Alzheimer's Disease Related Dementias Research Articles

Trends in observation stays for Medicare beneficiaries with and without Alzheimer's disease and related dementias.

There has been a marked rise in the use of observation care for Medicare beneficiaries visiting the emergency department (ED) in recent years. Whether trends in observation use differ for people with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) is unknown. Using a national 20% sample of Medicare beneficiaries ages 68+ from 2012 to 2018, we compared trends in ED visits and observation stays by AD/ADRD status for beneficiaries visiting the ED. We then examined the degree to which trends differed by nursing home (NH) residency status, assigning beneficiaries to four groups: AD/ADRD residing in NH (AD/ADRD+ NH+), AD/ADRD not residing in NH (AD/ADRD+ NH-), no AD/ADRD residing in NH (AD/ADRD- NH+), and no AD/ADRD not residing in NH (AD/ADRD- NH-). Of 7,489,780 unique beneficiaries, 18.6% had an AD/ADRD diagnosis. Beneficiaries with AD/ADRD had more than double the number of ED visits per 1000 in all years compared to those without AD/ADRD and saw a faster adjusted increase over time (+26.7 vs. +8.2 visits/year; p < 0.001 for interaction). The annual increase in the adjusted proportion of ED visits ending in observation was also greater among people with AD/ADRD (+0.78%/year, 95% CI 0.77-0.80%) compared to those without AD/ADRD (+0.63%/year, 95% CI 0.59-0.66%; p < 0.001 for interaction). Observation utilization was greatest for the AD/ADRD+ NH+ population and lowest for the AD/ADRD- NH- population, but the AD/ADRD+ NH- group saw the greatest increase in observation stays over time (+15.4 stays per 1000 people per year, 95% CI 15.0-15.7). Medicare beneficiaries with AD/ADRD have seen a disproportionate increase in observation utilization in recent years, driven by both an increase in ED visits and an increase in the proportion of ED visits ending in observation.

Harnessing diversity to study Alzheimer’s disease: A new iPSC resource from the NIH CARD and ADNI

The iDA Project (iPSCs to Study Diversity in Alzheimer's and Alzheimer's Disease-related Dementias) is generating 200 induced pluripotent stem cell lines from Alzheimer's Disease Neuroimaging Initiative participants. These lines are sex balanced, include common APOE genotypes, span disease stages, and are ancestrally diverse. Cell lines and characterization data will be shared openly.

Efficacy and safety of transcranial magnetic stimulation on cognition in mild cognitive impairment, Alzheimer's disease, Alzheimer's disease-related dementias, and other cognitive disorders: a systematic review and meta-analysis.

We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer's disease (AD), AD-related dementias, and nondementia conditions with comorbid cognitive impairment. Systematic review, Meta-Analysis. We searched MEDLINE, Embase, Cochrane database, APA PsycINFO, Web of Science, and Scopus from January 1, 2000, to February 9, 2023. RCTs, open-label, and case series studies reporting cognitive outcomes following TMS intervention were included. Cognitive and safety outcomes were measured. Cochrane Risk of Bias for RCTs and MINORS (Methodological Index for Non-Randomized Studies) criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42022326423). The systematic review included 143 studies (n = 5,800 participants) worldwide, encompassing 94 RCTs, 43 open-label prospective, 3 open-label retrospective, and 3 case series. The meta-analysis included 25 RCTs in MCI and AD. Collectively, these studies provide evidence of improved global and specific cognitive measures with TMS across diagnostic groups. Only 2 studies (among 143) reported 4 adverse events of seizures: 3 were deemed TMS unrelated and another resolved with coil repositioning. Meta-analysis showed large effect sizes on global cognition (Mini-Mental State Examination (SMD = 0.80 [0.26, 1.33], p = 0.003), Montreal Cognitive Assessment (SMD = 0.85 [0.26, 1.44], p = 0.005), Alzheimer's Disease Assessment Scale-Cognitive Subscale (SMD = -0.96 [-1.32, -0.60], p < 0.001)) in MCI and AD, although with significant heterogeneity. The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment. TMS was safe and well tolerated with infrequent serious adverse events.

Mapping racial and ethnic healthcare disparities for persons living with dementia: A scoping review.

We set out to map evidence of disparities in Alzheimer's disease and Alzheimer's disease related dementias healthcare, including issues of access, quality, and outcomes for racial/ethnic minoritized persons living with dementia (PLWD) and family caregivers. We conducted a scoping review of the literature published from 2000 to 2022 in PubMed, PsycINFO, and CINAHL. The inclusion criteria were: (1) focused on PLWD and/or family caregivers, (2) examined disparities or differences in healthcare, (3) were conducted in the United States, (4) compared two or more racial/ethnic groups, and (5) reported quantitative or qualitative findings. Key findings include accumulating evidence that minoritized populations are less likely to receive an accurate and timely diagnosis, be prescribed anti-dementia medications, and use hospice care, and more likely to have ahigher risk of hospitalization and receive more aggressive life-sustaining treatment at the end-of-life. Future studies need to examine underlying processes and develop interventions to reduce disparities while also being more broadly inclusive of diverse populations.

Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association.

Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease-related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease. In addition to the role of sleep disorders in stroke and cerebrovascular injury, mechanistic hypotheses linking sleep with brain health and biomarker data (blood-based, cerebrospinal fluid-based, and imaging) suggest direct links to Alzheimer disease-specific pathology. These potential mechanisms and the increasing understanding of the "glymphatic system," and the recognition of the importance of sleep in poststroke recovery, as well, support a biological basis for the indirect (through the worsening of vascular disease) and direct (through specific effects on neuropathology) connections between sleep disorders and brain health. Given promising evidence for the benefits of treatment and prevention, sleep disorders and disturbances represent potential targets for early treatment that may improve brain health more broadly. In this scientific statement, we discuss the evidence supporting an association between sleep disorders and disturbances and poor brain health ranging from stroke to dementia and opportunities for prevention and early treatment.

Creating Cultural and Lifestyle Awareness About Dementia and Co-morbidities.

Dementia is a major health concern in society, particularly in the aging population. It is alarmingly increasing in ethnic minorities such as Native Americans, African Americans, Hispanics/Latinos, and to some extent Asians. With increasing comorbidities of dementia such as diabetes, obesity, and hypertension, dementia rates are expected to increase in the next decade and beyond. Understanding and treating dementia, as well as determining how to prevent it, has become a healthcare priority across the globe for all races and genders. Awareness about dementia and its consequences such as healthcare costs, and caregiver burden are immediate needs to be addressed. Therefore, it is high time for all of us to create awareness about dementia in society, particularly among Hispanics/Latinos, Native Americans, and African Americans. In the current article, we discuss the status of dementia, cultural, and racial impacts on dementia diagnosis and care, particularly in Hispanic populations, and possible steps to increase dementia awareness. We also discussed factors that need to be paid attention to, including, cultural & language barriers, low socioeconomic status, limited knowledge/education, religious/spiritual beliefs and not accepting modern medicine/healthcare facilities. Our article also covers both mental & physical health issues of caregivers who are living with patients with dementia, Alzheimer's disease, and Alzheimer's disease-related dementias. Most importantly, we discussed possible measures to create awareness about dementia, including empowering community advocacy, promoting healthy lifestyle choices, education on the impact of nutrition, encouraging community participation, and continued collaboration and evaluation of the success of dementia awareness.

Food Insecurity, Memory, and Dementia Among US Adults Aged 50 Years and Older

Despite existing federal programs to increase access to food, food insecurity is common among US older adults. Food insecurity may affect Alzheimer disease and Alzheimer disease-related dementias via multiple mechanisms, yet there is almost no quantitative research evaluating this association. To examine whether food insecurity in older adults is associated with later-life cognitive outcomes. This cohort study of US residents aged 50 years and older from the US Health and Retirement Study was restricted to respondents with food insecurity data in 2013 and cognitive outcome data between calendar years 2014 and 2018. Analyses were conducted from June 1 to September 22, 2023. Food insecurity status in 2013 was assessed using the validated US Department of Agriculture 6-item Household Food Security Module. Respondents were classified as being food secure, low food secure, and very low food secure. Outcomes were dementia probability and memory score (standardized to 1998 units), estimated biennially between 2014 and 2018 using a previously validated algorithm. Generalized estimation equations were fit for dementia risk and linear mixed-effects models for memory score, taking selective attrition into account through inverse probability of censoring weights. The sample consisted of 7012 participants (18 356 person-waves); mean (SD) age was 67.7 (10.0) years, 4131 (58.9%) were women, 1136 (16.2%) were non-Hispanic Black, 4849 (69.2%) were non-Hispanic White, and mean (SD) duration of schooling was 13.0 (3.0) years. Compared with food-secure older adults, experiencing low food security was associated with higher odds of dementia (odds ratio, 1.38; 95% CI, 1.15-1.67) as was experiencing very low food security (odds ratio, 1.37; 95% CI, 1.11-1.59). Low and very low food security was also associated with lower memory levels and faster age-related memory decline. In this cohort study of older US residents, food insecurity was associated with increased dementia risk, poorer memory function, and faster memory decline. Future studies are needed to examine whether addressing food insecurity may benefit brain health.

Abstract 15835: Inhibition of Soluble Epoxide Hydrolase Reduces Cognitive Impairment and Improves Cerebral Hemodynamics in AD/ADRD

Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD) is an emerging global healthcare crisis. However, underlying mechanisms have not been understood well enough to translate into precision medicine. Recent human genetic evidence indicated that soluble hydrolase (sEH) is linked to AD/ADRD. Inhibition of sEH has been reported to improve cognition in AD mice due to its anti-inflammatory and neuronal protective effects. Here, we examined whether inhibition of sEH with TPPU could reduce cognitive impairments by improving cerebral hemodynamics in 18-month-old diabetes (DM)-related ADRD rats and 6 months of TgF344-AD rats. The myogenic responses of the middle cerebral artery (MCA) were impaired in both AD and ADRD rats and were normalized with TPPU. The inner diameters of MCA increased by 49.16 ± 17.02 % in DM rats but decreased by 16.06 ± 2.46% and 11.24 ± 0.05% in age-matched control and TPPU-treated DM rats when pressure was elevated from 40 to 180 mmHg. Similarly, TPPU-treated AD rats significantly enhanced the MCA constriction by 25%. Forced dilatation occurred at pressures &gt; 140 mmHg in MCAs in both rats and was rescued with TPPU treatment. Endothelial denuded MCAs from TPPU-treated DM rats constricted to 75.15 ± 4.25 % at a perfusion pressure of 140 mmHg and further constricted to 74.66 ± 4.01 % at 180 mmHg, compared to dilation of 155.48 ± 17.35 % and 172.78 ± 13.36 % in DM rats at the same pressures. The percentage of time spent with the novel object was 43.32 ± 8.04% and 83.23 ± 8.70% in DM and TPPU-treated DM rats, versus 75.68 ± 3.33% in non-DM rats. Impaired learning and short and long-term memory function examined with an 8-arm water maze in both DM and AD rats were rescued with TPPU treatment. These results provide the first evidence demonstrating that inhibition of sEH reverses cerebrovascular dysfunction and cognitive impairments in AD/ADRD.

An exploration of the cultural appropriateness of the family-centered function-focused care intervention.

The Family-centered Function Focused Care (Fam-FFC) intervention, is a nurse-family care partnership model aimed to improve the physical and cognitive recovery in hospitalized persons living with Alzheimer's Disease Related Dementias (ADRD) while improving the care partner's experiences. Discussions of patients' needs and preferences between nurses and the patient's close family members have been found to be useful in preventing excessive stress in persons with dementia, while lessening the anxiety of care partners. However, the efficacy of dementia-specific interventions is influenced in part by the degree to which the interventions are flexible and sensitive to the patient's and care-partner's condition, needs, and preferences, including cultural preferences. Therefore, the purpose of this study is to assess the cultural appropriateness of Fam-FFC using the Ecological Validity Model (EVM). This qualitative, descriptive study included 28 consented care partners drawn from a sample of 455 dyads enrolled in the Fam-FFC intervention. An interview guide was created based on the EVM. Participants provided demographic data. Thematic analysis was conducted to analyze transcribed interviews. The majority of the sample was female (79%), Non-Hispanic (96%) and half were married. One-half of the sample represented Black care partners and one-half were White. Seventy-nine percent lived with their family member with ADRD. Three major themes were identified from the thematic analysis including Care Partner Identity, Care Partner Preferences, and Goals of Care for functional recovery of their family member living with dementia. In this study care partners wanted more social services as well as home care that supported not just physical needs but also social and recreational needs. Findings from the study offer guidance on improving the Fam-FFC intervention including strengthening education and resources on partner self-care.

The Role of Rehabilitation for Early-Stage Alzheimer's Disease and Related Dementias: Practice and Priorities

The World Health Organization describes rehabilitation as interventions that focus on addressing disability through optimizing functional ability for individuals living with various health challenges in their unique daily life contexts. Rehabilitation services are typically seeking to enhance functional capacity and health, either in concert with, or in place of pharmacologic interventions. These services typically fall into 2 categories, restorative, where the client endeavors to return to a prior level of independent function, and compensatory, where s/he may not. In the latter case, clients might receive, and be trained to use, technology aids or other external supports to enable them to engage in a safe, healthy, and meaningful day-to-day life. For some populations, however, even enhanced functional capacity can present in the form of an insidious, albeit slower decline. So, what is, or should, rehabilitation's role be in progressive neurologic conditions? Specifically, what are the policy and practice implications of rehabilitation for (not in the presence of, but for) the care of persons living with neurodegenerative conditions such as Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD)?

Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension.

Dementia affects almost 50 million adults worldwide, and remains a major cause of death and disability. Hypertension is a leading risk factor for dementia, including Alzheimer disease and Alzheimer disease-related dementias. Although this association is well-established, the mechanisms underlying hypertension-induced cognitive decline remain poorly understood. By exploring the mechanisms mediating the detrimental effects of hypertension on the brain, studies have aimed to provide therapeutic insights and strategies on how to protect the brain from the effects of blood pressure elevation. In this review, we focus on the basic mechanisms contributing to the cerebrovascular adaptions to elevated blood pressure and hypertension-induced microvascular injury. We also assess the cellular mechanisms of neurovascular unit dysfunction, focusing on the premise that cognitive impairment ensues when the dynamic metabolic demands of neurons are not met due to neurovascular uncoupling, and summarize cognitive deficits across various rodent models of hypertension as a resource for investigators. Despite significant advances in antihypertensive therapy, hypertension remains a critical risk factor for cognitive decline, and several questions remain about the development and progression of hypertension-induced cognitive impairment.

The Impact of Routine Vaccinations on Alzheimer's Disease Risk in Persons 65 Years and Older: A Claims-Based Cohort Study using Propensity Score Matching.

Accumulating evidence suggests that adult vaccinations can reduce the risk of developing Alzheimer's disease (AD) and Alzheimer's disease related dementias. To compare the risk for developing AD between adults with and without prior vaccination against tetanus and diphtheria, with or without pertussis (Tdap/Td); herpes zoster (HZ); or pneumococcus. A retrospective cohort study was performed using Optum's de-identified Clinformatics® Data Mart Database. Included patients were free of dementia during a 2-year look-back period and were≥65 years old by the start of the 8-year follow-up period. We compared two similar cohorts identified using propensity score matching (PSM), one vaccinated and another unvaccinated, with Tdap/Td, HZ, or pneumococcal vaccines. We calculated the relative risk (RR) and absolute risk reduction (ARR) for developing AD. For the Tdap/Td vaccine, 7.2% (n = 8,370) of vaccinated patients and 10.2% (n = 11,857) of unvaccinated patients developed AD during follow-up; the RR was 0.70 (95% CI, 0.68-0.72) and ARR was 0.03 (95% CI, 0.02-0.03). For the HZ vaccine, 8.1% (n = 16,106) of vaccinated patients and 10.7% (n = 21,417) of unvaccinated patients developed AD during follow-up; the RR was 0.75 (95% CI, 0.73-0.76) and ARR was 0.02 (95% CI, 0.02-0.02). For the pneumococcal vaccine, 7.92% (n = 20,583) of vaccinated patients and 10.9% (n = 28,558) of unvaccinated patients developed AD during follow-up; the RR was 0.73 (95% CI, 0.71-0.74) and ARR was 0.02 (95% CI, 0.02-0.03). Several vaccinations, including Tdap/Td, HZ, and pneumococcal, are associated with a reduced risk for developing AD.

Cognitive Exercise for Persons with Alzheimer's Disease and Related Dementia Using a Social Robot.

Reminiscence therapy (RT) can improve the mood and communication of persons living with Alzheimer's Disease and Alzheimer's Disease related dementias (PLWD). Traditional RT requires professionals' facilitation, limiting its accessibility to PLWD. Social robotics has the potential to facilitate RT, enabling accessible, home-based RT. However, studies are needed to investigate how PLWD would perceive a robot-mediated RT (RMRT) and how to develop RMRT for positive user experience and successful adoption. In this paper, we developed a prototype of RMRT using a humanoid social robot and tested it with 12 participants (7 PLWD, 2 with mild cognitive impairment, and 3 informal caregivers). The robot automatically displayed a memory trigger on its tablet and engaged participants in a relatable conversation during RMRT. A mixed-method approach was employed to assess its acceptability and usability. Our results showed that PLWD had an overall positive user experience with the RMRT. Participants laughed and sang along with the robot during RMRT and demonstrated intention to use it. We additionally discussed robot control method and several critical problems for RMRT. The RMRT can facilitate both verbal and nonverbal social interaction for PLWD and holds promise for engaging, personalized, and efficient home-based cognitive exercises for PLWD.

Association Between Fluctuations in Blood Lipid Levels Over Time With Incident Alzheimer Disease and Alzheimer Disease-Related Dementias.

Prevention strategies for Alzheimer disease and Alzheimer disease-related dementias (AD/ADRDs) are urgently needed. Lipid variability, or fluctuations in blood lipid levels at different points in time, has not been examined extensively and may contribute to the risk of AD/ADRD. Lipid panels are a part of routine screening in clinical practice and routinely available in electronic health records (EHR). Thus, in a large geographically defined population-based cohort, we investigated the variation of multiple lipid types and their association to the development of AD/ADRD. All residents living in Olmsted County, Minnesota on the index date January 1, 2006, aged 60 years or older without an AD/ADRD diagnosis were identified. Persons with ≥3 lipid measurements including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in the 5 years before index date were included. Lipid variation was defined as any change in individual's lipid levels over time regardless of direction and was measured using variability independent of the mean (VIM). Associations between lipid variation quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Participants were followed through 2018 for incident AD/ADRD. The final analysis included 11,571 participants (mean age 71 years; 54% female). Median follow-up was 12.9 years with 2,473 incident AD/ADRD cases. After adjustment for confounding variables including sex, race, baseline lipid measurements, education, BMI, and lipid-lowering treatment, participants in the highest quintile of total cholesterol variability had a 19% increased risk of incident AD/ADRD, and those in highest quintile of triglycerides, variability had a 23% increased risk. In a large EHR derived cohort, those in the highest quintile of variability for total cholesterol and triglyceride levels had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this association are needed.

Riding the merry-go-round of racial disparities in ADRD research.

With the rapid expansion of the aging population, the burden of Alzheimer's disease related dementias (ADRD) is anticipated to increase in racialized and minoritized groups who are at disproportionately higher risk. To date, research emphasis has been on further characterizing the existence of racial disparities in ADRD through comparisons to groups racialized as White that are assumed to be normative. Much of the literature on this comparison insinuates that racialized and minoritized groups experience poorer outcomes due to genetics, culture, and/or health behaviors. This perspective shines a light on a category of ADRD research that employs ahistorical methodological approaches to describe racial disparities in ADRD that puts us on a merry-go-round of research with no benefits to society. This commentary provides historical context for the use of race in ADRD research and justification for the study of structural racism. The commentary concludes with recommendations to guide future research.

Driving predictors in a cohort of cognitively impaired Mexican American and non-Hispanic White individuals.

Individuals with Alzheimer's disease and Alzheimer's disease-related dementias may lose the ability to drive safely as their disease progresses. Little is known about driving prevalence in older Latinx and non-Hispanic White (NHW) individuals. We investigated the prevalence of driving status among individuals with cognitive impairment in a population-based cohort. This was a cross-sectional analysis of the cohort BASIC-Cognitive study in a community of Mexican American (MA) and NHW individuals in South Texas. Participants scored ≤25 on the Montreal Cognitive Assessment (MoCA), indicating a likelihood of cognitive impairment. Current driving status was assessed by the Harmonized Cognitive Assessment Protocol informant interview. Logistic regression was used to assess driving versus non-driving adjusted for pre-specified covariates. Chi-square and Mann-Whitney U tests were used to compare NHW and MA differences in driving outcomes from the American Academy of Neurology (AAN) questions for evaluating driving risk in dementia. There were 635 participants, 77.0 mean age, 62.4% women, and 17.3 mean MoCA. Of these, 360 (61.4%) were current drivers with 250 of 411 (60.8%) MA participants driving, and 121 of 190 (63.70%) NHW participants driving (p = 0.50). In fully adjusted models age, sex, cognitive impairment, language preference, and Activities of Daily Living scores were significant predictors for the likelihood of driving (p < 0.0001). Severity of cognitive impairment was inversely associated with odds of driving, but this relationship was not found in those preferring Spanish language for interviews. Around one-third of all caregivers had concerns about their care-recipient driving. There were no significant differences in MA and NHW driving habits and outcomes from the AAN questionnaire. The majority of participants with cognitive impairment were currently driving. This is a cause for concern for many caregivers. There were no significant ethnic driving differences. Associations with current driving in cognitively impaired persons require further research.

Alzheimer's Disease-Related Dementias Summit 2022: National Research Priorities for the Investigation of Post-Traumatic Brain Injury Alzheimer's Disease and Related Dementias.

Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD pathologies including multiple etiology dementia (MED). The National Institutes of Health hosts triennial ADRD summits to inform a national research agenda, and TBI was included for a second time in 2022. A multidisciplinary expert panel of TBI and dementia researchers was convened to re-evaluate the 2019 research recommendations for understanding TBI as an AD/ADRD risk factor and to assess current progress and research gaps in understanding post-TBI AD/ADRD. Refined and new recommendations were presented during the MED special topic session at the virtual ADRD Summit in March 2022. Final research recommendations incorporating broad stakeholder input are organized into four priority areas as follows: (1) Promote interdisciplinary collaboration and data harmonization to accelerate progress of rigorous, clinically meaningful research; (2) Characterize clinical and biological phenotypes of PTND associated with varied lifetime TBI histories in diverse populations to validate multimodal biomarkers; (3) Establish and enrich infrastructure to support multimodal longitudinal studies of individuals with varied TBI exposure histories and standardized methods including common data elements (CDEs) for ante-mortem and post-mortem clinical and neuropathological characterization; and (4) Support basic and translational research to elucidate mechanistic pathways, development, progression, and clinical manifestations of post-TBI AD/ADRDs. Recommendations conceptualize TBI as a contributor to MED and emphasize the unique opportunity to study AD/ADRD following known exposure, to inform disease mechanisms and treatment targets for shared common AD/ADRD pathways.

Frequency, Classification, and Timing of Movement Disorders in Rapidly Progressive Dementia (P14-11.004)

<h3>Objective:</h3> To compare and classify movement disorders in patients with specific causes of rapidly progressive dementia (RPD). <h3>Background:</h3> Many diseases present with RPD. The broad differential presents a unique challenge for the clinician who must rapidly organize and interpret tests to provide a timely clinical diagnosis for the patient with RPD. Movement disorders are associated with several different causes of RPD; their emergence, classification, and progression may provide clues to the specific diagnosis in patients with RPD. <h3>Design/Methods:</h3> Patients with RPD were prospectively enrolled between February 2016 and August 2022 at two tertiary care centers. Two neurologists independently determined etiologic diagnoses. A third neurologist systematically reviewed research records to identify movement disorders (e.g., parkinsonism, tremor, ataxia, myoclonus, dystonia, etc.) and classified these when present. Associations between movement disorders and specific causes of RPD were considered using Fisher’s exact test. <h3>Results:</h3> 154 patients met criteria for RPD (46.7% female). The median age-at-symptom onset was 66.0 years old (range: 18.3–84.7 years). Movement disorders were detected at presentation in 45/154 (29.2%) patients and in 73/154 (47.4%) patients at some point in the illness course. Gait disorders (n=40, 52.6%) were the most frequent movement disorder observed, followed by tremor (n=30, 40.5%), rigidity (n=24, 32.4%), ataxia (n=19, 25.7%) and myoclonus (n=19, 25.7%). Movement disorders were more commonly associated with prion disease (OR=3.65, 95% CI 1.27–11.93, p=0.008), and appeared on average 89 days after symptomatic onset. Detection of myoclonus (OR=6.80, 95%CI 2.0–22.54, p&lt;0.005) was associated with higher odds of CJD, with average time from symptom onset to myoclonus of 118 days. Bradykinesia was associated with Alzheimer disease related dementias (OR=7.38, 95%CI 1.54–46.14, p=0.004). <h3>Conclusions:</h3> Detection and classification of movement disorders may inform etiologic diagnosis in patients with RPD. <b>Disclosure:</b> Dr. Turcano has nothing to disclose. Mr. Satyadev has nothing to disclose. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Alzheimer’s Tennessee. Dr. Tipton has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Charlotte County Medical Society, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parabon Nanolabs. The institution of Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Barrow Law. Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer’s Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Horizon Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with American Academy of Neurology. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing Education, Inc. Dr. Day has a non-compensated relationship as a Clinical Director with AntiNMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.

The structural and social determinants of Alzheimer's disease related dementias.

The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Pain and Associated Factors in Nursing Home Residents

BackgroundUnderstanding factors associated with risk of pain allows residents and clinicians to plan care and set priorities, however, factors associated with pain in nursing home residents has not been conclusively studied. AimTo evaluate the association between pain and nursing home (NH) resident demographic and clinical characteristics. DesignRetrospective analysis of Minimum Data Set 3.0 records of nursing home residents residing in 44 Indiana NHs between September 27, 2011 and December 27, 2019 (N = 9,060). ResultsPain prevalence in this sample of NH residents was 23.7%. Of those with pain, 28.0% experienced moderate to severe/frequent pain and 54.6% experienced persistent pain. Risk factors for moderate to severe/frequent pain include female sex; living in a rural setting; intact, mildly, or moderately impaired cognition; arthritis; contracture; anxiety; and depression. In contrast, stroke and Alzheimer's disease and Alzheimer's-disease related dementias (AD/ADRD) were associated with decreased risk of reporting moderate to severe/frequent pain, likely representing both the under-assessment and under-reporting of pain among cognitively impaired NH residents. Risk factors for persistent pain included age <70, Black race, living in a rural location, intact cognition, contracture, and depression. ConclusionsPain remains a pressing problem for NH residents. In this study, we identified demographic and clinical factors associated with moderate to severe frequent pain and persistent pain. Residents with a diagnosis of AD/ADRD were less likely to report pain, likely representing the difficulty of evaluating pain in these residents. It is important to note that those with cognitive impairment may not experience any less pain, but assessment and reporting difficulties may make them appear to have less pain. Knowledge of factors associated with pain for NH residents has the potential for improving the ability to predict, prevent, and provide better pain care in NH residents.