National Norms for Hospitalizations Due to Ambulatory Care Sensitive Conditions among Adults in the US.

BACKGROUND: Ambulatory care sensitive conditions (ACSCs) are acute or chronic health issues that lead to potentially preventable hospitalizations when not treated in the outpatient primary care setting. OBJECTIVE: To describe national hospitalization rates due to ACSCs among adult inpatients in the US. DESIGN: A retrospective cross-sectional analysis of the 2018 US National Inpatient Sample (NIS) dataset from the Healthcare Cost and Utilization Project at the Agency of Healthcare Research and Quality was completed in the year 2022. PARTICIPANTS: Participants were adult inpatients from community hospitals in 48 states of the US and District of Columbia. MAIN MEASURES: ACSC admission rates were calculated using ICD-10 codes and the Purdy ACSC definition. The admission rates were weighted to the US inpatient population and stratified by age, sex, and race. KEY RESULTS: ACSC hospitalization rates varied considerably across age and average number of hospitalizations varied across sex and race. ACSC hospitalization rates increased with age, male sex, and Native American and Black race. The most common ACSCs were pneumonia, diabetes, and congestive heart failure. CONCLUSIONS: Previous studies have emphasized the importance of preventable hospitalizations, however, the national rates for ACSC hospitalizations across all ages in the US have not been reported. The national rates presented will facilitate comparisons to identify hospitals and health care systems with higher-than-expected rates of ACSC admissions that may suggest a need for improved primary care services.

Gut- and oral-dysbiosis differentially impact spinal- and bulbar-onset ALS, predicting ALS severity and potentially determining the location of disease onset.

BACKGROUND: Prior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field. METHODS: ALS patients diagnosed within 12 months and their spouses as healthy controls (n = 150 couples) were screened. For eligible sALS and bALS patients (n = 36) and healthy controls (n = 20), 16S rRNA next-generation sequencing was done in fecal and saliva samples after DNA extractions to examine gut- and oral-microbiome differences. Microbial translocation to blood was measured by blood lipopolysaccharide-binding protein (LBP) and 16S rDNA levels. ALS severity was assessed by Revised ALS Functional Rating Scale (ALSFRS-R). RESULTS: sALS patients manifested significant gut-dysbiosis, primarily driven by increased fecal Firmicutes/Bacteroidetes-ratio (F/B-ratio). In contrast, bALS patients displayed significant oral-dysbiosis, primarily driven by decreased oral F/B-ratio. For sALS patients, gut-dysbiosis (a shift in fecal F/B-ratio), but not oral-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.8006, P < 0.0001) and more severe symptoms (r = 0.9470, P < 0.0001). In contrast, for bALS patients, oral-dysbiosis (a shift in oral F/B-ratio), but not gut-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.9860, P < 0.0001) and greater disease severity (r = 0.9842, P < 0.0001). For both ALS subtypes, greater microbial translocation was associated with more severe symptoms (sALS: r = 0.7924, P < 0.0001; bALS: r = 0.7496, P = 0.0067). Importantly, both sALS and bALS patients displayed comparable oral-motor deficits with associations between oral-dysbiosis and severity of oral-motor deficits in bALS but not sALS. This suggests that oral-dysbiosis is not simply caused by oral/bulbar/respiratory symptoms but represents a pathological driver of bALS. CONCLUSIONS: We found increasing gut-dysbiosis with worsening symptoms in sALS patients and increasing oral-dysbiosis with worsening symptoms in bALS patients. Our findings support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease. Our study suggests correcting gut-dysbiosis as a therapeutic strategy for sALS patients and correcting oral-dysbiosis as a therapeutic strategy for bALS patients.

Preserving independence among under-resourced older adults in the Southeastern United States: existing barriers and potential strategies for research.

Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized health disparities reported in other populations and disciplines. In the U.S., the Southeastern region also known as "the Deep South", is an economically and culturally unique region ravaged by pervasive health disparities - thus it is critical to evaluate barriers to independent aging in this region along with strategies to overcome these barriers. The objective of this narrative review is to highlight unique barriers to independent aging in the Deep South and to acknowledge gaps and potential strategies and opportunities to fill these gaps. We have synthesized findings of literature retrieved from searches of computerized databases and authoritative texts. Ultimately, this review aims to facilitate discussion and future research that will help to address the unique challenges to the preservation of independence among older adults in the Deep South region.

Comparison of Two Methods for Implementing Comfort Care Order Sets in the Inpatient Setting: a Cluster Randomized Trial.

BACKGROUND: There is an ongoing need for interventions to improve quality of end-of-life care for patients in inpatient settings. OBJECTIVE: To compare two methods for implementing a Comfort Care Education Intervention for Palliative Care Consultation Teams (PCCT) in Veterans Affairs Medical Centers (VAMCs). DESIGN: Cluster randomized implementation trial conducted March 2015-April 2019. PCCTs were assigned to a traditional implementation approach using a teleconference or to an in-person, train-the-champion workshop to prepare PCCTs to be clinical champions at their home sites. PARTICIPANTS: One hundred thirty-two providers from PCCTs at 47 VAMCs. INTERVENTIONS: Both training modalities involved review of educational materials, instruction on using an electronic Comfort Care Order Set, and coaching to deliver the intervention to other providers. MAIN MEASUREMENTS: Several processes of care were identified a priori as quality endpoints for end-of-life care (last 7 days) and abstracted from medical records of veterans who died within 9 months before or after implementation (n = 6,491). The primary endpoint was the presence of an active order for opioid medication at time of death. Secondary endpoints were orders/administration of antipsychotics, benzodiazepines, and scopolamine, do-not-resuscitate orders, advance directives, locations of death, palliative care consultations, nasogastric tubes, intravenous lines, physical restraints, pastoral care visits, and family presence at/near time of death. Generalized estimating equations were conducted adjusting for potential covariates. KEY RESULTS: Eighty-eight providers from 23 VAMCs received teleconference training; 44 providers from 23 VAMCs received in-person workshop training. Analyses found no significant differences between intervention groups in any process-of-care endpoints (primary endpoint AOR (CI) = 1.18 (0.74, 1.89). Furthermore, pre-post changes were not significant for any endpoints (primary endpoint AOR (CI) = 1.16 (0.92, 1.46). Analyses may have been limited by high baseline values on key endpoints with little room for improvement. CONCLUSION: Findings suggest the clinical effectiveness of palliative care educational intervention was not dependent on which of the two implementation methods was used. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02383173.

Convergent Validity of In-Person Assessment of Inpatients With Traumatic Brain Injury Using the Brief Test of Adult Cognition by Telephone (BTACT).

OBJECTIVE: To examine convergent validity of the Brief Test of Adult Cognition by Telephone (BTACT) by determining correlation with established neuropsychological tests, administered an average of 4.4 days apart, in an inpatient traumatic brain injury (TBI) population. SETTING: Acute inpatient rehabilitation hospital. PARTICIPANTS: Fifty-five patients receiving inpatient rehabilitation for new-onset TBI (69.1% male; mean age = 37 years, SD = 14 years). DESIGN: Cross-sectional, secondary data analysis. MAIN MEASURES: BTACT; California Verbal Learning Test-second edition (CVLT-2); Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span; Trail Making Test; semantic fluency; phonemic fluency; Symbol Digit Modalities Test; Wisconsin Card Sorting Test. RESULTS: The BTACT was significantly associated with established neuropsychological tests across composite scores of overall cognition (r = 0.64, P < .001), episodic verbal memory (r = 0.66, P < .001), and executive function (r = 0.56, P < .001). For BTACT subtests, Word List Immediate Recall and Word List Delayed Recall were correlated with CVLT-2 learning trials total score (r = 0.57, P < .01) and long delay free recall (r = 0.60, P < .001), respectively. BTACT Digits Backward correlated with WAIS-IV Digit Span (r = 0.51, P < .01). BTACT Animal Fluency was associated with semantic fluency (r = 0.65, P < .01), phonemic fluency (r = 0.60, P < .01), and Trail Making Test Part B (r = 0.39, P < .01). CONCLUSION: BTACT composite scores of overall cognition, verbal memory, and executive function demonstrate initial convergent validity in a TBI inpatient population. Future research should examine validity in a larger sample of individuals with TBI.

Research Letter: Performance of the Brief Test of Adult Cognition by Telephone in a National Sample.

OBJECTIVE: To create a larger, more representative community comparison sample of the Brief Test of Adult Cognition by Telephone (BTACT) data to facilitate assessment of cognitive function in research studies. SETTING: National US community-based survey. PARTICIPANTS: In total, 6747 healthy adults aged 23 to 84 years (53% female; mean age = 55 years, SD = 13). DESIGN: Secondary data analysis of BTACT data collected from the National Survey of Midlife Development in the United States (MIDUS) II and MIDUS Refresher cohorts. MAIN MEASURES: The BTACT, a brief (15-20 minute) measure of global cognitive function validated for telephone administration. RESULTS: This article provides BTACT community comparison sample data based on age, sex, and education from a national sample. Similar to other cognitive measures, BTACT scores decreased with age and increased with education. CONCLUSIONS: The BTACT community comparison sample will facilitate investigation of cognitive functioning in large-scale traumatic brain injury research studies and will support secondary analysis of existing BTACT data gathered through the MIDUS study.

Refining understanding of life satisfaction in elderly persons with traumatic brain injury using age-defined cohorts: a TBI model systems study.

OBJECTIVE: Examine effects of age cohort on post-injury life satisfaction in elderly persons with TBIDesign: Retrospective cohortSetting: TBI Model Systems centers. PARTICIPANTS: 5,109 elderly participants with TBI in the TBI Model Systems National DatabaseInterventions: Not applicableMain Outcome Measures: Demographics, injury characteristics and cause, outcomes, age at time of analysis, time to follow commands, maximum follow-up period, and scores on the Satisfaction With Life Scale (SWLS) and Participation Assessment with Recombined Tools-Objective (PART-O) scores at 1, 2, 5, or 10 years post-injury. RESULTS: Life satisfaction post-TBI across groups increased with age. The young-old sub-group demonstrated the poorest life satisfaction outcomes, while the oldest sub-group experienced greatest life satisfaction. In contrast, participation decreased with age. CONCLUSIONS: Findings show diversity in satisfaction with life following moderate to severe TBI for three elderly age-cohorts. Differences may be due to variations in generation-based lived experience, in perceived meaningfulness of participation, could echo prior evidence of greater resilience in the oldest group, or could reflect bias within the study sample. Further research into between- and within- differences for elderly TBI age cohorts is needed to more precisely meet their needs for physical and functional rehabilitation as well as psychological supports.

The Relation Between Pet Ownership, Anxiety, and Depressive Symptoms in Late Life: Propensity Score Matched Analyses.

The purpose of this study was to explore the differences in anxiety and depressive symptoms between older adult pet owners and non-pet owners after accounting for various correlates. Research findings on the anxiety-relieving and antidepressant effects of late-life pet ownership are mixed and limited. This may be due in part to various characteristics that impact the likelihood of owning a pet. Propensity score matching was used to pair 169 pet owners with 169 non-pet owners aged 70 to 91 years who participated in the University of Alabama at Birmingham Study of Aging. One set of propensity scores was created using age, sex, race, rurality, marital status, and income, as well as self-reported health, difficulty with activities of daily living, and difficulty with instrumental activities of daily living. A second set of scores was created using age, sex, race, rurality, marital status, and income. Multiple linear regression analyses were then used to explore the relation between pet ownership status and anxiety or depressive symptoms, controlling for the other symptoms. Pet ownership was significantly associated with lower self-reported anxiety symptoms (ß = -0.14) but not depressive symptoms (ß = -0.03) in the data matched without health variables. When propensity score matching included health variables, pet ownership was related to neither symptoms of anxiety (ß = -0.08) nor depression (ß = 0.05). These results suggest that owning a pet in later life is related to fewer anxiety symptoms, over and above the impact of depressive symptoms, even after accounting for various demographic and economic covariates. However, general and functional health appear to be critical to this relation, but the direction of this relation could not be determined from our analyses (i.e., it is not clear whether the relation between pet ownership and anxiety symptoms is confounded by, mediates, or is mediated by health). This study is the first large-scale analysis to find a significant relation between pet ownership and fewer anxiety symptoms in older adults.

Association of peripheral artery disease with life-space mobility restriction and mortality in community-dwelling older adults.

OBJECTIVE: Symptomatic peripheral artery disease (PAD) impairs walking, but data on the impact of PAD on community mobility is limited. Life-space mobility measures the distance, frequency, and assistance needed as older adults move through geographic areas extending from their bedroom (life-space mobility score: 0) to beyond their town (life-space mobility score: 120). We evaluated the association of PAD with longitudinal life-space mobility trajectory. METHODS: Participants were part of the University of Alabama at Birmingham Study of Aging, a longitudinal study of community-dwelling older adults who were observed from 2001 to 2009. We limited our analysis to those who survived at least 6 months (N = 981). PAD was based on self-report with verification by physician report and hospital records. Our primary outcome was life-space mobility score assessed every 6 months. A multilevel change model (mixed model) was used to determine the association between PAD and life-space mobility trajectory during a median 7.9 years of follow-up. RESULTS: Participants had a mean age of 75.7 (standard deviation, 6.7) years; 50.5% were female, and 50.4% were African American. PAD prevalence was 10.1%, and 57.1% of participants with PAD died. In participants with both PAD and life-space restriction, defined as life-space mobility score <60, we observed the highest mortality (73.1%). In a multivariable adjusted mixed effects model, participants with PAD had a more rapid decline in life-space mobility by -1.1 (95% confidence interval [CI], -1.9 to -0.24) points per year compared with those without PAD. At 5-year follow-up, model-adjusted mean life-space mobility was 48.1 (95% CI, 43.5-52.7) and 52.4 (95% CI, 50.9-53.8) among those with and without PAD, respectively, corresponding to a restriction in independent life-space mobility at the level of one's neighborhood. CONCLUSIONS: Life-space mobility is a novel patient-centered measure of community mobility, and PAD is associated with significant life-space mobility decline among community-dwelling older adults. Further study is needed to mechanistically confirm these findings and to determine whether better recognition and treatment of PAD alter the trajectory of life-space mobility.

Two-point, parallel-beam focused laser differential interferometry with a Nomarski prism.

A Nomarski polarizing prism has been used in conjunction with a focused laser differential interferometer to measure the phase velocity of a density disturbance at sampling frequencies ≥10MHz. Use of this prism enables the simultaneous measurement of density disturbances at two closely spaced points that can be arbitrarily oriented about the instrument's optical axis. The orientation is prescribed by rotating the prism about this axis. Since all four beams (one beam pair at each measurement point) propagate parallel to one another within the test volume, any bias imparted by density fluctuations away from the measurement plane on the disturbance phase velocity is minimized. A laboratory measurement of a spark-generated shock wave and a wind tunnel measurement of a second-mode instability wave on a cone model in a Mach 6 flow are presented to demonstrate the performance of the instrument. High-speed schlieren imaging is used in both cases to verify the results obtained with the instrument.

Social and Demographic Predictors of Nutritional Risk: Cross-sectional Analyses From the UAB Study of Aging II.

Social factors may disparately affect access to food and nutritional risk among older adults by race and gender. This study assesses these associations using the Mini Nutritional Assessment among 414 community-dwelling persons 75+ years of age in Alabama. Descriptive analyses on the full sample and by African American men, African American women, white men, and white women showed that mean scores for the full Mini Nutritional Assessment differed by groups, with African American men and African American women having the highest nutritional risk. Multivariable analyses indicated that social factors affect nutritional risk differently by race and gender. Nutritional risk interventions are warranted for older adults.

The effect of donepezil on the cognitive ability early in the course of recovery from traumatic brain injury.

OBJECTIVE: To investigate the effect of donepezil on cognitive ability in patients who have sustained a traumatic brain injury (TBI). We hypothesized that donepezil, an acetylcholinesterase inhibitor, would enhance cognitive recovery beyond that of usual care in an acute rehabilitation facility. METHODS: This retrospective, longitudinal analysis included 55 patients who were non-randomly prescribed donepezil during acute care and compared them to 74 patients who received usual rehabilitation treatment. All 129 patients completed neuropsychological assessment at two time points. Donepezil was increased from 5 to 10 mg 7-10 days after initiation and maintained until follow-up cognitive assessment. MAIN OUTCOMES: Primary cognitive abilities of interest included processing speed, attention and memory. Cognitive and functional abilities were assessed by a standard neuropsychological battery for TBI. RESULTS: Propensity scores were used to adjust for differences between groups. Mixed effect model analysis showed no significant differences between treatment and control groups on all neuropsychological subtests over time. CONCLUSIONS: Acute administration of donepezil did not significantly improve measures of cognitive or functional ability beyond that of treatment as usual in patients with moderate-to-severe TBI.

Kilocalorie Expenditure and All-Cause Mortality in Older Male Veterans and Nonveterans.

The objective of this study was to determine the effect of self-reported leisure-time physical activity, converted to kilocalorie expenditure and expressed as average daily expenditure, on all-cause mortality among older males 65 years of age and older in the University of Alabama at Birmingham (UAB) Study of Aging (SOA). Mean age of participants was 75.4 years. Multivariable Cox proportional hazard models evaluated the predictors of overall survival. Kilocalorie expenditure (p = .01), Black race (p = .02), young age (p < .00), fewer depressive symptoms (p = .00), and absence of cognitive impairment (p < .00) were significant independent predictors of higher rates of survival. Low body mass index was a significant independent predictor of death (p = .03). Veteran status did not improve survival. Further study about kilocalorie expenditure and mortality could lead to reductions in premature mortality in community-dwelling older men in the Deep South.

G2019S-LRRK2 Expression Augments α-Synuclein Sequestration into Inclusions in Neurons.

UNLABELLED: Pathologic inclusions define α-synucleinopathies that include Parkinson's disease (PD). The most common genetic cause of PD is the G2019S LRRK2 mutation that upregulates LRRK2 kinase activity. However, the interaction between α-synuclein, LRRK2, and the formation of α-synuclein inclusions remains unclear. Here, we show that G2019S-LRRK2 expression, in both cultured neurons and dopaminergic neurons in the rat substantia nigra pars compact, increases the recruitment of endogenous α-synuclein into inclusions in response to α-synuclein fibril exposure. This results from the expression of mutant G2019S-LRRK2, as overexpression of WT-LRRK2 not only does not increase formation of inclusions but reduces their abundance. In addition, treatment of primary mouse neurons with LRRK2 kinase inhibitors, PF-06447475 and MLi-2, blocks G2019S-LRRK2 effects, suggesting that the G2019S-LRRK2 potentiation of inclusion formation depends on its kinase activity. Overexpression of G2019S-LRRK2 slightly increases, whereas WT-LRRK2 decreases, total levels of α-synuclein. Knockdown of total α-synuclein with potent antisense oligonucleotides substantially reduces inclusion formation in G2019S-LRRK2-expressing neurons, suggesting that LRRK2 influences α-synuclein inclusion formation by altering α-synuclein levels. These findings support the hypothesis that G2019S-LRRK2 may increase the progression of pathological α-synuclein inclusions after the initial formation of α-synuclein pathology by increasing a pool of α-synuclein that is more susceptible to forming inclusions. SIGNIFICANCE STATEMENT: α-Synuclein inclusions are found in the brains of patients with many different neurodegenerative diseases. Point mutation, duplication, or triplication of the α-synuclein gene can all cause Parkinson's disease (PD). The G2019S mutation in LRRK2 is the most common known genetic cause of PD. The interaction between G2019S-LRRK2 and α-synuclein may uncover new mechanisms and targets for neuroprotection. Here, we show that expression of G2019S-LRRK2 increases α-synuclein mobility and enhances aggregation of α-synuclein in primary cultured neurons and in dopaminergic neurons of the substantia nigra pars compacta, a susceptible brain region in PD. Potent LRRK2 kinase inhibitors, which are being developed for clinical use, block the increased α-synuclein aggregation in G2019S-LRRK2-expressing neurons. These results demonstrate that α-synuclein inclusion formation in neurons can be blocked and that novel therapeutic compounds targeting this process by inhibiting LRRK2 kinase activity may slow progression of PD-associated pathology.

Challenging Assumptions About African American Participation in Alzheimer Disease Trials.

OBJECTIVE: The authors investigated potential effects of increased African American participation in Alzheimer disease (AD) and mild cognitive impairment (MCI) clinical trials by examining differences in comorbid conditions and treatment outcome affecting trial design. METHODS: Using a meta-database of 18 studies from the Alzheimer's Disease Cooperative Study and the Alzheimer's Disease Neuroimaging Initiative, a cohort of 5,164 subjects were included for whom there were baseline demographic data and information on comorbid disorders, grouped by organ system. Meta-analysis was used to compare prevalence of comorbidities, dropouts, and rates of change on the cognitive subscale of the Alzheimer's Disease Assessment Scale by race. Clinical trial scenarios similar to recent therapeutic trials were simulated to determine effects of increased African American participation on statistical power. RESULTS: Approximately 7% of AD, 4% of MCI, and 11% of normal participants were African American. African American subjects had higher prevalence of cardiovascular disorders (odds ratio: 2.10; 95% confidence interval [CI]: 1.71-2.57) and higher rate of dropouts (odds ratio: 1.60; 95% CI: 1.15-2.21) compared with whites but lower rates of other disorders. There were no significant differences in rate of progression (-0.862 points/year; 95% CI: -1.89 to 0.162) by race and little effect on power in simulated trials with sample sizes similar to current AD trial designs. CONCLUSION: Increasing African American participation in AD clinical trials will require adaptation of trial protocols to address comorbidities and dropouts. However, increased diversity is unlikely to negatively affect trial outcomes and should be encouraged to promote generalizability of trial results.

Performance of the NINDS-CSN 5-minute protocol in a national population-based sample.

In 2006, the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards recommended a 5-Minute Protocol as a brief screening instrument for vascular cognitive impairment (VCI). We report demographically adjusted norms for the 5-Minute Protocol and its relation to other measures of cognitive function and cerebrovascular risk factors. We performed a cross-sectional analysis of 7199 stroke-free adults in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study on the NINDS-CSN 5-Minute Protocol score. Total scores on the 5-Minute Protocol were inversely correlated with age and positively correlated with years of education, and performance on the Six-Item Screener, Word List Learning, and Animal Fluency (all p-values <.001). Higher cerebrovascular risk on the Framingham Stroke Risk Profile (FSRP) was associated with lower total 5-Minute Protocol scores (p <.001). The 5-Minute Protocol also differentiated between participants with and without confirmed stroke and with and without stroke symptom histories (p <.001). The NINDS-CSN 5-Minute Protocol is a brief, easily administered screening measure that is sensitive to cerebrovascular risk and offers a valid method of screening for cognitive impairment in populations at risk for VCI.

Effect of APOE genotype status on targeted clinical trials outcomes and efficiency in dementia and mild cognitive impairment resulting from Alzheimer's disease.

BACKGROUND: The apolipoprotein E (APOE) ε4 genotype has been recommended as a potential inclusion or exclusion criterion in targeted clinical trials for Alzheimer's disease (AD) and mild cognitive impairment (MCI) resulting from AD, and has been implemented in trials of immunotherapeutic agents. METHODS: We tested this recommendation with clinical trial simulations using participants from a meta-database of 19 studies to create trial samples with APOE ε4 proportions ranging from 0% (all noncarriers) to 100% (all carriers). For each percentage of APOE ε4 carriers, we resampled the database randomly for 1000 trials for each trial scenario, planning for 18- or 24-month trials with samples from 50 to 400 patients per treatment or placebo group, up to 40% dropouts, and outcomes on the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog) with effect sizes from 0.15 to 0.75, and calculated statistical power. RESULTS: Enrichment of clinical trial participants based on APOE ε4 carrier status resulted in minimal increases in power compared with enrolling participants with the APOE ε3 genotype only or enrolling patients without regard to APOE genotype. Increased screening requirements to enhance the sample would offset gains in power. CONCLUSIONS: Although samples enriched for APOE ε4 carriers in AD or MCI clinical trials showed slightly more cognitive impairment and greater decline using the number APOE ε4 alleles as an inclusion criterion most likely would not result in more efficient trials, and trials would take longer because fewer patients would be available. The APOE ε4/εX (where X = 2, 3 or 4) genotype could be useful, however, as an explanatory variable or covariate if warranted by a drug's action.

Changes in Life-Space Mobility With Loss of Relatives and Friends Among Older Adults: Results From the UAB Study of Aging.

BACKGROUND AND OBJECTIVES: Increasing age brings a greater risk of death of friends and family (hereafter referred to as loss) potentially impacting individuals' life-space mobility (LSM) trajectory. RESEARCH DESIGN AND METHODS: Using the UAB study of aging, we examined differences in LSM trajectories of 1,000 community-dwelling older Alabamians (65 + years) with and without loss over 8.5 years. We measured LSM using UAB's Life-Space Assessment (LSA), a validated instrument assessing movement through zones ranging from their bedroom to out of town. We assessed loss every 6 months using a standard bereavement questionnaire capturing spousal, other relative, or friend loss. We used piecewise linear mixed-effects models to compare LSA trajectories. RESULTS: At baseline, those who later experienced loss, compared with those who did not were younger, more likely to be female, and overall in better health. Those without loss had a baseline mean LSA score of 49.5 and a decline of 0.08 points per year (p < .001). Those with loss had a baseline LSA score of 60 and declined by 1.0 point per year before loss (p < .001), accelerating to 1.8 points per year after loss (p < .001). DISCUSSION AND IMPLICATIONS: Those with loss do not experience acute decline postloss but do have an acceleration of the preexisting decline. Although additional research may explain the impact of loss on LSM; this finding suggests that more interventions such as social, mental, or health care services, may be needed for those who experience loss. Specifically, bereaved individuals may benefit from it.

Changes in multimorbidity among hospitalized adults in the US.

Objective: This investigation examines burden of comorbidity measured by the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI) among inpatients based on age, sex, and race. Methods: Cross-sectional analysis of 2012-2018 US NIS datasets. Participants were inpatients 55y+. ICD-9/10 codes for admitting diagnoses were used to calculate disease burden using the CCI and ECI. Unweighted mean CCI and ECI scores were compared across demographic variables. Results: An increase in mean CCI and ECI scores across age, sex, and races (p<.001) was identified. Compared to the youngest age group (55-59y), all age groups had higher mean CCI and ECI adjusting for time (p<.001). Increases were greatest in older age groups until age 80-84 for CCI and 85-89 for ECI. The female group had lower CCI adjusting for time (p<.001) compared to males. There was no difference between sex groups in mean ECI (p=.409). Compared with the White group, all other race groups had higher mean CCI adjusting for time (p<.001). Black inpatients had the highest CCI followed by Native American inpatients. Findings were similar for ECI, but with no difference between Hispanic and White groups (p=.434). Conclusions: Growing multimorbidity burden among adult inpatients across age, sex, and race supports the continued need for programs for preventing and reducing multimorbidity, especially among communities that experience health inequity including older, Black, and Native American patients.