bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot clinical trial: Electronic Memory and Management Aid/smart home partnership increases aid use at three‐month follow‐up in individuals with mild cognitive impairment
Authors: Schmitter‐Edgecombe Maureen , Luna Catherine , Brown Katelyn , Cunningham Reanne , Sumida Catherine , Holder Lawrence , Cook Diane 
Published: December 2021

AbstractBackgroundCognitive changes experienced by individuals with mild cognitive impairment (MCI) can impact everyday functioning and lower self‐confidence. The Electronic Memory and Management Aid (EMMA) is a senior‐friendly iOS tablet application designed to support everyday activities. To examine whether learning and sustained app use could be improved, we partnered EMMA with a smart home that delivered activity‐aware prompting.MethodIn a pilot trial, participants with MCI were randomly assigned to learn to use EMMA with (N = 14; M age = 74) or without (N = 15; M age = 71) smart home prompting. Training consisted of 5‐6 (two‐hour) structured sessions delivered in a 4‐week timeframe by a clinician in the participant’s home (half turned into smart homes). Real‐time data were collected on participant use of EMMA, with metrics averaged across these intervals: weeks 1‐2 (early‐training), 5‐6 (post‐training), 10‐11 (prompting turned off) and 15‐16 (follow‐up; prompting back on). Baseline, post‐training and follow‐up clinical data (coping, life satisfaction, everyday functioning) were also compared.ResultNo group differences emerged in age, education, estimated pre‐morbid ability (High Average), memory (Low Average) or executive functioning (Average). Participants in the partnered condition engaged daily with EMMA more times post‐training (M = 5.0) compared to the control (not‐partnered) condition (M = 2.0). Participants in the partnered condition also maintained a high level of engagement with EMMA even after prompting stopped (M = 5.0, M = 3.8 at follow‐up). This contrasted with significantly lowered use (M = 1.2 and M = 0.6, respectively) in the control condition. Similar patterns were found for usage rates of app components (event scheduling, calendar use) and advanced features (searches, alarms, pictures). Clinical data showed self‐reported positive changes in coping and life satisfaction that did not differ by condition; no significant changes were self‐reported in everyday functioning.ConclusionPartnering EMMA with a smart home that cued app use at opportune times and after periods of non‐use improved habit formation and earlier mastery of the tool. Once a habit was established, turning off the prompts did not impact use of the EMMA app, demonstrating the importance of habit formation and early mastery to sustain tool use.
Sex differences in the association between plasma and CSF p‐tau
Authors: Tsiknia Amaryllis A. , Sundermann Erin E. , Galasko Doug R. , Andrews Murray , Banks Sarah J. 
Published: December 2021

AbstractBackgroundMounting evidence from cerebrospinal fluid (CSF) studies suggests that women on the AD spectrum have higher levels of pathological tau in the CSF than men. Several studies suggest that plasma tau phosphorylated at threonine 181 (p‐tau181) is strongly associated with CSF biomarkers of tau and may constitute an accessible and informative biomarker of AD. However, sex stratified analyses of plasma and CSF tau associations are lacking. Here, we examine the relationship between plasma and CSF p‐tau181 separately in 476 men and 422 women on the AD continuum.MethodOur sample included 280 cognitively normal (CN), 453 mild cognitively impaired (MCI) and 165 AD dementia participants from ADNI with concurrent plasma p‐tau181 and CSF p‐tau181 determined by the Roche Elecsys assay. We stratified our sample by sex, to examine plasma p‐tau181 differences between diagnostic groups separately in men and women. Furthermore, we examined the association between plasma and CSF p‐tau181 separately in each sex, within each diagnostic group. Models were first adjusted for APOE ε4 status and age, and then additionally adjusted for amyloid status.ResultParticipants with AD dementia had higher levels of plasma p‐tau181 than controls in both sexes, while MCIs had higher plasma p‐tau than normal controls only among women. In the CN group, higher plasma p‐tau181 correlated with higher CSF p‐tau181 in women (β=0.18, P=0.025), but not men (β=0.025, P=0.75). In the MCI group, higher plasma p‐tau181 was associated with higher CSF p‐tau181 in both men (β=0.22, P=0.001) and women (β=0.56, P<0.001), but the association was significantly stronger in women (z=2.47, P=0.007). In the AD dementia group, higher plasma p‐tau181 was associated with higher CSF p‐tau181 in men (β=0.6, P=0.001) but not women (β=0.33, P=0.19). Our resultConclusionThese findings suggest that in women, associations between p‐tau181 levels in plasma and CSF are strongest early in the disease and weaker at later stages, while the opposite is true for men. Sex should be taken into account when interpreting plasma tau findings, and further investigation into sex‐specific relationships between plasma tau and CSF tau are warranted.
The effects of exercise on blood pressure and cognitive function in older adults with hypertension and subjective cognitive decline
Authors: Silva Narlon Cassio Boa Sorte , Petrella Andrea FM , Gill Dawn P , Owen Adrian M , Petrella Robert J 
Published: December 2021

AbstractBackgroundThe impact of exercise on cognition in older adults with hypertension and subjective cognitive decline (SCD) is unclear. In this study, we examined the influence of high‐intensity interval training (HIIT) combined with mind‐motor training on cognition and systolic blood pressure (BP) in older adults with hypertension and SCD.MethodWe randomized 128 community‐dwelling older adults (age mean [SD]: 71.1 [6.7], 47.7% females) with history of hypertension and SCD to either HIIT or a moderate‐intensity continuous training (MCT) group. Both groups received 15 minutes of mind‐motor training followed by 45 minutes of either HIIT or MCT. Participants exercised in total 60 minutes/day, 3 days/week for 6 months. We assessed changes in global cognitive functioning (GCF), Trail‐Making Test (TMT), systolic and diastolic BP, and cardiorespiratory fitness, using linear mixed regression models for repeated measurements. We also determined whether changes in cardiorespiratory fitness would be associated with changes in cognition and BP using hierarchical regression models adjusting for age and years of education.ResultAfter 6 months, participants in both groups had improved cardiorespiratory fitness (F[1, 69]= 34.795, p < 0.001), TMT A (F[1, 81.51]= 26.871, p < 0.001) and B (F[1, 79.49]= 23.107, p < 0.001). Both groups also had improved diastolic BP (F[1, 87.32] = 4.392, p = 0.039), with greatest effect within the HIIT group (estimated mean change [95% CI]: ‐2.64 mmHg, [‐4.79 to ‐0.48], p = 0.017),but no between‐group differences were noted. Improvement in cardiorespiratory fitness across groups was associated with improved TMT A (unstandardized B = 0.21, p = 0.044), but not TMT B (unstandardized B = 0.002, p = 0.84) or diastolic BP (unstandardized B = ‐0.070, p = 0.58). There were no within‐ or between‐group differences in GCF or systolic BP.ConclusionExercise of high‐ or moderate‐intensity seems to impart modest but positive effects on vascular health and lower‐level cognitive processing. The association between improvements in cardiorespiratory fitness and lower‐level cognition suggest a mechanistic effect. Future research in older adults with hypertension should consider modulating other aspects of exercise training or employ other exercise modalities to benefit cognition.
Machine learning algorithm selects transcripts in blood to distinguish Alzheimer’s disease and other neurodegenerative diseases
Authors: Huseby Carol J. , Delvaux Elaine , Brokaw Danielle , Coleman Paul D. 
Published: December 2021

AbstractBackgroundClinical diagnosis of neurodegenerative diseases is notoriously inaccurate and current methods are often expensive, time‐consuming, or invasive. Simple inexpensive and noninvasive methods of diagnosis could provide valuable support for clinicians when combined with cognitive assessment scores thereby reducing health care costs by ruling out or streamlining additional tests such as imaging. Biological processes leading to neuropathology are reflected in both the central nervous system and vascular peripheral system and progress silently for many years. Because Alzheimer’s disease (AD) symptoms often overlap with common disorders that may be treatable or reversible, an accurate diagnosis at the earliest time is crucial. A blood‐based screen to distinguish and classify neurodegenerative diseases is especially interesting having low cost, minimal invasiveness, and accessibility to almost any world clinic. Additionally, an inexpensive blood panel could also monitor disease progression, for example, marking the advancement beyond mild cognitive impairment (MCI).MethodThe study of blood‐based changes in mRNA gene expression presents a good strategy for differentiating patients of any neurodegenerative disease regardless of the proteins or their post‐translational modifications occurring in disease. Information about features selected for the classification may also guide insight into possible treatment strategies. Using existing public datasets, we developed a machine learning algorithm for application on transcripts present in blood.ResultOur machine learning algorithm generated small sets of transcripts which distinguish a number of neurodegenerative diseases with high sensitivity and specificity.ConclusionNeurodegenerative diseases such as AD are associated with changes in specific molecular pathways and signatures. Using RNA expression as blood biomarkers can also provide information for a pathophysiological relationship with disease and gives us the advantage of using the vast knowledge of gene expression to not only predict disease but also analyze the pathways involved. Our chosen transcripts reveal that neurodegenerative diseases have common themes which after removal bare the unique transcripts of each disease.
Assessing the needs of Black/African American dementia caregivers seeking emotional support
Authors: Fields Julie A , Forsberg Leah K , Knutson Matthew , Seifert Sara J , Farah‐Milller Emily A , Melius Jodi L , Miller Joel K , Knopman David S , Boeve Bradley F , Petersen Ronald C , Kramer Kevin M , Lunde Angela M 
Published: December 2021

AbstractBackgroundBlack/African Americans (B/AA) are nearly twice as likely as White/European Americans (W/EA) to have Alzheimer’s or other dementias and are more likely to provide care for persons with dementia (PwD). Evidence indicates that B/AA desire having someone to talk with who understands their caregiving challenges, yet are less likely than W/EA to ask for support. Further, community resources supporting caregivers’ ability to maintain health and well‐being developed with input from B/AA are lacking. We aimed to determine how a technology‐assisted caregiver matching service designed with user input could address diverse caregiver needs.MethodsFor this Phase I project, 32 caregivers of PwD (31% B/AA) participated in semi‐structured focus groups and completed surveys to provide input regarding characteristics deemed valuable in someone they would choose to be connected with for emotional support. Through an iterative process as new information emerged, a web‐based prototype and matching algorithm were developed.ResultsAge and sex distribution were similar between B/AA and W/EA (71 and 68 yrs; 90% and 86%, respectively). W/EA were most likely caring for a spouse/significant other (73%) whereas B/AA were caring for spouse/significant other (30%), a parent (30%;18% W/EA), a sibling (10%; 0% W/EA), or other (30%; 9%W/EA). Level of emotional support was rated “poor” (50% B/AA, 18% W/EA); “average” (0% B/AA, 14% W/EA); “good” (40% B/AA, 41% W/EA); and “excellent” (10%, 27% W/EA). Characteristics B/AA deemed “very important” or “absolutely essential” for a supportive match included living in close proximity, same ethnicity, similar lifestyle, and common values. Alternatively, W/EA selected similar age, living in close proximity, same sex, similar lifestyle, common values and interests, having the same caregiving relationship, and having the same diagnosis in their PwD (see chart).ConclusionIn this cohort, B/AA reported poorer levels of emotional support than W/EA. B/AA were equally likely to be supporting a spouse/significant other as a parent or other acquaintance, whereas W/EA provided support primarily for a spouse/significant other. Characteristics B/AA and W/EA consider important in a supportive caregiver match show important differences that should be considered when optimizing caregiving resources. Phase II will explore further in a much larger sample.
rPOP: Robust PET‐only processing and quantification of community‐acquired amyloid‐PET from the IDEAS Study
Authors: Iaccarino Leonardo , La Joie Renaud , Koeppe Robert , Siegel Barry A , Hillner Bruce E , Gatsonis Constantine , Whitmer Rachel A. , Carrillo Maria C. , Apgar Charles , Camacho Monica R , Nosheny Rachel L , Weiner Mike W. , Rabinovici Gil D. ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2021

AbstractBackgroundThe Imaging Dementia‐Evidence for Amyloid Scanning (IDEAS) Study collected over 15,000 community‐acquired amyloid‐PET scans, without structural MRI and with different acquisition times, tracers and scanners. Here we describe and validate rPOP (robust PET‐Only Processing), a pipeline for 18F‐Florbetapir (FBP), 18F‐Florbetaben (FBB) and 18F‐Flutemetamol (FLUTE) scans collected in IDEAS.MethodEach image undergoes automatic origin reset to center of mass, spatial normalization based on weighted PET templates (with SPM12) and data‐driven differential smoothing (with AFNI). We received n=740 (514 FBP, 182 FBB, 44 FLUTE) amyloid‐PET scans from the IDEAS–Brain Health Registry substudy (IDEAS‐BHR), with amyloid‐PET local visual reads available for N=663 scans. We performed semi‐quantification via rPOP and estimated neocortical Centiloids after tracer‐specific calibrations using the GAAIN VOIs with whole cerebellum reference. Centiloids were calculated for clinical groups (MCI or dementia), to compare rPOP‐based amyloid‐status (centiloids≥24.4) with visual reads. The pipeline was validated with n=1518 ADNI scans (n=1249 FBP, n=269 FBB), using MRI‐based amyloid‐status as a reference and testing the associations between rPOP‐ and MRI‐based centiloids.ResultrPOP successfully processed N=2233/2258 (98.9%) scans in the first pass, with N=24/25 warping‐related failures rescued with a manual reorientation and origin reset prior to warping. In IDEAS‐BHR, we observed the expected centiloids distribution (Figure 1A‐B) both according to visual reads and also stratifying by clinical stage amyloid‐negative, i.e. mean±sd Centiloids MCI/Dementia: 2±23/‐5±27; amyloid‐positive: MCI/Dementia: 65±42/80±37. There was high concordance (Table 1) between rPOP‐based amyloid status and both local visual reads (IDEAS‐BHR, Cohen’s k=0.72 [0.7‐0.74], ∼86% concordance). Very high concordance was also observed in the ADNI dataset (k=0.88 [0.87‐0.89], ∼94% concordance), with rPOP‐ and MRI‐based Centiloids being strongly linearly associated (R2:0.95, p<0.001), with a tighter relationship in images with better resolution (β= ‐0.016, p<0.001).ConclusionWith rPOP, we successfully derived Centiloids quantification from heterogeneous IDEAS amyloid‐PET scans and validated the pipeline with ADNI scans acquired in a research setting. These data show that community‐acquired amyloid‐PET scans can be successfully analyzed, enabling joint efforts by clinical sites and research centers.
Association of neighborhood socioeconomic disadvantage and cognitive decline
Authors: Marsh Karyn , Shao Yongzhao , Zhang Yian , Masurkar Arjun V , Vedvyas Alok , Chodosh Joshua 
Published: December 2021

AbstractBackgroundThere is increasing emphasis on research recruitment of persons of color to understand the influence of race/ethnicity on Alzheimer’s disease (AD) and AD‐related dementia (ADRD) risk. Normal persons with subjective cognitive decline (SCD) are considered at risk for future decline as SCD is thought to be a preclinical stage of AD/ADRD. Yet the validity of SCD across racial and ethnic groups is unclear. Race/ethnicity‐related conditions such as socio‐economic disadvantage, neighborhood segregation, and poor housing quality (neighborhood deprivation) are important factors in stress, discrimination and other social determinants of health and may provide more in‐depth explanations for SCD than race/ethnicity alone.MethodWe examined the role of neighborhood deprivation and compared this to the role of race/ethnicity in SCD using a validated instrument, the Brief Cognitive Rating Scale (BCRS). Using the Area Deprivation Index (ADI), we cross‐sectionally examined the relationship between neighborhood characteristics and SCD in a racially and ethnically diverse group of community‐residing older adults in New York City. For those having available addresses, we used data from participants with normal cognition in the NYU Alzheimer’s Disease Research Center (n=313) and conducted multivariable logistic regressions, comparing two models with the BCRS as our outcome: using the ADI without race/ethnicity and then with race/ethnicity, both adjusting for age, sex, education (years).ResultParticipant mean age was 72.8.0 ± 7.4 years; mean education was 16.3± 3.1 years. Seventy‐six percent of the cohort was female (n=232); 12.1% (n= 38) reported as Hispanic, 73.5% (n=230) non‐Hispanic (NH) White; 13.4% reported as NH Black or African‐American (n=42); and 3 were other. In multivariable logistic regressions of BCRS domain‐specific analysis, ADI was a significant predictor of BCRS‐measured SCD even when race/ethnicity was included as a covariate (p<0.05), suggesting independent influence of neighborhood deprivation.ConclusionNeighborhood characteristics may play an influential role in SCD regardless of race/ethnicity and thus are likely important risk factors for AD/ADRD. If larger and more diverse studies generate similar findings, neighborhood investment and recruitment goals for AD/ADRD studies will require more focus on neighborhoods with greater deprivation.
Comparison of plasma and CSF biomarkers across ethnoracial groups in ADNI
Authors: Windon Charles , Iaccarino Leonardo , Allen Isabel Elaine , Boxer Adam L. , Byrd Desiree , Okonkwo Ozioma C. , Weiner Mike W. , Mindt Monica Rivera , Rabinovici Gil D. 
Published: December 2021

AbstractBackgroundDifferences in CSF and plasma Alzheimer’s disease biomarkers between African Americans (AA), Latinos (LA), and non‐Hispanic Whites (NHW) have been reported. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) may offer insights into ethnoracial biomarker differences important for understanding disease trajectory variations among diverse populations.MethodWe queried the ADNI database for all participants with available plasma pTau181 and NfL (Simoa) and linked CSF biomarkers within 1 year of blood draw (Aβ42, pTau181, T‐tau, Elecsys). Baseline data for 47 AA and 43 LA with plasma biomarkers were matched to separate groups of NHW (1:3 nearest neighbor matching on propensity score), considering age, sex, education, CDR, APOE ε4 alleles and family history of dementia (Table 1). Cross‐sectional analyses compared biomarker levels between matched cohorts without (non‐parametric Mann‐Whitney U‐test) and with adjustment for demographics, clinical, biomarker, and medical characteristics (multi‐linear regression). Statistical threshold was set at two‐tailed p<0.05.ResultUnadjusted comparisons between AA and NHW revealed no significant differences in plasma NfL [29.3 (IQR: 21.6‐42.5) vs 35.5 (27.0‐49.6), p=.12], plasma pTau181 [14.5 (9.4‐22.9) vs 15.5 (10.1‐22.8), p=.83], CSF Aβ42 [933.1 (649.5‐1590.8) vs 926.7 (677.7‐1697.8), p=.83], CSF T‐tau [214.6 (152.4‐290.7) vs 251.9 (194.5‐351.4), p=.17] or CSF pTau181 [19.6 (14.4‐27.3) vs 22.7 (17.0‐33.3), p=.32] (Fig. 1a‐b). No significant differences were identified in any of the biomarkers after adjustment for relevant covariates. Unadjusted comparisons between LA and NHW revealed no significant differences in plasma NfL [36.7 (24.4‐50.4) vs 35.6 (25.6‐47.1), p=1], plasma pTau181 [18.0 (11.3‐25.0) vs 15.7 (10.9‐23.4), p=.81], or CSF Aβ42 [852.7 (787.1‐1213.0) vs 951.6 (651.1‐1530.5), p=1]. A trend towards lower CSF T‐Tau [216.5 (147.1‐270.5) vs 257.2 (197.2‐360.9), p=.076] and CSF pTau181 [19.4 (13.6‐27.9) vs 24.7 (17.5‐33.4), p=.076] in LA was observed (Fig. 2a‐b). After adjustment for covariates, LA were found to have significantly lower levels of CSF T‐tau (β=0.154, p<.05) and CSF pTau181 (β=0.164, p<.05), while differences in plasma markers were not significant.ConclusionNo significant biomarker differences between AA and NHW were observed. Lower CSF pTau181 and CSF T‐Tau in LA compared to NHW after covariate adjustment may represent subtle differences driven by biological factors or unmeasured sociocultural determinants (income, occupation, neighborhood environment); larger studies are needed.
Study design of gamma sensory stimulation at multiple dose levels in MCI patients
Authors: Hempel Evan , Hajos Mihaly , Williams Martin , Malchano Zach 
Published: December 2021

AbstractBackgroundNon‐invasive gamma sensory stimulation has been demonstrated to have beneficial effects on the hallmarks of AD pathophysiology in transgenic mouse models of AD. The Etude clinical trial is a translational clinical study examining dose‐ranging, safety, tolerability, and potential benefits of gamma sensory stimulation as a novel, non‐invasive treatment for Alzheimer’s disease.MethodTwo cohorts were planned to evaluate tolerability, safety and therapeutic effects by dose with results from the first cohort guiding dose escalation for the second. In the first cohort, 10 subjects were randomized to receive once or twice daily therapy for 12 months. When therapy was completed, safety and tolerability, as well as symptom progression, was evaluated and the second cohort was initiated; 3 subjects were enrolled at twice daily 1‐hour therapy for 12 months. All subjects received 40Hz audio‐visual therapy (Cognito Therapeutics, Cambridge MA) at home with assistance from a caregiver. Key criteria for subject enrolment were: adults 50 years and older, MMSE 24‐30, MCI due to AD diagnosis per NIA‐AA criteria, and an amyloid‐positive PET scan. Subjects were excluded for history of seizure, memantine use, alternate causes of cognitive impairment or MRI findings that prevented PET SUVr processing. Subjects were followed for safety, tolerability and changes to symptoms via clinical assessments, phone assessments, and electronic treatment diary. Tolerability was measured by device use, including treatment diary and device‐reported data, Zarit burden interview, and structured interviews at pre‐planned time points. Clinical progression was measured using MMSE, ADAS‐Cog, CDR, NPI, Clock‐Drawing Test, ADL, and QOL. Quantitative EEG, actigraphy, amyloid PET, volumetric MR are evaluated at regular intervals throughout the study as biomarkers.ResultThirty‐seven subjects were screened and 13 enrolled, of whom none terminated early and 3 are still active. An open‐label extension year was added to the protocol and 70% of subjects chose to re‐enroll. Review of MR imaging noted no ARIA and there were no unexpected related serious adverse events. Results on symptomatic and biomarker changes are being analyzed.ConclusionWe describe the design and methods of a translational dosing study which evaluates a novel therapeutic modality. All evaluated dosing regiments were safe and well‐tolerated by subjects.