Advancing responsible genomic analyses of ancient mollusc shells.

The analysis of the DNA entrapped in ancient shells of molluscs has the potential to shed light on the evolution and ecology of this very diverse phylum. Ancient genomics could help reconstruct the responses of molluscs to past climate change, pollution, and human subsistence practices at unprecedented temporal resolutions. Applications are however still in their infancy, partly due to our limited knowledge of DNA preservation in calcium carbonate shells and the need for optimized methods for responsible genomic data generation. To improve ancient shell genomic analyses, we applied high-throughput DNA sequencing to 27 Mytilus mussel shells dated to ~111-6500 years Before Present, and investigated the impact, on DNA recovery, of shell imaging, DNA extraction protocols and shell sub-sampling strategies. First, we detected no quantitative or qualitative deleterious effect of micro-computed tomography for recording shell 3D morphological information prior to sub-sampling. Then, we showed that double-digestion and bleach treatment of shell powder prior to silica-based DNA extraction improves shell DNA recovery, also suggesting that DNA is protected in preservation niches within ancient shells. Finally, all layers that compose Mytilus shells, i.e., the nacreous (aragonite) and prismatic (calcite) carbonate layers, with or without the outer organic layer (periostracum) proved to be valuable DNA reservoirs, with aragonite appearing as the best substrate for genomic analyses. Our work contributes to the understanding of long-term molecular preservation in biominerals and we anticipate that resulting recommendations will be helpful for future efficient and responsible genomic analyses of ancient mollusc shells.

Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Neuromorphometric associations with mood, cognition, and self-reported exercise levels in epilepsy and healthy individuals.

Regular physical activity may promote beneficial neuroplasticity, e.g., increased hippocampus volume. However, it is unclear whether self-reported physical exercise in leisure (PEL) levels are associated with the brain structure features demonstrated by exercise interventions. This pilot study investigated the relationship between PEL, mood, cognition, and neuromorphometry in patients with idiopathic generalized epilepsy (IGEs) compared to healthy controls (HCs). Seventeen IGEs and 19 age- and sex-matched HCs underwent magnetic resonance imaging (MRI) at 3T. The Baecke Questionnaire of Habitual Physical Activity, Profile of Mood States, and Montreal Cognitive Assessment (MoCA) assessed PEL, mood, and cognition, respectively. Structural MRI data were analyzed by voxel- and surface-based morphometry. IGEs had significantly lower PEL (p < 0.001), poorer mood (p = 0.029), and lower MoCA scores (p = 0.027) than HCs. These group differences were associated with reduced volume, decreased gyrification, and altered surface topology (IGEs < HCs) in frontal, temporal and cerebellar regions involved in executive function, memory retrieval, and emotional regulation, respectively. These preliminary results support the notion that increased PEL may promote neuroplasticity in IGEs, thus emphasizing the role of physical activity in promoting brain health in people with epilepsy.

Delirium Due to Potentially Avoidable Hospitalizations Among Older Adults.

BACKGROUND: Delirium is a common complication during acute care hospitalizations in older adults. A substantial percentage of admissions are for ambulatory care-sensitive conditions (ACSCs) or potentially avoidable hospitalizations-conditions that might be treated early in the outpatient setting to prevent hospitalization and hospital complications. METHODS: This retrospective cross-sectional study examined rates of delirium among older adults hospitalized for ACSCs. Participants were 39 933 older adults ≥65 years of age admitted from January 1, 2015 to December 31, 2019 to general inpatient units and ICUs of a large Southeastern academic medical center. Delirium was defined as a score ≥ 2 on the Nursing Delirium Screening Scale or positive on the Confusion Assessment Method for the Intensive Care Unit during admission, and ACSCs were identified from the primary admission diagnosis using standardized definitions. Generalized linear mixed models were used to examine the association between ACSCs and delirium, compared with admissions for non-ACSC diagnoses, adjusting for covariates and repeated observations for individuals with multiple admissions. RESULTS: Delirium occurred in 15.6% of admissions for older adults. Rates were lower for ACSC admissions versus admissions for other conditions (13.9% vs 15.8%, p < .001). Older age and higher comorbidity were significant predictors of the development of delirium. CONCLUSIONS: Rates of delirium among older adults hospitalized for ACSCs were lower than rates for non-ACSC hospitalization but still substantial. Optimizing the treatment of ACSCs in the outpatient setting is an important goal not only for reducing hospitalizations but also for reducing risks for hospital-associated complications such as delirium.

Evaluation of the Electronic Clinical Dementia Rating for Dementia Screening.

Importance: The Clinical Dementia Rating (CDR) is a well-validated instrument widely used to detect and stage dementia due to Alzheimer disease. The digital Electronic Clinical Dementia Rating (eCDR) can be remotely self-administered and automatically scored, with potential to facilitate efficient dementia screening and staging. Objective: To evaluate the association of the eCDR with the CDR and other in-clinic assessments for screening older adults for cognitive impairment. Design, Setting, and Participants: This multisite, cross-sectional study used baseline data from a longitudinal, observational study from 2020 to 2023, including up to 3 years of follow-up. Participants were enrolled from 3 Alzheimer Disease Research Centers and the Brain Health Registry. Participants (aged ≥55 years, with a study partner, and no acute or unstable major medical conditions) were recruited during in-clinic visits or by automated emails. Exposures: Participants completed the Uniform Data Set Version 3 (UDS; including the CDR) in supervised clinical research settings, and then completed the eCDR remotely, online and unsupervised, using their own device. Main Outcomes and Measures: The primary outcomes were eCDR scores (item; categorical box and global; continuous box and global), CDR scores (item; categorical box and global), and UDS assessment scores. Associations were evaluated using linear and logistic regressions. Results: A total of 3565 participants were contacted, and 288 were enrolled. Among 173 participants with item-level data (mean [SD] age, 70.84 [7.65] years; 76 women [43.9%]), eCDR to CDR concordance was 90% or higher for 33 items (63%) and 70% to 89% for 13 items (25%). Box (domain) level concordance ranged from 80% (memory) to 99% (personal care). The global score concordance rate was 81%. κ statistics were fair to moderate. Among 206 participants with box and global scores (mean [SD] age, 71.34 [7.68] years; 95 women [46.1%]), eCDR continuous global score was associated with CDR global (categorical) score with an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.70-0.87). Correlations between eCDR and in-clinic UDS assessments were similar to those between CDR sum of box scores and the same in-clinic assessments. Conclusions and Relevance: These findings suggest that the eCDR is valid and has potential use for screening and assessment of older adults for cognitive and functional decline related to Alzheimer disease. Instrument optimization and validation in diverse cohorts in remote settings are crucial for evaluating scalability and eCDR utility in clinical research, trials, and health care settings.

Evaluating the Generalizability of Predictive Classifiers Built from DESI Imaging Lipid Data across Mass Spectrometry Platforms.

In this study, we evaluate the generalizability of predictive classifiers built from DESI lipid data for thyroid fine needle aspiration (FNA) biopsy analysis and classification using two high-performance mass spectrometers (time-of-flight and orbitrap) suited with different DESI imaging sources operated by different users. The molecular profiles obtained from thyroid samples with the different platforms presented similar trends, although specific differences in ion abundances were observed. When using a previously published statistical model built to discriminate thyroid cancer from benign thyroid tissues to predict on a new independent data set obtained, agreement for 24 of the 30 samples across the imaging platforms was achieved. We also tested the classifier on six clinical FNAs and obtained agreement between the predictive results and clinical diagnosis for the different conditions. Altogether, our results provide evidence that statistical classifiers generated from DESI lipid data are applicable across different high-resolution mass spectrometry platforms for thyroid FNA classification.

Specialist Availability and Drug Adherence in Older Adults with Dementia Across Regions of the United States.

BACKGROUND: Access to specialists facilitates appropriate Alzheimer's disease and related dementia (ADRD) medication use and adherence. However, there is little information on the impact of specialists' availability on ADRD medication adherence, especially in regions of the United States (US) where specialists are scarce, e.g., the Deep South (DS). OBJECTIVE: To ascertain whether the availability of specialty physicians in the DS and other US regions predicts ADRD medication adherence among community-dwelling older adultsMethods:We conducted secondary analyses of claims data for 54,194 Medicare beneficiaries with ADRD in 2013-2015. Medication adherence was measured using the proportion of days covered (PDC). Multivariable-adjusted Modified Poisson regression was used to examine associations of adherence with physicians' availability by region. RESULTS: The race/ethnicity distribution was 81.44% white, 9.17% black, 6.24% Hispanic, 2.25% Asian, and 1% other; 71.81% were female, and 42.36% were older than 85 years. Beneficiaries across regions differed in all individual and contextual characteristics except sex and comorbidities. Neurologists and psychiatrists' availability was not significantly associated with adherence (DS = 1.00, 0.97-1.03 & non-DS = 1.01, 1.00-1.01). Race and having ≥1 specialist visits were associated with a lower risk of adherence in both regions (p < 0.0001). Advanced age, dual Medicare/Medicaid eligibility, and living in non-large metropolitan areas, were associated with adherence in the non-DS region. CONCLUSION: Among older Americans with ADRD, a context defined by specialist availability does not affect adherence, but other context characteristics related to socioeconomic status may. Research should further examine the influence of individual and contextual factors on ADRD treatment among older adults.

Building Families' Capacities: Community Forums with Parents and Occupational Therapists.

Background. Parents of a child considered to have special needs are at greater risk of stress and exhaustion. Although many occupational therapy interventions can help these children, they often require significant time and energy from families. Purpose. To document the perspectives of parents and occupational therapists regarding ways to offer services that help build families' capacities without overloading them. Method. A qualitative descriptive design guided online community forums with 41 parents and occupational therapists in Quebec, Canada. Findings. Nine key principles to build the capacities of families without overburdening them were identified. These include being sensitive to possible negative impacts of services, avoiding overwhelming the family with information or recommendations, taking the needed time, highlighting the positive, and offering flexible conditions for services. Implications. Our findings help identify how capacity-building rehabilitation services can be offered to families to optimize positive outcomes and minimize harms.

Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease.

Objective: To investigate hemispheric effects of directional versus ring subthalamic nucleus (STN) deep brain stimulation (DBS) surgery on cognitive function in patients with advanced Parkinson's disease (PD). Methods: We examined 31 PD patients (Left STN n = 17; Right STN n = 14) who underwent unilateral subthalamic nucleus (STN) DBS as part of a NIH-sponsored randomized, cross-over, double-blind (ring vs directional) clinical trial. Outcome measures were tests of verbal fluency, auditory-verbal memory, and response inhibition. First, all participants were pooled together to study the effects of directional versus ring stimulation. Then, we stratified the groups by surgery hemisphere and studied the longitudinal changes in cognition post-unilateral STN DBS. Results: Relative to pre-DBS cognitive baseline performances, there were no group changes in cognition following unilateral DBS for either directional or ring stimulation. However, assessment of unilateral DBS by hemisphere revealed a different pattern. The left STN DBS group had lower verbal fluency than the right STN group (t(20.66 = -2.50, p = 0.02). Over a period of eight months post-DBS, verbal fluency declined in the left STN DBS group (p = 0.013) and improved in the right STN DBS group over time (p < .001). Similarly, response inhibition improved following right STN DBS (p = 0.031). Immediate recall did not significantly differ over time, nor was it affected by implant hemisphere, but delayed recall equivalently declined over time for both left and right STN DBS groups (left STN DBS p = 0.001, right STN DBS differ from left STN DBS p = 0.794). Conclusions: Directional and ring DBS did not differentially or adversely affect cognition over time. Regarding hemisphere effects, verbal fluency decline was observed in those who received left STN DBS, along with the left and right STN DBS declines in delayed memory. The left STN DBS verbal fluency decrement is consistent with prior bilateral DBS research, likely reflecting disruption of the basal-ganglia-thalamocortical network connecting STN and inferior frontal gyrus. Interestingly, we found an improvement in verbal fluency and response inhibition following right STN DBS. It is possible that unilateral STN DBS, particularly in the right hemisphere, may mitigate cognitive decline.

Delirium Mediates Incidence of Hospital-Associated Disability Among Older Adults.

OBJECTIVE: To examine whether delirium predicts occurrence of hospital-associated disability (HAD), or functional decline after admission, among hospitalized older adults. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: General inpatient (non-ICU) units of a large regional Southeastern US academic medical center, involving 33,111 older adults ≥65 years of age admitted from January 1, 2015, to December 31, 2019. METHODS: Delirium was defined as a score ≥2 on the Nursing Delirium Screening Scale (NuDESC) during hospital admission. HAD was defined as a decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. Generalized linear mixed models were used to examine the association between delirium and HAD, adjusting for covariates and repeated observations with multiple admissions. We performed multivariate and mediation analyses to examine strength and direction of association between delirium and HAD. RESULTS: One-fifth (21.6%) of older adults developed HAD during hospitalization and experienced higher delirium rates compared to those not developing HAD (24.3% vs 14.3%, P < .001). Age, presence of delirium, Elixhauser Comorbidity Score, admission cognitive status, admission ADL function, and length of stay were associated (all P < .001) with incident HAD. Mediational analyses found 46.7% of the effect of dementia and 16.7% of the effect of comorbidity was due to delirium (P < .001). CONCLUSIONS AND IMPLICATIONS: Delirium significantly increased the likelihood of HAD within a multivariate predictor model that included comorbidity, demographics, and length of stay. For dementia and comorbidity, mediation analysis showed a significant portion of their effect attributable to delirium. Overall, these findings suggest that reducing delirium rates may diminish HAD rates.

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.

Development of an objective method to quantify hippocampal dentation.

Hippocampal dentation (HD) refers to a series of ridges (dentes) seen on the inferior aspect of the hippocampus. The degree of HD varies dramatically across healthy individuals, and hippocampal pathology may result in loss of HD. Existing studies show associations between HD and memory performance in healthy adults as well as temporal lobe epilepsy (TLE) patients. However, until now studies relied on visual assessment of HD as no objective methods to quantify HD have been described. In this work, we describe a method to objectively quantify HD by transforming the characteristic 3D surface morphology of HD into a simplified 2D plot for which area under the curve (AUC) was calculated. This was applied to T1w scans of 59 TLE subjects, each with one epileptic hippocampus and one normal appearing hippocampus. Results showed that AUC significantly correlated with the number of dentes based on visual inspection (p < .05) and correctly sorted a set of hippocampi from least to most prominently dentated. Intra- and inter-rater reliability was nearly perfect (ICC ≥ 0.99). AUC values were significantly lower in epileptic hippocampi compared to contralateral hippocampi (p = .00019), consistent with previously published findings. In the left TLE group, the AUC values from the contralateral hippocampi showed a positive trend (p = .07) with verbal memory acquisition scores but was not statistically significant. The proposed approach is the first objective, quantitative measurement of dentation described in the literature. The AUC values numerically capture the complex surface contour information of HD and will enable future study of this interesting morphologic feature.

Item Response Analysis of the Financial Capacity Instrument-Short Form.

OBJECTIVE: The Financial Capacity Instrument-Short Form (FCI-SF) is a performance-based measure of everyday financial skills that takes 15 min to administer. Although the FCI-SF has demonstrated excellent psychometric properties, advanced psychometric methods such as item response theory (IRT) can provide important information on the performance of individual test items in measuring financial capacity and in distinguishing between healthy and cognitively impaired individuals. METHOD: Participants were 272 older adults diagnosed with mild cognitive impairment (MCI) and 1,344 cognitively healthy controls recruited from the Mayo Clinic Study of Aging at the Mayo Clinic in Rochester, Minnesota and also from the Cognitive Observations in Seniors study at the University of Alabama at Birmingham. Participants in each study were administered the FCI-SF, which evaluates coin/currency calculation, financial conceptual knowledge, use of a checkbook/register, and use of a bank statement. RESULTS: A unidimensional two-parameter logistic model best fit the 37 FCI-SF Test items, and most FCI-SF items fit the unidimensional two-parameter model well. The results indicated that all FCI-SF items robustly distinguished cognitively healthy controls from persons with MCI. CONCLUSIONS: The study results showed that the FCI-SF performed well under IRT analysis, further highlighted the psychometric properties of the FCI-SF as a valid and reliable measure of financial capacity, and demonstrated the clinical utility of the FCI-SF in distinguishing between cognitively normal and cognitively impaired individuals.

Influential children in middle childhood peer culture: Effects of temperament and community culture.

For children in middle childhood, the social world, particularly the behavior and attitudes of their school peers, has been shown to be an important factor in their educational and mental health outcomes. In the school environment, some children seem to influence the attitudes and behavior of their peers more than others. The behavior patterns of children, as reflected in temperamental traits, have been shown to drive peer perception in important ways and might play a role in identifying the individuals and social processes that operate in peer influence. It seems likely that temperamental traits will have different effects on school peers, dependent on characteristics of the school attended. Fourth and fifth grade children from four rural counties in the southeastern portion of the United States were studied. Temperamental characteristics were assessed based on teacher perception of six characteristics. Peer perceptions of the extent to which each child was perceived to influence others in five areas of school culture (e.g., academics, sports) was measured through a peer nomination procedure. Additional status-related perceptions and behaviors of participating children were also assessed by peer nominations. Teacher ratings of temperamental behaviors were submitted to latent profile analyses resulting in a seven-cluster model. Results indicated temperamental profiles were significantly and meaningfully associated with peer perceptions of influence as well as social status. Further, demographic differences between two groups of schools were found to moderate the effects that temperament profile had on peer influence.

Development and implementation of an electronic Clinical Dementia Rating and Financial Capacity Instrument-Short Form.

Introduction: To address the need for remote assessments of cognitive decline and dementia, we developed and administered electronic versions of the Clinical Dementia Rating (CDR®) and the Financial Capacity Instrument-Short Form (FCI-SF) (F-CAP®), called the eCDR and eFCI, respectively. Methods: The CDR and FCI-SF were adapted for remote, unsupervised, online use based on item response analysis of the standard instruments. Participants completed the eCDR and eFCI first in clinic, and then at home within 2 weeks. Results: Of the 243 enrolled participants, 179 (73%) cognitively unimpaired (CU), 50 (21%) with mild cognitive impairment (MCI) or dementia, and 14 (6%) with an unknown diagnosis, 84% and 85% of them successfully completed the eCDR and eFCI, respectively, at home. Discussion: These results show initial feasibility in developing and administering online instruments to remotely assess and monitor cognitive decline along the CU to MCI/very mild dementia continuum. Validation is an important next step.

An evaluation of M2+ interference correction approaches associated with As and Se in ICP-MS using a multi-day dataset along with ICP-MS/MS/HR-ICP-MS based analysis and hierarchical modeling as a means of assessing bias in fortified drinking waters and single component matrices.

Three 1 2 mass oriented rare earth element (REE) M2+ correction approaches (fixed factor, a dual internal standard, and an in-sample) are evaluated for use in an ICP-MS environmental method update. The multi-variant-based evaluation includes analyzing the same 19 REE-fortified matrices on eight different days over a two-month period using two instrument tunes. These REE-fortified matrices were also analyzed using HR-ICP-MS and ICP-MS/MS to estimate the reference value for use in the principal component analysis (PCA) and hierarchical modeling evaluation. A fixed factor is unable to compensate for matrix and mass dependent drift and because of this it generates the largest across matrix, tune, and day 95th percent confidence bounds for the REE corrections on both As (1.1 ppb) and Se (23 ppb) using samples fortified with 100 ppb Nd, Sm & Gd. The PCA analysis indicated that M2+ ions cluster together across matrix, tune and day better than M1+ and these tighter correlations are reflected in reduced 95th percentile confidence bounds for dual M2+ internal standards (M2+; As = 0.3 ppb; Se = 5.4 ppb; n = 704) relative to M1+ internal standards (M1+; As = 0.6 ppb; Se = 12.0 ppb; n = 1056). The use of an in-sample M2+ correction produced comparable 95th percent confidence bounds (As = 0.2 ppb; Se = 3.4 ppb; n = 352) relative to the M2+ internal standard approaches. Finally, the hierarchical modeling indicated M2+ ions as internal standards tend to minimize the across day variability induced by cone changes and the daily reoccurring matrix shifts in the M2+/M1+ ratio associated with 250 ppm matrices of Na, Ca, and Mg. This internal standard driven reduction in variability can be beneficial in compliance monitoring methods.

Association of Performance on the Financial Capacity Instrument-Short Form With Brain Amyloid Load and Cortical Thickness in Older Adults.

Background and Objectives: To investigate the association of the Financial Capacity Instrument-Short Form (FCI-SF) performance and timing total scores with brain ß-amyloid and cortical thickness in cognitively unimpaired (CU) (at baseline) older adults. Methods: A total of 309 participants (aged 70 years or older) of the Mayo Clinic Study of Aging underwent 11C-Pittsburgh compound B PET amyloid imaging and MRI, and completed the FCI-SF. Abnormal amyloid PET was defined as standardized uptake value ratio ≥1.48 in an Alzheimer disease (AD)-related region of interest and reduced AD signature cortical thickness as ≤2.68 mm (neurodegeneration). A cohort of 218 (of the 309) participants had follow-up visits (every 15 months) with FCI-SF data for longitudinal analysis (number of visits including baseline, median [range]: 2 [2-4]). In the analysis, we used linear regression and mixed-effects models adjusted for age, sex, education, apolipoprotein E ε4 allele status, global cognitive z score, and previous FCI-SF testing. Results: Participants' mean age (SD) was 80.2 (4.8) years (56.3% male individuals). In cross-sectional analysis, abnormal amyloid PET (vs normal) was associated with a lower FCI-SF total score and slower total composite time. In longitudinal analysis, FCI-SF total score declined faster (difference in annualized rate of change, beta coefficient [ß] [95% confidence interval (CI)] = -1.123 [-2.086 to -0.161]) and FCI-SF total composite time increased faster (difference in annualized rate of change, ß [95% CI] = 16.274 [5.951 to 26.597]) for participants with neurodegeneration at baseline (vs those without). Participants who exhibited both abnormal amyloid PET and neurodegeneration at baseline had a greater increase in total composite time when compared with the group without abnormal amyloid and without neurodegeneration (difference in annualized rate of change, ß [95% CI] = 16.750 [3.193 to 30.307]). Discussion: Performance and processing speed on the FCI-SF were associated with imaging biomarkers of AD pathophysiology in CU (at baseline) older adults. Higher burdens of imaging biomarkers were associated with longitudinal worsening on FCI-SF performance. Additional research is needed to delineate further these associations and their predictive utility at the individual person level.

Geospatial Patterns of Antimicrobial Resistance Genes in the US EPA National Rivers and Streams Assessment Survey.

Antimicrobial resistance (AR) is a serious global problem due to the overuse of antimicrobials in human, animal, and agriculture sectors. There is intense research to control the dissemination of AR, but little is known regarding the environmental drivers influencing its spread. Although AR genes (ARGs) are detected in many different environments, the risk associated with the spread of these genes to microbial pathogens is unknown. Recreational microbial exposure risks are likely to be greater in water bodies receiving discharge from human and animal waste in comparison to less disturbed aquatic environments. Given this scenario, research practitioners are encouraged to consider an ecological context to assess the effect of environmental ARGs on public health. Here, we use a stratified, probabilistic survey of nearly 2000 sites to determine national patterns of the anthropogenic indicator class I integron Integrase gene (intI1) and several ARGs in 1.2 million kilometers of United States (US) rivers and streams. Gene concentrations were greater in eastern than in western regions and in rivers and streams in poor condition. These first of their kind findings on the national distribution of intI1 and ARGs provide new information to aid risk assessment and implement mitigation strategies to protect public health.

Cognitive Correlates of Impaired Testamentary Capacity in Alzheimer's Dementia.

BACKGROUND: Testamentary capacity (TC) is a legal construct about the ability to make or change a will. Although studies of financial and medical capacities have noted a strong association between capacity and cognition, no study has examined the cognitive correlates of TC in Alzheimer's disease (ad). METHODS: Study participants were 22 cognitively healthy controls and 20 persons with mild to moderate ad who were administered a neuropsychological battery and the Testamentary Capacity Instrument (TCI), a new performance-based measure of TC. Both TCI Element and TCI Total scores were calculated. TCI Total scores were calculated for the purposes of expanding correlational analyses (i.e., Pearson's product-moment) and are not intended for forensic TC evaluations. Final predictors were identified using linear and logistic regression modeling. RESULTS: All ad participants but one obtained TCI Totals that fell >2.5 standard deviations below the control group mean. Initial cognitive correlates of TCI performance were measures of general cognition, language, verbal memory, executive function, and processing speed. The four cognitive variables showing the highest t values and correlating with TCI Total score > 0.7 were entered into logistic and linear regression models. Final predictor models consisted of measures of verbal memory, executive function, and semantic knowledge and demonstrated shared variance of 0.71 (linear) and 0.82 (logistic). CONCLUSIONS: A diagnosis of ad dementia is associated with clinical impairment in TC and associated cognitive abilities and indicates that a legal assessment of TC is warranted. Second, the results offer insight into the cognitive basis of TC in persons with Alzheimer's dementia.