bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delays and underdiagnoses of dementia in the LMICs: Pathways and factors
Authors: Ellajosyula Ratnavalli , Narayanan Jwala , Hegde Soumya , Kamath Vikram , Murgod Uday , Easwaran Vandana , Seetaram Raghavendra , Srinivasan Murali , Watson Peter 
Published: December 2022

AbstractBackgroundTwo thirds of people with dementia live in low and middle income countries (LMICs)but only about 10% of these persons are estimated to receive a dementia diagnosis. Reasons are multiple and complex. Early diagnosis is essential for initiating treatment, referral for care services, and planning for the future. There is a paucity of data on the pathways to dementia diagnosis in LMICs. We investigated the pathways and factors contributing to delay in diagnosis in a specialist memory clinic from urban India.MethodConsecutive patients and their carers attending the specialist memory clinic in Bangalore, India with cognitive complaints underwent a detailed clinical assessment, neuropsychological testing, neuroimaging, and blood tests. Details of symptom onset, visits to various medical providers, diagnoses made were captured on a proforma. Effect of education, gender, dementia subtype, and age of onset on time to diagnosis were examined using univariate analysis of covariance.Result879 out of 1212 patients had dementia. Only 24 (2.39%) received a dementia diagnosis elsewhere. Approximately 20% of the patients were on dementia‐specific medications but the family and the patient were unaware of the diagnosis. The median time to diagnosis was 24 (range 3 to 180) months. 43% of the patients were diagnosed 24 months after symptom onset. Patients with young onset dementia, Alzheimer’s disease, and Frontotemporal dementia were diagnosed significantly later as compared to those with vascular dementia and dementia with Lewy bodies. Education and gender did not have an effect on the time to diagnosis.ConclusionBoth delay and lack of communication about the diagnosis of dementia appear to be important issues that need to be addressed to improve the early detection of dementia in India. Training of health providers appears an essential component in improving the early diagnosis of dementia. Findings from our study will be compared to literature from other LMICs and a comprehensive framework to improve early diagnosis of dementia in LMICs will be discussed.
Midlife proteome‐wide analysis identifies plasma biomarkers for 25‐year dementia risk linked to diverse pathophysiology
Authors: Walker Keenan A , Chen Jingsha , Shi Liu , Yang Yunju , Fornage Myriam , Zhou Linda , Schlosser Pascal , Surapaneni Aditya , Grams Morgan E , Duggan Michael R , Peng Zhongsheng , Gomez Gabriela , Tin Adrienne , Hoogeveen Ron C , Sullivan Kevin J , Ganz Peter , Lindbohm Joni V , Kivimaki Mika , Nevado‐Holgado Alejo J , Buckley Noel , Gottesman Rebecca F , Mosley Thomas H , Boerwinkle Eric , Ballantyne Christie M , Coresh Josef 
Published: December 2022

AbstractBackgroundA diverse set of biological processes have been implicated in the pathophysiology of Alzheimer’s disease (AD). However, there is limited understanding of the biological pathways mechanistically relevant in the earliest phase of disease and a lack of protein biomarkers available to capture the biological systems involved.MethodTo discover early biomarkers and further understand on a molecular level the systemic factors that may promote neurodegeneration, we used a large‐scale proteomic platform to relate 4,877 plasma proteins measured in middle‐aged adults to dementia risk over a 25‐year period (n=10,981; 1,874 incident dementia cases) in the Atherosclerosis Risk in Communities (ARIC) study (Figure 1). Associated proteins were related to 20‐year cognitive decline in the Whitehall II study, and to AD risk and CSF biomarkers in the European Medical Information Framework‐AD (EMIF‐AD) study.ResultProteome‐wide associations in ARIC discovered 32 dementia‐associated plasma proteins involved in proteostasis, immunity, synaptic function, and extracellular matrix organization (Figure 2). We replicated the relationship between 15 candidate proteins and neurocognitive outcomes in Whitehall or EMIF‐AD, and demonstrated that dementia‐associated plasma proteins are associated with cerebrospinal fluid markers of Aß42, p‐tau181, neurodegeneration, and neuroinflammation (Figure 3). We found many of the protein biomarkers were abnormally expressed in AD brain tissue, though some of the strongest midlife dementia‐associated proteins (e.g., GDF‐15) were not detected in brain. Using network analyses, we found an evolving plasma protein signature for dementia risk suggesting a dysregulation of specific immune pathways and disrupted proteostasis/autophagy and extracellular matrix organization in midlife ∼20 years before dementia onset, and abnormal coagulation/complement signaling ∼10 years before dementia onset (Figure 4). We used two‐sample Mendelian randomization to identify which midlife plasma proteins and protein networks may play a causal role in Alzheimer’s disease and demonstrated that many of the dementia‐associated proteins may play a causal role in systemic (e.g., vascular, inflammatory) diseases associated with increased AD/dementia risk. We used the totality of evidence to prioritize midlife plasma proteins as AD/dementia biomarkers linked to discrete pathophysiological processes.ConclusionThe current study identified multiple pathway‐specific biomarkers and potential therapeutic targets likely relevant in the earliest phase of the AD and related dementia.
Supporting Youth With A Parent Who Is Living Younger‐Onset Alzheimer’s: A Crucial Component In Integrated Care
Authors: Cose Diana Shulla 
Published: December 2022

AbstractSupporting Youth With A Parent Who Is Living Younger‐Onset Alzheimer's: A Crucial Component In Integrated Care Lorenzo's House, a nonprofit in Chicago, focuses on a transformative approach that supports children and young adults who are living with a parent with younger‐onset Alzheimer's. Youth are often affected by a parent's diagnosis at a neurobiologically vulnerable time in their lives. Youth frequently don't know how to explain their experience as a care partner with their peers, leaving them isolated and managing the ongoing change by themselves. By creating spaces specifically catered towards these young care partners, we are radically shifting the journey of what younger‐onset Alzheimer's looks like for children and young adults.We focus on the relationship between the parent diagnosed and their children, what children need as care partners, and what issues and struggles they face at a variety of ages in this journey. Our three youth programs focus on innovation to support youth living with a parent with younger‐onset Alzheimer's: Lorenzo's Camp, a camp designed by youth care partners, therapists, medical professionals ‐ intended to share common stories and build an alliance; the Light Club, a virtual youth care partner group injected with team building and relationship development; and lastly youth‐led advocacy work. Our model shifts the narrative for how youth experience being a member of a family that is navigating a younger‐onset Alzheimer's diagnosis.
PROGRESS IN DEVELOPING A LIGHT‐STABLE 4R TAU PET IMAGING AGENT: APN‐1701 FIH
Authors: Tempest Paul , Lin Yih‐Shyan , Tai Chin‐Yin , Ono Maiko , Russell David S , Sandiego Christine M , Carroll Vincent , Gunn Roger N , Margolin Richard A , Higuchi Makoto , Jang Ming‐Kuei 
Published: December 2022

AbstractBackgroundThe need for a light stable 4R tau PET tracer for use in diverse tauopathies is widely appreciated. We aimed to assess the initial human imaging profile of [18F]APN‐1701 as such a tracer and to compare its imaging profile to the well‐established but light‐sensitive tracer [18F]‐APN‐1607 that can detect 4R aggregates as well as 3R and mixed 3R/4R aggregates. [18F]APN‐1607 has progressed to a multicenter Phase 2 clinical trial for Alzheimer’s disease (AD); therefore, prior imaging data with it was considered valuable for comparison.MethodOne cognitively normal (CN) subject (male, 73yo) and one AD subject (female, 58 yo), who had undergone prior amyloid profiling using [18F]florbetapir PET and subsequent imaging with [18F]APN‐1607 in a proof‐of‐concept study and a test‐retest study, respectively, participated in the current study. Dynamic imaging with [18F]APN‐1701 was performed over 180 min to obtain kinetic data.ResultOverall, for both subjects [18F]APN‐1701 generally matched [18F]APN‐1607 findings, i.e., peak SUV values reached similar levels. The CN subject, who was amyloid negative, had slight, uniform cortical [18F]‐APN‐1701 uptake and more substantial uptake in the pallidum, pons and midbrain. SUVr images for the AD subject showed retention in similar brain regions for both tau tracers with the same rank order of regional SUV/SUVr. Notably, for this subject [18F]APN‐1701 continued to accumulate up to the end of image acquisition.Conclusion[18F]APN‐1701 demonstrates cortical uptake generally similar to [18F]APN‐1607 but its slow kinetics are unfavorable for further development.
PROGRESS TOWARDS AN A‐SYNUCLEIN PET TRACER
Authors: Tempest Paul , Tai Chin‐Yin , Ono Maiko , Skaddan Marc B , Wilcox Kyle C , Reed Aimee , Vaidyanathan Srirajan , Christoffersen Claus T , Kallunki Pekka , Bang‐Andersen Benny , Margolin Richard A , Kao Tzu‐Huei , Higuchi Makoto , Jang Ming‐Kuei 
Published: December 2022

AbstractBackgroundThe high value for Parkinson’s disease and related disorders of the availability of a potent, selective, brain penetrant α‐synuclein (α‐Syn) PET tracer is widely acknowledged. We aimed to develop such an agent by applying an established radiotracer development strategy that has been successfully used with another misfolded CNS protein target.MethodWe used a proprietary collection of CNS‐focused aggregated protein binding agents that APRINOIA had previously created to map the structure‐activity relationship of its tau PET tracer programs, including [18F]APN‐1607. This tracer has a unique binding site on aggregated tau and has recently been characterized by cryo‐EM.The collection was first screened for selective binding of α‐Syn aggregates vs. tau aggregates using recombinant fibrils. This was followed by fluorescence‐based binding to DLB and MSA tissues. These assays identified 16 promising compounds for progression into autoradiography and homogenate binding assays.ResultTritiation was successful for 13 of the hits. Self‐blocking studies confirmed specific binding in human brain tissue sections and homogenates. A lead compound was selected, and preliminary PK experiments in wild type mice indicated that brain uptake and clearance properties were compatible with a desirable PET tracer profile in a non‐diseased state. Further studies to evaluate the binding properties in the diseased state and optimize the lead are ongoing.ConclusionThe compound collection and tracer development strategy have led to the development of an advanced lead or potentially a viable α‐synuclein PET tracer.
Medical and Psychiatric Risk Factors for Dementia in Veterans with and without Traumatic Brain Injury (TBI): A Nationwide Cohort Study
Authors: Gardner Raquel C. , Barnes Deborah E , Bahorik Amber L , Li Yixia , Peltz Carrie , Yaffe Kristine 
Published: December 2022

AbstractBackgroundTraumatic brain injury (TBI) is an important risk factor for dementia and is especially common among Veterans. It is unknown whether TBI exposure moderates the effect of other common medical/psychiatric comorbidities that are also important risk factors for dementia in Veterans. If treatable or preventable comorbidities are either especially common or risky in TBI‐exposed Veterans, then this may have important public health implications for dementia prevention.MethodWe conducted a retrospective cohort study using the Nationwide Veterans Health Administrative inpatient and outpatient data (2001‐2019). We identified all Veterans age 55 years with prior TBI and without baseline dementia (N = 95,139) and age/sex/race‐matched 1:2 with Veterans without prior TBI or baseline dementia (N = 190,278). We compared prevalence of seven common medical/psychiatric comorbidities (hypertension, coronary artery disease (CAD), diabetes, cerebrovascular disease (CVD), epilepsy, depression, and post‐traumatic stress disorder (PTSD)) and associated risk of incident dementia among Veterans with versus without prior TBI. We tested for interaction of each comorbidity with TBI on risk of dementia. We calculated risk of dementia associated with each comorbidity using multivariable hazard ratios (adjusting for demographics and all other comorbidities) and Fine‐Grey competing risk of death. We estimated population attributable risk (PAR) of dementia due to each comorbidity.ResultAll comorbidities were more prevalent among Veterans with TBI compared to those without TBI: hypertension +12.5%, CAD +13.6%, diabetes +7.9%, CVD +10.8%, epilepsy +5.7%, depression +21.5%, PTSD +14.9%). All comorbidities were associated with elevated risk for dementia among Veterans with and without TBI. However, there was a significant interaction with TBI such that point estimates were slightly lower among Veterans with TBI (adjusted HRs 1.02‐1.31) versus Veterans without TBI (adjusted HRs 1.03‐1.82). However, the overall PARs for dementia were higher in Veterans with versus without TBI for several comorbidities (depression 8.7% vs. 7.4%; hypertension 3.8% vs. 1.6%; CVD 3.7% vs. 2.0%; epilepsy 2.1% vs. 1.1%), due to their higher prevalence in Veterans with TBI.ConclusionWhile treating or preventing medical/psychiatric comorbidities among all Veterans remains a high public health priority, targeting depression, hypertension, CVD, and epilepsy may be especially important for dementia risk reduction among Veterans with prior TBI.
Fluctuations in blood pressure measurement: the impact of time of day and ethnicity‐ A HABS‐HD Study
Authors: Large Stephanie E , Petersen Melissa , Hall James , O'Bryant Sid E. , Johnson Leigh 
Published: December 2022

AbstractBackgroundVascular risks including hypertension are significant factors in the development of Alzheimer’s and related dementias . Multiple blood pressure (BP) measurements are commonly used in clinical and research practice to assess this vascular risk. Anecdotal evidence suggests that the first BP measurement taken is more elevated than the second measurement as a participant may be nervous about the study. This study explores if the first measurement is elevated compared to the second and then explores the differences between morning and afternoon measurements.MethodData from 1705 participants (non‐Hispanic Whites and Mexican Americans) was collected from a community‐based epidemiological study of aging. The average age was 66, and the average education was 12 years. Participants are scheduled either for AM or PM visit. BP measurements are taken post the consent and then after the participant interview prior to the start of neuropsychological testing. The systolic (SBP) and diastolic blood pressure (DBP) changes were calculated by subtracting the second measurement from the first. T‐tests were performed comparing AM to PM groups. Chi‐square tests compared ethnicity and cognitive status in the AM and PM groups. One‐way ANOVAs examined group differences (ethnicity and AM/PM draw groups) in BP measurement.ResultResults showed significant differences in SBP change between the AM (M = ‐0.52, SD = 12.74) and PM (M = ‐4.03, SD = 10.89); t(1666)= 6.07, p < 0.000) draw and DBP change in the AM (M = 0.16, SD = 7.68) and PM (M = ‐2.32, SD = 6.68); t(1670)=7.09, p <0.000). Chi‐square tests demonstrated significant differences between the AM and PM groups in ethnicity X2(1, N= 1705) = 33.27, p = 0.000. There were no significant differences between the AM and PM regarding cognitive status (normal, MCI, dementia). ANOVAs demonstrated significant differences between the groups in SBP change (F[3, 1672] = 12.76, p <0.000) and DBP change (F[3, 1672] = 17.10, p <0.000).ConclusionThe study results demonstrate that there was a relationship between BP and measurement time, which supports evaluating when BP measurements are taken and how this may affect outcomes. Future studies should examine how the blood pressure measurements relate to current guidelines.
Motivational Interviewing Promotes Self‐Determination of LGBTQ Adults with Dementia and Caregivers in First Intervention Study
Authors: Petros Ryan , Fredriksen‐Goldsen Karen , Teri Linda 
Published: December 2022

AbstractBackgroundLGBTQ adults experience higher rates of dementia and rely more heavily on informal social support to meet care needs compared to cisgender, heterosexual peers. As dementia progresses and they enter new systems of care, LGBTQ adults must make important choices not only about health promoting behaviors and care plans generally, but also about identity disclosure, building and maintaining a care team with families of choice, and navigating potential discrimination specific to their identities as sexual and gender minorities. A culturally relevant intervention is urgently needed to protect self‐determination and meet their unique care needs.MethodUsing findings from a longitudinal study of LGBTQ adults, a team of interventionist researchers adapted Reducing Disabilities in Alzheimer’s Disease (RDAD) by integrating culturally relevant modifications and enhanced empowerment strategies through motivational interviewing (MI). The team developed and implemented a training protocol for study interventionists called “coaches,” trialed the intervention with 150 dyads of adults with dementia and care providers in the LGBTQ community, and collected case reports from coaches and qualitative data from trial participants to inform intervention adaptations.ResultMI added unique theoretical and practical contributions, resulting in a culturally relevant, efficacious intervention (Aging with Pride: IDEA), designed for adults with dementia and care providers in the LGBTQ community and adapted for online delivery during the COVID pandemic. Qualitative data from the trial demonstrates that participants discovered “new possibilities for managing changes” as dementia progressed and finished feeling “empowered rather than stuck.”ConclusionMI uniquely supported trial participants’ self‐determination to develop and implement strategies for dementia care and coping. Practice examples are included to illustrate applications of MI and relevant theory to promote self‐determination and implementation of strategies to navigate dementia for LGBTQ adults.
Hemispheric asymmetry and atypical lobar progression of Alzheimer‐type tauopathy
Authors: Tremblay Cécilia , Serrano Geidy E , Intorcia Anthony J , Sue Lucia I , Nelson Courtney M , Walker Jessica , Arce Richard , Fleisher Adam S , Pontecorvo Michael J. , Atri Alireza , Montine Thomas J. , Chen Kewei , Beach Thomas G 
Published: December 2022

AbstractBackgroundNeurofibrillary tau pathology spread in Alzheimer’s disease (AD) mostly shows a stereotypical pattern of topographical progression. Atypical patterns have also been described and associated with interhemispheric asymmetry. As histopathological studies that used bilateral sampling are limited, this study aimed to assess interhemispheric tau pathology differences and the presence of topographically atypical cortical spreading patterns.MethodImmunohistochemical staining for detection of tau pathology was performed in 23 regions of interest of 57 autopsy cases and compared between cortical regions and hemispheres.ResultFrequent mild (82% of cases) and occasional moderate (32%) interhemispheric density discrepancies were observed while marked discrepancies were uncommon (7%) and restricted to occipital regions. Left and right hemispheric tau pathology dominance was observed with similar frequencies, except in Braak stage VI that favored a left dominance. Interhemispheric Braak stage differences were observed in 16% of cases and was more frequent in advanced (IV‐VI) than early stages (I‐III). One atypical lobar topographical pattern, where occipital tau pathology density exceeded frontal lobe scores, was identified in 4 cases, favoring a left dominant asymmetry.ConclusionWe speculate that asymmetry and atypical topographical progression patterns may be associated with described atypical AD clinical presentations and progression characteristics, which should be tested by comprehensive clinicopathological correlations.
Reaching the Underserved in Dementia Research: IDEA (Innovations in Empowerment and Action)
Authors: Fredriksen‐Goldsen Karen , Teri Linda , Kim Hyun‐Jun , Jones Brittany R , La Fazia David M. , McKenzie Glenise , Petros Ryan , Brown Char , Emlet Charles A 
Published: December 2022

AbstractBackgroundExisting research has documented higher levels of cognitive impairment among marginalized populations, including among LGBT (lesbian, gay, bisexual, and transgender) older adults. Research has also found LGBT older adults living with cognitive impairment experience a unique and challenging context compared to their heterosexual and cisgender peers. However, there remains a paucity of research regarding culturally appropriate dementia interventions and services that are responsive to the needs, risks, and protective factors of such underserved populations.MethodAging with Pride: IDEA (Innovations in Dementia Empowerment and Action) is the first federally funded study to test an intervention designed to address the distinct needs of LGBT older adults with cognitive impairment and their caregivers. The study design compares a specialized LGBT enhanced program to a pre‐existing standard dementia program (RDAD), which provided the foundation for the project. This presentation will examine the ways in which the demographic profile and the recruitment and retention findings differ for this population compared to most existing dementia intervention research.ResultAmong the LGBT older adults living with cognitive impairment in this study, 74.8% identified as gay or lesbian and 7% as bisexual; 6.3% as transgender. Among caregivers, this was 69.9%, 15.4%, and 7%, respectively. People of color accounted for 16.8% of care recipients and 23.1% of caregivers. Care recipients were significantly more likely to initiate contact to enlist in the randomized controlled trial (RCT) compared to caregivers. One‐third of care recipients had a non‐partner/spouse caregiver supporting them in this dyadic intervention; 15.4% had a friend in the care partner role. The most common reason for study ineligibility was not having a care partner to participate and about 12% terminated from the program because of difficulty within the care partner/care recipient dyad.ConclusionThe current study built a strong research‐community partnership necessary for the development and implementation of the intervention. The information gained in this study regarding recruitment, retention, and implementation is valuable for developing interventions that can be tailored to the distinct needs of communities that have traditionally been underserved in dementia research.