Deplete and repeat: microglial CSF1R inhibition and traumatic brain injury.

Traumatic brain injury (TBI) is a public health burden affecting millions of people. Sustained neuroinflammation after TBI is often associated with poor outcome. As a result, increased attention has been placed on the role of immune cells in post-injury recovery. Microglia are highly dynamic after TBI and play a key role in the post-injury neuroinflammatory response. Therefore, microglia represent a malleable post-injury target that could substantially influence long-term outcome after TBI. This review highlights the cell specific role of microglia in TBI pathophysiology. Microglia have been manipulated via genetic deletion, drug inhibition, and pharmacological depletion in various pre-clinical TBI models. Notably, colony stimulating factor 1 (CSF1) and its receptor (CSF1R) have gained much traction in recent years as a pharmacological target on microglia. CSF1R is a transmembrane tyrosine kinase receptor that is essential for microglia proliferation, differentiation, and survival. Small molecule inhibitors targeting CSF1R result in a swift and effective depletion of microglia in rodents. Moreover, discontinuation of the inhibitors is sufficient for microglia repopulation. Attention is placed on summarizing studies that incorporate CSF1R inhibition of microglia. Indeed, microglia depletion affects multiple aspects of TBI pathophysiology, including neuroinflammation, oxidative stress, and functional recovery with measurable influence on astrocytes, peripheral immune cells, and neurons. Taken together, the data highlight an important role for microglia in sustaining neuroinflammation and increasing risk of oxidative stress, which lends to neuronal damage and behavioral deficits chronically after TBI. Ultimately, the insights gained from CSF1R depletion of microglia are critical for understanding the temporospatial role that microglia develop in mediating TBI pathophysiology and recovery.

The middle of the road: results from the aging semantic differential with four cohorts of medical students.

OBJECTIVES: To explore the presence of negative stereotypical attitudes among medical students and the extent to which attitudes changed over time. DESIGN: Analysis of pre- and postexperience administration of attitude measures to four cohorts of medical students (two cohorts as quasi-controls and two cohorts as curriculum "treatment" groups). SETTING: The curriculum of a community-based medical school in the United States. PARTICIPANTS: Four sequential cohorts of medical students. INTERVENTION: Experience in a required comprehensive vertically integrated curriculum. MEASUREMENTS: The Aging Semantic Differential (ASD), using an 85-year-old woman as the cue image. RESULTS: The reliability scores for all administrations were acceptable. The two control cohorts demonstrated no change in attitude scores, whereas the treatment cohorts reflected a slight shift toward more-positive scores. However, all cohorts had scores for all sittings that were in the neutral range; on average students routinely scored 70% of the 32 items neither positively nor negatively. CONCLUSION: These students seemed not to hold negative stereotypes as measured using the ASD. Although two of the 32 items prompted negative stereotyping, and six items elicited positive stereotyping, attitudes were neutral about older adults. Characteristics of the ASD itself or of the response set used in this study may have affected the results.

Geriatric content in medical school curricula: results of a national survey.

Despite recent gains in establishing academic sections, divisions, and departments of geriatrics in medical schools, much remains to be done to meet the medical needs of an aging population. To better understand how medical schools are educating students in geriatric-related topics, all U.S. allopathic and osteopathic medical schools were surveyed in two waves, in 1999 and 2000, using a questionnaire based on recommendations from the Education Committee of the American Geriatrics Society. Responding schools were more likely to address diseases and conditions of aging, psychosocial issues, and ethical issues and less likely to cover anatomic changes, nutrition, knowledge of healthcare financing, outcome measurement, and cultural aspects of aging. Although limited, the results indicate that medical schools have increased coverage of aging-related material, although further expansion of geriatric content will be necessary to meet the needs of an aging society.

Cross-sectional and longitudinal association between antihypertensive medications and cognitive impairment in an elderly population.

BACKGROUND: The effect of antihypertensive medications on cognitive function has not been well studied. The authors' objectives were to investigate the cross-sectional and longitudinal association between the use of antihypertensive medications and cognitive function and to compare different antihypertensive medication classes with regard to this association in an elderly population. METHODS: The medical records of a convenience sample of patients (n = 993 cross-sectional and 350 longitudinal; mean age, 76.8 +/- 0.3 years; 74% women; 87% White) followed at a geriatric practice were reviewed. Data abstracted included demographics, medical history (Alzheimer's disease [AD] or vascular dementia [VaD]), use of antihypertensive medications, and results of cognitive assessments (the Mini-Mental Status Examination [MMSE] and the Clock Draw Test [CDT]). RESULTS: In the cross-sectional analysis, antihypertensive use was not associated with MMSE (p >.05), CDT (p >.05), or dementia diagnosis (odds ratio for AD, 0.8; 95% confidence interval [CI], 0.6 to 1.2; odds ratio for VaD, 1.6; 95% CI, 0.6 to 4.0). In the longitudinal analysis, antihypertensive use was associated with a lower rate of cognitive decline on the MMSE (-0.8 +/- 2 points in users vs -5.8 +/- 2.5 points in nonusers; p =.007) and on the CDT (-0.3 +/- 0.8 points in users vs -2.2 +/- 0.8 points in nonusers; p =.002), and with a lower risk for the development of cognitive impairment (odds ratio, 0.56; 95% CI, 0.38 to 0.83; p =.004). The trend was similar in patients with baseline AD (p =.02). Patients taking diuretics (p =.007), angiotensin-converting enzyme inhibitors (p =.016), and beta-blockers (p =.014) had a lower rate of cognitive decline, and patients taking angiotensin receptor blockers (p =.016) had improved cognitive scores. CONCLUSIONS: Antihypertensive use, particularly diuretics, angiotensin-converting enzymes inhibitors, beta-blockers, and angiotensin receptor blockers, may be associated with a lower rate of cognitive decline in older adults, including those with AD. Until a randomized clinical trial confirms our results, findings of this observational study should be interpreted with caution.

Does Medicaid pay more to a program of all-inclusive care for the elderly (PACE) than for fee-for-service long-term care?

BACKGROUND: In rebalancing from nursing homes (NHs), states are increasing access of NH-certified dually eligible (Medicare/Medicaid) patients to community waiver programs and Programs of All-Inclusive Care for the Elderly (PACE). Prior evaluations suggest Medicaid's PACE capitation exceeds its spending for comparable admissions in alternative care, although the latter may be underestimated. We test whether Medicaid payments to PACE are lower than predicted fee-for-service outlays in a long-term care admission cohort. METHODS: Using grade-of-membership methods, we model health deficits for dual eligibles aged 55 or more entering waiver, PACE, and NH in South Carolina (n = 3,988). Clinical types, membership vectors, and program type prevalences are estimated. We calculate a blend, fitting PACE between fee-for-service cohorts, whose postadmission 1-year utilization was converted to attrition-adjusted outlays. PACE's capitation is compared with blend-based expenditure predictions. RESULTS: Four clinical types describe population health deficits/service needs. The waiver cohort is most represented in the least impaired type (1: 47.1%), NH entrants in the most disabled (4: 38.5%). Most prevalent in PACE was a dementia type, 3 (32.7%). PACE's blend was waiver: 0.5602 (95% CI: 0.5472, 0.5732) and NH: 0.4398 (0.4268, 0.4528). Average Medicaid attrition-adjusted 1-year payments for waiver and NH were $4,177 and $77,945. The mean predicted cost for PACE patients in alternative long-term care was $36,620 ($35,662 and $37,580). PACE's Medicaid capitation was $27,648-28% below the lower limit of predicted fee-for-service payments. CONCLUSIONS: PACE's capitation was well under outlays for equivalent patients in alternative care-a substantial savings for Medicaid. Our methods provide a rate-setting element for PACE and other managed long-term care.

Five-year survival in a Program of All-inclusive Care for Elderly compared with alternative institutional and home- and community-based care.

BACKGROUND: Community-based services are preferred to institutional care for people requiring long-term care (LTC). States are increasing their Medicaid waiver programs, although Program of All-Inclusive Care For Elderly (PACE)-prepaid, community-based comprehensive care-is available in 31 states. Despite emerging alternatives, little is known about their comparative effectiveness. METHODS: For a two-county region of South Carolina, we contrast long-term survival among entrants (n = 2040) to an aged and disabled waiver program, PACE, and nursing homes (NHs), stratifying for risk. Participants were followed for 5 years or until death; those lost to follow-up or surviving less than 5 years as on August 8, 2005 were censored. Analyses included admission descriptive statistics and Kaplan-Meier curves. To address cohort risk imbalance, we employed an established mortality risk index, which showed external validity in waiver, PACE, and NH cohorts (log-rank tests = 105.42, 28.72, and 52.23, respectively, all p < .001; c-statistics = .67, .58, .65, p < .001). RESULTS: Compared with waiver (n = 1,018) and NH (n = 468) admissions, PACE participants (n = 554) were older, more cognitively impaired, and had intermediate activities of daily living dependency. PACE mortality risk (72.6% high-to-intermediate) was greater than in waiver (58.8%), and similar to NH (71.6%). Median NH survival was 2.3 years. Median PACE survival was 4.2 years versus 3.5 in waiver (unstratified, log rank = .394; p = .53), but accounting for risk, PACE's advantage is significant (log rank = 5.941 (1); p = .015). Compared with waiver, higher risk admissions to PACE were most likely to benefit (moderate: PACE median survival = 4.7 years vs waiver 3.4; high risk: 3.0 vs 2.0). CONCLUSION: Long-term outcomes of LTC alternatives warrant greater research and policy attention.

Does it stick? Effects of an integrated vertical undergraduate aging curriculum on medical and surgical residents.

Experts acknowledge the unmet need for all physicians to have basic knowledge of aging and competency in geriatric care given the context of population aging. The University of South Carolina (USC) School of Medicine implemented a highly successful program of aging-oriented undergraduate medical training, including a geriatrics vertical curriculum and its senior mentor program-a required, 4-year experience matching students with older community volunteers, referred to herein as the integrated vertical curriculum in geriatrics (IVC). In earlier work, it was established that IVC graduating classes were significantly more likely to report exposure to and coverage of various geriatrics topics than prior USC classes or other U.S. medical graduates. Here the results of a follow-up survey of USC graduating classes before and after exposure to the IVC and contemporaneous Medical University of South Carolina (MUSC) graduates after two to three years of residency (before the initiation of a senior mentor program at MUSC) is reported. Of 403 graduates, 227 returned questionnaires (response rate 56%). Significantly more IVC (2004) than pre-IVC (2003) and 2003 and 2004 MUSC graduates rated themselves fairly or very well prepared by their undergraduate education to treat older adults seen in residency (95% vs 77% and 52%; P<.001). Implications of this and other findings are discussed.

Use of a questionnaire to screen for frailty in the elderly: an exploratory study.

BACKGROUND AND AIMS: In a pilot study of community-dwelling geriatric clinic patients (N=48, aged 63-90) we examined the use of a questionnaire to classify frailty status by comparing it with standardized markers of frailty. The questionnaire, developed by Strawbridge et al. in 1998, defines frailty as difficulty in more than one of four domains of functioning: physical, cognitive, sensory, and nutritive. METHODS: Subjects were classified as frail or not frail by questionnaire and assignment was compared with testing of physical and cognitive measures in cross-sectional analysis. Demographic variables, functional inventories, physical activity levels, clinician impression of frailty, and 3-year health outcomes were also examined. RESULTS: Thirty-three percent of subjects were classified as frail. Frailty classification by the Strawbridge questionnaire was correlated to Timed Up and Go and repetitive Sit-to-Stand tests, bimanual dexterity and cognitive tests. A discrepancy was found between assignment of cognitive difficulty, by questionnaire and cognitive performance. When overall Strawbridge frailty scores were modified to account for those with poor cognitive performance who did not report cognitive difficulty, the prevalence of frailty increased to 42%. At 3-year follow-up, the modified Strawbridge frailty classification (p<0.05) and clinician impression of frailty (p<0.01) were both significant predictors of death and institutionalization combined. CONCLUSIONS: This study serves as an initial inquiry into the potential validity and utility of the Strawbridge frailty questionnaire as a simple screening tool to identify patients who may warrant detailed functional testing.

Assessing geriatrics in undergraduate medical education: two different approaches.

Most medical schools do not have a separate course in geriatrics, but rather incorporate geriatrics into existing courses. Tracking and assessing curriculum content is more difficult in this setting. This paper describes and compares two approaches to assess curriculum content in geriatrics: a survey of course directors and a course objectives review. The results suggest that course directors report more geriatric content when asked as part of a regular survey than they identify as specific course objectives. Course objectives may be more reflective of the actual emphasis placed on aging-related material in courses. These two approaches appear to be complementary. Medical educators may find both self-report and course objective analysis to be useful and complementary in tracking geriatric material in the undergraduate medical curriculum.