Characterization of Change in Cognition Before and After COVID-19 Infection in Essential Workers at Midlife.

Background: Research into COVID-19-related cognitive decline has focused on individuals who are cognitively impaired following hospitalization for COVID-19. Our objective was to determine whether cognitive decline emerged after the onset of COVID-19 and was more pronounced in patients with postacute sequelae of SARS-CoV-2 infection (PASC). Methods: We analyzed longitudinal cognitive data collected during a cohort study of essential workers at midlife that continued through the COVID-19 pandemic. We used longitudinal discontinuity models, a form of causal modeling, to examine the change in cognitive performance among 276 participants with COVID-19 in comparison to contemporaneously-collected information from 217 participants who did not have COVID-19. Cognitive performance across four domains was measured before and after the pandemic. Eligible study participants were those with validated COVID-19 diagnoses who were observed before having a verified COVID-19 infection who survived their initial infection, and for whom post-COVID-19 information was also available. Results: The mean age of the COVID-19 group was 56.0 ± 6.6 years old, while the control group was 58.1 ± 7.3 years old. Longitudinal models indicated a significant decline in cognitive throughput (ß = -0.168, P = .001) following COVID-19, after adjustment for pre-COVID-19 functioning, demographics, and medical factors. Associations were larger in those with more severe COVID-19 and those who reported PASC. Observed changes in throughput were equivalent to 10.6 years of normal aging. Conclusion: Findings from this longitudinal causal modeling study revealed that COVID-19 and PASC appeared to cause clincially relevant cognitive deterioration.

Health Outcomes of Elder Orphans: An Umbrella and Scoping Review of the Literature.

Objectives: As the population of elder orphans grows, little research has investigated the health outcomes of these socially and physically isolated older adults without caregiving support. Umbrella and scoping reviews were performed for studies examining health outcomes of older adults experiencing elements of elder orphanhood. Methods: Studies published 2010- June 2021 and indexed on PubMed, Web of Science, CINAHL, Medline, or SocINDEX were eligible. Results of included studies were examined both by individual category and overall to determine overlapping outcomes. Results: Umbrella review returned 1,686 studies, with 14 meeting criteria for social isolation (n=10) and physical isolation (n=4). The scoping review of studies examining unmet caregiving need returned 3,741 results: five met inclusion criteria. Discussion: Included studies reviewed differing health outcomes in older adults, with a focus on dementia, frailty, and healthcare utilization. Further studies are needed that appraise targeted policies and interventions to improve health outcomes of elder orphans.

Prevalence of Mild and Severe Cognitive Impairment in World Trade Center Exposed Fire Department of the City of New York (FDNY) and General Emergency Responders.

Background: The emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations. Methods: A sample of WTC-exposed-FDNY responders (n = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests. The prevalences of domain-specific impairments were estimated based on the results of norm-referenced tests, and the Montreal Cognitive Assessment (MoCA), Jak/Bondi criteria, Petersen criteria, and the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria were used to diagnose MCI. NIA-AA criteria were also used to diagnose severe cognitive impairment. Generalized linear models were used to compare prevalence estimates of cognitive impairment to a large sample of WTC-exposed-non-FDNY responders from the General Responder Cohort (GRC; n = 7102) who completed the MoCA during a similar time frame. Result: Among FDNY responders under 65 years, the unadjusted prevalence of MCI varied from 52.57% to 71.37% depending on the operational definition of MCI, apart from using a conservative cut-off applied to MoCA total scores (18 < MoCA < 23), which yielded a markedly lower crude prevalence (24.31%) compared to alternative criteria. The prevalence of MCI was higher among WTC-exposed-FDNY-responders, compared to WTC-exposed-non-FDNY-GRC-responders (adjusted RR = 1.53, 95% C.I. = [1.24, 1.88], p < .001) and meta-analytic estimates from different global, community, and clinical populations. Following NIA-AA diagnostic guidelines, 4.96% of WTC-exposed-FDNY-responders met the criteria for severe impairments (95% CI = [2.91% to 7.82%]), a prevalence that remained largely unchanged after excluding responders over the age of 65 years. Discussion: There is a high prevalence of mild and severe cognitive impairment among WTC-responders highlighting the putative role of occupational/environmental and disaster-related exposures in the etiology of accelerated cognitive decline.

The Flynn effect and cognitive decline among americans aged 65 years and older.

To contribute to our understanding of cohort differences and the Flynn effect in the cognitive decline among older Americans, this study aims to compare rates of cognitive decline between two birth cohorts within a study of older Americans and to examine the importance of medical and demographic confounders. Analyses used data from the National Health and Aging Trends Study (2011-2019), which recruited older Americans in 2011 and again in 2015 who were then followed for 5 years. We employed mixed-effect models to examine the linear and quadratic main and interaction effects of year of birth while adjusting for covariates such as annual round, sex/gender, education, race/ethnicity, heart disease, hypertension, diabetes, test unfamiliarity, and survey design. We analyzed data from 11,167 participants: 7,325 from 2011 to 2015 and 3,842 from 2015 to 2019. The cohort recruited in 2015 was born, on average, 5.33 years later than that recruited in 2011 and had higher functioning than the one recruited in 2011 across all observed cognitive domains that persisted after adjusting for covariates. In multivariable-adjusted analyses, a 1-year increase in year of birth was associated with increased episodic memory (ß = 0.045, SE = 0.001, p < .001), orientation (ß = 0.034, SE = 0.001, p < .001), and executive function (ß = 0.036, SE = 0.001, p < .001). Participants born 1 year later had slower rates of decline in episodic memory (ß = 0.004, SE = 0.000, p < .001), orientation (ß = 0.003, SE = 0.000, p < .001), and executive function (ß = 0.001, SE = 0.000, p = .002). Additionally, sex/gender modified this relationship for episodic memory (-0.007, SE = 0.002, p < .001), orientation (-0.005, SE = 0.002, p = .008), and executive function (-0.008, SE = 0.002, p < .001). These results demonstrate the persistence of the Flynn effect in old age across cognitive domains and identified a deceleration in the rate of cognitive decline across cognitive domains. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Inequalities in accelerated cognitive decline: Resolving observational window bias using nested non-linear regression.

INTRODUCTION: Limited observational windows lead to conflicting results in studies examining educational differences in Alzheimer's disease and related dementias (ADRD) risk, due to observational window bias relative to onset of accelerated cognitive decline. This study tested a novel model to address observational window bias and tested for the presence and sources of disparities in accelerated cognitive declines due to ADRD. METHODS: The sample examined 167,314 cognitive assessments from 32,441 Health and Retirement Study participants. We implemented a parametric non-linear nested longitudinal regression and reported multivariable-adjusted nodal incidence ratios (aNIR). RESULTS: University degrees were associated with lower incidence (aNIR = 0.253, 95% confidence interval [CI] = [0.221 to 0.289], p < 0.001), while black participants had a higher incidence (aNIR = 1.995, [1.858 to 2.141], p < 0.001) of accelerated cognitive decline, adjusting for demographic, sociobehavioral, and medical risk factors. Sex-stratified analyses identified diminished educational returns for women and increased incidence among minoritized women. DISCUSSION: Addressing observational window bias reveals large social inequalities in the onset of accelerated cognitive declines indicative of ADRD. HIGHLIGHTS: This study identifies observational window bias as a source of conflicting results among previous studies of educational achievement in Alzheimer's disease and related dementias (ADRD) disparities. The study locates preclinical accelerated cognitive decline, which is indicative of ADRD while occurring 10+ years prior to symptom onset, as a site to study ADRD disparities that mitigates observational window bias. A novel method, nested non-linear regression, is developed to test for differences in the onset of accelerated cognitive decline. Educational and racial/ethnic disparities are demonstrated in the onset of accelerated cognitive decline, as are their intersecting differences with sex/gender.

Cross-sectional association between posttraumatic stress and cognition is moderated by pulmonary functioning in world trade center responders.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptomatology and poorer pulmonary function are highly prevalent psychiatric and medical conditions. In the present study, we tested for the individual, additive, and modifying associations of PTSD symptomatology and pulmonary function with cognitive performance. METHODS: In this cross-sectional study, a total of 1,401 World Trade Center (WTC) responders (mean age = 53, SD = 8 years, 92% males) participated in the study. Cogstate assessment measured cognitive performance. PTSD symptomatology was measured using the trauma-specific version of the posttraumatic stress disorder checklist (PCL-17) adapted for the WTC attacks. The 1-second forced expiratory volume and forced vital capacity (FEV1/FVC) ratio was used to measure pulmonary function. Linear regressions with cognitive performance as the outcome were conducted to assess individual, additive, and moderating associations of PTSD symptomatology and pulmonary function. RESULTS: Higher PTSD symptomatology and poorer pulmonary function were negatively associated with cognitive performance. A 10% increase on the FEV1/FVC ratio moderated the association between PTSD symptomatology and cognition, whereby its association with cognition was stronger when PTSD symptomatology was higher (est. = 0.01, 95%CI = 0.004, 0.01, p < 0.001). When stratified by responder type, these associations persisted in trained (est. = 0.01, 95%CI = 0.01, 0.02, p < 0.001), but not in non-trained (est. = 0.004, 95% C.I. = -0.01, 0.02, p = 0.39) responders. CONCLUSIONS: In the presence of higher PTSD, better pulmonary functioning is associated with better cognitive performance. Early intervention efforts to mitigate preventable cognitive decline in high-risk populations should be studied, especially since intervention in one modality may have an impact on others.

Behavioral meaures of psychotic disorders: Using automatic facial coding to detect nonverbal expressions in video.

Emotional deficits in psychosis are prevalent and difficult to treat. In particular, much remains unknown about facial expression abnormalities, and a key reason is that expressions are very labor-intensive to code. Automatic facial coding (AFC) can remove this barrier. The current study sought to both provide evidence for the utility of AFC in psychosis for research purposes and to provide evidence that AFC are valid measures of clinical constructs. Changes of facial expressions and head position of participants-39 with schizophrenia/schizoaffective disorder (SZ), 46 with other psychotic disorders (OP), and 108 never psychotic individuals (NP)-were assessed via FaceReader, a commercially available automated facial expression analysis software, using video recorded during a clinical interview. We first examined the behavioral measures of the psychotic disorder groups and tested if they can discriminate between the groups. Next, we evaluated links of behavioral measures with clinical symptoms, controlling for group membership. We found the SZ group was characterized by significantly less variation in neutral expressions, happy expressions, arousal, and head movements compared to NP. These measures discriminated SZ from NP well (AUC = 0.79, sensitivity = 0.79, specificity = 0.67) but discriminated SZ from OP less well (AUC = 0.66, sensitivity = 0.77, specificity = 0.46). We also found significant correlations between clinician-rated symptoms and most behavioral measures (particularly happy expressions, arousal, and head movements). Taken together, these results suggest that AFC can provide useful behavioral measures of psychosis, which could improve research on non-verbal expressions in psychosis and, ultimately, enhance treatment.

Incidence of Dementia Before Age 65 Years Among World Trade Center Attack Responders.

Importance: Reports suggest that the individuals who served in rescue operations following the terrorist attacks on the World Trade Center (WTC) have poorer brain health than expected. Objective: To assess the incidence of dementia before age 65 years in a prospective study of WTC responders and to compare incidence among responders with severe exposures to debris vs responders not exposed to building debris or who wore personalized protective equipment (PPE). Design, Setting, and Participants: This prospective cohort study was conducted from November 1, 2014, to January 1, 2023, in an academic medical monitoring program available to verified WTC responders residing on Long Island, New York. Responders 60 years of age or younger without dementia at the time of their first cognitive assessment were followed up every 18 months, on average, for up to 5 years. Exposures: Exposure severity was based on responses to a detailed questionnaire of WTC exposures and exposure-related activities that included exposures to fine particulate dust and potentially neurotoxic debris, duration of work, and the use of PPE. Exposure level was divided into 5 categories ranging from low to severe. Main Outcomes and Measures: Incidence of all-cause dementia before age 65 years was the primary outcome. Dementia was diagnosed following standard guidelines relying on repeated measures of cognition. Results: Of 9891 responders, 5010 were eligible for inclusion in this study of cognitive function (median [IQR] age, 53 [48-57] years; 4573 [91.3%] male). There were 228 cases of dementia identified during 15 913.1 person-years of follow-up. Increasing WTC exposure severity was associated with incremental increases in the incidence rate of dementia per 1000 person-years (low, 2.95 [95% CI, 1.07-11.18]; mild, 12.16 [95% CI, 10.09-14.79]; moderate, 16.53 [95% CI, 13.30-20.81]; high, 30.09 [95% CI, 21.35-43.79]; and severe, 42.37 [95% CI, 24.86-78.24]). Adjusting for social, demographic, and relevant medical factors, each unit increase in exposure severity was associated with increased incidence of dementia (adjusted hazard ratio, 1.42 [95% CI, 1.18-1.71]; P < .001; mean risk difference, 9.74 [95% CI, 2.94-32.32] per 1000 person-years; P < .001). Conclusions and Relevance: In this cohort study of WTC responders who survived these unique exposures and participated in a longitudinal follow-up study of cognition from 2014 through 2022, when compared with responders with the lowest exposure levels or responders who used PPE, more severe exposure to dust or debris was significantly associated with a higher risk of dementia before 65 years of age. This study suggests that the reliable use of PPE might help prevent the onset of dementia before age 65 years among individuals exposed to an uncontrolled building collapse. Future research is warranted to determine cerebral biomarkers for individuals with exposure-associated dementia.

Robust language-based mental health assessments in time and space through social media.

In the most comprehensive population surveys, mental health is only broadly captured through questionnaires asking about "mentally unhealthy days" or feelings of "sadness." Further, population mental health estimates are predominantly consolidated to yearly estimates at the state level, which is considerably coarser than the best estimates of physical health. Through the large-scale analysis of social media, robust estimation of population mental health is feasible at finer resolutions. In this study, we created a pipeline that used ~1 billion Tweets from 2 million geo-located users to estimate mental health levels and changes for depression and anxiety, the two leading mental health conditions. Language-based mental health assessments (LBMHAs) had substantially higher levels of reliability across space and time than available survey measures. This work presents reliable assessments of depression and anxiety down to the county-weeks level. Where surveys were available, we found moderate to strong associations between the LBMHAs and survey scores for multiple levels of granularity, from the national level down to weekly county measurements (fixed effects ß = 0.34 to 1.82; p < 0.001). LBMHAs demonstrated temporal validity, showing clear absolute increases after a list of major societal events (+23% absolute change for depression assessments). LBMHAs showed improved external validity, evidenced by stronger correlations with measures of health and socioeconomic status than population surveys. This study shows that the careful aggregation of social media data yields spatiotemporal estimates of population mental health that exceed the granularity achievable by existing population surveys, and does so with generally greater reliability and validity.

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Optimization of [18F]-FDOPA Brain PET Acquisition Times for Assessment of Parkinsonism in the Clinical Setting.

BACKGROUND AND PURPOSE: Fluorine 18-fluoro-L-dopa ([18F]-FDOPA) was approved by the FDA in 2019 and reimbursed by the Centers for Medicare & Medicaid Services in 2022 for use with PET to visualize dopaminergic nerve terminals in the striatum for evaluation of parkinsonism. We sought to determine the optimal image acquisition time for [18F]-FDOPA PET by evaluating rater-estimated FDOPA positivity and image quality across 4 time points. MATERIALS AND METHODS: Brain PET/CT was acquired 90 minutes following injection of 185 megabecquerel (5 mCi) of [18F]-FDOPA. PET was acquired in list mode for 20 minutes, and data were replayed to represent 15-, 10-, and 5-minute acquisitions. By means of MIMneuro, PET/MR imaging or PET/CT was independently graded for FDOPA positivity and image quality by 2 readers, blinded to the clinical report and diagnosis. Expert neuroradiologist clinical reads were used as the criterion standard. RESULTS: Twenty patients were included, average age 65.6 years, 55% women. Image-quality ratings decreased with shorter acquisition times for both readers (reader 1, ρ = 0.23, P = .044; reader 2, ρ = 0.24, P = .036), but there was no association between abnormality confidence scores and acquisition time (reader 1, ρ = -0.13, P = .250; reader 2, ρ = -0.19, P = .100). There was a high degree of consistency in intra- and interrater agreement and agreement with the expert reads when using acquisition times of ≥10 minutes (maximal confidence score consistency [ρ = 0.92] and interrater agreement [κ = 0.90] were observed at 15 minutes), while image quality was consistently rated as low and FDOPA positivity ratings were inconsistent when using a 5-minute acquisition time. CONCLUSIONS: Our study suggests that image-quality ratings were stable after 15 minutes and that between-subject abnormality detection rates were highly consistent between the 2 readers when acquired for at least 10 and up to 20 minutes but were inconsistent at 5 minutes. Shorter [18F]-FDOPA PET acquisition times may help maximize patient comfort while increasing throughput in the clinical setting.

Cognitive Decline After Divorce and Widowhood: Is Marital Loss Always a Loss?

Background and Objectives: We used longitudinal data to determine whether the type of marital loss is associated with the rate of cognitive change before and after divorce or widowhood. Previous research found that relationship status was associated with older adults' cognitive performance: married persons performed better on memory assessments and had lower dementia risk than unmarried-cohabitating, never-married, divorced, and widowed persons. However, the end of a marriage may cause distress or reduce distress because a stressor disappears. Questions thus remain about the mechanisms by which marital change affects cognitive outcomes and, specifically, whether termination of marriage can improve cognitive performance for some. Research Design and Methods: Using data from the 1998-2016 waves of the Health and Retirement Study (N = 23,393), we conducted two analyses. First, we used trajectory analysis to create clusters of participants with similar cognitive trajectories and tested the association between participants' cluster membership and marital loss type. Second, we used multilevel modeling to analyze the relationship between participants' cognitive scores while married and following divorce or widowhood and linked these to marital features. Results: Participants who divorced showed no difference in trajectory distribution; widowed participants were more likely to be in the lower-performing and more quickly declining groups. Participants had lower rates of decline following divorce (ß = .136, p < .001), while widowed participants had accelerated decline following spousal death (ß = -0.183, p < .001) and an immediate decline following spousal death (ß = -0.113, p = .028). Discussion and Implications: We found that the type of marital loss was important, and predicted improvements in cognition for some and decrements for others, with individuals who were divorced performing best while those who were widowed or separated but not divorced performing worse.

A novel approach to model cumulative stress: Area under the s-factor curve.

OBJECTIVE: Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to model the accumulation of stressors, and to determine whether the rate of change in stressors or traditional composite scores of stressors are stronger predictors of health outcomes. METHOD: We used factor analysis to estimate a stress-factor score and then, to operationalize the accumulation of stressors we examined five approaches to aggregating information about repeated exposures to multiple stressors. The predictive validity of these approaches was then assessed in relation to different health outcomes. RESULTS: The prediction of chronic conditions, body mass index, difficulty with activities of daily living, executive function, and episodic memory later in life was strongest when the accumulation of stressors was modeled using total area under the curve (AUC) of estimated factor scores, compared to composite scores that have traditionally been used in studies of cumulative stress, as well as linear rates of change. CONCLUSIONS: Like endogenous, biological markers of stress reactivity, AUC for individual trajectories of self-reported stressors shows promise as a data reduction technique to model the accumulation of stressors in longitudinal studies. Overall, our results indicate that considering different quantitative models is critical to understanding the sequelae and predictive power of psychosocial stressors from midlife to late adulthood.

Mediterranean diet intervention among World Trade Center responders with post-traumatic stress disorder: Feasibility and outcomes of a pilot randomized controlled trial.

Objective: Responders of the World Trade Center (WTC) disaster suffer from co-morbidities. A Mediterranean Diet (MedDiet) nutrition intervention with physical activity was implemented among WTC responders with overweight/obesity and post-traumatic stress disorder (PTSD). Methods: WTC Health Program members (N = 62), 45-65 years, males 87%, body mass index (BMI) 27-45 kg/m2 randomized to MedDiet (n = 31) or usual nutrition counseling (n = 31). The 10-week intervention included online nutrition education, text messages, and group experiential cooking; both groups had three in-person individual nutrition counseling. Anthropometrics, serum biomarkers, psychosocial factors, MedDiet score, and PTSD symptoms were assessed at baseline, post-intervention, and 3-months (follow-up). The primary outcome was intervention feasibility and secondary outcomes were within- and between-group changes of all measures at post-intervention and follow-up. Nonparametric Wilcoxon rank sum tests for between-group comparisons and Wilcoxon signed rank tests for pre-post within-group comparisons. Results: A total of 58(94%) and 46(74%) participants completed the post-intervention and follow-up measurements, respectively. Both groups experienced significant improvements in anthropometrics, MedDiet score, oxidized low-density lipoprotein, and PTSD symptoms. Baseline median (range) were weight 100.42 (73.66-135.17) kg, BMI 33.20 (27.50-41.75) kg/m2, and Waist circumference (WC) 109.22 (90.17-150.62) cm. Median % weight loss at post-intervention was MedDiet: -3% (-11%-7%), p = 0.0002; Control: -1% (-13%-4%), p = 0.008 and at follow-up MedDiet: -2% (-14%-12%), p = 0.07; Control: -2% (-20%-3%), p = 0.006. The overall BMI was reduced by -0.68 kg/m2 (-4.61-2.09) kg/m2 p < 0.0001 at post-intervention and by -0.60 kg/m2 (-6.91-3.39) kg/m2, p < 0.0009 at follow-up. Overall, median WC was reduced (p < 0.0001); post-intervention -3.81 cm (-33.00-3.30)cm and follow-up -4.45(-38.10-4.57)cm. There were group differences in HbA1c (p = 0.019) and serum ω6/ω3 (p = 0.029) at post-intervention. Conclusion: Online intervention with personal counseling was feasible in this population. Improvements in anthropometrics, MedDiet score, selected serum biomarkers and PTSD symptoms were found in both groups; group differences in HbA1c and serum ω6/ω3. A larger study with a delayed control is needed to better assess intervention effects.

Behavioral Impairments and Increased Risk of Cortical Atrophy Risk Scores Among World Trade Center Responders.

Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.

Quantifying Healthy Aging in Older Veterans Using Computational Audio Analysis.

BACKGROUND: Researchers are increasingly interested in better methods for assessing the pace of aging in older adults, including vocal analysis. The present study sought to determine whether paralinguistic vocal attributes improve estimates of the age and risk of mortality in older adults. METHODS: To measure vocal age, we curated interviews provided by male U.S. World War II Veterans in the Library of Congress collection. We used diarization to identify speakers and measure vocal features and matched recording data to mortality information. Veterans (N = 2 447) were randomly split into testing (n = 1 467) and validation (n = 980) subsets to generate estimations of vocal age and years of life remaining. Results were replicated to examine out-of-sample utility using Korean War Veterans (N = 352). RESULTS: World War II Veterans' average age was 86.08 at the time of recording and 91.28 at the time of death. Overall, 7.4% were prisoners of war, 43.3% were Army Veterans, and 29.3% were drafted. Vocal age estimates (mean absolute error = 3.255) were within 5 years of chronological age, 78.5% of the time. With chronological age held constant, older vocal age estimation was correlated with shorter life expectancy (aHR = 1.10; 95% confidence interval: 1.06-1.15; p < .001), even when adjusting for age at vocal assessment. CONCLUSIONS: Computational analyses reduced estimation error by 71.94% (approximately 8 years) and produced vocal age estimates that were correlated with both age and predicted time until death when age was held constant. Paralinguistic analyses augment other assessments for individuals when oral patient histories are recorded.

ASSESSMENT AND CHARACTERIZATION OF COVID-19 RELATED COGNITIVE DECLINE: RESULTS FROM A NATURAL EXPERIMENT.

Background: Cognitive impairment is the most common and disabling manifestation of post-acute sequelae of SARS-CoV-2. There is an urgent need for the application of more stringent methods for evaluating cognitive outcomes in research studies. Objective: To determine whether cognitive decline emerges with the onset of COVID-19 and whether it is more pronounced in patients with Post-Acute Sequelae of SARS-CoV-2 or severe COVID-19. Methods: This longitudinal cohort study compared the cognitive performance of 276 patients with COVID-19 to that of 217 controls across four neuroinflammation or vascular disease-sensitive domains of cognition using data collected both before and after the pandemic starting in 2015. Results: The mean age of the COVID-19 group was 56.04±6.6 years, while that of the control group was 58.1±7.3 years. Longitudinal models indicated a significant decline in cognitive throughput ((ß=-0.168, P=.001) following COVID-19, after adjustment for pre-COVID-19 functioning, demographics, and medical factors. The effect sizes were large; the observed changes in throughput were equivalent to 10.6 years of normal aging and a 59.8% increase in the burden of mild cognitive impairment. Cognitive decline worsened with coronavirus disease 2019 severity and was concentrated in participants reporting post-acute sequelae of SARS-CoV-2. Conclusion: COVID-19 was most likely associated with the observed cognitive decline, which was worse among patients with PASC or severe COVID-19. Monitoring patients with post-acute sequelae of SARS-CoV-2 for declines in the domains of processing speed and visual working memory and determining the long-term prognosis of this decline are therefore warranted.

Racial/Ethnic Disparities in Prostate Cancer 5-Year Survival: The Role of Health-Care Access and Disease Severity.

INTRODUCTION: Prostate cancer (PCa) exhibits one of the widest racial and socioeconomic disparities. PCa disparities have also been widely linked to location, as living in more deprived regions was associated with lower healthcare access and worse outcomes. This study aims to examine PCa survival across various USA counties in function of different socioeconomic profiles and discuss the role of potential intermediary factors. METHODS: The SEER database linked to county-level SES was utilized. Five-year PCa-specific survival using the Kaplan-Meier method was performed for five racial/ethnic categories in function of SES quintiles. Multilevel Cox proportional hazards regression was performed to assess the relationship between county-level SES and PCa survival. Multivariate regression analysis was performed to examine the role of healthcare utilization and severity. RESULTS: A total of 239,613 PCa records were extracted, and 5-year PCa-specific survival was 94%. Overall, living in counties in the worst poverty/income quintile and the worst high-school level education increased PCa mortality by 38% and 33%, respectively, while the best bachelor's-level education rates decreased mortality risk by 23%. Associations varied considerably upon racial/ethnic stratification. Multilevel analyses showed varying contributions of individual and area-level factors to survival within minorities. The relationship between SES and PCa survival appeared to be influenced by healthcare utilization and disease stage/grade. DISCUSSION: Racial/ethnic categories responded differently under similar county-level SES and individual-level factors to the point where disparities reversed in Hispanic populations. The inclusion of healthcare utilization and severity factors may provide partial early support for their role as intermediaries. Healthcare access (insurance) might not necessarily be associated with better PCa survival through the performance of biopsy and or/surgery. County-level education plays an important role in PCa decision making as it might elucidate discussions of other non-invasive management options. CONCLUSIONS: The findings of this study demonstrate that interventions need to be tailored according to each group's needs. This potentially informs the focus of public health efforts in terms of planning and prioritization. This study could also direct further research delving into pathways between area-level characteristics with PCa survival.

Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders.

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Functional changes in neural mechanisms underlying post-traumatic stress disorder in World Trade Center responders.

World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have a high prevalence of chronic WTC-related post-traumatic stress disorder (WTC-PTSD). We investigated neural mechanisms underlying WTC-PTSD by applying eigenvector centrality (EC) metrics and data-driven methods on resting state functional magnetic resonance (fMRI). We identified how EC differences relate to WTC-exposure and behavioral symptoms. We found that connectivity differentiated significantly between WTC-PTSD and non-PTSD responders in nine brain regions, as these differences allowed an effective discrimination of PTSD and non-PTSD responders based solely on analysis of resting state data. Further, we found that WTC exposure duration (months on site) moderates the association between PTSD and EC values in two of the nine brain regions; the right anterior parahippocampal gyrus and the left amygdala (p = 0.010; p = 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, a dimensional measure of symptom severity was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Functional neuroimaging can provide effective tools to identify neural correlates of diagnostic and dimensional indicators of PTSD.