Higher cardiovascular burden and peripheral inflammation are associated with small vessel vascular disease, a predominantly dysexecutive cognitive profile, and a higher likelihood of conversion to vascular dementia. The digital clock drawing test, a digitized version of a standard neuropsychological tool, is useful in identifying cognitive dysfunction related to vascular etiology. However, little is known about the specific cognitive implications of vascular risk, peripheral inflammation, and varying levels of overall brain integrity. The current study aimed to examine the role of cardiovascular burden, peripheral inflammation, and brain integrity on digitally acquired clock drawing latency and graphomotor metrics in non-demented older adults.

The final prospectively recruited IRB-consented participant sample included 184 non-demented older adults (age: 69±6 years, education: 16±3 years, 46% female, 94% white) who completed digital clock drawing, vascular assessment, blood draw, and brain MRI. Digital clock drawing variables of interest included: total completion time (TCT), pre-first hand latency (PFHL), digit misplacement, hour hand distance from center, and clock face area (CFA). Cardiovascular burden was calculated using the revised version of the Framingham Stroke Risk Profile (FSRP-10). Peripheral inflammation was operationalized using interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-a), and high sensitivity C-reactive protein (hsCRP). The brain integrity composite was comprised of bilateral entorhinal cortex volume, bilateral ventricular volume, and whole brain leukoaraiosis.

Over and above age and cognitive reserve, hierarchical regressions showed FSRP-10, inflammatory markers, and brain integrity explained an additional 13.3% of the variance in command TCT (p< 0.001), with FSRP-10 (p=0.001), IL-10 (p= 0.019), and hsCRP (p= 0.019) as the main predictors in the model. FSRP-10, inflammatory markers, and brain integrity explained an additional 11.7% of the variance in command digit misplacement (p= 0.009), with findings largely driven by FSRP-10 (p< 0.001).

Overall, in non-demented older adults, subtle behavioral nuances seen in digital clock drawing metrics (i.e., total completion time and digit misplacement) are partly explained by cardiovascular burden, peripheral inflammation, and brain integrity over and above age and cognitive reserve. These nuanced behaviors on digitally acquired clock drawing may associate with an emergent disease process or overall vulnerability.

Funding sources: Barber Fellowship; K07AG066813; R01 AG055337; R01 NR014810; American Psychological Foundation Dissertation Award; APA Dissertation Research Award

Individuals with Parkinson's disease (PD) have varying trajectories of cognitive decline. One reason for this heterogeneity may be "cognitive reserve": where higher education/IQ/current mental engagement compensates for increasing brain burden (Stern et al., 2020). With few exceptions, most studies examining cognitive reserve in PD fail to include brain metrics. This study's goal was to examine whether cognitive reserve moderated the relationship between neuroimaging indices of brain burden (diffusion free water fraction and T2-weighted white matter changes) and two commonly impaired domains in PD: executive function and memory. We hypothesized cognitive reserve would mitigate the relationship between higher brain burden and worse cognitive performance.

Participants included 108 individuals with PD without dementia (age mean=67.9±6.3, education mean=16.6±2.5) who were prospectively recruited for two NIH-funded projects at the University of Florida. All received neuropsychological measures of executive function (Trails B, Stroop, Letter Fluency) and memory (delayed recall: Hopkin's Verbal Learning Test-Revised, WMS-III Logical Memory). Domain specific z-score composites were created using data from age/education matched non-PD peer controls (N=62). For the Cognitive Reserve (CR) proxy, a z-score composite included years of education, WASI-II Vocabulary, and Wechsler Test of Adult Reading. At the time of testing, participants completed multiple MRI scans (T1-weighted, diffusion, Fluid Attenuated Inversion Recovery) from which the following were extracted: 1) whole-brain free water within the white matter (a measure of microstructural integrity and neuroinflammation), 2) white matter hyperintensities/white matter total volume (WMH/WMV), and bilaterally-averaged edge weights of white matter connectivity between 3) dorsolateral prefrontal cortex and caudate and 4) entorhinal cortex and hippocampi. Separate linear regressions for each brain metric used executive function and memory composites as dependent variables; predictors were age, CR proxy, respective brain metric, and a residual centered interaction term (brain metric*CR proxy). Identical models were run in dichotomized short and long disease duration groups (median split=6 years).

In all models, a lower CR proxy significantly predicted worse executive function (WMH/WMV: beta=0.49, free water: beta=0.54, frontal edge weight: beta=0.49, p's<0.001) and memory (WMH/WMV: beta=0.42, free water: beta=0.35, temporal edge weight: beta=0.39, p's <0.01). For neuroimaging metrics, higher free water significantly predicted worse executive function (beta=-0.39, p=0.002) but not memory. No other brain metrics were significant predictors of either domain. Accounting for PD duration, higher free water predicted worse executive function for those with both short (beta=-0.49, p=0.04) and long disease duration (beta=-0.48, p=0.02). Specifically in those with long disease duration, higher free water (beta=-0.57 p=0.02) and lower edge weights between entorhinal cortex and hippocampi (beta=0.30, p=0.03) predicted worse memory. Overall, no models contained significant interactions between the CR proxy and any brain metric.

Results replicate previous work showing that a cognitive reserve proxy relates to cognition. However, cognitive reserve did not moderate brain burden's relationship to cognition. Across the sample, greater neuroinflammation was associated with worse executive function. For those with longer disease duration, higher neuroinflammation and lower medial temporal white matter connectivity related to worse memory. Future work should examine other brain burden metrics to determine whether/how cognitive reserve influences the cognitive trajectory of PD.

Research shows that highly educated individuals have at least 20 graphomotor features associated with clock drawing with hands set for '10 after 11' (Davoudi et al., 2021). Research has yet to understand clock drawing features in individuals with fewer years of education. In the current study, we compared older adults with < 8 years of education to those with > 9 years of education on number and pattern of graphomotor feature relationships in the clock drawing command condition.

Participants age 65+ from the University of Florida (UF) and UF Health (N= 10,491) completed both command and copy conditions of the digital Clock Drawing Test (dCDT) as a part of a federally-funded investigation. Participants were categorized into two education groups: < 8 years of education (n= 304) and > 9 years of education (n= 10,187). Propensity score matching was then used to match participants from each subgroup (n= 266 for each subgroup) on the following demographic characteristics: age, sex, race, and ethnicity (n= 532, age= 74.99±6.21, education= 10.41±4.45, female= 42.7%, non-white= 32.0%). Network models were derived using Bayesian Structure Learning (BSL) with the hill-climbing algorithm to obtain optimal directed acyclic graphs (DAGs) from all possible solutions in each subgroup for the dCDT command condition.

Both education groups retained 13 of 91 possible edges (14.29%). For the < 8 years of education group (education= 6.65±1.74, ASA= 3.08±0.35), the network included 3 clock face (CF), 7 digit, and 3 hour hand (HH) and minute hand (MH) independent, or “parent,” features connected to the retained edges (BIC= -7395.24). In contrast, the > 9 years of education group (education= 14.17±2.88, ASA= 2.90±0.46) network retained 1 CF, 6 digit, 5 HH and MH, and 1 additional parent features representing the total number of pen strokes (BIC= -6689.92). Both groups showed that greater distance from the HH to the center of the clock also had greater distance from the MH to the center of the clock [ßz(< 8 years)= 0.73, ßz(> 9 years)= 0.76]. Groups were similar in the size of the digit height relative to the distance of the digits to the CF [ßz(< 8 years)= 0.27, ßz(> 9 years)= 0.56]. Larger HH angle was associated with larger MH angle across groups [ßz(< 8 years)= 0.28, ßz(> 9 years)= 0.23].

Education groups differed in the ratio of dCDT parent feature types. Specifically, copy clock production in older adults with < 8 years of education relied more heavily on CF parent features. In contrast, older adults with > 9 years of education relied more heavily on HH and MH parent features. Individuals with < 8 years of education may more infrequently present the concept of time in the clock drawing command condition. This study highlights the importance of considering education level in interpreting dCDT scores and features.

Recent research has found that machine learning based analysis of patient speech can be used to classify Alzheimer’s Disease. We know of no studies, however, which systematically explore the value of pausing events in speech for detecting cognitive limitations. Using retrospectively acquired voice data from paragraph memory tests, we created two types of pause features: a) the number and duration of pauses, and b) frequency components in speech immediately following pausing. Multiple machine learning models were used to assess how these features could effectively discriminate individuals classified into two groups: Cognitively Compromised versus Cognitively Well.

Participants (age> 65 years, n= 67) completed the Newcomer paragraph memory test and a neuropsychological protocol as part of a federally funded prospective IRB approved investigation at the University of Florida. Participant vocal recordings were acquired for the immediate and delay conditions of the test. Speaker diarization was performed on the immediate free recall test condition to separate voices of patients from examiners. Features extracted from both test conditions included a) 3 pause characteristics (total number of pauses, total pause duration, and length of the longest pause), and b) 20 Mel Frequency Cepstral Coefficients (MFCC) pertaining to speech immediately (2.7 seconds) following pauses. These were combined with demographics (age, sex, race, education, and handedness) to create a total of 105 features that were used as inputs for multiple machine learning analytic models (random forest, logistic regression, naive Bayes, AdaBoost, Gradient Boost, and multi-layered perceptron). External neuropsychological metrics were used to initially classify Cognitively Compromised (i.e., < -1.0 standard deviation on > two of five test metrics: total immediate, delay, discrimination Hopkins Verbal Learning Test-Revised (HVLT-R),

Controlled Oral Word Association (COWA) test, category fluency ('animals')). Pearson Product Moment Correlations were used to assess the linear relationships between pauses and speech frequency categories and neuropsychological metrics.

Neuropsychology metric classification using -1SD cut-off identified 27% (18/67 participants) as Cognitively Compromised. The Cognitively Compromised group and the Cognitively Well group did not show any difference in distributions of individual pause/frequency features (Mann Whitney U-test, p> 0.11). A negative correlation was found between total duration of short pauses and HVLT total immediate free recall, while a positive correlation was found between MFCC-10 and HVLT total immediate free recall. The best classification model was AdaBoost Classifier which predicted the Cognitively Compromised label with 0.91 area under receiver operating curve, 0.81 accuracy, 0.43 sensitivity, 1.0 specificity, 1.0 precision, 0.6 f1 score.

Pause characteristics and frequency profiles of speech immediately following pauses from a paragraph memory test accurately identified older adults with compromised cognition, as measured by verbal learning and verbal fluency metrics. Furthermore, individuals with reduced HVLT immediate free recall generated more pauses, while individuals who recalled more words had higher power in mid-frequency bands (10th MFCC). Future research needs to replicate how paragraph recall pause characteristics and frequency the profile of speech immediately following pauses potentially provides a low resource alternative to automatic speech recognition models for detecting cognitive impairments.

Chronic musculoskeletal pain is associated with neurobiological, physiological, and cellular measures. Importantly, we have previously demonstrated that a biobehavioral and psychosocial resilience index appears to have a protective relationship on the same biomarkers. Less is known regarding the relationships between chronic musculoskeletal pain, protective factors, and brain aging. This study investigates the relationships between clinical pain, a resilience index, and brain age. We hypothesized that higher reported chronic pain would correlate with older appearing brains, and the resilience index will attenuate the strength of the relationship between chronic pain and brain age.

Participants were drawn from an ongoing observational multisite study and included adults with chronic pain who also reported knee pain (N = 135; age = 58.3 ± 8.1; 64% female; 49% non-Hispanic Black, 51% non-Hispanic White; education Mdn = some college; income level Mdn = $30,000 - $40,000; MoCA M = 24.27 ± 3.49). Measures included the Graded Chronic Pain Scale (GCPS), characteristic pain intensity (CPI) and disability, total pain body sites; and a cognitive screening (MoCA). The resilience index consisted of validated biobehavioral (e.g., smoking, waist/hip ratio, and active coping) and psychosocial measures (e.g., optimism, positive affect, negative affect, perceived stress, and social support). T1-weighted MRI data were obtained. Surface area metrics were calculated in FreeSurfer using the Human Connectome Project's multi-modal cortical parcellation scheme. We calculated brain age in R using previously validated and trained machine learning models. Chronological age was subtracted from predicted brain age to generate a brain age gap (BAG). With higher scores of BAG indicating predicated age is older than chronological age. Three parallel hierarchical regression models (each containing one of three pain measures) with three blocks were performed to assess the relationships between chronic pain and the resilience index in relation to BAG, adjusting for covariates. For each model, Block 1 entered the covariates, Block 2 entered a pain score, and Block 3 entered the resilience index.

GCPS CPI (R2 change = .033, p = .027) and GCPS disability (R2 change = 0.038, p = 0.017) significantly predicted BAG beyond the effects of the covariates, but total pain sites (p = 0.865) did not. The resilience index was negatively correlated and a significant predictor of BAG in all three models (p < .05). With the resilience index added in Block 3, both GCPS CPI (p = .067) and GCPS disability (p = .066) measures were no longer significant in their respective models. Additionally, higher education/income (p = 0.016) and study site (p = 0.031) were also significant predictors of BAG.

In this sample, higher reported chronic pain correlated with older appearing brains, and higher resilience attenuated this relationship. The biobehavioral and psychosocial resilience index was associated with younger appearing brains. While our data is cross-sectional, findings are encouraging that interventions targeting both chronic pain and biobehavioral and psychosocial factors (e.g., coping strategies, positive and negative affect, smoking, and social support) might buffer brain aging. Future directions include assessing if chronic pain and resilience factors can predict brain aging over time.

Research shows that highly educated individuals have at least 20 graphomotor features associated with clock drawing with hands set for '10 after 11' (Davoudi et al., 2021). Research has yet to understand clock drawing features in individuals with fewer years of education. In the current study, we compared older adults with < 8 years of education to those with > 9 years of education on number and pattern of graphomotor feature relationships in the clock drawing copy condition.

Participants age 65+ from the University of Florida (UF) and UF Health (N= 10,491) completed command and copy digital Clock Drawing Tests (dCDT) as a part of a federally-funded investigation. Participants were categorized into two groups: < 8 years of education (n= 304) and > 9 years of education (n= 10,187). Propensity score matching was used to match participants from each subgroup (n= 266 for each subgroup) on the following: age, sex, race, and ethnicity (n= 532, age= 74.99±6.21, education= 10.41±4.45, female= 42.7%, non-white= 32.0%). Network models were derived using Bayesian Structure Learning (BSL) with the hill-climbing algorithm to obtain optimal directed acyclic graphs (DAGs) from all possible solutions in each subgroup for the dCDT copy condition.

The < 8 years of education group (education= 6.65±1.74, ASA= 3.08±0.35), retained 12 of 91 possible edges (13.19%, BIC= -7775.50). The network retained 2 clock face (CF), 5 digit, and 5 hour hand (HH) and minute hand (MH) independent, or “parent,” features connected to the retained edges. In contrast, the > 9 years of education group (education= 14.17±2.88, ASA= 2.90±0.46) network retained 15 of 91 possible edges (16.48%, BIC= -8261.484). The network retained 2 CF, 6 digit, 4 HH and MH, and an additional 3 total stroke parent features. Both groups showed that greater distance from the HH to the clock center also had greater distance from the MH to the clock center (ßz= 0.73, both). Groups were similar in digit width size relative to digit height [ßz(< 8 years)= 0.72, ßz(> 9 years)= 0.74]. Digit height size related to CF area [ßz(< 8 years)= 0.44, ßz(> 9 years)= 0.62] and CF area related to the digit distance to the CF across groups [ßz(< 8 years)= 0.39, ßz(> 9 years)= 0.46]. Greater distance from the MH to the clock center was associated with smaller MH angle [ßz(< 8 years)= -0.35, ßz(> 9 years)= -0.31], whereas greater digit misplacement was associated with larger MH angle across groups [ßz(< 8 years)= 0.14, ßz(> 9 years)= 0.29].

Education groups differed in the ratio of dCDT parent feature types. Specifically, copy clock production in older adults with < 8 years of education relied more evenly across CF, digit, and MH and HH parent features. In contrast, those with > 9 years of education differed in the additional reliance on total stroke parent features. Individuals with < 8 years of education may more heavily rely upon visual referencing when copying a clock. This study highlights the importance of considering education level in interpreting dCDT scores and features.

To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.

Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.

Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total combined command/copy scores out of all groups. The mx/dysMCI group scored lower than the CN group on all command indices (p < .050, all analyses); and lower than the SbCI group on drawing efficiency (p = .011). The aMCI group scored lower than the CN group on spatial reasoning (p = .019). Smaller effect sizes were obtained for the four copy indices.

These results suggest that DCTclock command/copy parameters can dissociate CN, SbCI, and MCI subtypes. The larger effect sizes for command clock indices suggest these metrics are sensitive in detecting early cognitive decline. Additional research with a larger sample is warranted.

To describe the epidemiology of patients with nonintestinal carbapenem-resistant Enterobacterales (CRE) colonization and to compare clinical outcomes of these patients to those with CRE infection.

A secondary analysis of Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae 2 (CRACKLE-2), a prospective observational cohort.

A total of 49 US short-term acute-care hospitals.

Patients hospitalized with CRE isolated from clinical cultures, April, 30, 2016, through August 31, 2017.

We described characteristics of patients in CRACKLE-2 with nonintestinal CRE colonization and assessed the impact of site of colonization on clinical outcomes. We then compared outcomes of patients defined as having nonintestinal CRE colonization to all those defined as having infection. The primary outcome was a desirability of outcome ranking (DOOR) at 30 days. Secondary outcomes were 30-day mortality and 90-day readmission.

Of 547 patients with nonintestinal CRE colonization, 275 (50%) were from the urinary tract, 201 (37%) were from the respiratory tract, and 71 (13%) were from a wound. Patients with urinary tract colonization were more likely to have a more desirable clinical outcome at 30 days than those with respiratory tract colonization, with a DOOR probability of better outcome of 61% (95% confidence interval [CI], 53%–71%). When compared to 255 patients with CRE infection, patients with CRE colonization had a similar overall clinical outcome, as well as 30-day mortality and 90-day readmission rates when analyzed in aggregate or by culture site. Sensitivity analyses demonstrated similar results using different definitions of infection.

Patients with nonintestinal CRE colonization had outcomes similar to those with CRE infection. Clinical outcomes may be influenced more by culture site than classification as “colonized” or “infected.”

To investigate associations between multimodal analgesia and post-operative pain among patients undergoing transoral robotic surgery for oropharyngeal squamous cell carcinoma.

Records of patients who underwent surgery from 5 September 2012 to 30 November 2016 were abstracted. Associations were assessed using multivariable analysis.

A total of 216 patients (mean age of 59.1 years, 89.4 per cent male) underwent transoral robotic surgery (92.6 per cent were human papilloma virus positive, 87.5 per cent had stage T1–T2 tumours, and 82.9 per cent had stage N0–N1 nodes). Gabapentin (n = 86) was not associated with a reduction in severe pain. Ibuprofen (n = 72) was administered less often in patients with severe pain. Gabapentin was not associated with increased post-operative sedation (p = 0.624) and ibuprofen was not associated with increased bleeding (p = 0.221). Post-operative opioid usage was not associated with surgical duration, pharyngotomy, bilateral neck dissections, tumour stage, tumour size, subsite or gabapentin.

Scheduled low-dose gabapentin was not associated with improved pain control or increased respiratory depression. Ibuprofen was not associated with an increased risk of bleeding and may be under-utilised.

The implementation of mandatory influenza vaccination policies among healthcare personnel (HCP) is controversial. Thus, we examined the affect of mandatory influenza vaccination policies among HCP working in outpatient settings.

Four Veterans’ Affairs (VA) health systems and three non-VA medical centers.

We analyzed rates of influenza and other viral causes of respiratory infections among HCP working in outpatient sites at 4 VA health systems without mandatory influenza vaccination policies and 3 non-VA health systems with mandatory influenza vaccination policies.

Influenza vaccination was associated with a decreased risk of influenza (odds ratio, 0.17; 95% confidence interval [CI], 0.13–0.22) but an increased risk of other respiratory viral infections (incidence rate ratio, 1.26; 95% CI, 1.02–1.57).

Our fitted regression models suggest that if influenza vaccination rates in clinics where vaccination was not mandated had equalled those where vaccine was mandated, HCP influenza infections would have been reduced by 52.1% (95% CI, 51.3%–53.0%). These observations, their possible causes, and additional strategies to reduce influenza and other viral respiratory illnesses among HCP working in ambulatory clinics warrant further investigation.