bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial biological evaluations of a novel microtubule‐based PET ligand in Alzheimer’s disease
Authors: Damuka Naresh , Orr Miranda E. , Macauley Shannon L. , Shively Carol A. , Lockhart Samuel N. , Bansode Avinash , Kim Jeongchul , Frye Brett M. , Register Thomas C. , Mintz Akiva , Whitlow Christopher T. , Craft Suzanne , Solingapuram Sai Kiran K. 
Published: February 2022

AbstractBackgroundMicrotubule (MT) integrity is critical for cell function and viability. Abnormal MT‐stability in AD is commonly attributed to hyperphosphorylation of the MT‐associated protein, tau. However, the time course of MT instability in disease progression remains unknown. In vivo MT imaging offers an opportunity to gain critical information on MT changes in relation to staging of ADRDs. Our lab reported the first brain‐penetrant MT PET ligand, [11C]MPC‐6827 and evaluated in vivo imaging in normal rodents and non‐human primates (NHP). Herein we report its initial biological evaluations in (a) neuronal cells, (b) tau knock‐out mice, and (c) aged NHPs (Caribbean‐origin vervets) with changes in AD‐related biomarkers.MethodIn vitro [11C]MPC‐6827 cell uptake assay was performed in patient‐derived SH‐SY5Y cells with different MT destabilizing and stabilizing agents. Radioactive binding efficiency was determined as %ID (injected dose)/mg of protein present in each well. Dynamic 0‐60 min brain microPET/CT imaging was performed in tau knock‐out and wild type mice (n=4). Four vervets (20‐29y) with different cerebrospinal fluid (CSF) Aβ42 levels (2 high levels‐1461, 1614 and 2 low levels‐579,732) underwent 0‐120 min brain PET/CT imaging with [11C]MPC‐6827. ROIs were drawn on the whole‐brain and SUVR values were calculated from co‐registered PET/MR images.ResultIn vitro cell uptake assays with [11C]MPC‐6827 in SH‐SY5Y cells displayed high uptake with MT destabilizing agents and low uptake with stabilizing agents. MicroPET imaging demonstrated higher radioactive brain uptake in tau knockout over wild‐type mice. Vervets with low CSF Aβ42 levels showed high radioactive brain uptake and the youngest vervet (20y) displayed lowest brain uptake.ConclusionConsistent with our in vitro cell uptake and in vivo rodent imaging experiments, [11C]MPC‐6827 increased with MT destabilizations. Radioactive uptake was inversely related to CSF Aβ levels and directly related to age in a NHP model of AD (Fig 1). Collectively our data suggest that [11C]MPC‐6827 is more selective towards destabilized MTs. On‐going experiments include rigorous PET imaging analyses, determination of metabolic plasma‐blood parameters, and correlations with Aβ42 and tau levels. Nonetheless, our promising results support the high translational utility of [11C]MPC‐6827 to image MTs in ADRDs.
Understanding proxy decision‐makers’ perspectives of frailty and frailty tools to support decision‐making for persons with dementia
Authors: Shapkin KImberly , Bent Haley , Callaway Lorna , Cooper Mary Elizabeth , Randhawa Sukhjeet Kaur , Murphy Angela , Lazar Faye , Cuthbert Colleen 
Published: February 2022

AbstractBackgroundProxy decision‐makers’ for persons with dementia (PwD) have identified feeling uninformed about the prognosis and progression of dementia and unsupported by healthcare professionals. One aim of our study was to explore how frailty is understood and if frailty tools may assist with decision‐making.MethodWe conducted a qualitative inquiry using focus groups to explore decision‐makers understanding of frailty and their perspectives of using frailty tools. Proxy decision‐makers were identified as formal agents of a PwD. Focus groups were recorded and transcribed verbatim. Data was analyzed and interpreted using thematic analysis.ResultAnalysis revealed the prevailing theme to be, frailty is understood as a mosaic. Decision‐makers’ primarily consider frailty a physical phenomenon, closely paralleling Fried’s (2000) frailty phenotype: weight loss, low activity, slow gait, weakness and fatigue. Participants also associated frailty with cognitive decline and emotional instability. Applying the term frailty to PwD produced an ambivalent response in participants, although the term itself was considered as acceptable to describe physical decline. Participants valued the Clinical Frailty Scale to aid in the understanding of the progression of physical decline, but felt the limited recognition of cognitive decline was a barrier. The fluctuating course of dementia also limited the utility of using a tool with fixed categories.ConclusionFrailty is a recognizable term to proxy decision‐makers, but is understood in a variety of ways, primarily as a physical phenomenon. Given the ambivalence in using this term and decision‐makers’ focus on cognitive changes, discussing frailty has little to add to improve supporting decision‐making in dementia.
Apolipoprotein ε genotype modifies the association between blood‐brain barrier permeability and both grey and white matter integrity in older adults
Authors: Schimmel Samantha J. , Shashikumar Niranjana , Pechman Kimberly R. , Gifford Katherine A. , Landman Bennett A. , Blennow Kaj , Zetterberg Henrik , Hohman Timothy J. , Jefferson Angela L. , Moore Elizabeth E. 
Published: February 2022

AbstractBackgroundBlood‐brain barrier (BBB) permeability has been implicated in Alzheimer’s disease and is associated with decreased cerebral blood flow and cognitive impairment. However, associations between BBB permeability and structural brain changes remain unknown. This study relates the cerebrospinal fluid (CSF)/plasma albumin ratio, a proxy measure for BBB permeability, to grey matter volumes and white matter integrityMethodVanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=148, 72±6 years, 41% female, 32% apolipoprotein E (APOE) ε4 positive) underwent fasting lumbar puncture for CSF sampling and blood draw for plasma sampling. Participants underwent 3T T1‐weighted imaging to quantify grey matter volumes and diffusion tensor imaging (DTI) to quantify white matter integrity. Voxel‐wise analyses using non‐parametric permutations cross‐sectionally related the CSF/plasma albumin ratio to DTI metrics, adjusting for demographic and health variables, diagnosis, and APOE‐ε4 status. Linear regressions related the CSF/plasma albumin ratio to grey matter volumes, adjusting for identical covariates plus intracranial volume. Follow‐up models tested interactions with APOE‐ε4 status.ResultIn the entire sample, the CSF/plasma albumin ratio was unrelated to grey matter volumes and white matter integrity (p‐values>0.28) but interacted with APOE‐ε4 status on total grey matter (p‐value=0.02), frontal lobe (p‐value=0.01), and occipital lobe volumes (p‐value=0.04). Stratification suggested a higher CSF/plasma albumin ratio, indicating impaired BBB function, related to smaller grey matter volumes among APOE‐ε4 carriers. The CSF/plasma albumin ratio also interacted with APOE‐ε4 status on white matter integrity in the temporal and frontal lobes (p‐values<0.05), with associations present in APOE‐ε4 non‐carriers.ConclusionIncreased BBB permeability is associated with decreased grey matter volume in APOE‐ε4 carriers, specifically in the frontal and occipital lobes. APOE‐ε4 may act as a vascular modifier in these regions, such that increased BBB permeability exacerbates underlying neurotoxicity and neurodegeneration. In contrast, the association between increased BBB permeability and compromised white matter integrity is driven by APOE‐ε4 non‐carriers. Taken together, these results suggest that BBB permeability may be an etiology of neurodegeneration in APOE‐ε4 carriers and highlight the importance of APOE‐ε4 status when studying BBB effects on brain health.
Spousal dementia caregivers' use of technology during the COVID‐19 global pandemic: Lessons learned from the NYU family support program
Authors: O'Connor Maureen K , Donley Tiffany , Salant Rebecca , Nicholson Roscoe , Epstein Cynthia , Nguyen Andrew Huy , Stevenson Elizabeth , Shirk Steven , Mittelman Mary S 
Published: February 2022

AbstractBackgroundDaily routines have been drastically impacted by COVID‐19, including healthcare appointments, home services, and many recreational opportunities. Spousal dementia caregivers (CGs) are particularly vulnerable during COVID‐19, as many rely on family members, daycare, in‐home assistance, and other respite opportunities. We conducted qualitative interviews in May/June 2020 to understand the impact of COVID‐19 on dementia CGs and how they experienced the switch of all the NYU ADRD Family Support Program (FSP) services to telehealth.MethodA total of 10 spousal CGs participated in videoconference interviews about their COVID‐19 experiences and the FSP’s transition to the telehealth format. Semi‐structured interviews were conducted by one of two interviewers who were external to the FSP to encourage freedom of discussion. All sessions were recorded and transcribed. De‐identified transcripts were coded by two independent coders using NVivo, with discrepancies resolved by a third researcher.ResultCGs ranged in age from 54 to 86; 7 were female, 8 were non‐Hispanic White, and 2 were Black. All were New York City residents living with the person with dementia; 2 households had additional adult family members. Qualitative analysis revealed several major themes related to COVID‐19 experiences: fears surrounding COVID‐19 and staying healthy; changes in daily routines; the impact of reduced respite and support services; adaptation to technology that enabled increased contact with family/friends. Feedback about the telehealth adaptation of the FSP included observations about new group dynamics and decreased barriers to involvement due to the ability to participate from home, reducing the need for transportation and other logistics related to traveling.ConclusionDespite significant challenges due to COVID‐19, CGs reported benefit and support from the FSP in the new telehealth format. One participant described the FSP as “indispensable” and expressed how much members relied on each other during COVID‐19. In addition, we learned that the telehealth FSP not only served as a source of support during the crisis but that there were perceived advantages to this format, including reductions in barriers to in‐person services (finding transportation, travel time, getting respite care for the person with dementia). We recommend continuing the option of telehealth services for dementia CGs after the COVID‐19 crisis.
Socio‐psychological impact of COVID‐19 on a diverse cohort of older adult research participants in New York
Authors: Loizos Maria , Sewell Margaret , Neugroschl Judith A , Zhu Carolyn W , Li Clara , Zeng Xiaoyi , Pun Kelly , Velasco Nelly , Tocco Carly , Sheppard Faye , Ardolino Allison , Meuser Caroline , Greenberg Jonathan , Evans Kirsten , Kinsella Michael T , Aloysi Amy , Grossman Hillel , Sano Mary 
Published: February 2022

AbstractBackgroundDuring the spring of 2020, New York was overwhelmed by COVID‐19 and older adults as well as ethnic minorities were disproportionately affected. The Alzheimer’s Disease Research Center (ADRC) located in East Harlem in New York City, serves a predominantly low income, Latinx community. It was imperative to gauge the impact of COVID‐19 on our diverse group of older adult research participants.MethodParticipants enrolled in the ADRC with a Clinical Dementia Rating Scale of 0 (75%) or .5 (24%) completed evaluations between May and December 2020 for the National Alzheimer’s Cooperative Center Uniform Data Set (NACC UDS) and were administered a 33‐item COVID‐19 questionnaire over the telephone that was modified from the questionnaire provided by NACC. The 15–20 minute survey asked questions about social, psychological, and emotional experiences with COVID‐19, including whether they had lost a loved one to COVID, as well as items targeting the psychological sequelae of the pandemic (depression, isolation, a sense of loss of control, for example).Result198 participants completed the questionnaire. Of these, 55% were non‐Hispanic White, 15% were non‐Hispanic Black, 14% were Hispanic, and 16% were Asian. The overall sample’s mean age was 76.4±7.5, mean education 15.80±3.1years, and 62.6% were male. Survey results indicated that 89% felt the pandemic had been disruptive to their lives, and 30% had lost a loved one to COVID. Sixty‐three percent of participants reported being in touch remotely with friends or family nearly every day, and 24% 2‐3x/week. Thirty two percent reported feeling they could not control important things in their life and feeling anxious (46%), bored (41%), and lonely (30%). Twenty seven percent reported feeling depressed and 23% experienced sleep problems.ConclusionIn this diverse sample of community dwelling older adults, most were able to remain in close contact with family and friends, and many reported the pandemic as disruptive. However, fewer reported experiencing a loss of control as well as psychological or emotional distress (i.e., depression) which may reflect adaptive mechanisms worthy of further study.
Visual entrainment responses are altered in patients with mild cognitive impairment and Alzheimer’s disease
Authors: Springer Seth D. , Wiesman Alex I. , May Pamela E. , Schantell Mikki D. , Christopher‐Hayes Nicholas , Johnson Hallie J. , Willet Madelyn P. , Eastman Jacob A. , Wolfson Sara L. , Johnson Craig M. , Murman Daniel L. , Wilson Tony W. 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia in later life. AD is histologically characterized by the accumulation of extracellular amyloid‐β (Aβ) plaques and intracellular hyperphosphorylated‐tau neurofibrillary tangles. Recent research has indicated that visual entrainment may be useful in clearing Aβ‐ and tau‐load in the central nervous system in mouse models of AD. However, human studies in this area are rare and the degree to which patients with AD exhibit aberrations in visual entrainment are unknown, as is the impact of entrainment on amyloid and tau‐load.MethodWe recorded magnetoencephalography (MEG) during a 15‐Hz visual entrainment paradigm in amyloid‐positive patients on the AD spectrum and compared their neural responses to biomarker‐negative, demographically‐matched, cognitively‐normal controls. MEG data were imaged using a beamformer and virtual sensor data were extracted from the peak responses.ResultOur results indicated that participants on the AD spectrum exhibited significantly stronger entrainment relative to baseline in primary visual cortices. However, interestingly, the two groups exhibited roughly equal absolute levels of entrainment, which suggests lower spontaneous levels of 15‐Hz activity in the AD spectrum group. Additionally, we found that higher absolute levels of entertainment predicted greater MoCA scores.ConclusionThis pattern of results indicates that the increased entrainment in patients on the AD spectrum was compensatory and that those patients who were closer to the level seen in controls had better cognitive performance. Overall, these results indicate that entrainment may be altered in humans with AD and should be further examined in future studies.
Exploring older adults' experiences using technology during a viral pandemic
Authors: Barber Justin M , Scherer Sally , Rhodus Elizabeth K , Kelly Parsons R , Johnson Julia , Hall Megan , Snyder Katherine , Coy Beth , Boggess Bailee , Lowry Kimberly , Shaffer Andrea , McRoberts Tyler , Jicha Gregory A , Gibson Allison , Bardach Shoshana H 
Published: February 2022

AbstractBackgroundOlder adults are at greater risk for morbidity and mortality associated with COVID‐19. Spatial distancing and sequestering practices are recommended to limit viral exposure. Older adults adopting these practices are at increased risk of social isolation and adverse health outcomes. Remote technologies offer various platforms for satisfying socialization and healthcare needs while sequestering. Understanding how older adults are using technology has implications for wellbeing during a pandemic.MethodResearchers attempted to contact all participants enrolled in the University of Kentucky Alzheimer's Disease Research Center longitudinal study via telephone to survey technology use (n = 706). Participants were contacted directly, except for demented participants, whose primary caregivers were contacted to respond on their behalf, when possible. Participants and caregivers gave their assent verbally to complete the voluntary survey, the procedures of which were approved by the IRB. The surveys consisted of validated instruments to gauge the extent of use of and comfort with technology. Spearman correlations, chi‐square tests, and t‐tests were used to explore data.ResultUltimately, 384 participants were reached and 332 consented to participate. Most reported reliable home internet access (91.5%) and some internet use (90.6%). Recent feelings of loneliness were not related to any technology‐related variables (all ps > 0.29) other than decreasing with greater willingness to use telehealth (Rho = ‐0.11, p = 0.06). Those who reported a lack of comfort with technology (n = 76) were less likely to text messaging (67% vs 78%) and social media (56% vs 69%), ps ≤ 0.06, but felt socially connected using technology at similar levels (82% vs 75%), p = 0.22. Nearly 70% of this group reported they would use technology more with training. Across all participants, willingness to use telehealth was not related to frequency of frustration with tech (Rho = 0, p = 0.99).ConclusionThe results suggest that some older adults’ use of technology is limited by familiarity. Lack of familiarity does not appear to create a barrier to using telehealth nor does frustration with technology appear to limit telehealth use. The findings have implications for supporting older adults sequestered during a pandemic but potentially more broadly.
Frailty syndrome in early‐onset autosomal dominant Alzheimer disease, in the PSEN1‐E280A kindred
Authors: Garcia‐Cifuentes Elkin , Aguillon David , Velez Juan Esteban , Gómez Manuela , Gómez‐Henck Clara , Deossa‐Restrepo Gloria , Saldarriaga Jonathan , Jaramillo‐Jimenez Alberto , Ciro Jorge Alberto Osorio , Borda Miguel German , Cano‐Gutierrez Carlos Alberto , Lopera Francisco 
Published: February 2022

AbstractBackgroundDementia has become a healthcare priority. As no disease‐modifying treatment is available, treatment is aimed to act through prevention. Frailty have been defined as a geriatric multidimensional syndrome. Being a treatable condition, interest has raised to describe the relationship between Dementia and Frailty. This study describes frailty in the Autosomal Dominant Alzheimer Disease, through the largest ADAD known group.MethodA total of 75 participants (14 with MCI and 61 with Dementia) were included in this cross sectional study. They underwent a complete assessment that included a standardized clinical examination, neuropsychological evaluation and functional scales. Frailty was assessed through the Short Physical Performance Battery (SPPB) and the Time up and Go Test (TUG) . Multivariate analyses was conducted to evaluate which variables were associated with being frail in presenile onset of ADAD.ResultIn the 75 patients who underwent the study, median age was of 49 years old with a cognitive profile of 18.67 % individuals with MCI, 21 % with Mild, 28 % with Moderate and 25 % Severe Dementia. According to the frailty phenotype: 60 % were non‐frail and 40 % frail. When analyzing, SPPB and TUG components: Median Gait Speed in MCI and mild dementia groups were statistically significantly lower than moderate and severe dementia (p< 0.005) and significantly greater TUG was found in moderate and severe dementia groups when compared with MCI and mild dementia(p<0.005) Both, clinical severity grouped in moderate – severe dementia (OR 6.85; CI 2.07‐22.65 p< 0.000) and hypertension (OR 5.80; CI1.56‐21.49 <0.002) are significantly associated with being frail.ConclusionThis study is the first description of frailty syndrome in ADAD with a presenile onset. The prevalence found in this population is similar than in previous reports in older adults and thus reasserts the adaptability of frailty evaluation in young patients with special clinical conditions. Our data supports the existing relationship between frailty and dementia. As the cause of dementia in our patients is purely genetic, effects of aging are controlled and excluded. This enrich science and lights up the search of new mechanisms linking both conditions.
The dementia journey survey: A community engagement approach for inclusivity in dementia care research
Authors: Iroanyah Ngozi Faith 
Published: February 2022

AbstractBackgroundApproximately 560,000 people live with dementia (PLWD) in Canada, yet research on the experiences of ethnoculturally diverse people with dementia is largely unknown. As a result, healthcare programs and services do not reflect the dementia related needs of these communities. Additionally, 60% of primary care physicians indicated feeling uncomfortable supporting patients with dementia, despite being the first point of access for additional dementia healthcare. To address these gaps, a national collaboration was developed by the Alzheimer Society of Canada (ASC) and the College of Family Physicians of Canada (CFPC) to understand more diverse experiences of PLWD with their healthcare providers.MethodUsing a mixed methods design, paper and online surveys were created for PLWD and caregivers, and online surveys were created for family physicians. CFPC registered family physicians were invited to participate through professional channels. PLWD, and caregivers were recruited through Alzheimer Society provincial chapters and community partners. To ensure inclusivity of underrepresented populations, a targeted community engagement strategy was developed to connect with members of various ethnocultural groups across Canada using a multi‐tiered selection process of cultural community‐based organizations. Qualitative analysis will include thematic analysis using a standard process to code data and generate themes. Quantitative analysis will use descriptive statistics.ResultThis survey is the first of its kind in Canada that investigates the relationships between PLWD and caregivers with their primary health providers and utilizes a defined and consistent approach to community outreach and engagement. The survey bridges the knowledge gap in dementia care research, focusing on inclusivity of ethnocultural communities which has resulted in increased uptake of the survey and will provide richer data for resource creation.ConclusionFindings from the survey will inform the ASC‐CFPC collaboration in creating resources to increase physician comfort with managing all patients with dementia. It will also guide the development of new resources and educational materials for PLWD and caregivers. The community engagement strategy will help create and strengthen community relationships with ethnoculturally diverse communities through a mutual knowledge sharing and community building.