Cross-national neuropsychological research is needed to understand the social, economic, and cultural factors associated with cognitive risk and resilience across global aging populations. Memory and language have been shown to be sensitive to age-related cognitive decline and pathological cognitive aging processes and may be more sensitive to subtle cognitive decline than measures of global cognitive function. Thus, we aimed to derive and validate harmonized cognitive domain scores for memory and language across population-based studies in the US and Mexico.

Data came from the Health and Retirement Study (HRS) Harmonized Cognitive Assessment Protocol (HCAP) and the Mexican Health and Aging Study (MHAS) Ancillary Study on Cognitive Aging (Mex-Cog). We used confirmatory factor analysis methodology to create statistically co-calibrated cognitive domains of memory and language. We performed differential item functioning (DIF) analysis to evaluate measurement differences across studies, using a cultural neuropsychological approach to identify comparable items across studies (i.e., cross-study anchors). We evaluated harmonized scores by examining their relationship to age and education in each study.

We included 3347 participants from the HRS-HCAP study [Mage=76.6(7.5), 60% female] and 2042 participants from the Mex-Cog study [Mage=68.1(9.0), 59% female]. Education was classified according to the International Standard Classification of Education in the following categories (HRS-HCAP and Mex-Cog, respectively): none or early childhood education: (0.7%; 50.5%), primary education (4.1%; 22.3%), lower secondary education (7.1%; 15.7%), upper secondary education (41.1%; 3.0%), and any college (47.1%; 8.5%). DIF analyses revealed that 5 out of the 7 memory items and 1 out of the 12 language items demonstrated statistical evidence of measurement differences across studies, meaning that these items measured each underlying cognitive construct differently across studies. After adjusting for DIF by not allowing the items with DIF to be cross-study anchors, harmonized memory and language scores showed generally the expected associations with age and education in each study. Increasing age was associated with lower memory (r=-0.40 in HRS-HCAP; r=-0.44 in Mex-Cog) and language (r=-0.31 in HRS-HCAP and r=-0.67 in Mex-Cog) scores. Increasing years of education was associated with better memory and language scores, with mean scores ranging from z=-0.86 and z=-0.29 among those with a primary education or lower to z=0.33 and z=0.90 among those with any college, for HRS-HCAP and Mex-Cog, respectively.

A cultural neuropsychology approach to statistical harmonization facilitates the generation of harmonized measures of cognitive functioning in cross-national studies. Future work can utilize these harmonized cognitive scores to investigate determinants of late-life cognitive decline and dementia in the US and Mexico.

The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS).

The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery was used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data.

For the eight domains of cognitive functioning identified (orientation, memory [immediate, delayed, and recognition], set shifting, attention/speed, language/fluency, and visuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where fit must be perfect and is not informative. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94).

The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used to operationalize notions of neurocognitive impairment, and as a starting point for prioritizing pre-statistical harmonization and evaluating configural invariance in cross-national research.

Preclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.

Effects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).

Following 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.

The data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.

Sunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.

To conduct a contemporary detailed assessment of outpatient antibiotic prescribing and outcomes for positive urine cultures in a mixed-sex cohort.

Multicenter retrospective cohort review.

The study was conducted using data from 31 Veterans’ Affairs medical centers.

Outpatient adults with positive urine cultures.

From 2016 to 2019, data were extracted through a nationwide database and manual chart review. Positive urine cultures were reviewed at the chart, clinician, and aggregate levels. Cases were classified as cystitis, pyelonephritis, or asymptomatic bacteriuria (ASB) based upon documented signs and symptoms. Preferred therapy definitions were applied for subdiagnoses: ASB (no antibiotics), cystitis (trimethoprim-sulfamethoxazole, nitrofurantoin, β-lactams), and pyelonephritis (trimethoprim-sulfamethoxazole, fluoroquinolone). Outcomes included 30-day clinical failure or hospitalization. Odds ratios for outcomes between treatments were estimated using logistic regression.

Of 3,255 cases reviewed, ASB was identified in 1,628 cases (50%), cystitis was identified in 1,156 cases (36%), and pyelonephritis was identified in 471 cases (15%). Of all 2,831 cases, 1,298 (46%) received preferred therapy selection and duration for cases where it could be defined. The most common antibiotic class prescribed was a fluoroquinolone (34%). Patients prescribed preferred therapy had lower odds of clinical failure: preferred (8%) versus nonpreferred (10%) (unadjusted OR, 0.74; 95% confidence interval [CI], 0.58–0.95; P = .018). They also had lower odds of 30-day hospitalization: preferred therapy (3%) versus nonpreferred therapy (5%) (unadjusted OR, 0.55; 95% CI, 0.37–0.81; P = .002). Odds of clinical treatment failure or hospitalization was higher for β-lactams relative to ciprofloxacin (unadjusted OR, 1.89; 95% CI, 1.23–2.90; P = .002).

Clinicians prescribed preferred therapy 46% of the time. Those prescribed preferred therapy had lower odds of clinical failure and of being hospitalized.