Novel Approach to Identify Severe Maternal Morbidity Clusters: A Latent Class Analysis.

OBJECTIVE: Whether clusters exist within severe maternal morbidity (SMM), a set of life-threatening heterogeneous conditions, is not known. Our primary objective was to identify SMM clusters using a data-driven clustering technique, their associated predictors and outcomes. STUDY DESIGN: From 2008 to 2017, we used a delivery database supplemented by state data and medical record abstraction from a single institution in Pennsylvania. To identify SMM clusters, we applied latent class modeling that included 23 conditions defined by 21 Centers for Disease Control SMM indicators, intensive care unit (ICU) admission, or prolonged postpartum length of stay. Logistic regression models estimated risk for SMM clusters and associations between clusters and maternal and neonatal outcomes. RESULTS: Among 97,492 deliveries, 2.7% (N = 2,666) experienced SMM by any of the 23 conditions. Four clusters were identified as archetypes of SMM. Deliveries labeled as Hemorrhage (37.7%, N = 1,004) were characterized by blood transfusions and sickle cell anemia; Critical Care (28.1%, N = 748) by ICU admission and amniotic embolism; Vascular (24.5%, N = 654) by cerebrovascular conditions; and Shock (9.8%, N = 260) by ventilatory support and shock. Hypertensive disorders of pregnancy, depression, and Medicaid insurance were associated with Shock cluster. People in all clusters had a high risk of maternal death within 1 year (odds ratio: 12.0, 95% confidence interval: 6.2-23). Infants born to those in the shock cluster had the highest odds of neonatal death, low Apgar scores, and neonatal ICU admission. CONCLUSION: We identified four novel SMM clusters that may help understand the collection of conditions defining SMM, underlying pathways and the importance of comorbidities such as depression and social determinants of health markers that amplify the well-established risk factors for SMM such as hypertensive disorders of pregnancy. KEY POINTS: · A total of 2.7% of deliveries experienced SMM events.. · There are four distinct SMM clusters: Hemorrhage, Critical Care, Vascular, and Shock.. · Not all SMM clusters bear the same risk for adverse perinatal outcomes..

Brain age is not a significant predictor of relapse risk in late-life depression.

INTRODUCTION: Late-life depression (LLD) has been associated cross-sectionally with lower brain structural volumes and accelerated brain aging compared to healthy controls (HC). There are few longitudinal studies on the neurobiological predictors of recurrence in LLD. We tested a machine learning (ML) brain age model and its prospective association with LLD recurrence risk. METHODS: We recruited individuals with LLD (n=102) and HC (n=43) into a multi-site 2-yr longitudinal study. Individuals with LLD were enrolled within 4 months of remission. Remitted LLD participants underwent baseline neuroimaging and longitudinal clinical follow-up. Over 2 years, 43 LLD participants relapsed (REL) and 59 stayed in remission (REM). We used a previously developed ML brain age algorithm to compute brain age at baseline and we evaluated brain age group differences (HC vs. LLD and HC vs. REM vs. REL). We conducted a Cox proportional hazards model to evaluate whether baseline brain age predicted time to relapse. RESULTS: We found that brain age did not significantly differ between HC and LLD as well as HC, REM, and REL groups. Brain age did not significantly predict time to relapse. DISCUSSION: In contrast to our hypothesis, we found that brain age did not differ between non-depressed controls and individuals with remitted LLD, and brain age was not associated with subsequent recurrence. This is in contrast to existing literature which has identified baseline brain age differences in late life but in line with work that shows no differences between those who do and do not relapse on gross structural measures.

Anxiety in late-life depression is associated with poorer performance across multiple cognitive domains.

OBJECTIVE: Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains. METHOD: Older adults with major depressive disorder (N = 228, ages 65-91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning. RESULTS: Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity. CONCLUSIONS: Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.

A preliminary investigation of worry, cortical amyloid burden, and stressor-evoked brain and cardiovascular reactivity in older adults.

Worry is a transdiagnostic symptom common to many neurocognitive disorders of aging, including early stages of Alzheimer's disease and related dementias (ADRD). Severe worry is associated with amyloid burden in cognitively intact older adults, yet the mechanisms underlying this association are not well understood. We hypothesize that this relationship involves altered brain and cardiovascular reactivity to acute stressors, a brain-body phenotype that also increases risk for cardiovascular disease. Twenty cognitively normal older adults (age 60 to 80) with varying levels of worry severity underwent positron emission tomography using Pittsburgh Compound-B and functional magnetic resonance imaging. We examined associations of worry severity and amyloid burden with cardiovascular reactivity, brain activation, and brain connectivity using a cognitive stressor task. Worry severity was not associated with global amyloid burden, but was associated with greater resting levels of cardiovascular physiology and lower systolic blood pressure reactivity. Worry severity also was associated with altered stressor-evoked activation and effective connectivity in brain circuits implicated in stress processing, emotion perception, and physiological regulation. These associations showed small to medium effect sizes. These preliminary findings introduce key components of a model that may link severe worry to ADRD risk via stressor-evoked brain-body interactions.

A Preliminary Analysis of Stress Burden and Cognitive Function and Clinically Adjudicated Cognitive Outcomes in Black American Adults.

BACKGROUND: The combination of exposure to multiple stressors and psychological distress may contribute to the disproportionate burden of dementia risk among Black Americans. This study estimates the effect of an index of stress and psychological distress (ie, "stress burden") on cognitive function and clinically adjudicated cognitive outcomes among older Black American adults, and examines sleep as a mediator. METHODS: The sample included 204 Black adults (79% female; mean age = 64 years) from Pittsburgh, PA, USA. Stress burden comprised 3 self-reported stress and distress measures assessed in 2016: discrimination, psychological distress, and posttraumatic stress. Potential mediators included actigraphy-assessed sleep duration and efficiency from 2018. Cognitive battery and clinical adjudication in 2019 assessed cognitive function and clinically adjudicated outcomes. Causal mediation analysis estimated the direct effect between stress burden and cognitive outcomes, and indirect effects through sleep, after adjusting for sociodemographics and hypertension. RESULTS: Higher stress burden had a significant direct effect on lower executive functioning and visuospatial performance. However, there were no significant indirect effects (ie, mediation) by sleep disturbances on any domain of cognitive function assessed. Also, there were no significant direct or indirect effects on clinically adjudicated outcomes. CONCLUSIONS: Multiple stressors often co-occur and may contribute to racial disparities in cognitive health. Findings suggest that higher stress burden had negative effects on functioning in executive and visuospatial domains in this community-based sample of older Black American adults. However, there was no evidence of mediation by sleep. Findings highlight the importance of continued work to identify modifiable pathways between stress burden and cognitive health disparities.

Hippocampal subfield volume in older adults with and without mild cognitive impairment: Effects of worry and cognitive reappraisal.

Studies have confirmed that anxiety, especially worry and rumination, are associated with increased risk for cognitive decline, including Alzheimer's disease and related dementias (ADRD). Hippocampal atrophy is a hallmark of ADRD. We investigated the association between hippocampus and its subfield volumes and late-life global anxiety, worry, and rumination, and emotion regulation strategies. We recruited 110 participants with varying worry severity who underwent magnetic resonance imaging and clinical interviews. We conducted cross-sectional regression analysis between each subfield and anxiety, worry, rumination, reappraisal, and suppression while adjusting for age, sex, race, education, cumulative illness burden, stress, neuroticism, and intracranial volume. We imputed missing data and corrected for multiple comparisons across regions. Greater worry was associated with smaller subiculum volume, whereas greater use of reappraisal was associated with larger subiculum and CA1 volume. Greater worry may be detrimental to the hippocampus and to subfields involved in early ADRD pathology. Use of reappraisal appears protective of hippocampal structure. Worry and reappraisal may be modifiable targets for ADRD prevention.

Assessing depression recurrence, cognitive burden, and neurobiological homeostasis in late life: Design and rationale of the REMBRANDT Study.

Background: Late-life depression is characterized by disability, cognitive impairment and decline, and a high risk of recurrence following remission. Aside from past psychiatric history, prognostic neurobiological and clinical factors influencing recurrence risk are unclear. Moreover, it is unclear if cognitive impairment predisposes to recurrence, or whether recurrent episodes may accelerate brain aging and cognitive decline. The purpose of the REMBRANDT study (Recurrence markers, cognitive burden, and neurobiological homeostasis in late-life depression) is to better elucidate these relationships and identify phenotypic, cognitive, environmental, and neurobiological factors contributing to and predictive of depression recurrence. Methods: Across three sites, REMBRANDT will enroll 300 depressed elders who will receive antidepressant treatment. The goal is to enroll 210 remitted depressed participants and 75 participants with no mental health history into a two-year longitudinal phase focusing on depression recurrence. Participants are evaluated every 2 months with deeper assessments occurring every 8 months, including structural and functional neuroimaging, environmental stress assessments, deep symptom phenotyping, and two weeks of 'burst' ecological momentary assessments to elucidate variability in symptoms and cognitive performance. A broad neuropsychological test battery is completed at the beginning and end of the longitudinal study. Significance: REMBRANDT will improve our understanding of how alterations in neural circuits and cognition that persist during remission contribute to depression recurrence vulnerability. It will also elucidate how these processes may contribute to cognitive impairment and decline. This project will obtain deep phenotypic data that will help identify vulnerability and resilience factors that can help stratify individual clinical risk.

Sex differences in plasma proteomic markers in late-life depression.

Previous studies have shown significant sex-specific differences in major depressive disorder (MDD) in multiple biological parameters. Most studies focused on young and middle-aged adults, and there is a paucity of information about sex-specific biological differences in older adults with depression (aka, late-life depression (LLD)). To address this gap, this study aimed to evaluate sex-specific biological abnormalities in a large group of individuals with LLD using an untargeted proteomic analysis. We quantified 344 plasma proteins using a multiplex assay in 430 individuals with LLD and 140 healthy comparisons (HC) (age range between 60 and 85 years old for both groups). Sixty-six signaling proteins were differentially expressed in LLD (both sexes). Thirty-three proteins were uniquely associated with LLD in females, while six proteins were uniquely associated with LLD in males. The main biological processes affected by these proteins in females were related to immunoinflammatory control. In contrast, despite the smaller number of associated proteins, males showed dysregulations in a broader range of biological pathways, including immune regulation pathways, cell cycle control, and metabolic control. Sex has a significant impact on biomarker changes in LLD. Despite some overlap in differentially expressed biomarkers, males and females show different patterns of biomarkers changes, and males with LLD exhibit abnormalities in a larger set of biological processes compared to females. Our findings can provide novel targets for sex-specific interventions in LLD.

Heterogeneity of Cognition in Older Adults with Remitted Major Depressive Disorder: A Latent Profile Analysis.

OBJECTIVES: To identify data-driven cognitive profiles in older adults with remitted major depressive disorder (rMDD) with or without mild cognitive impairment (MCI) and examine how the profiles differ regarding demographic, clinical, and neuroimaging measures. DESIGN: Secondary cross-sectional analysis using latent profile analysis. SETTING: Multisite clinical trial in Toronto, Canada. PARTICIPANTS: One hundred seventy-eight participants who met DSM-5 criteria for rMDD without MCI (rMDD-MCI; n = 60) or with MCI (rMDD + MCI; n = 118). MEASUREMENTS: Demographic, clinical, neuroimaging measures, and domain scores from a neuropsychological battery assessing verbal memory, visuospatial memory, processing speed, working memory, language, and executive function. RESULTS: We identified three latent profiles: Profile 1 (poor cognition; n = 75, 42.1%), Profile 2 (intermediate cognition; n = 75, 42.1%), and Profile 3 (normal cognition; n = 28, 15.7%). Compared to participants with Profile 3, those with Profile 1 or 2 were older, had lower education, experienced a greater burden of medical comorbidities, and were more likely to have MCI. The profiles did not differ on the severity of residual symptoms, age of onset of rMDD, number of depressive episodes, psychotropic medication, cerebrovascular risk, ApoE4 carrier status, or family history of depression, dementia, or Alzheimer's disease. The profiles differed in cortical thickness of 15 regions, with the most prominent effects for left precentral and pars opercularis, and right inferior parietal and supramarginal. CONCLUSION: Older patients with rMDD can be grouped cross-sectionally based on data-driven cognitive profiles that differ from the absence or presence of a diagnosis of MCI. Future research should determine the differential risk for dementia of these data-driven subgroups.

Anxiety in late-life depression: Associations with brain volume, amyloid beta, white matter lesions, cognition, and functional ability.

OBJECTIVES: Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aß) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD. PARTICIPANTS AND MEASUREMENTS: Older adults with major depression (N = 121, Ages 65-91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aß standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity. RESULTS: Greater anxiety severity was associated with lower OFC volume (ß = -68.25, t = -2.18, p = .031) and greater cognitive dysfunction (ß = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aß SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (ß = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety. CONCLUSIONS: Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.

White Noise-Is Anxiety in Late-Life Associated With White Matter Hyperintensity Burden?

OBJECTIVE: We investigated the relationship between anxiety phenotypes (global anxiety, worry, and rumination) and white matter hyperintensities (WMH), with special consideration for the roles of age and executive function (EF). Our hypotheses were 1) anxiety phenotypes would be associated with WMH and 2) EF would moderate this relationship. DESIGN: Cross-sectional. SETTING: Participants were recruited from the local community (Pittsburgh, PA). PARTICIPANTS: We recruited 110 older adults (age ≥ 50) with varying worry severity and clinical comorbidity. INTERVENTIONS: Not applicable. MEASUREMENTS: Demographics (age, sex, race, education), clinical measures (cumulative illness burden, global anxiety, worry, and rumination), EF, and WMH quantified with magnetic resonance imaging. RESULTS: Lower global anxiety and worry severity were significantly correlated with higher WMH volume, though the global anxiety relationship was not significant after controlling for age. Rumination as not associated with WMH burden. EF was not correlated with either global anxiety, worry, rumination, or WMH. However, in those with advanced age and/or greater WMH burden, there was an association between worry and EF as well as EF and WMH. CONCLUSION: Longitudinal studies are needed in order to clarify the complex interactions between anxiety phenotypes, WMH, and EF.

"And Does That Necessarily Mean Absolutely Alzheimer's?" An Analysis of Questions Raised Following Amyloid PET Results Disclosure.

INTRODUCTION: Amyloid PET scans provide individuals with mild cognitive impairment (MCI) information about their risk of progressing to Alzheimer's dementia (AD). Given the wide-ranging implications of this information, best practice guidelines are needed to support researchers and clinicians disclosing these high-stakes test results. To inform the development of such guidelines, this analysis aims to describe questions and concerns raised during the disclosure of amyloid PET results in the context of MCI. METHODS: Qualitative description was performed to analyze (n = 34) transcripts of audio-recorded amyloid PET results disclosure sessions involving MCI care dyads. The analysis focused on characterizing the frequency and nature of questions raised during an open question-and-answer (Q&A) period following the return of scan results using a standardized protocol. RESULTS: Nearly all (n = 32/34) dyads posed questions during Q&A. Questions fell within six main categories with the most common being requests for clarification regarding AD/MCI, and next steps given the result. Questions were interspersed with comments reflecting the need for emotional support. Independently administered assessments of comprehension of results showed that, following the disclosure and Q&A, 31/32 participants with MCI and 31/31 care partners scored ≥4 on a 5-point scale. The number of questions asked by care partners during Q&A positively correlated with their level of comprehension (n = 31, Spearman's r = 0.370, p = 0.040). DISCUSSION: This analysis highlights the value of providing opportunities for patients and their family members to ask questions upon learning patients' brain amyloid status. Disclosing clinicians should be prepared to provide clarification, resources, and support to patients and families during the return of amyloid PET results.

About time: neurocognitive correlates of stimulus-bound and other time setting errors in the Clock Drawing Test.

OBJECTIVE: Previous findings suggest that time setting errors (TSEs) in the Clock Drawing Test (CDT) may be related mainly to impairments in semantic and executive function. Recent attempts to dissociate the classic stimulus-bound error (setting the time to "10 to 11" instead of "10 past 11") from other TSEs, did not support hypotheses regarding this error being primarily executive in nature or different from other time setting errors in terms of neurocognitive correlates. This study aimed to further investigate the cognitive correlates of stimulus-bound errors and other TSEs, in order to trace possible underlying cognitive deficits. METHODS: We examined cognitive test performance of participants with preliminary diagnoses associated with mild cognitive impairment. Among 490 participants, we identified clocks with stimulus-bound errors (n = 78), other TSEs (n = 41), other errors not related to time settings (n = 176), or errorless clocks (n = 195). RESULTS: No differences were found on any dependent measure between the stimulus-bound and the other TSErs groups. Group comparisons suggested TSEs in general, to be associated with lower performance on various cognitive measures, especially on semantic and working memory measures. Regression analysis further highlighted semantic and verbal working memory difficulties as being the most prominent deficits associated with these errors. CONCLUSION: TSEs in the CDT may indicate underlying deficits in semantic function and working memory. In addition, results support previous findings related to the diagnostic value of TSEs in detecting cognitive impairment.

Race and sex differences in the longitudinal changes in multidimensional self-reported sleep health characteristics in aging older adults.

OBJECTIVES: We examined within-individual changes in self-reported sleep health as community-dwelling older adults age as well as potential differences in these changes by self-reported sex and racial identity. METHODS: Participants were from the United States and enrolled in the Rush Memory and Aging Project, Minority Aging Research Study, or Religious Orders Study (N = 3539, 20% Black, 75% female, mean 78years [range 65-103]), and they received annual, in-person clinical evaluations (median 5 visits [range 1-27]). A sleep health composite score measured the number of poor sleep characteristics among satisfaction, daytime sleepiness, efficiency, and duration. Mixed effects models estimated associations of age, race, sex, and their interactions on the composite and individual sleep measures, accounting for key confounders. RESULTS: As they aged, Black participants shifted from reporting two poor sleep characteristics to one poor sleep characteristic, while White participants shifted from one poor characteristic to two. Regardless of age, sex, and race, participants reported that they "often" felt satisfied with their sleep and "sometimes" had trouble staying asleep. Females over age 85 and males of all ages reported the most daytime sleepiness, and older White participants (>age 90) reported the most difficulty falling asleep. CONCLUSIONS: Although self-reported sleep characteristics were typically stable across age, identifying race and sex differences in self-reported sleep health can help guide future research to understand the mechanisms that underlie these differences.

Change in patient-centered outcomes of psychological well-being, sleep, and suicidality following treatment with intravenous ketamine for late-life treatment-resistant depression.

OBJECTIVE: To examine whether psychological well-being, sleep, and suicidality improved with treatment with intravenous (IV) ketamine for late-life treatment-resistant depression (TRD). METHODS: This is an analysis of secondary outcomes in an open-label late-life TRD study examining the safety, tolerability, and feasibility of IV ketamine infusions. In the acute phase, participants (N = 25) aged 60 years or older received twice-a-week IV ketamine for 4 weeks. Then, participants with Montgomery-Asberg Depression Rating Scale (MADRS) total score <10 or ≥ 30% reduction from baseline proceeded to the continuation phase, an additional four weeks of once-a-week IV ketamine. The secondary outcomes analyzed here are based on the National Institute of Health Toolbox Psychological Well-Being subscales for Positive Affect and General Life Satisfaction, the Pittsburgh Sleep Quality Index, and the Scale for Suicidal Ideation. RESULTS: Psychological well-being, sleep, and suicidality improved during the acute phase and those improvements were sustained during the continuation phase. Greater improvements in measures of psychological well-being and sleep were seen in participants who had greater improvements in MADRS scores and moved onto the continuation phase. All but one of the few participants with high suicidality at baseline improved; there were no cases of treatment-emergent suicidality. CONCLUSIONS: Psychological well-being, sleep, and suicidality improved in participants with late-life TRD who received IV ketamine for 8 weeks. A future larger and longer controlled trial is needed to confirm and extend these findings. REGISTRATION: ClinicalTrials.gov identifier: NCT04504175.

The relationship of white matter microstructure with psychomotor disturbance and relapse in remitted psychotic depression.

BACKGROUND: Psychomotor disturbance is common in psychotic depression and is associated with relapse. In this analysis, we examined whether white matter microstructure is associated with relapse probability in psychotic depression and, if so, whether white matter microstructure accounts for the association between psychomotor disturbance and relapse. METHODS: We used tractography to characterize diffusion-weighted MRI data in 80 participants enrolled in a randomized clinical trial that compared efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo in the continuation treatment of remitted psychotic depression. Cox proportional hazard models tested the relationships between psychomotor disturbance (processing speed and CORE score) at baseline, white matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) in 15 selected tracts at baseline, and relapse probability. RESULTS: CORE was significantly associated with relapse. Higher mean MD was significantly associated with relapse in the each of the following tracts: corpus callosum, left striato-frontal, left thalamo-frontal, and right thalamo-frontal. CORE and MD were each associated with relapse in the final models. LIMITATIONS: As a secondary analysis with a small sample size, this study was not powered for its aims, and is vulnerable to types I and II statistical errors. Further, the sample size was not sufficient to test the interaction of the independent variables and randomized treatment group with relapse probability. CONCLUSIONS: While both psychomotor disturbance and MD were associated with psychotic depression relapse, MD did not account for the relationship between psychomotor disturbance and relapse. The mechanism by which of psychomotor disturbance increases the risk of relapse requires further investigation. CLINICAL TRIAL REGISTRATION: Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II); NCT01427608. URL: https://clinicaltrials.gov/ct2/show/NCT01427608.

Retired night shift workers exhibit poorer neurocognitive function compared to retired day workers.

STUDY OBJECTIVES: Shift work is associated with compromised cognitive function, and with chronic exposure, may place shift workers at elevated risk for dementia. However, evidence of cognitive impairment among former night shift workers is mixed, possibly due to inconsistencies regarding retirement status, work history classification, and cognitive assessments. To address these limitations, this study compared neurocognitive function between retired night shift workers and retired day workers using a well-characterized sample and a rigorous neurocognitive test battery. METHODS: Participants (N = 61; mean age: 67.9 ± 4.7 years; 61% females; 13% non-white) were 31 retired day workers and 30 retired night shift workers equated on age, sex, race/ethnicity, premorbid IQ, years retired, and diary-assessed habitual sleep characteristics. Participants completed a neurocognitive battery assessing six cognitive domains (language, visuospatial ability, attention, immediate and delayed memory, executive function) and self-reported cognitive function. Linear regression models compared groups on individual cognitive domains, adjusting for age, sex, race/ethnicity, education level, and habitual sleep quality. RESULTS: Retired night shift workers scored lower than retired day workers on attention (B = -0.38, 95% CI [-0.75, -0.02], p = .040) and executive function (B = -0.55, 95% CI [-0.92, -0.17], p = .005). In post hoc analyses, attention and executive function were unrelated to diary-assessed habitual sleep characteristics (disruption, timing, and irregularity) in retired night shift workers. CONCLUSIONS: The observed cognitive weaknesses in retired night shift workers may suggest increased risk for future dementia. Retired night shift workers should be followed to determine whether observed weaknesses progress.

Longitudinal cognitive evaluation before and after delivery among people with preeclampsia.

BACKGROUND: Cognitive impairments related to preeclampsia after pregnancy have been reported; however, it is not known if weaknesses in cognition occur before and shortly after delivery. OBJECTIVE: This study aimed to assess the feasibility of longitudinal cognitive testing before and after delivery, and to investigate whether those with preeclampsia have cognitive weaknesses during the third trimester of pregnancy and at 1 and 3 months postpartum. We hypothesized that people with preeclampsia would have lower cognition scores across all time points compared with normotensive people. STUDY DESIGN: This longitudinal, prospective, observational study in a single institution enrolled people (N=30) at ≥28 weeks of gestation with preeclampsia (N=16) or normotension (N=14). People with chronic hypertension, neurologic or developmental disabilities, moderate or severe depression or anxiety, or current substance use were excluded. Subjective (Everyday Cognition Scale) and objective assessment of executive function (Stroop Color-Word Interference Test, Trail-Making Test), attention and working memory (Digit Span subtest), and information processing speed (Digit Symbol Substitution Test) was conducted, and Z-scores were calculated. Baseline characteristics (eg, prepregnancy body mass index) were collected from the medical record. Generalized linear models were used to estimate associations. RESULTS: We enrolled 37% (30/81) of eligible people and retained 80% (24/30) and 53% (16/30) at 1 and 3 months postpartum, respectively. People with preeclampsia reported more memory problems (ß=0.87; 95% confidence interval, 0.44-1.31), and scored worse on attention and working memory (ß=-0.94; 95% confidence interval, -1.42 to -0.45) and executive function (Stroop test ß=-0.86; 95% confidence interval, -1.53 to -0.19) domains compared with normotensive people after adjusting for time, age, education, and prepregnancy body mass index. CONCLUSION: Longitudinal assessment of cognition in pregnant preeclamptic and normotensive people is feasible. People with preeclampsia reported worse subjective memory and had lower scores in attention, working memory, and executive function.

Design of the think PHRESH longitudinal cohort study: Neighborhood disadvantage, cognitive aging, and alzheimer's disease risk in disinvested, black neighborhoods.

BACKGROUND: Black Americans have disproportionately higher rates and earlier onset of Alzheimer's disease and related dementias (ADRD) relative to White Americans. We currently lack a comprehensive understanding of how the lived experience and broader societal factors, including cumulative exposure to structural racism and the mechanisms underlying the risks, may contribute to elevated ADRD risk in Black Americans. METHODS: The Think PHRESH study builds on existing, community-based research infrastructure, from the ongoing Pittsburgh Hill/Homewood Research on Neighborhood Change and Health (PHRESH) studies, to examine the contributions of dynamic neighborhood socioeconomic conditions across the lifecourse to cognitive outcomes in mid- and late-life adults living in two historically disinvested, predominantly Black communities (anticipated n = 1133). This longitudinal, mixed-methods study rests on the premise that neighborhood racial segregation and subsequent disinvestment contributes to poor cognitive outcomes via factors including (a) low access to educational opportunities and (b) high exposure to race- and socioeconomically-relevant stressors, such as discrimination, trauma, and adverse childhood events. In turn, these cumulative exposures foster psychological vigilance in residents, leading to cardiometabolic dysregulation and sleep disruption, which may mediate associations between neighborhood disadvantage and ADRD risk. This premise recognizes the importance of potential protective factors that may promote cognitive health, including neighborhood social cohesion, safety, and satisfaction. The proposed study will leverage our existing longitudinal data on risk/protective factors and biobehavioral mediators and will include: (1) up to three waves of cognitive assessments in participants ages 50 years + and one assessment in participants ages 35-49 years; clinical adjudication of ADRD will be completed in participants who are 50+, (2) extensive surveys of risk and protective factors, (3) two assessments of blood pressure and objectively measured sleep, (4) a comprehensive assessment of life and residential history; and (5) two rounds of in-depth qualitative interviews to reveal lifecourse opportunities and barriers experienced by Black Americans in achieving optimal cognitive health in late life. DISCUSSION: Understanding how structural racism has influenced the lived experience of Black Americans, including dynamic changes in neighborhood conditions over time, is critical to inform multi-level intervention and policy efforts to reduce pervasive racial and socioeconomic disparities in ADRD.