bluuebunny/crossref_metadata_2025 huggingface dataset:
User evaluation of registry‐supported recruitment: The Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) Research and Education (CARE)
Authors: Tzuang Marian , Grill Joshua D , Tsoh Janice Y. , Huang Daren , Nam Bora , Gallagher‐Thompson Dolores , Hinton Ladson , Meyer Oanh L. , Park Van Ta
Published: January 2025

Background

The Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) Research and Education (CARE) is a recruitment registry that has enrolled over 10,000 AANHPI participants who expressed willingness to participate in Alzheimer’s disease and related dementias (ADRD), aging, caregiving, and other health research. We report survey results from 24 of the 28 study principal investigators (“users”) who utilized CARE between January 2021 and October 2023 to support their study recruitment.

Method

Users answered five questions on a 4‐point Likert scale (0 = Strongly disagree to 3 = Strongly agree) related to (1) user experience, (2) usefulness in accelerating recruitment, (3) improving AANHPI representation, (4) whether they would use the registry again, and (5) whether they would recommend the registry to others. The survey also included open‐ended questions for suggestions to improve the registry and collect information on products (e.g., publications) for each of the CARE‐supported studies.

Result

Among 24 CARE‐supported studies with available user survey data, 14 (58%) were related to ADRD or dementia caregiving, 10 (42%) recruited specific AANHPI sub‐groups (e.g., Chinese, Korean), and 10 (42%) were funded by the National Institutes of Health. Half of users learned about CARE through word of mouth. All users agreed or strongly agreed they would recommend the registry to others and that the referral request process was well‐organized. Also, 83% and 93% agreed or strongly agreed that CARE accelerated their study recruitment and improved the representation of AANHPI participants in their study, respectively. Lastly, 96% of users agreed or strongly agreed they would submit a referral again for future research. Open‐ended responses identified several study‐level characteristics (e.g., in‐person requirement, stringent eligibility criteria) of the referred studies as challenges to successful recruitment from the registry. Collectively, these studies have produced 12 peer‐reviewed publications and 32 abstracts at professional conferences.

Conclusion

Users overall reported positive experiences with the referral process and indicated that CARE can aid recruitment and diversify study samples. CARE provides a promising recruitment source to support studies seeking to include AANHPI participants.
Feasibility and acceptability of APOE genotyping in Dutch Brain Research Registry participants
Authors: Waterink Lisa , van der Lee Sven J , Nijland Daphne , Visser Leonie N.C. , Pijnenburg Yolande A.L. , Sikkes Sietske A.M , van der Flier Wiesje M. , Zwan Marissa D.
Published: January 2025

Background

Participant recruitment for Alzheimer’s disease (AD) research and clinical trials is challenging. Online registries can be used to identify and pre‐screen eligible participants. Additional APOE genotyping has the potential to better identify individuals at‐risk for AD. Our goal was to assess feasibility and acceptability of APOE genotyping in cognitively‐normal, older registrants of Dutch Brain Research Registry (DBRR).

Methods

9,511 registrants over the age of 50 with no self‐reported diagnosis of mild cognitive impairment or dementia were invited for APOE genotyping. Registrants were informed that they would not receive their results, yet that results may be used to pre‐screen participants for future studies for which it might be relevant to learn their genetic risk. After providing consent on an elaborate online informed consent procedure including a video, participants were enrolled, and received a buccal swab at home. Feasibility was measured in response rate (%interested/invited), enrolment rate (%enrolled/interested), and completion rate (%returned swabs/enrolled). To assess acceptability, participants answered online questions about our information provision, the project’s aim, and motivation for study participation. APOE genotyping is currently ongoing.

Result

3,393 registrants were interested (35% response rate), of which 3,158 actually enrolled (93% enrolment rate; 57% female; median age [IQR] = 68 [63, 73]), and 2,602 successfully returned the buccal swab (82% completion rate; Figure 1). 20% of enrolled registrants report having subjective memory complaints, and 45% had a first‐degree relative with dementia. Of 1,065 registrants that declined participation, 344 registrants provided reasons which were mostly time related (n = 104;30%), health‐issues (n = 61;18%), or wanting to receive results of APOE genotyping (n = 59;17%). Only 8% (n = 26) replied not wanting to learn their genetic risk. Among the enrolled registrants 2,093 filled out the survey, of which the vast majority was content with our information provision (87‐97%), and had good comprehension about the project’s aim (91‐98%). Most endorsed reasons to participate was ‘to contribute to scientific research’ (97%) and ‘to participate in future research to learn their genetic risk of dementia’ (34%).

Conclusion

Our results suggest that APOE genotyping within an online research registry is feasible and well received for pre‐screening to accelerate inclusion for preclinical AD trials.
Social, environmental, and cognitive correlates of community‐dwelling older adults coping poorly with reduced social contact: A quasi‐experiment set in Australia’s COVID‐19 lockdown in 2020
Authors: Chander Russell J , Numbers Katya T. , Chen Rory , Samtani Suraj , Kochan Nicole A. , Brodaty Henry , Sachdev Perminder S.
Published: January 2025

Background

The effects of the COVID‐19 pandemic extend beyond the viral impact and include social and psychological effects of the ensuing lockdowns and restrictions. Australia’s lengthy lockdowns present an opportunity to study changes in the physical and mental wellbeing of older adults resulting from extended social isolation, a known risk factor for dementia, in the absence of high infection or mortality rates.

Method

Sydney Memory and Ageing Study, Sydney Centenarian Study, and CogSCAN study participants were mailed questionnaires about in‐person and remote social contact and access to resources during the 2020 Sydney lockdown. Responses were linked to existing medical history and cognitive status data from 2018‐2019. Respondents were classified based on self‐reported poor outcomes (PO), defined as feeling worse because of the pandemic in three domains: overall health, emotional and psychological health, and physical activity. Cognitive impairment was defined as presence of DSM‐V neurocognitive disorders as determined by clinical consensus, MMSE <27, or ACE‐III <88. Factors associated with PO were explored.

Result

Of the 335 participants who responded to the COVID‐19 questionnaire by January 2021, 75 (22.4%) met criteria for cognitive impairment. None of the respondents reported ever being symptomatic at the time of study. Only 19 (5.7%) personally knew someone who had COVID‐19. Most (156, 46.7%) participants had no POs, 112 had one, and 67 had two or more. Cognitive status was not associated with POs. Compared to no POs, PO participants actively reduced in‐person contact, overall social contact, had more difficulty accessing food and medical resources. Despite PO participants communicating more frequently with friends and family by phone, and reporting having changed their social support, they also had lower scores in questionnaires for life satisfaction and loneliness.

Conclusion

Older adults who reported poorer outcomes during lockdown had greater reduced social contact. Despite efforts to adapt their social support networks through increased phone‐based social interactions, they still reported worse life satisfaction and more loneliness. Difficulties in adapting to changing social circumstances and isolation may confer a greater susceptibility to loneliness. Further work is needed to understand the relationship between susceptibility to loneliness and future dementia risk.
Instruments to measure the roles, experiences, and identities of caregivers of individuals with Alzheimer’s disease and related dementias: A scoping review
Authors: Dowling Maritza , Rook Erin , Klenczar Brittany , Hancock Kari A. , OHala Max , Yamada Cody , Mendizabal Stephanie , Anderson Joel G , Flatt Jason D.
Published: January 2025

Background

The growing number of people living with Alzheimer’s disease and related dementias (ADRD) has led to an increased interest in the experiences of informal caregivers. Effective instruments to measure both negative and positive aspects of caregiving and validated with diverse caregiver populations, are needed to inform the design and evaluation of targeted interventions. This study (a) reviews extant literature on instruments developed to measure the range of roles and experiences of unpaid caregivers of people living with ADRD, (b) describes characteristics of the populations used to validate these instruments, and (c) discusses the usefulness, applicability, and generalizability of current measures

Method

A scoping review was performed following the methodological framework of Aromataris and Munn (2020). In November 2023, five databases (PubMed, Scopus, Embase, PsycINFO, CINAHL) were searched including publications from 1980‐2023. We included studies that (a) described the development of instruments to assess informal (unpaid) ADRD caregiver experiences, (b) discussed their psychometric properties, and (c) described the sample used in the validation process. Covidence software was used to screen the retrieved studies and relevant data were extracted and summarized using an a priori data extraction tool.

Result

The search yielded 11,928 articles; 90 met inclusion criteria. The majority of instruments measured negative aspects of caregiving (burden, hassles, psychological distress, strain, dysfunctional thoughts, isolation, grief) although a growing number of instruments focused on positive aspects of caregiving (personal growth, self‐actualization, rewards and satisfaction, resilience, hope, self‐efficacy, reciprocity). The psychometric rigor of the instruments varied widely with most samples being relatively small and mainly including spouses or children, possibly limiting generalizability of construct‐relevant interpretations. While recent instruments have focused on new constructs associated with caregiving (loss of personhood, discrimination, stigma), validation studies have not been conducted with representative populations of caregivers from both traditional and non‐traditional family structures or diverse racial/ethnic groups.

Conclusion

The interpretability and meaningfulness of inferences from existing ADRD caregiving measures depend on the relevance and utility of those instruments in the applied setting. This review highlights the need for developing measures that capture the multifaceted experiences of a diverse and more representative sample from the full spectrum of ADRD caregivers.
“I assume that my doctor will then guide me”: Attitudes and Expectations in the Context of Dementia Risk Estimation
Authors: Hübner Constanze , Baumeister Annika , Gerards Michelle , Cantero‐Fortiz Yahveth , Ribaldi Federica , Braun Julia , Boada Mercè , Frisoni Giovanni B. , Jessen Frank , Rostamzadeh Ayda , Schwegler Carolin , Schmitz‐Luhn Björn , Woopen Christiane
Published: January 2025

Background

Driven by (bio‐)medical and technical developments, advanced non‐invasive methods for estimating the risk of Alzheimer’s dementia (ADD) are increasingly emerging. In the future, such methods could eventually become available for individuals in asymptomatic and preclinical stages of Alzheimer’s disease (e.g. individuals with subjective cognitive decline (SCD)). Disclosure of individual ADD risk can bring new challenges for those affected, which can be linked to ethically relevant aspects such as identity and self‐perception. Such considerations can become more and more relevant in the context of ADD risk estimation in clinical care. In a qualitative approach, the ethical subproject of the PreTAD project (The Predictive Turn in Alzheimer’s Disease: Ethical, Clinical, Linguistic and Legal Aspects) aims, among other objectives, to investigate the attitudes and expectations of persons with various experiences with ADD regarding ADD risk estimation.

Method

In the qualitative part of the study, n = 30 interviews out of N = 40 are intended to be conducted with first‐degree relatives of persons with ADD and patients with SCD diagnosed ≤4 weeks or >4 weeks ago. The interviews address inter alia attitudes, individual experiences, and expectations regarding ADD risk estimation. Thematic analysis (Kuckartz & Rädiker 2023) is employed to analyze interview transcripts.

Result

Preliminary analysis of n = 23 interviews revealed a spectrum of attitudes and expectations regarding ADD risk estimation shaped by individual experiences with ADD, care experience, or the healthcare system. Across groups, the majority expressed a positive attitude toward ADD risk estimation. The hypothetical offer of ADD risk estimation was frequently perceived as a way of gaining control by learning about one’s risk status. Hopes regarding potential risk knowledge included the anticipated opportunity to proactively engage in one’s health under medical guidance and the chance to initiate self‐determined advance care measures, which was emphasized by individuals with care experience. Potential psychological strain due to risk knowledge was rather mentioned by individuals with SCD.

Conclusion

Preliminary findings highlighted diverse expectations associated with ADD risk knowledge touching upon ethically relevant aspects such as (self‐)responsibility and self‐determination. Our findings can serve as valuable starting points for an ethically guided approach to handling ADD risk estimation in clinical practice.
NEuroBioStand project: a European metrological research framework for standardising p‐tau measurements in plasma
Authors: Giangrande Chiara , Vaneeckhoutte Hélène , Delatour Vincent , Vinh Joëlle , Verdier Yann , Vanmechelen Eugeen , Koertvelyessy Peter , Blennow Kaj , Zetterberg Henrik , Gobom Johan
Published: January 2025

Background

NEuroBioStand is an EU‐funded project aimed at developing a metrological research framework for standardising blood‐based biomarkers of neurodegenerative diseases (NDDs) with the objective of implementation and commercialisation of promising assays for NDD biomarkers fulfilling requirements of the in vitro diagnostic regulation (IVDR).

P‐tau is currently included in the AT(N) framework for AD diagnosis together with other biomarkers and amyloid‐β and tau in CSF have been developed into regulatory approved biomarkers in CSF. The standardisation of the measurements for this biomarker is important to establish common cut‐off values and reference ranges.

Method

Recombinant phosphorylated protein and synthetic phosphopeptide materials were sourced as candidate primary calibrators together with their labelled internal standards. Purity was evaluated for the protein and peptide materials by high resolution mass spectrometry coupled to liquid chromatography (LC‐HRMS) and mass fraction was determined by amino acid analysis (AAA). A candidate reference measurement procedure (RMP) is being developed by LC‐HRMS for high accuracy measurement of different phosphorylated epitopes in plasma.

Result

The first step towards the standardisation of this biomarker is the definition of the measurand: NEuroBioStand consortium has defined the clinically relevant phosphorylated isoforms to develop protein and peptide candidate primary calibrators. P‐tau181, P‐tau217 and P‐tau231 have been prioritized and fit for purpose calibrators have been characterised in terms of purity and mass fraction by amino acids analysis and LC‐MS. In particular, the full characterisation of the phosphorylation status of protein candidate primary calibrators has been carried out to determine the site occupancy of the most relevant phosphorylation sites by using the SI‐traceable quantified phosphorylated peptide materials. The development of a multiplexing SI‐traceable candidate RMP in plasma is in progress with the aim of standardising concentrations of the prioritised phosphorylated epitopes and thus calculating the ratio of phosphorylated to non‐phosphorylated fragments.

Conclusion

NEuroBioStand consortium gathers national metrology institutes, clinicians, academics and IVD‐providers to achieve traceability to SI units for fluid biomarkers in NDD. The development of a RMP will allow the certification of candidate matrix‐based reference materials that will be used to harmonise measurements of P‐tau in plasma across different analytical platforms, thus standardising cut‐off values and reference ranges.
Randomized controlled feasibility trial to reduce stigma related to dementia among community health workers in Brazil: Preliminary results
Authors: Godoy Carolina , Oliveira Deborah , de Paula Tassiane , Barbosa Matheus Ghossain , Boaventura Vinicius , Evans‐Lacko Sara , Ferri Cleusa P
Published: January 2025

Background

Dementia awareness and education are currently limited among healthcare workers and the general public, contributing towards the generation and propagation of stigma and discrimination against people with dementia worldwide. It is crucial to promote evidence‐based anti‐stigma interventions with a focus on stigma reduction.

Method

This is a randomized and controlled feasibility trial of a group intervention aimed at improving knowledge and reducing stigma related to dementia among Community Health Workers (CHWs) (Trial Registration: RBR‐10xp637m). The Intervention Group (IG) (n = 70) received a 9‐hour intervention involving reflexive, educational, visual, and social contact activities related to dementia, and the Control Group (CG) (n = 62) was not intervened. Beyond sociodemographic characteristics, we collected data on dementia related stigma. For this preliminary analysis we will present data on: (1) negative attitudes (a composed score from 8 related question – the higher the score the more negative are the attitudes); (2) knowledge on dementia (a composed score from 5 related question – the higher the score the better the knowledge) and (3) a single question on the importance of dementia diagnosis disclosure (the higher the score the more important the participant think this is). The follow‐up questionnaires were reapplied 30 and 90 days after the intervention, using the same set of questions. We estimated and present the Mean Change (SD) in the IG and in the CG, the T‐test (p‐value), and the Mean Difference (95% CI).

Result

There was no significant difference in any baseline measures between IG and CG. The preliminary results show that, compared to the CG, a significant increase in knowledge was achieved in the IG both at 30‐ (p = 0.007) and 90‐day follow up (p = 0.020), and a significant reduction in negative attitudes in both measure points (p<0.000 and p = 0.000 at 30‐ and 90‐day follow up, respectively).

Conclusion

The preliminary findings indicate the intervention can lead to a sustained increase in knowledge and a shift in negative attitudes among CHWs over time. Further analysis are being carried out, including a qualitative assessment of the intervention, which will help improve the intervention to be applied in a randomized‐ controlled trial in the future.
A Study on the Expression Profile of Genes Coding for Secretory Proteins Using in vitro Model of Alzheimer’s Disease
Authors: Singh Ravinder , Sunkaria Aditya
Published: January 2025

Background

Age‐related neurological illness like Alzheimer's disease (AD) is steadily becoming more prevalent among the aged population in India and around the world. Cognitive deficits are caused by a progressive loss of normal brain functions. Increased production of amyloid (Aβ) and the development of neurofibrillary tangles (NFTs) are the two most significant pathogenic events that take place during AD progression. Until today, many attempts have been made towards discovering novel targets which are more precise and could identify the progression of the disease at very early stage.

Method

In the present study the Human Protein Atlas (HPA) database was used to filter out total human secretome. Using single cell type proteome of the HPA database, neuronal proteins were compared with total human secretome to discover overlapping proteins and their respective genes. Further, Alzheimer's disease associated genes were extracted using DisGeNet database and ranked according to their gene‐disease association (gda) score. Further, different proteoforms of Aβ were used to treat neuronal cells in vitro to mimic early stages of AD like pathology. The expression of secretory protein genes from in vitro model system has been analysed.

Result

Out of 1678 genes, 24 neuronal genes were identified that were coding for secretory proteins. These genes were further categorized according to their proteins function. Specific primers for the top gda score genes were designed and expression analyses were conducted. Analyses revealed modulation in the expression of APOE, MAPT, NPY, NGF, and RELN genes.

Conclusion

The aim of this study was to discover early‐stage biomarkers for Alzheimer's disease. In the present study we have tried to identify modulation in the genes coding for secretory proteins which might be reflected at protein levels also. Currently our lab is working on to fully understand the modulation of AD secretome which would enable us to identify AD specific early stage biomarkers.
Sleep, autonomic function, and cognition in the U.S. POINTER trial
Authors: Shaltout Hossam A , Hayden Kathleen M. , Garcia Katelyn R , Leng Xiaoyan , Howard Marjorie , Scales Margaret , Culkin Margaret C. , Baker Laura D , Snyder Heather M , Papp Kathryn V , Bailey Margie J , Brinkley Tina E
Published: January 2025

Background

Sleep disorders have been associated with cognitive impairment and dementia risk. Measures of autonomic function including baroreflex sensitivity (BRS) and heart rate variability (HRV) have also been associated with sleep quality. The extent to which sleep disorders are linked to autonomic function and alter the risk of Alzheimer’s disease (AD) in older adults remains unclear. We investigated the association between sleep measures and autonomic function measures in 193 participants enrolled in the U.S. POINTER trial (mean age: 67.8±5.4 years, 65% female, 35% people of color).

Method

Continuous blood pressure and ECG recordings were used to assess baroreflex sensitivity (BRS), blood pressure variability (BPV), HRV measured as root mean square of successive differences (rMSSD) and standard deviation of beat to beat interval (SDNN), and sympathovagal balance (LF/HF ratio). Sleep quality was assessed by multiple measures including the apnea‐hypopnea index (AHI), oxygen desaturation index (ODI), sleep duration, sleep efficiency, and wake after sleep onset (WASO). Linear regression was used to examine cross‐sectional associations between the outcomes of interest adjusting for age, sex, race/ethnicity, education, and site.

Result

The majority of participants had normal sleep breathing pattern, with AHI and ODI ≤15 (n = 154, 80.0%). Individuals with AHI or ODI >15 have lower BRS (p<0.025), lower SDNN (p<0.026) and slightly higher LF/HF ratio and BPV (p = 0.09). BRS was positively associated with sleep duration (p = 0.04), high frequency alpha (p = 0.039), and sleep efficiency (p = 0.005), as well as global cognition (p = 0.038), episodic memory (p = 0.004), and mini‐mental state examination (MMSE) score (p = 0.06). BRS was also negatively correlated with WASO (p = 0.011). There was also a positive association between SDNN and 3MSE (p = 0.025), with similar trends for the association between rMSSD and both global cognition and processing speed (p = 0.08). Adjusting for AHI or ODI score strengthened the associations between autonomic function and cognition.

Conclusion

In this cohort of older adults, measures of autonomic function were inversely correlated with sleep disorders and positively correlated with cognitive function. Sleep disorders are linked to alterations in autonomic function, which are likely to exert significant downstream effects on cardiovascular health and brain function. These effects may potentially influence the development of AD.
Altered Cerebral Blood Flow as a Screening Test for Neurodegenerative Disease: A Comparative Analysis of Arterial Spin Labeled Magnetic Resonance Imaging and 18F‐Fluorodeoxyglucose Positron Emission Tomography
Authors: Fajardo Andres Ricaurte , Kovanlikaya Ilhami , Yasen Weiye , Mahmud Meem , Ivanidze Jana , Li Yi , de Leon Mony J. , Butler Tracy A , Nordvig Anna S , Chiang Gloria
Published: January 2025

Background

Early detection of Alzheimer’s disease (AD) can improve prognosis, given new anti‐amyloid therapies. Both positron emission tomography (PET) and magnetic resonance (MR) imaging biomarkers are currently used (1). 48F‐Fluorodeoxyglucose‐PET (FDG‐PET) can detect neurodegeneration‐related hypometabolism but is costly and not easily accessible (2). Cerebral blood flow (CBF), assessed using arterial spin labelling magnetic resonance imaging (ASL‐MRI), is closely linked to metabolism in neurodegenerative disease (2). In a recent case series of seven neurodegenerative patients, we described concordance between CBF and (i) FDG‐PET and (ii) amyloid/tau PET (3). In this clinical cohort, ASL‐MRI was used to triage patients with cognitive concerns.

Method

A retrospective analysis included patients aged 25‐85 with cognitive symptoms, who underwent ASL‐MRI and either (i) FDG‐PET (n = 65) and/or (ii) amyloid PET or CSF sampling for amyloid/tau (n = 44). CBF maps were standardized and independently assessed by two neuroradiologists for a typical AD pattern (temporoparietal) or lobar (≥2 lobes) hypoperfusion. FDG avidity was compared against a normative database for regional hypometabolism. The sensitivity and specificity of ASL‐MR in identifying AD was assessed, as well as discordance with FDG‐PET.

Result

82 patients met inclusion criteria (mean age 68±13), interrater reliability for lobar hypoperfusion was 84%. Temporoparietal hypoperfusion was 81% specific, but only 52% sensitive for biomarker‐proven AD; lobar hypoperfusion increased sensitivity to 78%, but specificity decreased to 43%. Using temporoparietal hypoperfusion, there was 29% discordance with FDG‐PET. Using lobar hypoperfusion, there was 38% discordance.

Conclusion

ASL‐MRI is a promising, non‐invasive screening tool for early detection and diagnosis of AD and other neurodegenerative diseases. Understanding the discordance between ASL‐MRI and FDG‐PET warrants further attention. In routine assessments for cognitive complaints, ASL‐MRI should be added to the screening protocol MRI.

Bibliography:

1. Haidar H, Majzoub RE, Hajeer S, Abbas LA. Arterial spin labeling (ASL‐MRI) versus fluorodeoxyglucose‐PET (FDG‐PET) in diagnosing dementia: a systematic review and meta‐analysis. BMC Neurol. 2023 Oct 24;23(1):385.

2. Minoshima S, Cross D, Thientunyakit T, Foster NL, Drzezga A. 18F‐FDG PET Imaging in Neurodegenerative Dementing Disorders: Insights into Subtype Classification, Emerging Disease Categories, and Mixed Dementia with Copathologies. J Nucl Med. 2022 Jun;63(Suppl 1):2S‐12S.

3. Accepted publication, AJNR.
4D flow MRI of CSF dynamics: relations to CSF morphology and Aβ status
Authors: Vikner Tomas P. , Johnson Kevin M. , Hudson Sarah C. , Pompa Christian C. , Cadman Robert V. , Bevis William B. , Betthauser Tobey J. , Chin Nathaniel A. , Eisenmenger Laura B. , Johnson Sterling C. , Rivera‐Rivera Leonardo A.
Published: January 2025

Background

Cerebrospinal fluid (CSF) dynamics are increasingly studied to understand potential pathologic coupling with neurological disorders. In Alzheimer’s disease (AD), CSF dynamics may be altered secondary to AD‐related atrophy and enlarged CSF spaces. Additionally, animal studies suggest that altered CSF dynamics could impair clearance of metabolic waste, leading to accumulation of amyloid‐beta (Aβ). However, assessment of human CSF dynamics has typically been limited to the cerebral aqueduct using 2D phase contrast MRI. In this work, we used 4D flow MRI to enable volumetric characterization of CSF flow dynamics in the human brain, to study its associations with CSF morphology and Aβ burden from 11C‐PiB PET.

Method

Cardiac‐resolved 4D flow MRI was used to assess CSF motion in N=69 participants (age 69±8 years; 17 Aβ+) from the Wisconsin Registry for Alzheimer’s Prevention, using a clinical 3T scanner (GE Premier) and a velocity encoding of 5 cm/s. Region‐averaged velocity waveforms were acquired in the spinal canal (SC), fourth ventricle (4V), cerebral aqueduct (CA), third ventricle (3V), the foramens of Monro (FMo), and the lateral ventricles (LV), segmented from T1‐weighted volumes. The waveforms were characterized by root‐mean‐square (RMS) velocity and were evaluated in relation to total CSF volume and Aβ status from an established PiB global distribution volume ratio threshold >1.16.

Result

Velocity waveforms demonstrated cardiac‐pulsatility in all regions of interest (ROIs) (Figure 1), with RMS velocities ranging from high in the SC (6.56±2.29 mm/s) to low in the lateral ventricles (right LV 0.31±0.15 mm/s). RMS velocities were related to total CSF volume for the SC (R=‐0.24; p=0.043), CA (R=0.27; p=0.034), 3V (R=‐0.28; p=0.018), left LV (R=‐0.39; p=0.002), and right LV (R=‐0.35; p=0.009) (Figure 2). In preliminary analysis, RMS velocities were higher in Aβ+ compared to Aβ‐ for the SC (p=0.048) and right LV (p=0.024) (Figure 3).

Conclusion

4D CSF flow MRI is feasible for the assessment of CSF dynamics throughout the ventricular system. Total CSF volume was related to RMS velocities in 5/8 ROIs, highlighting the influence of CSF morphology on CSF dynamics. Finally, Aβ status was related to RMS velocity in 2/8 ROIs, indicating that altered CSF dynamics could play a role in incipient AD.
Metabolic Hyperconnectivity in Underrepresented Individuals with long‐COVID
Authors: Machado Luiza Santos , Silveira Maiele Dornelles , de Bastiani Marco Antônio , Povala Guilherme , Borelli Wyllians Vendramini , Senger Joana Emilia , da Silva Ana Paula Bornes , da Ros João Pedro Uglione , de Mello Guilherme Bastos , Jotz Arthur Viana , Kadan Matheus Fakhri , Peixoto Guilherme G. Schu , Radaelli Graciane , Pascoal Tharick A. , Rosa‐Neto Pedro , Matushita Cristina Sebastião , Soder Ricardo Benardi , Schumacher‐Schuh Artur Francisco , Souza Diogo O. , Lourenco Mychael V , de Paula Faria Daniele de Paula , Coutinho Artur Martins , da Costa Jaderson Costa , de Souza Débora Guerini , Zimmer Eduardo R.
Published: January 2025

Background

Long‐COVID is characterized by persistent symptoms post‐infection with SARS‐CoV‐2. This condition includes neurological manifestations and has been proposed as a potential risk factor for the development of dementia. Individuals presenting with dementia due to Alzheimer's disease have dysfunctional brain metabolism, including metabolic brain network (MBN) hypoconnectivity. However, whether long‐COVID alters brain metabolic architecture remains elusive. Here, we aimed to evaluate the brain metabolic connectivity in a Brazilian cohort of individuals presenting with long‐COVID.

Method

[18F]FDG‐PET images were acquired from 52 community‐dwelling Brazilians above 50 year old. Standardized uptake value ratio (SUVr) parametric maps were processed to a common 8 mm FWHM and generated using the pons as the reference region (Figure 1). We extracted the mean values of regions of interest using the ICBM152 atlas. [18F]FDG‐PET MBNs were constructed using a novel multiple sampling scheme, which assembles a stable group representative MBN based on bootstrap (n = 2000). Adaptive Synthetic Sampling Approach for Imbalance (ADASYN) was used to account for group imbalance and generated the ADA‐MBNs. Graph measures, including density, global efficiency, average degree, and assortativity coefficient were computed. Data were corrected for multiple comparisons using the False Discovery Rate (FDR) method (p<0.05).

Result

41 individuals with long‐COVID and 11 healthy controls (HC) were included (Table 1). We observed that long‐COVID individuals present PET hyperconnectivity in both MBN and ADA‐MBN. (Figure 2a‐b). The long‐COVID group presented increased density, global efficiency and average degree whereas assortativity coefficient were reduced in both MBN and ADA‐MBN.

Conclusion

Our findings showed that individuals with long‐COVID presented a brain metabolic hyperconnectivity, which is supported by increased density and average degree and may indicate a potential compensatory mechanism within the brain. In addition, the increase in global efficiency indicates that the brain of long‐COVID individuals exchanges metabolic information more efficiently, but the decreased assortativity coefficient suggests vertices with different properties connect to each other. Further longitudinal studies should follow these individuals for assessing microstructural and cognitive changes.
Longitudinal beta‐amyloid measured with [C‐11]PiB accumulates at an accelerated rate in Down syndrome compared to neurotypical populations
Authors: McVea Andrew K , DiFilippo Alexandra H , McLachlan Max , Bettcher Brecca , Zammit Matthew D , Betthauser Tobey J. , Converse Alexander K , Murali Dhanabalan , Stone Charles K , Hartley Sigan L , Johnson Sterling C. , Tudorascu Dana , Laymon Charles M , Cohen Annie , Minhas Davneet S , Mathis Chester , Ances Beau , Zaman Shahid , Mapstone Mark , Head Elizabeth , Klunk William E , Handen Benjamin L , Christian Bradley T. ,   ABC‐DS Investigators
Published: January 2025

Background

Trisomy 21 in Down syndrome (DS) is associated with an earlier accumulation of beta‐amyloid (Aβ) plaques and a higher rate of Alzheimer’s Disease due to the triplication of the amyloid precursor protein gene. In this study we compare accumulation rates of Aβ measured with [C‐11]PiB PET between large longitudinal cohorts of DS and neurotypical (NT) participants at a single site.

Methods

Participants imaged at the University of Wisconsin with ≥2 PiB scans and ≥2 years between scans were included in this study. DS participants were included from the Alzheimer’s Biomarker Consortium–DS (ABC‐DS) study (n = 57) and NT participants from studies enriched with familial risk for AD (n = 162) with several participants having 10+ years of PiB data. An identical imaging procedure was conducted for all subjects and reconstructed PET images were processed using a standardized pipeline and converted into SUVR images using the cerebellar grey matter reference region. Global PiB SUVR, defined by grey matter regions from the AAL atlas, was used as a metric for Aβ deposition and input into a trajectory model (Betthauser, 2021) to estimate time from Aβ(+) (SUVR ≥ 1.40) for each scan (Figure 1). Using this model the PiB data were normalized in time and then fit using the logistic growth curve () with t50 set to 0. Nonspecific binding (NS), found by taking the average SUVR of all Aβ(‐) subject scans (n=491) at our site, and carrying capacity (K), represented by the highest total binding seen in any participant scanned, were set to 1.12 and 2.40 respectively. Aβ accumulation rate (r) was calculated by fitting all normalized participant data across each population.

Results

Rate of Aβ accumulation for DS was 0.25±0.02 and 0.17±0.01/yr for NT, corresponding to 0.065 and 0.038 SUVR/yr respectively when becoming Aβ(+). No overlap in 95% CI between the DS (0.21‐0.29) and NT (0.15‐0.19) populations was observed.

Conclusions

There was a faster rate of Aβ accumulation observed in our DS cohort compared to NT by 47%. However, the high variability in Aβ rates requires further investigation towards understanding how genetic and lifestyle factors contribute to this process.
Target trial emulation analysis linking dampened circadian rest‐activity rhythms and dementia
Authors: Sun Haoqi , Yang Jingyun , Vialle Ricardo A , Gao Chenlu , Cai Ruixue , Haghayegh Shahab , Gao Lei , Rutter Martin K , Hu Kun , Li Peng
Published: January 2025

Background

Previous studies have linked disrupted circadian rest‐activity rhythms (RARs) with increased risks for Alzheimer’s disease and related dementias. However, these findings may be confounded due to the observational nature and offer limited insights into causality. We aimed to employ target trial emulation to estimate potential causal effects of RARs on dementia development.

Method

Using the UK Biobank data, we emulated a target randomized trial including 86,802 participants with ≥6 days of actigraphy. Cycle‐by‐cycle amplitudes of the ∼24‐h RARs were computed from actigraphy using uniform‐phase empirical mode decomposition. Two emulated trial arms were defined (1) a ‘robust RARs’ arm within which all participants had higher than cohort median amplitudes averaged over six consecutive days, and (2) a ‘dampened RARs’ arm where all participants had lower (than cohort median) values in six consecutive days. The primary outcome was time to all‐cause dementia, and the secondary outcome was time to death. Covariates considered included age, sex, race, college education (yes/no), body mass index, socioeconomic status (Townsend deprivation index), number of active medications, history of circulatory (yes/no), nervous system (yes/no), and mental or behavioral health conditions (yes/no). In the emulated trial, the baseline was defined as the beginning of actigraphy. The g‐formula and cause‐specific Cox proportional hazards model, complemented by bootstrapping for 95% confidence intervals (CI), were used for analysis.

Result

Over an 8‐year follow‐up, 467 participants developed all‐cause dementia, and 2,769 died. The ‘dampened RARs’ arm exhibited a significantly higher risk of death than the ‘robust RARs’ arm. Also, a higher cumulative incidence of dementia was observed in the ‘dampened RARs’ arm after accounting for death as a competing risk. At 8 years post‐baseline, the cumulative incidence of dementia was 0.84% (95% CI: 0.71%–1.1%) in the ‘dampened RARs’ arm, versus 0.56% (0.46%–0.70%) in the ‘robust RARs’ arm (i.e., dampened RARs lifestyle had a 1.5‐fold increased risk compared to a robust RARs lifestyle).

Conclusion

The findings from this multivariable‐adjusted target trial emulation suggest that perturbed RARs may be causally associated with increased risk of all‐cause dementia. These results underscore the importance of maintaining robust RARs for dementia prevention.
Patterns in the Diagnosis and Management of Early Alzheimer’s Disease in Community‐Based Settings in the United States
Authors: Juday Timothy R , Holub Ashley A , Betts Keith A. , Mattke Soeren , Kitchen Sophie A , Liu Hongjiao , Malik Amyn , Batrla Richard , Frech Feride H , Khachaturian Ara S
Published: January 2025

Background

With the changing care landscape for early Alzheimer’s disease (AD), optimizing the diagnostic and management process is key. This study assessed the correlation between patient and physician characteristics and outcomes related to the diagnosis, referral, and treatment process for early AD in community‐based settings.

Method

This cross‐sectional study conducted between August and September 2023 abstracted medical chart data for patients aged 50‐89 years who were diagnosed with early AD (mild cognitive impairment [MCI] or mild AD) within the past 2 years and had a clinic visit within the past year. Generalized estimating equation models accounting for clustering at the physician level were conducted to determine the association between patient and physician characteristics and the use of biomarker/imaging assessments, referrals for cognitive/behavioral concerns, and beta‐amyloid therapies.

Result

The study included 1,284 patient charts (817 MCI and 467 mild AD). Factors positively correlated with receiving biomarker/imaging assessments included younger age (<65 vs. 65+ years, adjusted odds ratio (aOR: 1.73; 95% CI: 1.22, 2.44), and physician type (neurologist vs. PCP [aOR: 2.55; 95% CI: 1.49, 4.38]). Non‐Hispanic ethnicity was also associated with lower odds of biomarker/imaging assessments (aOR = 0.58; CI = 0.37‐0.91). Patients with mild AD had increased odds of referral (aOR: 1.27; 95% CI: 1.05, 1.53) compared to patients with MCI. Younger patients (aOR: 2.82; 95% CI: 1.32, 6.06) also had increased odds of receiving beta‐amyloid therapy. While not significant, receipt of biomarker/imaging test (aOR: 2.04; 95% CI: 0.85, 4.93) and female sex (aOR: 1.44; 95% CI: 0.94, 2.21) were associated with increased odds of receiving beta‐amyloid therapy (p = ns). Likewise, patients with urban/suburban residence had increased odds of a referral (aOR: 1.31; 95% CI: 0.89, 1.94) and beta‐amyloid therapy (aOR: 1.41; 95% CI: 0.48, 4.13).

Conclusion

As the care environment continues to evolve, future research should explore better measures and impact of insurance coverage policies, physician education and health care system readiness as it relates to the management of early AD, and other chronic disorders affecting memory, movement and mood.
The Effect of Loneliness on Plasma AD Biomarkers in Cognitively Normal Elderly
Authors: Plaska Chelsea Reichert , Bruno Davide , Cejudo Jaime Ramos , Osorio Ricardo S. , Zetterberg Henrik , Blennow Kaj , Pomara Nunzio
Published: January 2025

Background

Social isolation (SI) and loneliness are related to several negative health outcomes, including cognitive decline and dementia. While both males and females experience increased SI as a function of age, studies have found that females experience greater loneliness than males, despite males reporting more physical isolation and smaller social networks. Females, independent of SI‐status, are also at increased risk of Alzheimer’s disease (AD). These sex‐related differences in SI and AD‐risk prompted us to examine whether sex and loneliness influenced the plasma AD biomarkers in a cohort of elderly individuals.

Method

Participants were enrolled in the Memory Education and Research Initiative (MERI) program. MERI participants completed a neuropsychological battery, clinical and psychiatric evaluation, and blood draw. Plasma Aβ40, Aβ42, and PTau231 concentrations were determined using single‐molecule array (SIMOA) platform. Plasma Aβ42/Aβ40 ratio was calculated. MERI participants were included if they gave blood, were cognitively‐normal defined by MMSE>27, age 50 years older, and completed the Profile of Mood States scale (POMS). POMS‐Loneliness item was coded to a dichotomous variable (0‐Not Lonely; 1‐Lonely).

Result

A total of 459 MERI participants (mean age=71 years; 59% females) were included. There were no significant differences between males and females for education, HAM‐D total score, or MMSE, only age. A 2x2 analysis of covariance (ANCOVA) with sex (male, female) and loneliness (not lonely, lonely), and age as a covariate, revealed a significant interaction between sex and loneliness with Aβ42 (p=0.014). Lonely females had significantly lower Aβ42 than males who are lonely. The same analysis revealed a significant main effect of sex on Aβ40 (p=0.014) and PTau231 (p=0.007); females had higher Aβ40 and lower PTau231, respectively. There were no significant main effects or interactions for Plasma ratio Aβ42/Aβ40.

Conclusion

Cognitively‐normal females who reported being lonely, as compared with males, had lower levels of plasma Aβ42 but not lower levels of plasma Aβ42/Aβ40 ratio, a better predictor of a positive amyloid PET scan. Future studies should examine if the results reflect increased brain amyloid deposition in lonely females. If so, interventions that mitigate loneliness may reduce overall risk for AD in females.
Automated Thigh Tissue Segmentation by Vision Transformers: Application for Early Alzheimer's Diagnosis
Authors: Kasani Sara Hosseinzadeh , Dolatshahi Mahsa , Naghashzadeh Mahshid , Commean Paul K. , Rahmani Farzaneh , Liu Jingxia , Lloyd LaKisha , Nguyen Caitlyn , Hantler Nancy , McBee‐Kemper Abby , Ly Maria , Yu Gary Z , Ippolito Joseph E. , Mittendorfer Bettina , Sirlin Claude , Morris John C. , Benzinger Tammie L.S. , Raji Cyrus A.
Published: January 2025

Background

Within the research field of neurodegenerative disorders, unbiased analysis of body fat composition, particularly muscle mass, is gaining attention as a potential biological marker for refining Alzheimer’s disease risk. The objective of this study was to employ a deep learning model for fully automated and accurate segmentation of thigh tissues, potentially contributing to early Alzheimer's diagnostics.

Method

In an IRB‐approved study, 49 participants underwent thigh Dixon MRI scans with a TR=9.99s, TE=2.46s, flip angle=10°, and slice thickness= 5mm. The Dixon Fat/Water images were semi‐automatically segmented by an expert operator in all available slices to obtain the bone, intermuscular fat (InterFat), intramuscular fat (IntraFat), Subcutaneous Adipose Tissue (SAT), Muscle, and Gluteus. We trained and compared the performance of baseline and state‐of‐the‐art deep neural networks, namely, UNet, VNet, and two vision transformers (ViTs): UNETR and SwinUNETR. The performance of the trained models was tested on all data sets using a 3‐fold cross‐validation scheme.

Result

We found SwinUNETR outperformed the others with a mean dice similarity coefficient 96.20 (± 0.51), 80.91 (± 0.55), 50.56 (± 1.43), 95.26 (± 0.80), 98.70), 86.72 (± 1.12) in Bone, InterFat, IntraFat, SAT, Muscle, and Gluteus, respectively. Bland–Altman analysis and scatter plot (Figure 1) indicated that the differences between manual annotations and predictions by the SwinUNETR model were relatively minor for Bone volume, Intramuscular Fat volume, Muscle volume, and Gluteus volume classes. The overall mean difference is ‐88.8cm3 with a 95% confidence interval (CI) of [‐159.53, ‐18.13]. Biases [95% CI] for each tissue class were 5.44cm3 [−8.61, 19.50] for Bone volume, 51.74cm3 [−22.72, 126.20] for InterFat volume, 11.15cm3 [2.76, 19.53] for IntraFat volume, ‐191.09cm3 [−309.54, ‐72.64] for SAT volume, 15.16cm3 [−6.37, 36.70] for Muscle volume, and 18.76cm3 [2.20, 35.32] for Gluteus volume.

Conclusion

This study highlighted the use of ViTs for the automated segmentation of thigh tissues in MR which may allow for the detection of subtle changes in muscle mass and fat composition, that are of increasing interests in their associations with the neurodegenerative processes in Alzheimer's disease.