bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progress on the Development of the Lewy Body Dementia‐Domain Rating Scale
Authors: Taylor John‐Paul , Boeve Brad F. , Rodriguez‐Porcel Federico E , Kane Joseph PM , Lewis Simon JG , Postuma Ronald B , Quinn Joseph F , Walker Zuzana , Aarsland Dag , Leroi Iracema , Taylor Angela , Ikeda Manabu , Galasko Douglas R. 
Published: December 2023

AbstractBackgroundNo specific clinical rating scale currently exists for Lewy body dementia (LBD). Clinical rating scales developed for other diseases are therefore used instead for LBD clinical trials. However, these scales are not optimized for LBD and may not sufficiently reflect the complex array of LBD‐related phenomenology, making it more difficult to interpret outcome data from LBD clinical trials.MethodA working group comprised of 14 members bridging various international LBD‐focused research groups was convened to develop the first iteration of the LBD‐DRS with a focus on inclusion of key LBD related symptom domains, ensuring that any scale is mapped to regulatory expectations, and an emphasis on being patient‐centered. This draft was then subsequently presented to a broader stakeholder group (»50 participants) at the International Lewy body Dementia Conference in June 2022 for further feedback, leading to a further iteration of the scale.ResultThe LBD‐DRS has been designed to capture ratings of the frequency and severity of symptoms across the key domains relevant to LBD – cognitive, neuropsychiatric, motor, autonomic and sleep – as well as the functional impact and perceived burden of symptoms for patients and their care partners. An international Delphi exercise is now planned with many LBD‐relevant stakeholders, which will be coupled with workgroup engagement (for example, with patient‐caregiver groups) to further develop the scale with the resulting final draft anticipated for pilot use in the near future.ConclusionsIn this presentation we will elaborate on the development of the scale, key areas that it will cover as well as challenge points and next steps. Upon completion of the development and refinement of the LBD‐DRS, we propose that this scale will have utility as valid and LBD specific outcome measure in LBD clinical trials.
ATN Cerebrospinal Fluid Biomarkers in Dementia with Lewy Bodies: Initial Results from the United States Dementia with Lewy Bodies Consortium
Authors: Jain Lavanya , Khrestian Maria , Formica Shane , Tuason Elizabeth D. , Pillai Jagan A. , Rao Stephen M. , Oguh Odinachi , Lippa Carol , Lopez Oscar L. , Berman Sarah , Tsuang Debby W , Zabetian Cyrus P , Irwin David J , Galasko Douglas R. , Litvan Irene , Marder Karen , Honig Lawrence S. , Fleisher Jori E , Galvin James E , Bozoki Andrea , Taylor Angela , Sabbagh Marwan , Wint Dylan , Leverenz James B , Bekris Lynn M. 
Published: December 2023

AbstractBackgroundNeuropathological hallmarks of AD, amyloid plaques and neurofibrillary tangles, have been described in dementia with Lewy bodies (DLB). Less is known about changes in pre‐mortem cerebrospinal fluid (CSF) amyloid and tau biomarker status in DLB. CSF biomarkers for amyloid (A), tau (T), and neurodegeneration (N) can be utilized to define pre‐mortem pathological status. The overall aim of this investigation was to utilize the ATN research framework to characterize pre‐mortem AD‐related pathology longitudinally in a rigorously characterized cohort of DLB from the Dementia with Lewy Bodies Consortium (DLBC) study. Our hypothesis was that ATN biomarkers would identify DLB with coexistent AD and ATN status would remain the same after 12 months.MethodCerebrospinal fluid (CSF) samples from an AD/ADRD cohort were obtained from the Cleveland Alzheimer’s Disease Research Center (CADRC), Cleveland Clinic Lou Ruvo Center for Brain Health Aging and Neurodegenerative Disease Biobank (CBH‐biobank) and DLBC. CSF Aβ40, Aβ42, Aβ42/40 (A), p‐Tau181 (T), and t‐Tau (N), were evaluated. The cohort was subtyped by CSF ATN category and sub‐group of DLB cases were neuropathologically evaluated. A sub‐cohort of DLB cases had longitudinal data with an evaluation at baseline and 12 months later.ResultDLB patients who were positive for both CSF Aβ42/40 (A+) and p‐Tau181 (T+) remained positive from baseline to 12 months. In contrast, some DLB patients who were positive for CSF Aβ42/40 (A+), but negative for p‐Tau181 (T‐), changed from CSF Aβ42/40 positive to negative at 12 months (p‐value = 0.0153) in the A+T‐N‐ and A+T‐N+ group. Findings from a small DLB subgroup with post‐mortem neuropathologic analyses indicated that most of the cases that were p‐Tau181 positive (T+) also had high Braak stage.ConclusionThese findings suggest that DLB patients who are positive for CSF Aβ42/40 (A+), but negative for p‐Tau181 (T‐), may have CSF Aβ42/40 levels that can fluctuate over time. In the small DLB subgroup with post‐mortem neuropathologic analysis, there appeared to be a relationship between AD pathologic change and ATN findings that warrants further study in a larger autopsied cohort to fully understand the relationship between ATN status and underlying AD neuropathologic change in DLB.
Associations of Alzheimer’s disease Plasma Biomarkers' and slow wave sleep within Black and White Cognitively Normal Older‐Adults
Authors: Azad Dishari Zaman , White Payton Gabrielle , Cesar Oliver , Kovbasyuk Zanetta , Gonzalez Moses , Wahab Ariana , Mullins Anna E , Kam Korey , Parekh Ankit , Rapoport David M , Ayappa Indu , Jean‐Louis Girardin A , Varga Andrew , Osorio Ricardo S , Bubu Omonigho 
Published: December 2023

AbstractBackgroundWe studied whether plasma levels of Aβ40, Aβ42, Aβ42/Aβ40, Tau, tau/Aβ42 and NfL are associated with slow wave sleep, and if this association varied within non‐Hispanic Whites and Blacks/African‐Americans.MethodThis was a cross‐sectional analysis of baseline data from 171 cognitively normal older‐adults, volunteering in active NYU studies on memory and sleep. Plasma Aβ40, Aβ42, Tau and NfL were measured using single molecule array (SIMOA). Non‐rapid eye movement sleep (NREM) slow wave sleep (SWS) duration was assessed from 2 nights of in‐lab NPSGs. Associations of NREM SWS duration and plasma AD biomarker levels were examined by applying adjusted generalized linear models and Pearson correlation analysis after data normalization. Analyses were adjusted for age, sex, BMI, race, and education.ResultOf the 171 subjects (128 Whites and 43 Blacks), 112 (65.5%) were females, and mean (SD) age was 68.6 (6.6) years, BMI was 27.6 (6.1) kg/m**2, and education was 16.9 (2.1). There were no racial differences in age, sex, and BMI, SWS and AHI4%. In comparison to whites, blacks had significantly lower years of education (14.2 vs. 17.2, p <.01). Black/African‐American subjects had significantly lower plasma Aβ40 (248.3 vs. 262.5 pg/ml) and NfL levels (11.4 vs. 15.2 pg/ml). p<.05 for both. There were no significant racial differences in levels of plasma Aβ42, Aβ42/Aβ40, Tau, Tau/Aβ40 and Tau/Aβ42. NREM SWS duration was not associated with plasma Aβ42, Aβ40 or tau in the overall sample. However, in Whites, SWS negatively correlated with plasma Aβ42 (r = ‐0.28, p< = 0.05). In Black/African‐Americans, SWS positively correlated with plasma Aβ42 (r = 0.48, p = 0.05). In Whites, SWS negatively correlated with plasma Aβ40 (r = ‐0.087, p = 0.72), though not significant. In Black/African‐Americans, SWS positively correlated with plasma Aβ40 levels (r = 0.32, p = 0.04). In Whites, SWS negatively correlated with plasma Tau (r = ‐0.153, p = 0.27), though not significant. In Black/African‐Americans, SWS positively correlated with plasma Tau levels (r = 0.52, p = 0.04). NREM SWS was not associated with plasma tau/Aβ42, plasma tau/Aβ40 or plasma NfL in the overall sample and across racial‐subgroups.ConclusionRace‐specific relationships between NREM SWS and plasma Aβ42, Aβ40 & Tau might propose differences in SDOH mechanisms that may affect sleep and AD‐risk in older‐adults.
Main lifetime occupational skill and later‐life cognitive function among older adults in the United States, South Africa, India, and Mexico
Authors: Kobayashi Lindsay C , O'Shea Brendan Q , Wixom Caroline , Langa Kenneth M , Weir David R , Lee Jinkook , Wong Rebeca , Gross Alden L. 
Published: December 2023

AbstractBackgroundOccupations are a potential source of later‐life cognitive reserve, but it is unknown how lifetime occupational skill level relates to cognitive function amongst older populations across diverse country contexts. We conducted a cross‐national comparison of the associations between main lifetime occupational skill and later‐life cognitive function among men and women living in four economically and socially distinct countries.MethodData were from population‐based studies of aging and their Harmonized Cognitive Assessment Protocol (HCAP) sub‐studies in the US, South Africa, India, and Mexico (N = 10,037). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations (ISCO‐2008) in categories of never worked (reference); level 1 (manual labor occupations such as cleaner, construction worker, agricultural worker); level 2 (intermediate occupations such as secretaries, sales assistants, trades workers); and level 3 or 4 (professional or managerial occupations such as teachers, medical practitioners, business owners). Cognitive function was assessed from HCAP measures representing orientation, memory, language, and executive function, standardized to the US population distribution. Sampling‐weighted regression models adjusted for age, minority status, education, and parental education estimated country‐specific associations between main lifetime occupational skill and later‐life cognitive function in men and women.ResultThe mean (SD) age of participants ranged from 68.1 (9.0) years (Mexico) to 76.6 (7.5) years (US; Table 1). Lifetime occupational skill levels varied by country, with the proportion never having worked ranging from 4% (US) to 32% (India), and the proportion with a main lifetime occupation at skill levels 3 or 4 ranging from 6% (India) to 31% (US; Table 1). We observed positive gradients between increasing main lifetime occupational skill and later‐life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa (Table 2; Figure 1).ConclusionMain lifetime occupations may be a source of later‐life cognitive reserve, with heterogeneity in this association across countries. While further longitudinal research with more detail on occupations is needed, this study suggests that enriching occupational opportunities in low‐resource global settings may help to promote population cognitive health.
Advancing Engagement and Enrollment of Older Black Americans in Alzheimer’s disease and Dementia‐Related Research
Authors: Cesar Oliver , White Payton Gabrielle , Arthur Matthew , Kovbasyuk Zanetta , Azad Dishari Zaman , Browne Laurel Y , Petersen Karyn , Jean‐Louis Girardin A , Osorio Ricardo S , Bubu Omonigho Michael M 
Published: December 2023

AbstractBackgroundThe under‐enrollment of racial and ethnic minorities in clinical trials limits the development of culturally tailored disease treatments and preventative strategies. For example, African Americans experience a greater risk of Alzheimer’s disease (AD), yet they remain woefully underrepresented in AD research. This limits understanding of how AD may operate differently in black populations, who have a higher burden of socio‐structural determinants of health. To improve older black American enrollment, The NYU Healthy Brain Aging and Sleep Center (HBASC) team developed a method tailored toward increasing minority enrollment in clinical trials by collaborating with community‐based organizations and minority populations to reexamine barriers to trial participation.MethodHBASC conducted a single‐site (New York Metropolitan Area) longitudinal study examining sleep and AD in healthy black adults (aged 60‐75). From the study, barriers to trial enrollment were evaluated on a systemic and individual level. The degree to which each level directly or indirectly contributed to barriers to enrollment was further explored using a series of steps and practices seeking to engage underrepresented communities in research. In doing so, team members established and implemented a community‐focused method called FEED. Study personnel demonstrated the feed method by Finding groups, organizations, and trusted community members to collaborate with, Educating community members, Engaging community members through events and educational seminars, and Delivering resources to the community.ResultThrough collaborations with community leaders and organizations, the study team performed community outreach events, raising disease awareness, sustaining trustful relationships, and providing educational resources. The study team saw ∼50% increase in black participant enrollment through the FEED method. Increased engagement in medical research was accomplished when underrepresented communities were empowered with the tools and resources to make knowledgeable decisions.ConclusionDiverse populations of patients face complex and multifaceted barriers to enrollment in clinical trials. A FEED framework will help address these barriers at an individual and systemic level.
Sensitivity of NIH ToolBox Motor tests to detect amyloid positivity in cognitively normal older adults
Authors: Persad Carol C , Maher Amanda Cook , Brush David M. , Bross Jordan R , Perrin Cameron K , Fisher Jordan , Murphy YiLu , Koeppe Robert A. , Giordani Bruno 
Published: December 2023

AbstractBackgroundChanges in motor functioning and particularly lower motor functioning such as balance and gait have been shown to be an early predictor of dementia (Kueper et al 2017). Based on these results, it has been suggested that balance and gait measures should be a regular component of a clinical dementia risk evaluation. The NIH Toolbox (NIHTB) has developed motor‐based tasks along with its cognitive battery. The aim of this study was to evaluate the utility of several of the NIHTB‐Motor task performance to predict amyloid status in cognitively normal older adults.MethodData from 45 cognitively normal adults age 65+ who were part of a larger study examining changes in driving behavior as predictors of cognitive decline were included in this study. Participants were divided into two groups based on PiB PET imaging and amyloid positivity determined using a centiloid scale: values ≥20 were considered positive, values ≤10 were negative; values between 10 and 20 were considered indeterminate and not included (n = 9)). Twenty nine participants were amyloid negative (OCN‐) and 16 were positive (OCN+). Data from the standing balance, grip strength and 2‐minute walking endurance tasks were analyzed using independent sample t‐tests.ResultThere were no differences in age or education between the two groups. However, there was a significant correlation between age and standing balance uncorrected score. As a result, fully corrected scores were used for this analysis. There was a significant difference between the OCN‐ and OCN+ for the fully corrected standing balance standard score (t = 1.7, p<0.04) such that the OCN+ group had lower balance scores compared to the OCN‐ group. No significance differences were found for grip strength or the 2‐minute walking endurance task.ConclusionThe Standing Balance task from the NIHTB may be a sensitive marker to identify individuals who are at higher risk of developing cognitive impairment and dementia. The NIHTB tasks were designed to be easy to administer in a relatively short amount of time with normative data, and these results suggest the Standard Balance task should be included as a routine measure of dementia risk.
Dementia‐related stigma among health professionals, carers, people living with dementia and the general public in Brazil
Authors: Godoy Carolina , Oliveira Déborah , Ferri Cleusa P 
Published: December 2023

AbstractBackgroundPeople living with dementia (PLWD) often experience stigma and discrimination; however, there is a dearth of research on this topic in middle‐income countries, where the majority of people living with dementia reside.MethodWe conducted a secondary analysis of a database from Alzheimer’s Disease International on the beliefs, attitudes and behavioural intentions towards PLWD among four groups (general public, health professionals, carers and PLWD). We compared the groups using logistic regression adjusted for age, sex and education.ResultAbout 33% health professionals believed that dementia is a consequence of natural ageing. When compared to the general public, caregivers (OR = 0.80; CI95%0.65 – 0.97), and healthcare professionals (OR = 0.55; CI95%0.44 – 0.68), were significantly less likely to believe this, regardless of gender, age, and education. Nearly 25% of health professionals believed that communication with PLWD is difficult. Among everyone who agreed with this statement, women compared to men were less likely to have this belief (OR = 0.75; CI95%0.58 – 0.97), and when compared to the general public, health professionals (OR = 0.73; CI95%, 0.58 – 0.92), were less likely to agree with this, regardless of gender, age, and education. Approximately 50% of all participants believed that people do not want to be friends with people with dementia. Those of younger age (OR = 0.98; CI95% 0.97 – 0.99), and health professionals (OR = 0.73, CI95%, 0.57 – 0.94), were less likely to agree with this statement compared to older participants and the general public, respectively. Nearly 45% of the general public believed that it was important to remove responsibilities from the person with dementia so as not to stress them, and carers (OR = 0.50; CI95%, 0.41 – 0.61), were significantly less likely to have such an opinion when compared to the general public, regardless of gender, age, and education.ConclusionThe proportion of stigma may be even greater than that found, given the high level of education of the participants, which does not represent the general level of education in Brazil. More detailed studies on the stigma related to dementia should be carried out, exploring different scenarios in Brazilian society to better inform societal interventions to reduce dementia‐related stigma.
Brain microRNA‐101 levels influence the risk for Alzheimer’s disease and regulate proteins involved in the disease
Authors: Lahiri Debomoy K. , Wang Ruizhi , Maloney Bryan , Beck John S. , White Fletcher A , Greig Nigel H , Sambamurti Kumar , Counts Scott E. 
Published: December 2023

AbstractBackgroundSmall non‐coding microRNA (miRNA) play a vital role in regulating various biological and pathological processes, including Alzheimer’s disease (AD), brain injury, and head trauma. AD hallmarks include brain amyloid plaques and neurofibrillary tangles (NFTs). Amyloid plaques are the abnormal aggregation of amyloid‐β peptides (Aβ) derived from Aβ precursor protein (APP), and NFTs consist mostly of hyper‐phosphorylated tau proteins. We have recently shown that miRNAs, such as miR‐20b, miR‐153, and miR‐298, can independently regulate AD‐related protein expression (Wang et al‐Mol Psychiatry‐2022). APOE ε4 increases the risk of AD; however, the role of brain miR101 levels in APOE’s influence is presently unknown. Here, we studied the role of miR‐101‐3p (miR‐101) in AD risk and in regulating levels of critical proteins such as APP, GSK3β, and ECE1 implicated in AD.MethodTemporal lobes (TL), cerebellum (CB), and posterior cingulate cortices (PCC) were obtained from non‐cognitively impaired (NCI) and AD subjects, and quantitative RT‐PCR measured miR‐101 levels. The target specificity of miR‐101 was tested using dual reporter clones expressing the 3'‐UTRs of either APP, ECE1, or GSK3β mRNAs. Human microglia and differentiated neuroblastoma (SKNSH) cells were transfected with miR‐101 for 72 hours, and cellular RNA, total proteins, and secreted proteins were analyzed by ELISA and Westerns to understand miR‐101‐mediated regulation.ResultTL and CB regions showed that increased miR‐101 levels were associated with reduced AD risk in the absence of the APOEε4 allele. Interestingly, miR‐101 may increase AD risk in the presence of two APOEε4 alleles. Transfection of miR‐101 altered the translation of several AD‐related proteins, including aggregation‐prone proteins, processing enzymes, and cytokines. Mechanistically, miR‐101 treatment reduced ECE1 and GSK3β mRNA 3’‐UTR activities in reporter clones and protein levels.ConclusionWe have shown that miR‐101 levels modify AD risk in an APOE allele‐dependent manner. Notably, miR‐101 targets the 3’‐UTRs of ECE1 and GSK3β and reduces their expression, making it a key regulator of AD‐related proteins across species and cell types. Our combined results suggest that miR‐101 is critical in regulating essential proteins relevant to AD pathogenesis and could potentially be a novel “multi‐hit” drug target for AD and other neurodegenerative diseases. NIH grants to DKL and SEC.
Reshaping the path of vascular cognitive impairment with progressive resistance training: A 12‐Month Randomized Trial
Authors: Falck Ryan S , Tam Roger , Dao Elizabeth , Barha Cindy K , Hsiung Ging‐Yuek Robin , Crockett Rachel A , Alkeridy Walid Ahmed , Best John R. , Grant Sofia , Field Thalia S. , Silva Nárlon Cássio Boa Sorte , Brinke Lisanne F Ten , Liu‐Ambrose Teresa 
Published: December 2023

AbstractBackgroundSubcortical ischaemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Importantly, SIVCI is considered the most treatable form of cognitive impairment, due to its modifiable risk factors such as hypertension and diabetes mellitus. Exercise training is a promising intervention to delay the progression of SIVCI, as it actively targets these cardiometabolic risk factors. Despite the demonstrated benefits of resistance training on cognitive function and emerging evidence suggesting resistance training may reduce the progression of white matter hyperintensities, research on SIVCI has predominantly focused on the use of aerobic exercise. Thus, we examined the efficacy of a 12‐month, twice‐weekly progressive resistance training (RT) program on cognitive function in older adults with SIVCI.MethodWe conducted a 12‐month single‐blinded, randomized controlled trial with 91 adults with SIVCI who were randomly allocated to: 1) progressive RT; or 2) balance and tone exercises (BAT; control). Study eligibility included: 1) age 55 years and older; 2) neuroimaging evidence of cerebral small vessel disease at study entry; 3) mild cognitive impairment, as indicated by Montreal Cognitive Assessment scores < 26/30; and 4) the absence of dementia. Measurements occurred at baseline, 6 months, and 12 months. The primary outcome for cognitive function was the Alzheimer’s Disease Assessment Scale‐Cognitive‐Plus (ADAS‐Cog 13 with additional cognitive tests). Gait speed over 4 meters was also assessed as impaired mobility is common among those with SIVCI.ResultForty‐five participants were randomized to the RT group and 46 to the BAT group. Mean baseline age was 74.6 years (SD = 5.7 years), 66% of participants were female, and the median Fazekas score was 1. After adjusting for baseline, participants in the RT group had significantly better ADAS‐Cog Plus performance at 12 months vs. BAT (estimated mean difference [RT – BAT]:‐0.20; 95% CI:[‐0.39, ‐0.01]; p = 0.039). In addition, participants in RT had significantly faster gait speed at 12 months vs. BAT (estimated mean difference: ‐0.08 m/s; 95% CI: [‐0.16, 0.00]; p = 0.047).ConclusionThe prevalence and burden of SIVCI will only increase due to the world’s aging population. Our results suggest progressive resistance training should be considered in the management and treatment of individuals with SIVCI.