Associations of Lifetime Cognitive Enrichment With Incident Alzheimer Disease Dementia, Cognitive Aging, and Cognitive Resilience.

BackgroundNeuropsychiatric symptoms (NPS) in Alzheimer's disease and related dementias (AD/ADRD) greatly increase mortality and caregiver burden. However, examinations of NPS have been limited by a lack of global, comprehensive assessments of psychiatric symptomatology in AD/ADRD. Comparing symptoms in AD/ADRD with older adults without dementia is of key importance for distinguishing pathological from normal aging. Here, we examine data collected using the Structured Clinical Interview for DSM‐5‐Research Version (SCID‐5‐RV), which is a gold‐standard measure of psychiatric symptoms, and compare frequencies in individuals with AD/ADRD to a control group of older adults without dementia.MethodThe study sample comprised 237 participants, including 49 older adults without dementia (M age = 63.2±13.1), and 188 individuals with AD/ADRD (M age=69.9±10.1; 78 Alzheimer's disease dementia, 110 other dementia). Item‐level data on the SCID‐5‐RV was collected, including all symptom questions (skip rules were not used). Prevalence of symptom endorsement was compared between the AD/ADRD and control groups, using Pearson's Chi‐squared test or Fisher's exact test.ResultCompared to older adults without dementia, the AD/ADRD group endorsed more frequent sleep problems, including fatigue, excessive sleepiness, daytime napping, prolonged nonrestorative sleep, and difficulty waking (all p < .05). Depression‐related symptoms were among the most endorsed within both groups, but the ADRD group had more frequent depressed mood, anhedonia, avolition, feelings of guilt (all p < .05). Notably, suicidality was present in 10% of the AD/ADRD group and 0% of controls (p < .05). While the AD/ADRD group reported more anxiety in terms of worry, irritability, restlessness, and muscle tension, controls exhibited more panic and phobia symptoms (all p < .05). The AD/ADRD group also reported more psychomotor agitation and verbal aggression (p < .05), and, unsurprisingly, more difficulties thinking and concentrating (p < .05). Overall, this points to psychiatric phenotypes in AD/ADRDConclusionThe results highlight important differences between reported psychiatric symptoms in those with AD/ADRD compared to unimpaired older adults. These findings can be used to develop measures that capture relevant neuropsychiatric constructs for use in neurodegenerative populations, and suggest specific symptoms that comprise psychiatric phenotypes that might point to pathological vs. normal aging.

High Occurrence of Dementia in Older Adults Returning to Community From Prison

Alzheimer disease and related dementias (ADRD), currently incurable neurodegenerative diseases, can threaten patients' financial status owing to memory deficits and changes in risk perception. Deteriorating financial capabilities are among the earliest signs of cognitive decline, but the frequency and extent of adverse financial events before and after diagnosis have not been characterized. To describe the financial presentation of ADRD using administrative credit data. This retrospective secondary data analysis of consumer credit report outcomes from 1999 to 2018 linked to Medicare claims data included 81 364 Medicare beneficiaries living in single-person households. Occurrence of adverse financial events in those with vs without ADRD diagnosis and time of adverse financial event from ADRD diagnosis. Missed payments on credit accounts (30 or more days late) and subprime credit scores. Overall, 54 062 (17 890 [33.1%] men; mean [SD] age, 74 [7.3] years) were never diagnosed with ADRD during the sample period and 27 302 had ADRD for at least 1 quarter of observation (8573 [31.4%] men; mean [SD] age, 79.4 [7.5] years). Single Medicare beneficiaries diagnosed with ADRD were more likely to miss payments on credit accounts as early as 6 years prior to diagnosis compared with demographically similar beneficiaries without ADRD (7.7% vs 7.3%; absolute difference, 0.4 percentage points [pp]; 95% CI, 0.07-0.70:) and to develop subprime credit scores 2.5 years prior to diagnosis (8.5% vs 8.1%; absolute difference, 0.38 pp; 95% CI, 0.04-0.72). By the quarter after diagnosis, patients with ADRD remained more likely to miss payments than similar beneficiaries who did not develop ADRD (7.9% vs 6.9%; absolute difference, 1.0 pp; 95% CI, 0.67-1.40) and more likely to have subprime credit scores than those without ADRD (8.2% vs 7.5%; absolute difference, 0.70 pp; 95% CI, 0.34-1.1). Adverse financial events were more common among patients with ADRD in lower-education census tracts. The patterns of adverse events associated with ADRD were unique compared with other medical conditions (eg, glaucoma, hip fracture). Alzheimer disease and related dementias were associated with adverse financial events years prior to clinical diagnosis that become more prevalent after diagnosis and were most common in lower-education census tracts.

Alzheimer's disease and related dementias (AD/ADRD) continue to be a public health challenge. People with HIV (PWH) are at risk for neurocognitive disorders and may be at risk for AD/ADRD. However, studies examining clinical and sociodemographic factors associated with AD/ADRD among PWH are lacking. Therefore, the aim of this cross-sectional study was to determine the association between selected sociodemographic (age, gender, race, and rurality) and clinical (depression and encephalopathy) factors with AD/ADRD among PWH. Data were obtained from the South Carolina Revenue and Fiscal Affairs (RFA) Office and the South Carolina Alzheimer's Disease Registry ( N = 13 390). Multivariable logistic regression models were used to determine the association between age, gender, race, rurality, depression, and encephalopathy, and AD/ADRD among PWH. Among the study population ( N = 13 390), 5% ( n = 601) were found to have AD/ADRD. There was a dose-response relationship between age group and AD/ADRD whereas the age group increased, the association increased. For example, those who were aged 80 years and older were 80 times more likely to have AD/ADRD compared to those aged 18-29 years [adjusted odds ratio (aOR): 80.4; 95% confidence interval (CI): 40.2-160.8]. Additionally, male sex (aOR: 1.3; 95% CI: 1.9-1.6) and encephalopathy (aOR: 2.4; 95% CI: 1.9-3.2) were positively associated with AD/ADRD for PWH. AD/ADRD interventions may be warranted among PWH, especially among older adults, men, and those with encephalopathy. Future studies should examine potential pathways between clinical and sociodemographic characteristics and AD/ADRD among PWH.

The aim of this study was to evaluate the association of cardiovascular health (CVH) with cognitive outcomes, including incident Alzheimer's dementia, rate of cognitive decline, and measures of brain injury and structure. This study consisted of 1702 Black or African American and White participants living in the south side of Chicago, Illinois, and enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. CVH was based on seven risk factors, including diet, physical activity, body mass index, smoking, dyslipidemia, hypertension, and diabetes. In a multivariable-adjusted model, CVH was associated with a lower risk of Alzheimer's dementia. The hazard ratio per 1 additional point in CVH score was 0.84 (95% CI 0.76, 0.94). CVH was also associated with a slower rate of cognitive decline and less volume (injury) in white matter hyperintensities. Promoting CVH in communities with Black residents may lower the future risk of Alzheimer's dementia.

Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. We test the hypothesis that domain specific literacy is associated with Alzheimer's disease (AD) dementia and AD pathology after controlling for cognition. Participants were community-based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years, and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined postmortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p < 0.001), and the association persisted after controlling for cognition (hazard ratio = 1.50, p = 0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β= 0.07, p = 0.035). Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition.

Intensive care unit (ICU) utilization has increased among patients with Alzheimer disease and related dementia (ADRD), although outcomes are poor. To compare ICU discharge location and subsequent mortality between patients with and patients without ADRD enrolled in Medicare Advantage. This observational study used Optum's Clinformatics Data Mart Database from years 2016 to 2019 and included adults aged >67 years with continuous Medicare Advantage coverage and a first ICU admission in 2018. Alzheimer disease and related dementia and comorbid conditions were identified from claims. Outcomes included discharge location (home vs other facilities) and mortality (within the same calendar month of discharge and within 12 months after discharge). A total of 145 342 adults met inclusion criteria; 10.5% had ADRD and were likely to be older, female, and have more comorbid conditions. Only 37.6% of patients with ADRD were discharged home versus 68.6% of patients who did not have ADRD (odds ratio [OR], 0.40; 95% CI, 0.38-0.41). Both death in the same month as discharge (19.9% vs 10.3%; OR, 1.54; 95% CI, 1.47-1.62) and death in the 12 months after discharge (50.8% vs 26.2%; OR, 1.95; 95% CI, 1.88-2.02) were twice as common among patients with ADRD. Patients with ADRD have lower home discharge rates and greater mortality after an ICU stay than patients without ADRD.

To understand the effects of accountable care organizations (ACOs) on use of surgery in patients with Alzheimer disease and related dementias (ADRD). Retrospective national cohort study of all Medicare beneficiaries identified in a 20% sample between 2010 and 2017. The primary exposure was participation in ACOs. The primary outcome was use of 1 of 6 common surgical procedures (aortic valve replacement [AVR], abdominal aortic aneurysm [AAA] repair, colectomy, carotid artery repair, major joint repair, and prostatectomy). Multivariable logistic regression models were fit using beneficiary-year as the unit of analysis to estimate the likelihood of undergoing each procedure among patients with ADRD and without ADRD, stratified by ACO participation. Additional models were fit to determine how the relationship between ACO participation and surgery was altered based on procedure urgency and the availability of minimally invasive technology. Adjusted odds for use of surgery were lower among patients with ADRD compared with patients without ADRD for all procedures. ACO participation had varying impact on patients with ADRD, with higher odds of AVR and major joint surgery and lower odds of carotid artery repair. Availability of minimally invasive technology increased the likelihood of AVR and AAA repair among patients with ADRD; however, ACO participation reduced these effects. The effect of ACO participation on the likelihood of undergoing surgery did not vary by urgency of the procedure. The likelihood of undergoing surgery is overall lower among patients with ADRD and may vary by ACO participation for specific procedures.

This perspective paper addresses the US Hispanic/Latino (herein, Latino) experience with regards to a significant public health concern-the underrepresentation of Latino persons in Alzheimer's disease and related dementias (AD/ADRD) clinical trials. Latino individuals are at increased risk for AD/ADRD, experience higher disease burden, and low receipt of care and services. We present a novel theoretical framework-the Micro-Meso-Macro Framework for Diversifying AD/ADRD Trial Recruitment-which considers multi-level barriers and their impact on Latino trial recruitment. Based on a review of the peer-reviewed literature and our lived experience with the Latino community, we drew from our interdisciplinary expertise in health equity and disparities research, Latino studies, social work, nursing, political economy, medicine, public health, and clinical AD/ADRD trials. We discuss factors likely to impede or accelerate Latino representation, and end with a call for action and recommendations for a bold path forward. In the 200+ clinical trials conducted with over 70,000 US Americans, Latino participants comprise a fraction of AD/ADRD trial samples. Efforts to recruit Latino participants typically address individual- and family-level factors (micro-level) such as language, cultural beliefs, knowledge of aging and memory loss, limited awareness of research, and logistical considerations. Scientific efforts to understand recruitment barriers largely remain at this level, resulting in diminished attention to upstream institutional- and policy-level barriers, where decisions around scientific policies and funding allocations are ultimately made. These structural barriers are comprised of inadequacies or misalignments in trial budgets, study protocols, workforce competencies, healthcare-related barriers, criteria for reviewing and approving clinical trial funding, criteria for disseminating findings, etiological focus and social determinants of health, among others. Future scientific work should apply and test the Micro-Meso-Macro Framework for Diversifying AD/ADRD Trial Recruitment to examine structural recruitment barriers for historically underrepresented groups in AD/ADRD research and care.

Long-term dietary flavonoid intake and risk of Alzheimer disease and related dementias in the Framingham Offspring Cohort

The contribution of modifiable risk factors to cases of mild cognitive impairment (MCI) and Alzheimer's disease and related dementias (AD/ADRD) among Hispanic/Latin (a,o,x) adults is unclear. To determine the population attributable fraction (PAF), the proportion of MCI and AD/ADRD cases that would be eliminated with elimination of modifiable risk factors. This was a cross-sectional analysis nested within a prospective cohort study (2018 - 2023) of Mexican American older adults. Logistic regression estimated the odds of probable MCI or AD/ADRD (defined by education-specific cutoff scores on the Montreal Cognitive Assessment) associated with age, sex, education, medical comorbidities, cigarette smoking, and alcohol consumption. We calculated the PAF for MCI and AD/ADRD associated with individual and combined risk factors. Among 1,272 participants, the prevalence of MCI was 48% and of AD/ADRD was 23%. Having no more than a high school education was associated with a PAF for MCI of 17% (95% CI, 10 - 24%) and a PAF for AD/ADRD of 52% (95% CI, 40 - 64%). Heart disease and diabetes were each associated with a PAF for MCI of 5% (95% CI, 3 - 7% and 95% CI, 1 - 10% respectively). A history of stroke was associated with a PAF for AD/ADRD of 7% (95% CI, 3 - 11%). The elimination of all modifiable risk factors was associated with 28% of MCI and 55% of AD/ADRD cases. Low educational attainment and cardiovascular comorbidities greatly contribute to cases of MCI and AD/ADRD among Mexican American adults.

Background: Emerging evidence suggests a potential link between heavy metals and Alzheimer's disease and related dementias (AD/ADRD). This study compiled epidemiological evidence from research published over the past 11 years on the impact of metals on AD/ADRD in women. Women have unique risk factors for late onset of AD/ADRD, in addition to genetic factors, apolipoprotein E allele (APOE4), and longer life expectancy. Furthermore, women are twice likely as men to experience depression, which increases their risk of developing AD/ADRD. Our narrative review underscored the necessity of a sex-specific approach to address women's vulnerability to AD/ADRD. Methods: Electronic databases, including PubMed, Google Scholar, NIOSH Toxline, and Scopus, were thoroughly searched to identify primary epidemiological studies on older women exposed to metals and published between 2014 to 2024. Results: We identified 34 epidemiological studies that met the inclusion criteria. The findings revealed a complex interplay between environmental metals such as lead (Pb), cadmium (Cd), arsenic (As), manganese (Mn), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and calcium (Ca) and the risk of AD/ADRD in women. Significant adverse effects were reported for Cu, Cd, As, Pb, and Mn while significant protective effects were found between Se, Fe, and Zn in blood and AD/ADRD among older women. However, some studies also reported no correlations. Conclusions: Overall, our review identified contrasting results regarding the effects of metals on AD/ADRD in women. Future studies should collect additional evidence to understanding the effects of heavy metals on AD/ADRD in women for developing preventive measures.

Alzheimer's disease and related dementias (AD/ADRDs) pose a significant global public health challenge, underscored by the intricate interplay of genetic and environmental factors that differ across ancestries. To effectively implement equitable, personalized therapeutic interventions on a global scale, it is essential to identify disease-causing mutations and genetic risk and resilience factors across diverse ancestral backgrounds. Exploring genetic-phenotypic correlations across the globe enhances the generalizability of research findings, contributing to a more inclusive and universal understanding of disease. This study leveraged biobank-scale data to conduct the largest multi-ancestry whole-genome sequencing characterization of AD/ADRDs. We aimed to build a valuable catalog of potential disease-causing, genetic risk and resilience variants impacting the etiology of these conditions. We thoroughly characterized genetic variants from key genes associated with AD/ADRDs across 11 genetic ancestries, utilizing data from All of Us, UK Biobank, 100,000 Genomes Project, Alzheimer's Disease Sequencing Project, and the Accelerating Medicines Partnership in Parkinson's Disease, including a total of 25,001 cases and 93,542 controls. We prioritized 116 variants possibly linked to disease, including 18 known pathogenic and 98 novel variants. We detected previously described disease-causing variants among controls, leading us to question their pathogenicity. Notably, we showed a higher frequency of APOE ε4/ε4 carriers among individuals of African and African Admixed ancestry compared to other ancestries, confirming ancestry-driven modulation of APOE-associated AD/ADRDs. A thorough assessment of APOE revealed a disease-modifying effect conferred by the TOMM40:rs11556505, APOE:rs449647, 19q13.31:rs10423769, NOCT:rs13116075, CASS4:rs6024870, and LRRC37A:rs2732703 variants among APOE ε4 carriers across different ancestries. In summary, we compiled the most extensive catalog of established and novel genetic variants in known genes increasing risk or conferring resistance to AD/ADRDs across diverse ancestries, providing clinical insights into their genetic-phenotypic correlations. The findings from this investigation hold significant implications for potential clinical trials and therapeutic interventions on a global scale. Finally, we present an accessible and user-friendly platform for the AD/ADRDs research community to help inform and support basic, translational, and clinical research on these debilitating conditions (https://niacard.shinyapps.io/MAMBARD_browser/).

Housing insecure veterans are aging, but the prevalence of Alzheimer's disease and related dementias (AD/ADRD) in the population is unknown. We calculated the prevalence of AD/ADRD diagnoses in 2018 among veterans that experienced homelessness, were at-risk for homelessness, or were stably housed. We determined acute care (emergency department, hospitalizations, psychiatric hospitalizations), and any long-term care (nursing home, and community-based) use by housing status among veterans with an AD/ADRD diagnosis. The overall prevalence of AD/ADRD diagnoses for homeless, at-risk, and stably housed veterans was 3.66%, 13.48%, and 3.04%, respectively. Housing insecure veterans with AD/ADRD used more acute care, and were more likely to have a nursing home admission compared to stably housed veterans. At risk, but not homeless veterans, were more likely to use US Department of Veterans Affairs-paid home and community-based care than stably housed veterans. The prevalence of AD/ADRD diagnoses is greater among housing insecure veterans than stably housed veterans.

ABSTRACTBackgroundGoals of care (GOC) conversations are an evidence‐based practice that help clarify and align patient values and preferences for medical care with treatment options. Little is known about how clinicians document the content of GOC conversations for patients with Alzheimer's disease and related dementias (AD/ADRD) in the electronic health record (EHR) and whether this may differ across hospitals. We aimed to assess the content of GOC documentation for hospitalized patients with and without AD/ADRD.MethodsWe performed a retrospective cross‐sectional study to assess documented content within a standardized GOC note written for seriously ill hospitalized adult patients admitted to 21 hospitals between 2021 and 2023. Seriously ill patients had a predicted 90‐day mortality greater than 30% as determined by an artificial intelligence mortality prediction score. Patients with AD/ADRD were identified using diagnostic codes placed by clinicians in the EHR.ResultsOur review of GOC documentation across 21 hospitals identified 5475 patients with GOC notes. The study sample had a median age of 76 years and was 52% male, 13% nonwhite, 81% with Medicare insurance, and 14% with AD/ADRD. Compared to patients without AD/ADRD, patients with AD/ADRD were more likely to have documentation of family presence at the GOC conversation (93% vs. 76%, p = < 0.001), a surrogate decision‐maker (60% vs. 54%, p = 0.003), and patient prognosis (84% vs. 78%, p = < 0.001). Patients with AD/ADRD were less likely to have documentation of patient presence at the GOC conversation (28% vs. 64%, p = < 0.001) and patient values and preferences for medical care (65% vs. 69%, p = < 0.05).ConclusionsHospitalized patients with AD/ADRD are infrequently present in GOC conversations and less likely to have their values and preferences for medical care documented within a GOC note. Further research is needed to explore the reasons for these findings.