New York State Psychiatric Institute

Transgender and gender-expansive young people, ages 13–24 years, experience disproportionate HIV risk yet are among those with the lowest US PrEP uptake rates (< 10%). Factors influencing PrEP outcomes for this population are poorly understood. This study examines the effects of gender minority stressors, gender affirmation, and heavy substance use on their PrEP outcomes using data from the CDC’s 2018 START study (N = 972). A conceptual model integrating the gender minority stress and gender affirmation models was developed, mapping relevant START items onto it. Structural equation modeling (Mplus-8.9) was used to examine factors related to their PrEP intentions. Most participants were 18–24 (68%), trans-female (46%), white (45%), and reported heavy substance use (40%). Medical discrimination increased internalized transphobia (b = 0.097, SE = 0.034, p = 0.005) and perceived stigma (b = 0.087, SE = 0.034, p = 0.010). Family rejection increased perceived stigma (b = 0.181, SE = 0.032, p < 0.001) and heavy substance use (b = 0.260, SE = 0.053, p < 0.001). Perceived stigma also increased heavy substance use (b = 0.106, SE = 0.037, p = 0.004). Perceived stigma (b=-0.085, SE = 0.027, p = 0.002) and heavy substance use (b=-0.161, SE = 0.031, p < 0.001) decreased PrEP intentions, while gender affirmation increased them (b = 0.045, SE = 0.019, p = 0.020). A 1-point increase in gender affirmation reduced heavy substance use risk by -0.179 (SE = 0.030, p < 0.001) in the presence of family rejection and by -0.074 (SE = 0.041, p = 0.074) when perceived stigma was present. This study underscores heavy substance use as a potential barrier to PrEP uptake for transgender/gender-expansive youth. Future research could explore how gender affirmation acts as a protective factor against the negative impact of family rejection and perceived stigma on heavy substance behaviors among these populations.

Feeding and eating disorders (FEDs) are a heterogeneous grouping of disorders at the mind‐body interface, with typical onset from childhood into emerging adulthood. They occur along a spectrum of disordered eating and compensatory weight management behaviors, and from low to high body weight. Psychiatric comorbidities are the norm. In contrast to other major psychiatric disorders, first‐line treatments for FEDs are mainly psychological and/or nutrition‐focused, with medications playing a minor adjunctive role. Patients, carers and clinicians all have identified personalization of treatment as a priority. Yet, for all FEDs, the evidence base supporting this personalization is limited. Importantly, disordered eating and related behaviors can have serious physical consequences and may put the patient's life at risk. In these cases, immediate safety and risk management considerations may at least for a period need to be prioritized over other efforts at personalization of care. This paper systematically reviews several key domains that may be relevant to the characterization of the individual patient with a FED aimed at personalization of management. These domains include symptom profile, clinical subtypes, severity, clinical staging, physical complications and consequences, antecedent and concomitant psychiatric conditions, social functioning and quality of life, neurocognition, social cognition and emotion, dysfunctional cognitive schemata, personality traits, family history, early environmental exposures, recent environmental exposures, stigma, and protective factors. Where possible, validated assessment measures for use in clinical practice are identified. The limitations of the current evidence are pointed out, and possible directions for future research are highlighted. These also include novel and emerging approaches aimed at providing more fine‐grained and sophisticated ways to personalize treatment of FEDs, such as those that utilize neurobiological markers. We additionally outline remote measurement technologies designed to delineate patients’ illness and recovery trajectories and facilitate development of novel intervention approaches.

Background Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD). AimsWe use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis. Method Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses. ResultsAlthough our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD. Conclusions We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

The negative symptoms of schizophrenia include diminished emotional expression, avolition, alogia, anhedonia, and asociality, and due to their low responsiveness to available treatments, are a primary driver of functional disability in schizophrenia. This narrative review has the aim of providing a comprehensive overview of the current research developments in the treatment of negative symptoms in schizophrenia, and begins by introducing the concepts of primary, secondary, prominent, predominant, and broadly defined negative symptoms. We then compare and contrast commonly used research assessment scales for negative symptoms and review the evidence for the specific utility of widely available off-label and investigational treatments that have been studied for negative symptoms. Mechanism of action/putative treatments included are antipsychotics (D2R antagonists), N-methyl-d-aspartate receptor (NMDAR) and other glutamatergic modulators, serotonin receptor (5-HTR) modulators, anti-inflammatory agents, antidepressants, pro-dopaminergic modulators (non-D2R antagonists), acetylcholine modulators, oxytocin, and phosphodiesterase (PDE) inhibitors. With the caveat that no compounds are definitively proven as gold-standard treatments for broadly defined negative symptoms, the evidence base supports several potentially beneficial off-label and investigational medications for treating negative symptoms in schizophrenia, such as monotherapy with cariprazine, olanzapine, clozapine, and amisulpride, or adjunctive use of memantine, setrons such as ondansetron, minocycline, and antidepressants. These medications are widely available worldwide, generally tolerable and could be considered for an off-label, time-limited trial for a predesignated period of time, after which a decision to switch or stay can be made based on clinical response. Among investigational medications, NMDAR agonists, muscarinic agonists, and LB-102 remain under study. Suggestions for future research include reducing placebo effects by designing studies with a smaller number of high-quality study sites, potentially increasing the use of more precise rating scales for negative symptoms, and focused studies in people with predominant negative symptoms.

Drug development in schizophrenia is limited by the differential scaling of the active treatment and placebo arms of a study, such that, as the number of sites increases, the magnitude of placebo response disproportionately increases. The objective of this article was to identify factors conducive to efficient recruitment as a step towards trial designs allowing recruitment of more participants per site, leading to reduced variability, and potentially a smaller placebo effect. Using the information of 554 individuals, we calculated the percentage of individuals who were screened, consented, and retained in our research, along with rationale for nonconsent. Independent t tests and Chi-squared tests were performed to compare participant characteristics. Out of the 273 individuals who were fully screened, 84 did not progress to the consented stage owing to various reasons, leading to a total of 189 individuals who were screened and consented and a total of 365 individuals who were either incompletely screened or not consented into a study. Individuals with an externally validated medical history showed the highest yield in being consented and retained in research as new participants. In particular, chart reviews from clinics were highly efficient (25.8%) in facilitating new participants’ enrollment, even when these individuals were not actively/prospectively seeking research. The most common reason for nonconsent was difficulty in telephone or email contact. Consenting and nonconsenting participants were similar in demographics, and recruitment sources only differed in their reported substance use. Referrals and chart reviews from known clinics were the most efficient method in retaining new participants, highlighting the importance of external validation and communication between research and clinical staff within a system. Consenting participants showed no significant differences from the database as a whole, demonstrating that the study samples were representative. Future studies should aim to confirm the present findings at other academic and commercial research centers.

The Clubhouse model of psychosocial rehabilitation has supported the recovery of people with serious mental illness for over 75 years, but many of the roughly 350 Clubhouses are not well-integrated into the larger health care system, limiting their reach. This article examines Clubhouses’ and psychiatric providers’ interactions and experiences to understand the nature of and barriers to partnerships. The directors of Clubhouses affiliated with Clubhouse International were surveyed, examining their attitudes and practices around collaboration with psychiatric providers. To provide context, psychiatric providers were also surveyed regarding their understanding of and experiences with Clubhouses. Findings reveal broad support among both Clubhouse directors and psychiatrists for enhancing partnerships, despite current barriers, limited interactions, and the need for greater mutual understanding. Key considerations that emerged include the importance of maintaining the Clubhouse model's distinct non-clinical, community-based, and member-directed identity in any integration efforts.

Background Community‐based centers for people living with dementia (PLWD) have been implemented as part of the National Plan of dementia in Chile, delivering a multicomponent and multiprofessional intervention to support the PLWD and their families, integrating social and clinical aspects. We sought to examine the implementation and adaptation of these centers, transitioning from adult day services to a community‐based dementia care model that has escalated to a public policy. Method We conducted a realistic evaluation using multiple qualitative data collection strategies and informants to analyze complex interventions, in 4 of a total of 9 centers. Key informants of the centers’ implementation were identified and participated in individual interviews or focus groups, at different levels (macro‐level of centralized policy, n:4; meso‐level of intervention deliverers and center coordinators, n: 27; and micro‐level of user family caregivers, n:14). Interviews and focus groups were audio‐recorded and transcribed. Rapid qualitative analysis was used with predetermined codes describing implementation according to the Active Implementation Frameworks and Implementation Outcomes. Result At a macro‐level of implementation, the centers have not experienced relevant transformations, and fidelity is tensioned due to lack of updated centralized technical orientations. At a meso‐level, the centers’ intervention has been adapted to improve sustainability and appropriateness, which has enhanced their scalability. Engagement with the local service network and tailoring according to geographic and cultural context, emerged as implementation drivers. Relevant points of agreement and disagreement regarding implementation among actors were identified. Conclusion The implementation of community centers for PLWD in Chile, at a policy macro‐level the program has been continuous and stable. Most relevant implementation drivers and adaptations are identified at a meso‐level, which stresses the need to identify core components and processes for standardization and later evaluation and monitoring. Points of agreement and disagreement among the three levels are key for understanding priorities for improvement and impact.

Background Community‐based centers for people living with dementia (PLWD) have been implemented as part of the National Plan of dementia in Chile, delivering a multicomponent intervention to support PLWD and their families. There is limited knowledge on their implementation, and we had previously informed with respect to the implementation outcomes of the first center, called Kintun. This work offers an update on findings describing implementation outcomes of three more centers, with different implementation times and geographic locations in Chile. Method We conducted a realistic evaluation using multiple qualitative data collection strategies and diverse informants to analyze complex interventions considering 4 centers. For every center, key informants were identified at different levels (macro‐level of centralized policy, meso‐level of center coordinators and health service supervisors, and micro‐level of intervention deliverers and family caregivers) who participated in individual interviews or focus groups. Table 1 summarizes informants, data collection strategies, and implementation outcomes. Rapid qualitative analysis was used with predetermined codes describing implementation outcomes according to the Active Implementation Frameworks (Blanchard et al, 2017) and implementation outcomes by Proctor et al (2011). Result At a macro‐level of implementation, the centers have not experienced relevant transformations, but the lack of updated centralized technical orientations menace fidelity. At a meso and micro level, the centers have been adapted to improve sustainability and appropriateness, supporting their scalability. Differences in core components characterize a transition from adult day services to a multicomponent intervention, following a progressive interprofessional approach. Examples of implementation drivers were engagement with the local health network and and tailoring the intervention according to geographical and cultural context. Relevant implementation aspects of agreement and disagreement among actors were the appropriateness of the program and the program components, respectively. Conclusion Most relevant implementation drivers and adaptations to community centers for PLWD in Chile are identified at micro and meso levels, which stresses the need to define intervention components for standardization and monitoring, providing an implementation frame for new centers. Points of agreement and disagreement among the three levels are key for understanding priorities for improvement

Background Neural flexibility (NF) during tasks was associated with cognitive aging, while that during rest was not associated with aging and cognition in a healthy aging population. However, NF has not been studied in AD. We aim to evaluate whether AD is associated with alterations in NF and probe its predictive utility for AD conversion. Method The study included 862 older adults with valid resting‐state fMRI data: 461 who are cognitively normal (CN, 53.5%), 294 with Mild cognitive impairment (MCI, 34.1%), and 107 with Alzheimer’s Disease (AD, 12.4%) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The MRI images were processed using fMRIPrep, and the mean time series of each node was extracted according to the Power Atlas parcellation scheme. We performed dynamic community detection based on generalized Louvain methods. We defined the NF of a node as the number of times that a node changed its community assignment across the sliding windows, normalized by the total number of possible changes and computed global NF (GNF) and network‐level NF. We performed linear mixed models on NF to explore the effect of AD group indicators on NF controlling for the age at scan, gender, education level, and the random intercept of site. We then evaluated the dementia transition of neural flexibility using survival analysis. In the non‐demented participants at baseline, we performed Cox‐proportional hazard regression analysis with each NF. Results NF is significantly higher in AD group than the CN group on global, CON, MRN, SMN‐H, SMN‐M, VAN, and VIS networks (Figure 1); neural flexibility is significantly higher in the MCI group than the CN group in the VIS network (Figure 1). Among n = 670 non‐demented participants at baseline, n = 53 (8.6%) participants converted to dementia during the follow‐ups. Higher neural flexibility in VIS was positively associated with AD transition (HR = 1.323, 95%CI 1.002 to 1.747, p = 0.049, per 1 standard deviation in NF, Figure 2), controlling for age, gender, and education. Conclusion We found that NF during resting was higher in AD patients and predicted dementia transition. Thus, NF can be a valuable biomarker of AD, and more validation and mechanistic studies need to be performed.

Background Our goal in this study was to identify paths from APOE e4 to neurobehaviors itemized on a neuropsychiatric inventory that involved neuropathologies associated with e4 (amyloid, tau, cerebral amyloid angiopathy, and Lewy bodies) or cognition mediators (memory or global cognitive status), as well as direct paths from e4 to cognition or neurobehaviors. Method A total of 1199 cases with available neurobehavioral, cognition and neuropathological data were included. We then conducted a series of causal mediation analyses in R in which e4 always served as the independent variable and Neuropsychiatric Inventory (NPI) neurobehavioral items, when included in the mediation, the outcome. Neuropathologies or cognition served as mediators. Result Multiple significant indirect paths from e4 through neuropathologies to neurobehaviors were identified. More refined analyses indicated that neuritic plaques and Braak stage, but not extent of diffuse amyloid plaques, drove the findings. A significant direct effect of e4 to memory was also identified. Additionally, Lewy body disease, when treated as an exposure, had a direct effect on hallucinations in keeping with known features of the disease. Conclusion We found strong evidence for partial mediation of NPI symptoms by cognition, suggesting that cognitive limitations that may have influenced understanding (or misunderstanding) the environment with impacts on maladaptive behavior. In addition, neuritic amyloid plaque levels and Braak stage, but not diffuse amyloid plaque extent, were key in NPI mediated associations suggesting the possibility that synaptic failure play an important role in multiple neurobehavioral symptoms in dementia, including psychosis. Last, we found strong evidence that e4 may have direct effects on cognition when we used verbal episodic memory as an outcome, suggesting that medial temporal regions that support memory may be sensitive to non‐amyloidogenic and non‐tau related pathophysiological processes.

Background Percent slowing of decline is frequently used as a metric of outcome in Alzheimer’s disease (AD) clinical trials, but it may be misleading. Our objective was to determine whether percent slowing of decline or Cohen’s d is the more valid and informative measure of efficacy. Method Outcome measures of interest were percent slowing of decline; Cohen’s d effect size, and number‐needed‐to‐treat (NNT). Data from a graphic were used to model the inter‐relationships among Cohen’s d, placebo decline in raw score units, and percent slowing of decline with active treatment. NNTs were computed based on different magnitudes of d. Last, we tabulated recent AD anti‐amyloid clinical trials that reported percent slowing and for which we computed their respective d’s and NNTs. Result We demonstrated that d and percent slowing were independent. While percent slowing of decline was dependent on placebo decline and did not include variance in its computation, d was dependent on both group mean difference and pooled standard deviation. We next showed that d was a critical determinant of NNT, such that NNT was uniformly smaller when d was larger. In recent AD associated trials including those focused on anti‐amyloid biologics (aducanumab, lecanemab, gantenerumab, and donanemab), d’s were below 0.23 and thus small, while percent slowing was in the 12%‐27% range and NNTs ranged from 14‐34. Conclusion Standardized effect size is a more meaningful outcome than percent slowing of decline because it determines group overlap, which can directly influence NNT computations, and yield information on the likelihood of minimum clinically important differences. In AD, greater use of effect sizes, NNTs, rather than relative percent slowing, will improve the ability to interpret clinical trial results and evaluate the clinical meaningfulness of statistically significant results.

Background Early detection of dementia and cognitive impairment is recommended for persons 65 years and older during wellness primary care visits. The importance of early detection has increased with the availability of new treatments for early Alzheimer's disease (AD). However, there is no clear approach for early detection in primary care. Odor identification deficits predict AD in epidemiological studies and may be useful for early detection. Our objective was to compare the accuracy of a short odor identification test with a short cognitive screening test for the detection of dementia and cognitive impairment in elderly persons with cognitive concerns. Method This was a cross‐sectional study of 600 participants 65 years and older, without known mild cognitive impairment (MCI) or dementia, with cognitive concerns, attending primary care practices in New York City. The odor identification test was the Brief Smell Identification Test (BSIT). The comparator test was the Mini Mental Status Exam II (MMSE). Cognitive diagnoses were made using the National Alzheimer’s Coordinating Center Uniform Data set (NACC‐UDS) version 3 forms with slight modifications by a diagnosis consensus committee. Test performance was compared using Receiver Operating Characteristic analyses. Result The mean age of the sample was 72.65 ± 6.31 years, 73.3% were female, 63.3% were Hispanic, 17.5% non‐Hispanic Black, and 27.0% non‐Hispanic White; 23.5% had normal cognition, 27.6% had cognitive impairment‐not mild cognitive impairment (MCI), 31.1% had amnestic MCI, 5.6% had non‐amnestic MCI, and 12% had dementia. The MMSE was superior to the BSIT in detecting dementia (AUC 0.89 vs 0.78, p =0.0007, Figure Panel A) and any cognitive impairment (AUC 0.79 vs 0.63, p <0.0001, Figure Panel B). Combining abnormal scores in the BSIT (< 9) to MMSE (< 24) improved the MMSE’s specificity (0.98 combined vs. 0.92 MMSE alone) and positive predictive value (PPV) in detecting cognitive impairment (0.98 combined vs. 0.95 MMSE alone). Conclusion The MMSE was superior to the BSIT in detecting dementia and cognitive impairment in primary care but using both tests improved specificity and PPV for identifying persons with subjective complaints needing further cognitive and biomarker evaluation.

Background While the association between sleep quality and brain health is well established, the role of aging in this relationship is largely unknown. This study aimed to examine the interaction between sleep and age on cortical thickness using samples from large‐scale cohort studies. Age was examined in both linear and non‐linear (quadratic) terms, in order to determine the presence of critical age ranges that may exhibit more significant sleep‐related brain structural changes. Method Sample included 700 adults (mean age 59.63 [age range 36‐90], 55.9% female) from the Human Connectome Project‐Aging (HCP‐A). Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Magnetic resonance imaging (MRI) data was obtained from T1‐weighted structural images using a 3T scanner, and cortical thickness indices were derived using the FreeSurfer pipeline. The interaction between sleep and age on cortical thickness was tested using the moderation analysis using linear regression models, with sex, race, and use of sleep medication as covariates. The same analyses are planned on a separate dataset from the Nathan Klein Institute (NKI) cohort in order to replicate these findings. Result There was a significant interaction term between the PSQI and non‐linear age term (age²) on the insula (b=0.67, CI=0.03‐1.30, p=.04) and the middle temporal cortical thickness (b=0.58, CI=0.03‐1.13, p=.04), indicating that sleep quality may be associated with cortical thickness distinctly in different age groups. A visual examination of this relationship indicated that cortical thickness for individuals between the ages 53 and 78. Conclusion Age may have a significant role in the relationship between sleep and cortical thickness. Middle‐aged and older adults may be most vulnerable to sleep‐related changes in the brain structures. These findings will be tested using a separate dataset.

Background High blood pressure (BP) level and variability has been linked to stroke, cerebral small vessel disease (CSVD), cognitive decline, and dementia. However, it is unclear whether sex/gender influences the association of BP level and variability with CSVD. Therefore, we aimed to examine sex‐differences in the association of CSVD with 24‐h BP level and variability. Methods We used 374 participants aged ≥40y from the Maracaibo Aging Study (women, 73.5%; mean age, 59.1y) who underwent 24‐h ambulatory BP monitoring and brain magnetic resonance imaging (MRI) scans. The 24‐h systolic BP variability was quantified as the average real variability (ARV) index. Markers of CSVD were visualized on MRI scans and included log‐transformed white matter hyperintensities (log‐WMH) volume, and the presence (yes/no) of lacunes, cerebral microbleeds (CMB), or enlarged perivascular spaces (EPVS). The association of 24‐h systolic BP level and variability with markers of CSVD was analyzed using adjusted logistic and linear regression separately for men and women. Results Overall, men had greater log‐WMH volume (median, 2.9 vs. 2.5 cm³) and higher proportion of lacunes (18.2% vs. 8.7%) than women (P≤0.011). The proportion of CMB and EPVS was similar between women and men (P≥0.522). A higher 24‐h systolic BP level was associated with log‐WMH in men (adjusted β‐coefficient, 0.37; 95% CI 0.08, 0.21) and women (adjusted β‐coefficient, 0.16; 95% CI, 0.01, 0.09) as well as the presence of lacunes in both groups (the OR for men was 2.31 [95% CI, 1.08‐4.95] and for women was 1.55 [95% CI, 1.02‐2.37]). Only in women, a higher 24‐h ARV systolic BP was associated with log‐WMH (adjusted β‐coefficient, 0.19; 95% CI, 0.02, 0.10), lacunes (OR, 1.81; 95% CI, 1.15‐2.84), and EPVS (OR, 1.67; 95% CI, 1.07‐2.60). Conclusions We found sex‐differences in the association 24‐h BP level and variability with markers of CSVD. In men, high 24‐h BP level had a greater impact on the burden of WMH and lacunes than in women whereas high 24‐h BP variability seems to be a risk for CSVD only in women. These results suggest the potential influence of sex in the relationship between vascular risk factors and CSVD.

Background Cognitive impairment is associated with mortality. However, evidence using population‐based studies is scarce, is limited to one cognitive assessment, and lacks the inclusion of non‐fatal adverse health outcomes. Therefore, we aimed this study to (i) investigate the association of cognitive function with mortality and cardiovascular risk and (ii) determine whether cognitive tests improve the risk‐stratification of endpoints beyond conventional risk factors. Methods We analyzed 946 participants aged ≥55y from a population‐based study who underwent cognitive function and were followed for fatal and nonfatal endpoints between 2001‐2016. Conventional risk factors included age, sex, education, body mass index, smoking, alcohol, antihypertensive treatment, office systolic and diastolic blood pressure, serum total cholesterol, diabetes mellitus, and previous history of cardiovascular diseases. Cognitive function examination included the mini‐mental state examination (MMSE) and selective reminder tests ([SRT], total retrieval, long‐term retrieval, and delayed recall). Our primary endpoint was total mortality and major adverse cardiovascular endpoints (MACE). Statistics included Cox proportional models and the generalized R ² statistic to test model fit. Results The mean age was 66.3±7.5 years old and 640 (67.6%) were women. During a median follow‐up of 8.5 years, 267 participants died and 187 experienced MACE. The incidence of mortality and MACE per quartiles of MMSE and SRT ranged from 13.1 (95% confidence interval [CI], 8.7‐18.9) to 23.8 (95% CI, 18.3‐30.4) among participants with the highest quartile and from 28.8 (95% CI, 14.9‐47.7) to 43.8 (26.3‐66.2) among participants with the lowest quartile. A lower MMSE score was associated with a higher risk of mortality (hazard ratios [HR] per each ‐4.3 lower MMSE, 1.23; 95% CI, 1.02‐1.48) and MACE (HR, 1.27; 95% CI, 1.09‐1.47). A lower SRT‐delayed recall score was associated with 1.19 (95% CI, 1.04‐1.37) and 1.24 (95% CI, 1.04‐1.46) higher folds of mortality and MACE endpoints. On top of conventional risk factors, the inclusions of MMSE and SRT improved the model performance (R ² ranged from 0.51% to 1.65%; P≤0.028). Conclusions In this population‐based study, cognitive impairment is associated with mortality and CV risk. Given the aging global population, the assessment of cognitive function might help reduce the risk of major preventable health outcomes.

Background The IDEAL study is a randomized clinical trial investigating the psychosocial, behavioral, and cognitive impacts of genetic risk disclosure for late‐onset Alzheimer’s disease (LOAD) among Latinos. Methods We used address‐based sampling in northern Manhattan to recruit Latinos aged 40‐64 for a community‐based survey and clinical trial. Data collection encompasses demographics, Alzheimer’s disease (AD) family history, knowledge and beliefs about AD and genetics, current mental health status, acculturation, impact of COVID‐19, familism, fatalism, caregiver status, and prior AD genetic testing. Eligible participants are invited to complete an education session and provide informed consent before receiving genetic testing for APOE, a key LOAD predictor. The clinical trial component will include 400 participants, who are randomized to learn their LOAD risk by age 85 based on either Latino ethnicity and family history alone or the same factors plus APOE genotype. Risk information is provided through semi‐structured genetic counseling sessions. Psychological impacts, health‐related behavioral changes, and memory performance are evaluated six weeks, nine months, and fifteen months post‐dislosure via surveys and in‐depth qualitative interviews. Results From 91,433 invited households, 5,542 (6.1%) responded, and 2,087 (2.3%) were eligible and completed the Baseline survey. Most were 40‐49 years old (41.2%), women (70.5%), identified as Dominican (53.7%), had some college education (63.2%), and completed the survey in English (74.6%). About half reported a family history of AD (48.6%). Conclusion This study addresses gaps in understanding of impacts of AD genetic risk disclosure among Latinos and contributes valuable insights through its mixed‐methods approach.

Background The increasing number of natural disasters and wars will result in complex emergencies affecting how individuals age. Additionally, the continued complex crises in certain areas of the globe exacerbates risks for chronic health conditions and poverty. Implementing ethical and community‐engaged research in these complex humanitarian settings requires tailored approaches. The South Texas Alzheimer’s Disease Research Center and the Rio Grande Valley Alzheimer’s Disease Resource Center for Minority Aging Research have adopted the humanitarian lens perspective deployed in the Maracaibo Aging Study in Venezuela to promote the recruitment and retention of older adults and their care partners in the Texas/Mexico border. Our objective is to identify and share key issues in recruitment for aging research in a complex humanitarian setting. Method Listening sessions, focus groups, and interviews were carried out to understand barriers, facilitators, beliefs, and preferences of older adults, care partners of people living with dementia, promotoras/community health workers, family physicians, and community‐based organizations to understand their expectations better. Elements of the humanitarian framework and capacity building were informed by the qualitative data and guidance from a senior coalition. Result Located in the Texas/Mexico border, the Rio Grande Valley constitutes one of the most impoverished areas in the nation. Competing needs, lack of incentives for participation in research, and fear associated with increasing health care costs were the most frequently cited barriers among residents. We decided to implement several aspects of humanitarian work that were related to efficient research and as a response to community expectations. Advocacy for integrating services into primary and community care was supported through staff training, task‐sharing, and establishing referral and follow‐up mechanisms. Diversifying the research workforce with bilingual and multicultural junior investigators and promotoras further addressed the cultural fluidity. As a result, a research registry of over 400 individuals was built, and more than 400 have participated in different aging studies. Conclusion Humanitarian settings in high‐income and low‐and middle‐income countries share many implementation needs, including scaling up efforts and tackling multiple challenges simultaneously. Community‐engaged aging research in humanitarian settings requires consideration and assessment of evidence‐based planning and execution and impact evaluation.

Background Inexpensive, non‐invasive tests may improve the identification of persons at increased risk for cognitive decline and dementia. We compared impairment in odor identification and global cognition with neuro‐imaging biomarkers to predict cognitive decline and dementia in the population‐based Mayo Clinic Study of Aging (MCSA). Method At the 2008 assessment, 647 participants who were ≥ 55 years old with at least one follow‐up had the following procedures: modified Blessed Information‐Memory‐Concentration Test (BIMCT), 12‐item Brief Smell Identification Test (BSIT), brain magnetic resonance imaging (MRI), and Positron Emission Tomography (PET) amyloid imaging with 11C‐Pittsburgh compound B (11C‐PiB). A subsample (n=556) also had 18F‐fluorodeoxyglucose (18F‐FDG) PET scans. The utility of these baseline measures to predict cognitive decline (cognitively unimpaired to mild cognitive impairment [MCI] or dementia, or MCI to dementia) was examined during follow‐up (mean 8.1 SD 3.4 years). Transition to dementia was a secondary outcome. Result Among 647 participants without dementia (mean age 74.0 SD 8.1 years; 54.4% male) at baseline, 102 participants manifested cognitive decline and 34 participants transitioned to dementia. In Cox regression survival analyses for cognitive decline, PiB PET showed the strongest predictive utility (hazard ratio HR 5.05, 95% CI = 3.32‐7.69, p<.001). Impaired BSIT (HR 3.46, 95% CI = 2.34‐5.11, p<.001), impaired BIMCT (HR 3.63, 95% CI 2.46‐5.36, p<.001), MRI and FDG measures were also significant predictors. After adjusting for age, sex and education, these predictors remained significant with attenuated effects (PiB HR 3.89, 95% CI 2.54‐5.95, p<.001; BSIT HR 2.77, 95% CI 1.85‐4.14, p<.001; BIMCT HR 3.3, 95% CI 2.21‐4.95, p<.001). After adding these demographic variables in the model, the combination of BSIT and BIMCT showed strong predictive utility (C‐index=0.85), similar to PiB PET (C‐index=0.84). Combining all predictors showed a C‐index of 0.89. These measures showed similar but stronger results for dementia transition. Conclusion Tests of global cognition and odor identification provide a brief, non‐invasive, inexpensive method comparable to PET amyloid imaging for identifying community‐dwelling persons likely to decline cognitively or transition to dementia. Other potential uses for this combination include identification of persons likely to benefit from disease‐modifying medications and determination of eligibility for prevention trials.