents aged 65 and older. PARTICIPANTS: Participants were 5,924 community residents (61.4% black; 38.6% white) who answered questions about informal caregiving responsibilities during a structured interview about a broad range of health and social factors. METHODS: Data were collected during an in-home interview. Multiple logistic and linear regression models were used to examine the association between caregiving and race, gender, age, marital status, and education. RESULTS: More than 16% of residents had provided care to others during the previous 12 months, and 10.3% were currently providing care. Compared with whites, blacks were 30% more likely to be caregivers, spent almost 13 more hours each week in caregiving activities, and were more likely to assist friends. The probability of caregiving increased significantly with age for married persons, decreased with age for unmarried persons, and was lower for men compared with women. The time spent providing care each week increased significantly with age for married persons and did not differ between men and women. CONCLUSIONS: Although physicians and other healthcare providers typically view older people as the recipients of informal care, individuals older than age 65 provide a substantial amount of care to others with health problems and disability. Most research has focused on the needs of young and middle-aged caregivers, and little is known about the needs of these older caregivers. Future research should use sampling strategies that provide adequate numbers of white and non-white participants for meaningful comparisons. This will permit identification of racial and cultural differences in caregiving so that interventions can be tailored to specific groups.

Six-year effect of depressive symptoms on the course of physical disability in community-living older adults.

BACKGROUND: Late-life depression affects physical health and impedes recovery from physical disability. But whether milder symptoms that occur frequently in the general population increase the risk of developing a disability or decrease the likelihood of recovery remains unclear. OBJECTIVE: To examine the effect of mild symptoms of depression, assessed by a reduced version (10 items, ranging from 0-10) of the Center for Epidemiological Studies-Depression Scale, on the course of physical disability, assessed by items from the Katz Activities of Daily Living Scale, the Rosow-Breslau Functional Health Scale, and the Nagi Index. METHODS: A population-based longitudinal study was conducted, with 6 follow-up interviews of 3434 community-dwelling persons aged 65 years and older in East Boston, Mass. RESULTS: The likelihood of becoming disabled increased with each additional symptom of depression (for the Katz measure: odds ratio, 1.16 per symptom; 95% confidence interval, 1.13-1.19; for the Rosow-Breslau measure: odds ratio, 1.14; 95% confidence interval, 1.11-1.16; and for the Nagi measure: odds ratio, 1.17; 95% confidence interval, 1.14-1.19). As the number of depressive symptoms increased, the likelihood of recovering from a physical disability decreased (for the Katz measure: odds ratio, 0.96; 95% confidence interval, 0.93-0.99; for the Rosow-Breslau measure: odds ratio, 0.86; 95% confidence interval, 0.84-0.89; and for the Nagi measure: odds ratio, 0.89; 95% confidence interval, 0.87-0.91). This effect was not accounted for by age, sex, level of educational attainment, body mass index, or chronic health conditions. CONCLUSION: Mild depressive symptoms in older persons (those aged > or =65 years) are associated with an increased likelihood of becoming disabled and a decreased chance of recovery, regardless of age, sex, and other factors that contribute to physical disability.