Citations

Abstract Older adults with dementia account over 15% of intensive care unit (ICU) admissions and face higher risks of functional decline and complications. We systematically evaluated the difference in ICU-related outcomes in patients with and without dementia, (e.g., mortality, resuscitation and code status decisions, complications, duration of life support and hospital stay). Searches were performed in MEDLINE, EMBASE, SCOPUS, and Web of Science between 2003 and 2024. A random-effects meta-analysis was done of odds ratios (OR) and mean differences (MD) and their corresponding 95% confidence intervals (CI) were calculated. Fifteen studies, including 1,231,037 patients (12% with dementia), met the inclusion criteria. Adjusted analysis showed that patients with dementia had a higher risk of ICU mortality (OR = 1.05, 95% CI 1.00–1.11), 30-day mortality (OR = 1.54, 95% CI 1.47–1.62) and 12-month mortality (OR = 1.95, 95% CI 1.88–2.02). They were less likely to receive mechanical ventilation (OR = 0.73, 95% CI 0.62–0.85, I2 0.0%) and more likely to develop delirium (OR = 4.80, 95% CI 1.81–12.72). In patients with dementia, ICU stays were slightly shorter (MD = –1 day, 95% CI –1.7 to –0.4), and discharge home was less common (OR = 0.40, 95% CI 0.39–0.42). Older adults with dementia experienced greater risk of mortality and delirium, alongside less aggressive intervention use and healthcare utilization (i.e., shorter ICU stays). These findings underscore the need for prospective studies to optimize ICU decision-making and post-discharge care for this vulnerable population.

Abstract Background Artificial intelligence (AI) augmented laboratory tests can improve quality, efficiency, cost-effectiveness, and staff satisfaction. However, the clinical success of these tests can introduce unforeseen challenges for model retraining. This study describes the discovery of an “AI label feedback loop” in a clinically implemented AI-augmented kidney stone composition test. Methods An AI-augmented kidney stone composition test (V1) has been previously deployed for clinical kidney stone characterization. After several years of clinical use, a retrained model (V2) was developed using 6 times more data. Model performance of both V1 and V2 were evaluated across 3 datasets: a recent production validation (hold-out) set (mostly AI-influenced labels), the original V1 validation set (pre-AI, entirely human-labeled), and a subset of recent cases with exclusively human-generated or human-corrected labels. Results V2 demonstrated a 10% lower concordance rate than V1 when evaluated on the recent production hold-out set, despite a much larger training dataset. Performance between V1 and V2 was similar when applied to the pre-AI validation set. Notably, V2 outperformed V1 on the recent subset of cases with human-only or human-corrected labels, particularly for less-common stone types. These findings revealed an AI label feedback loop, confounding retraining and evaluation. Conclusions The integration of AI into clinical practice can potentially influence reported test results, complicating the development and evaluation of future models. To mitigate AI label feedback loops, ongoing human annotation and careful validation set construction are essential. These strategies can ensure reliable performance assessment and support the safe evolution of clinical AI systems.

Abstract Delirium is a common yet underdiagnosed medical emergency involving acute deficits in cognition and attention. It affects over 20% of hospitalized patients and up to 80% of ICU patients, with increased prevalence in older adults. Delirium is associated with increased mortality, prolonged hospitalization, long-term cognitive decline, and substantial healthcare costs. However, current screening tools are subjective and difficult to implement consistently. Traditional EEGs show diagnostic utility; however, they are costly and require specialized interpretation. We conducted a prospective pilot study evaluating a point-of-care, single-channel EEG device for delirium detection in hospitalized older adults. EEG spectra were utilized to calculate a ‘bispectral EEG’ (BSEEG) score reflecting the ratio of slow to fast brain waves. Twenty-two postoperative patients (mean age 75; 59.09% female) were assessed daily for up to seven days using both the BSEEG and the gold standard 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM). ROC analysis was utilized to determine an optimal threshold BSEEG score to indicate delirium positivity. BSEEG scores were significantly higher in the 3D-CAM-positive group than in the 3D-CAM-negative group (1.60 and 1.45, respectively; p < 0.05). A BSEEG threshold of 1.5 demonstrated 77.78% sensitivity and 56.10% specificity for delirium. In contrast, route clinical screenings (Delirium Triage Screen and Brief CAM) showed 0.00% sensitivity and 96.30% specificity, and failed to detect all true delirium cases. Although further validation in larger cohorts is needed, these findings suggest that the point-of-care single-channel EEG is a promising, non-invasive screening tool for delirium screening, particularly in fast-paced clinical settings.

Abstract Caregivers for people with neurodegenerative disease (PWNDs) often experience mental and physical health problems, especially when caring for PWNDs who have deficits in emotional functioning. We studied 65 PWNDs and their caregivers both during active caregiving and after caregiving had ended to determine: (a) how caregiver health changes after caregiving ends; and (b) whether PWNDs’ emotional functioning predicts these changes. PWND emotional functioning was assessed in the laboratory by measuring their generation of preparatory physiological activity (e.g., increased heart rate) to an upcoming emotional event (i.e., emotion eliciting films). Caregiver mental and physical health were measured using the Short-Form Health Survey (SF36) during active caregiving and again after caregiving had ended. Results indicated that, overall, caregivers reported increases in mental health, (t(36) = 2.58, p = .014, 95% CI [1.31, 10.93]) but decreases in physical health (t(36) = -2.35, p = .025, 95% CI [-7.26, -0.53]) across the two measurement periods. Using latent change score models, PWNDs’ preparatory physiological response impairments were associated with better caregiver mental health trajectories (β = -0.37, SE = 0.04, p = .003) such that smaller PWND preparatory responses predicted greater improvements in caregiver mental health (β = 9.92, SE = 2.84, p < .001). There was no association with changes in caregiver physical health. Smaller preparatory physiological responses in PWNDs may indicate diminished emotional responding, which is linked with lower caregiver mental health during active caregiving. Once caregiving ends, these caregivers may be most likely to “rebound” and show improvements in mental health.

Abstract Mobility and cognition impairments are common in older adults, but neurodegenerative pathology contributions are unclear. We examined cross-temporal associations of Alzheimer’s Disease (AD)-specific and nonspecific neurodegenerative plasma biomarkers neurofilament light (NfL) with incident mobility and cognitive impairment in the Atherosclerosis Risk in Communities (ARIC) study. We hypothesized NfL would show stronger associations with mobility impairment than p-tau181 in a subset of 1,227 cognitively normal participants with biomarker data and no mobility impairment (mean age=75.5±5.0, 56% female, 23% Black) at visit 5 (2011-13). Participants were classified into five functional groups using data from up to four exams: no impairment (n = 587; referent), mobility impairment only (n = 266; gait speed< 0.8m/s), cognitive impairment only (n = 69; adjudicated dementia), dual impairment (n = 243; both) or decline-free death (n = 262) over a mean 6.3 years (0-11 years) of follow-up. A multinomial regression model estimated association of functional groups with p-tau-181 and NfL jointly, adjusted for cardiovascular and demographic factors, BMI, and kidney function. Relative prevalence ratios (RPR; 95% CI) are presented per one-unit higher log-base-2 transformed biomarker (doubling). For mobility and cognitive functional outcomes, p-tau-181 was more robustly supported [Mobility: RPR=1.36, (1.04,1.77); Cognitive: RPR=1.73, (1.10,2.70); Dual: RPR=1.78, (1.15,2.77)] than NfL [Mobility: RPR=1.14, (0.85,1.53); Cognitive: RPR=1.20, (0.70,2.05); Dual: RPR=1.65, (0.86,3.16)]; higher pTau-181 [RPR=1.60, (1.23,2.09)] and higher NfL [RPR=1.94, (1.39,2.71)] were associated with higher risk of decline-free death. A p-tau-181-x-NfL interaction term was not supported. Findings did not support NfL associations with functional outcomes with consideration of p-tau-181. AD blood biomarkers may help identify individuals at greater risk for multifaceted disability.

Abstract Inpatient boarding (holding patients in the emergency department [ED] while awaiting an inpatient bed) is associated with increased risk of delirium, medication safety events, and hospital mortality in older adults. We investigated boarding trends across age strata to determine if older patients had elevated rates compared to younger patients. Administrative data for ED encounters resulting in admission from 3 healthcare systems (2 Midwest, 1 Northeast) from 1/1/19 to 12/31/24 were reviewed. Age was categorized by strata: < 21, 21-64, 65-74, 75-84, and ≥ 85. Based on the CMS Age Friendly Hospital Measures, the proportion of patients boarding for 3+ hours was calculated within each year and age strata. Boarding rates varied substantially by system and age group. At Systems 1 (S1) and 3 (S3), ≥ 85 patients had the highest rates (S1: 54.9%, S3: 70.9% in 2024) and, at System 2 (S2), all adult patients (21+) had similar rates (20.5-22.4% in 2024). Boarding rates increased in all systems over the study period. At S1 and S3, < 21 patients had the highest average yearly increase in boarding (S1: 7.4%, S3: 3.9%). At S2, boarding increased most in ≥ 85 (23.9%). In this multisystem evaluation, approximately one in two older adults experience ED boarding, with the oldest patients (≥ 85) facing the greatest exposure to boarding in recent years. These findings taken alongside known delays and safety risks associated with boarding and patient care complexity amongst the oldest adults may result in disproportionate harm to some of the most vulnerable patients.

Abstract Although slower gait speed is associated with cognitive impairment, endurance may be more predictive in older adults with faster gait speed. We examined moderating effects of endurance on the relationship of gait speed with incident mild cognitive impairment (MCI) or dementia in cognitively normal ARIC participants (n = 2242, mean age=78.6 + 4.3, 58% female, 19% Black). At the sixth exam, endurance was assessed as distance walked at a fast pace (Two Minute Walk, 2MW); usual 4-meter gait speed was also assessed. Cognitive status was adjudicated during the 6th-9th exams (mean follow-up 5.1 years). Multinomial logistic regression models with a 2MW-x-gait speed interaction term estimated relative risk ratios (RRR) of MCI and dementia relative to normal cognition per SD higher gait speed or 2MW distance, adjusting for demographic and cardiovascular factors. Results used representative continuous gait speed and continuous 2MW distance values. Longer 2MW distance was associated with lower risk of MCI and dementia at gait speed <1m/s [e.g. gait speed=0.8: MCI RRR=0.59, 95%CI(0.42, 0.83); dementia RRR=0.29, (0.13, 0.63)] and with dementia at gait speed>1m/s [gait speed=1.2: RRR=0.28, (0.09, 0.81)], but not with MCI (RRR=0.85, (0.57, 1.26)]. Conversely, faster gait speed was associated with lower risk of MCI at low 2MW [100 m; RRR=0.84, (0.74, 0.94)], but was attenuated at high 2MW (150 m; RRR=0.91, (0.84, 1.00)]. A 2MW-x-gait speed interaction term was supported (p = 0.04), primarily driven by differential MCI associations. Combining endurance and gait speed may be especially helpful in identifying cognitively normal older adults at risk for impending early-stage cognitive impairment.

Abstract Faster gait speed and better endurance have been cross-sectionally and jointly associated with a lower likelihood of dementia. However, gait speed associations plateau above 1m/s, suggesting gait speed may be less predictive at near normal speeds. This study examined prospective associations of gait speed, endurance, and moderating effects of endurance on gait speed associations with incident dementia among ARIC participants without dementia at Visit 6 (2016-2017) who completed assessments of endurance ( 2- Minute Walk (2MW), meters) and usual-pace 4-meter gait speed (m/s) (n = 2767, mean age 78+/- 4.3 years, 43% male, 18% Black). Dementia was adjudicated using neuropsychological tests, functional assessments, informant interviews, and medical/vital record surveillance over a median of 3.3 years follow-up. Cox regression models estimated the hazard ratio (HR, 95% CI) for dementia, incorporating gait speed, 2MW, gait speed-by-2MW interaction, demographic, and cardiovascular factors. In separate models, each standard deviation higher 2MW [HR = 0.62, (0.50,0.76)] and faster gait speed [HR = 0.63, (0.50,0.81)] were associated with lower incident dementia risk. However, when jointly adjusting for 2MW and gait speed, higher 2MW was associated with a 32% lower incident dementia risk [HR = 0.68,(0.51, 0.90)], but faster gait speed was not statistically associated with incident dementia [HR = 0.85, (0.62,1.16)]. Moderating effects were not supported (gait speed-x-2MW interaction, p = 0.14). Although both endurance and gait speed predict dementia, endurance may be more informative across the gait speed spectrum, whereas gait speed may be more feasible for clinical settings. Longer follow-up and more dementia events may better inform differential utilities of gait speed and endurance measures.

Abstract Impaired kidney function is a risk factor for cognitive decline and dementia, but most studies use serum creatinine-based equations to estimate kidney function as estimated glomerular filtration rate (eGFR); these equations include age, also a strong driver of cognitive impairment, and produce eGFR estimates with substantial error compared to gold-standard objective measures of GFR (mGFR). The purpose of this study was to determine eGFR and mGFR associations with cognitive function in African American adults, a population disproportionately impacted by both chronic kidney disease and dementia. We conducted a cross-temporal analysis of 368 participants (Age: 66.4 ± 7.4y, 75% Female) in the Genetic Epidemiology Network of Arteriopathy study with eGFR (CKD-EPI 2021 Creatinine Race-Free Equation) and mGFR assessed. eGFR was assessed using the CKD-EPI 2021 Creatinine Race-Free Equation and mGFR (urinary clearance of non-radiolabeled iothalamate). Memory (Rey Auditory Verbal Learning Test; RAVLT) and executive function (Digit Symbol Substitution Test; DSST) were assessed. Linear regression models were used to relate eGFR, mGFR, and serum creatinine to cognitive function with and without adjustment for age and sex. In unadjusted models, eGFR was positively associated with DSST scores (β = 0.19, 95%CI:0.11, 0.27) and RAVLT scores (β = 0.10, 95%CI:0.04, 0.16). mGFR was marginally associated with DSST scores (β = 0.07, 95%CI:-0.00, 0.14), but not RAVLT scores (β = 0.03, 95%CI:-0.01, 0.07). Associations of serum creatinine with cognitive function were mostly null to marginal. Age and sex adjustment greatly attenuated all associations. The observed differential renal function associations with cognition suggest age may largely explain prior reported associations.

Abstract Multiple lines of evidence suggest that calorie restriction may slow biological processes related to aging and extend lifespan. To determine whether calorie restriction affects mitochondrial function, we treated fibroblasts from adult donors with serum samples obtained from participants of the CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) study. The CALERIE study enrolled healthy, non-obese middle-aged (average 38y.o) participants to examine the effects of long-term calorie restriction. We studied the serum samples of 177 participants (calorie restriction CR = 121, ad libitum AL = 56) who had specimens available at two timepoints (12 and 24 months). We assessed the basal and maximal mitochondrial respiration of fibroblasts treated with dilute serum for 24 hours. Our results show that the baseline basal and maximal mitochondrial respiration of fibroblasts is positively correlated with the adiposity of the serum donor (R = 0.112, P = 0.137; R = 0.183, P = 0.015, respectively). Interestingly, treatment of fibroblasts with serum collected after 12 months of calorie restriction causes a decrease in both basal and maximal mitochondrial respiration (P = 0.1854; P = 0.0623, respectively). Fibroblasts treated with serum collected after 24 months of calorie restriction exhibited a further reduction in both basal and maximal mitochondrial respiration (P = 0.0174; P = 0.0092, respectively). These findings suggest that the serum of individuals on long term calorie restriction diet comprises factors that can reduce oxidative phosphorylation. This reduction in bioenergetic capacity may align with the theory that calorie restriction leads to a cellular energy-conserving state, which could have implications for cellular aging and metabolism.