bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of subjective memory complaints at age 90+ and their cross‐sectional association with cognition: The 90+ Study
Authors: Melikyan Zarui A. , Aguirre Colette , Al‐Darsani Zeinah , Jiang Luohua , Kawas Claudia H. , Corrada María M. M. 
Published: December 2023

AbstractBackgroundSubjective memory complaints (SMC) present in 8‐33% of older adults younger than 90, and associated with worse cognition in cross‐sectional studies. However, the prevalence of SMC and its cross‐sectional association with objectively measured cognition at age 90+ are unknown. The aims are to: (1) determine the prevalence of SMC and (2) examine the cross‐sectional association of SMC with cognitive diagnosis and cognitive test scores in individuals aged 90 and older.MethodWe analyzed data from 1,112 participants of
The 90+ Study
, a longitudinal study of aging and cognition in people age 90 and older. SMC was assessed at baseline using an item from the Geriatric Depression Scale (GDS): “Do you think you have more problems with memory than most?” Cognitive diagnosis was determined from a neurological exam without knowledge GDS scores and catergorized as normal, cognitive impairment no dementia (CIND), and dementia. Cognitive tests measured verbal memory, verbal fluency, and executive function. We assessed the association between SMC and cognitive diagnosis using multinomial logistic regression and estimated the odds ratios of having CIND or dementia in those with SMC vs. No SMC. We used linear regression models stratified by congitive diagnosis to analyze the relationship between SMC and test scores. All analyses were adjusted for age, sex, education, and total GDS.ResultMean age was 93 years, 68% were women, 46% had college education or higher, and 16% had SMC. Participants reporting SMC had 1.69 times higher odds of a CIND diagnosis and 4.07 times higher odds of a dementia diagnosis compared to No SMC (Figure). SMC was associated with worse performance on memory and animal fluency in normal, and on memory only in CIND. SMC was not associated with performance on cognitive tests in participants with dementia (Table 2).ConclusionIn this cohort of adults aged 90+, SMC prevalence was comparable to reports in older adults <90. Cross‐sectionally, SMC was associated with higher odds of cognitive impairment, and with poorer performance on memory in participants without dementia, potentially reflecting insight into their cognition. Our findings suggest that SMC is a useful indicator of memory impairment after age 90.
Ethnoracial differences in the prevalence of amyloid abnormality
Authors: Jansen Willemijn J. , Oomens Julie Elisabeth , Vos Stephanie J. B. , Maserejian Nancy Nairi , Verhey Frans R.J. , Reiman Eric M. , Visser Pieter Jelle ,   the Amyloid Biomarker Study Group
Published: December 2023

AbstractBackgroundPrevalence estimates of amyloid positivity in persons across the AD clinical spectrum are important to reduce screen failure rates and improve recruitment efficiency in anti‐amyloid trials. We have previously estimated the prevalence according to age, sex, education and APOE genotype. It is however unknown whether these prevalence estimates generalize to diverse ethnoracial groups. We here aim to estimate the prevalence of amyloid abnormality in Black, White and Asian persons without dementia and examine associations with age, sex, educational level and APOE‐e4 carrier status.MethodWe selected 7,419 participants (6,083 with normal cognition; 1,336 with MCI) from 9 Amyloid Biomarker Study cohorts, including 291 Black, 6,310 White and 818 Asian participants. Amyloid positivity was determined with a PET (n = 5,714) or CSF (n = 1,705) biomarker, using data‐driven or study‐specific cutoffs. Generalized estimating equations were used to estimate the age‐related prevalence by ethnoracial group and to evaluate moderation by APOE‐e4 carrier status while adjusting for sex and education.ResultThe mean age was 70.9+‐7.4 years, 3,848 (57%) were women, and 20% were APOE‐e4 carriers. In persons with normal cognition, the age‐related prevalence of amyloid positivity was higher for White (25%) than for Black (17%) and Asian (16%) participants (p = 0.016). Among APOE‐e4 carriers with normal cognition, the prevalence of amyloid abnormality was again higher for White (46%) than for Black (29%) and Asian (30%) participants (Asian vs Black p‐value = 0.046, Asian vs White p‐value<0.001, Black vs White p‐value<0.001). Among APOE‐e4 noncarriers, no differences among the ethnoracial groups were identified (p = 0.56). In persons with MCI, White (59%) and Asian (60%) participants had abnormal amyloid more often than Black participants (43%; p<0.001). Ethnoracial differences were similar for APOE‐e4 carriers and noncarriers with MCI.ConclusionIn persons with normal cognition, the prevalence of amyloid abnormality among APOE‐e4 carriers was ∼15% higher for White than for Black and Asian participants, while among APOE‐e4 noncarriers no ethnoracial differences were found. In persons with MCI, both White and Asian participants ∼15% more often had abnormal amyloid than Black participants, irrespective of APOE‐e4 carrier status. Ethnoracial status may be an important factor to consider in the design of AD clinical trials.
In vivo data‐driven patterns of Tau accumulation associated with AD progression using 18F‐MK‐6240 PET
Authors: Fonov Vladimir S , Nazneen Tahnia , Rosa‐Neto Pedro , Collins D Louis 
Published: December 2023

AbstractBackgroundAlzheimer’s disease is a neurodegenerative disease associated with accumulation of amyloid beta and tau neurofibrillary tangles following a pattern known as Braak stages (Braak 1995,2011). Recent papers (Pascoal 2020) indicate possibility to recapitulate Braak histo‐pathological stages in vivo using tau tangles PET tracer 18F‐MK‐6240, using manually defined regions of interest. This study analyzes patterns of Tau accumulation associated with AD in a completely data‐driven fashion.MethodWe used T1w MRI and 18F‐MK‐6240 Pet scans from healthy controls in the community or outpatients at the McGill University Research Centre for Studies in Aging. The following number of datasets from each diagnostic group [n scans total (m unique participants)]: cognitively normal: 347(194), mild cognitive impairment: 163(99), Alzheimer’s disease dementia: 114(77).T1w MRIs were pre‐processed (non‐uniformity correction, intensity normalization, stereotaxic registration, brain masking, tissue classification); FALCON (Fonov 2020) was used to extract the mid‐cortical surface.PET scans were linearly registered to the T1w MRI and the standardized uptake value ratio (SUVR) was calculated using whole cerebellum grey matter as the reference. SUVR values were sampled along cortical mid‐surfaces and geodesically smoothed with a 10mm gaussian and resampled to the cortical surface of MNI2009c template (Fonov 2011).ResultFigure 1 shows Mean SUVR values on top of Figure 1, and latent factors at the bottom. Overall low values of tau in the temporal, partial and occipital region are associated with normal cognition (F1). Tau changes in the temporal lobe (F2, similar to stage 1&2) are associated with a slight cognitive change. Change in parietal and posterior temporal areas (F3, similar to stage 3&4) are associated with even more cognitive loss. Finally changes in the motor strip and ventral portion of the occipital lobe and remaining cortex (F4 and F5) are associated with the very advanced stages (5&6) of cognitive decline.ConclusionWe discovered patterns of tau accumulation associated with progression of cognitive decline in a completely data‐driven fashion .
ALZpath Dx: A novel accessible, validated, and scalable phosphorylated‐tau 217 (pTau217) assay in blood
Authors: Portbury Stuart D , Chaby Lauren , Jeromin Andreas 
Published: December 2023

AbstractBackgroundBlood‐based biomarkers for phosphorylated tau demonstrate strong diagnostic accuracy and compare favorably with current corresponding CSF and neuroimaging biomarkers. Of the four major pTau assays in use (pTau181, pTau217, and pTau231, Nfl), pTau217 appears to be the most robust marker, consistently outperforming plasma pTau 181, neurofilament light, and imaging markers. pTau217 has been shown to correlate with post‐mortem AD pathology, with the ability to differentiate AD from other types of dementia and predict future progression from both normal cognition and mild cognitive impairment to AD.(1,2) Additionally, pTau217 can be used to monitor AD progression because longitudinal increases in pTau217 is indicative of worsening of brain atrophy and cognition in AD.(3) pTau217, therefore, represents a cost‐effective and accessible blood‐based biomarker for tau pathophysiology, that can transform the AD diagnostic field.MethodALZpath has developed reagents for pTau217 and establish a robust and scalable fit for purpose plasma‐based ultra‐sensitive assay utilizing a proprietary monoclonal pTau217 antibody.ResultThe ultra‐sensitive blood‐based ELISA assay, using a peptide calibrator, has been developed on the semi‐automated single‐molecule array Simoa® platform. The assay has been launched for clinical use as laboratory‐developed test (LDT). Evaluation in independent clinical cohorts with multiple co‐morbidities is currently being established to advance to an in‐vitro diagnostic (IVD).ConclusionThe ALZpath pTau217 Simoa® assay is now a fit for purpose validated assay now available for commercial use. Clinical use of this assay is described in Snyder et al. Gouda et al. and Ashton et al. AAIC 2023.
Passively monitored smartphone battery percentage relates to disease severity in frontotemporal dementia: A proof‐of‐concept study
Authors: Paolillo Emily W. , Casaletto Kaitlin B. , Clark Annie L , Taylor Jack C , Heuer Hilary W. , Wise Amy B. , Dhanam Sreya , Sanderson‐Cimino Mark E. , Saloner Rowan , Kramer Joel H. , Kornak John , Kremers Walter K. , Forsberg Leah K. , Boeve Brad F. , Rosen Howard J. , Boxer Adam L. , Staffaroni Adam M. ,   the ALLFTD Consortium
Published: December 2023

AbstractBackgroundFrontotemporal dementia (FTD) is a leading cause of dementia in individuals under age 65. Due to limitations in access to in‐person evaluations, there is an urgent need to examine remote, accessible, and low‐burden assessment techniques for FTD. Unobtrusive monitoring of at‐home computer use in older adults has shown that those with mild cognitive impairment (MCI) have significant declines in computer use over time. To extend these findings, we characterized daily trajectories in smartphone battery percentage, a proxy of smartphone use, and examined relationships with clinical indicators of disease severity in FTD.MethodParticipants included 250 adults enrolled in the ALLFTD Mobile App study (mean age = 53.9 [SD = 14.9]; 59% women; 94% White). To assess clinical disease severity, all participants completed the FTLD Clinical Dementia Rating scale (CDR®+NACC FTLD), a brief neuropsychological battery, the Neuropsychiatric Inventory Questionnaire (NPI‐Q), and brain MRI. The ALLFTD Mobile App was installed onto participants’ smartphones for remote, passive, continuous monitoring of smartphone use (average days of monitoring = 82 [range = 7‐541]). Battery percentage was collected every 15 minutes. Linear mixed effects models examined linear, quadratic, and cubic effects of time of day (i.e., hour; modeled as person‐specific random effects) and their interactions with each measure of disease severity on battery percentage. Models covaried for age.Result57% of participants were clinically normal, 21% had MCI, and 22% had dementia. CDR®+NACC FTLD Global score interacted with hour such that participants with MCI and dementia had flatter battery curves (i.e., less change in battery percentage throughout the day – a proxy of less smartphone use) than clinically normal participants (ps<0.001). Additional models showed that worse memory (hour3 x memory score: 𝛃 = 0.59, p<0.001) and executive functioning (hour3 x executive score: 𝛃 = 0.64, p<0.001), more neuropsychiatric symptoms (hour3 x NPI‐Q: 𝛃 = ‐0.22, p = 0.004), and smaller gray matter volumes (controlling for intracranial volume; hour3 x volume: 𝛃 = 0.49, p<0.001) were also statistically significantly related to less battery usage throughout the day.ConclusionThese findings are proof‐of‐concept that passively acquired smartphone data, specifically battery usage, can provide insights about disease progression in FTD. Results support future research focusing on the development of passively collected digital metrics sensitive to clinical declines in neurodegenerative disease.
The impact of breathing patterns on CSF flow and global brain BOLD signal while awake: A study using real‐time phase‐contrast MRI and fast rsfMRI
Authors: Lee Jeyeon , Kang Daehun , In Myung‐Ho , Shu Yunhong , Bernstein Matt A , Ghatamaneni Sujala , Nunez Nicolas A , Park John G , Maihle Nita J , Nedelska Zuzana , Ganji Sandeep , Cogswell Petrice M , Gunter Jeffrey L. , III John Huston , Botha Hugo , Graff‐Radford Jonathan , Jones David T. , Petersen Ronald C. , Lowe Val J. , Min Hoon‐Ki 
Published: December 2023

AbstractBackgroundThe cardiac and respiratory cycles have been suggested as major drivers of cerebrospinal fluid(CSF) flow. The glymphatic system, one of the mechanisms for the clearance of amyloid‐beta and tau proteins, relies heavily on the movement(flow) of the CSF, and thus, investigating the forces that modulate the CSF flow is essential for understanding the glymphatic flux. Because breathing is trainable through exercise and self‐directed methods, various breathing methods may enhance the CSF flow.MethodReal‐time phase‐contrast MRI(pc‐MRI) was used to measure the CSF flow at the foramen magnum on a 3T. Fast resting‐state fMRI(rsfMRI;TR400ms) was conducted on a compact 3T. Under an IRB‐approved protocol, participants were instructed to breathe slowly and deeply, and subsequently switch to their spontaneous breathing. For rsfMRI data preprocessing, we performed motion correction, skull stripping, spatial smoothing(4mm), temporal filtering(0.01 to 0.1Hz), and linear and quadratic temporal trends removal. fMRI time courses were then normalized to Z‐score at each voxel before being averaged. On the pcMRI, the phase was summed in a CSF region‐of‐interest and plotted vs time. Additionally, we confirmed for possible confounding effects such as head motion or motion‐induced susceptibility changes.ResultrsfMRI findings showed that deep breathing promoted large oscillations in the CSF flow in the ventricles, while spontaneous breathing did not(Figure 1). Additionally, deep breathing resulted in large oscillations in lobar cortical regions. Similar results were observed in the pcMRI, with larger CSF velocity through the foramen magnum during the deep breathing compared to the spontaneous breathing(Figure 2A‐B). The cumulative summation result showed that the volume of CSF flow was increased during deep breathing(Figure 2C).ConclusionThis study provides new evidence that slow and deep breathing promotes CSF flow and global brain BOLD signal, which may be useful in promoting circulation in the brain. The study’s findings also open new avenues for research in the field of neurovascular coupling and mechanisms associated with glymphatic clearance. As hampered CSF flow and/or worsen glymphatic clearance have been shown to associate with pathological aging and dementia, including Alzheimer’s disease and Parkinson’s disease, future research is needed explore the potential of breathing training methods as a non‐pharmacological intervention to support brain health.
REAL AD – A realistic screening approach for preclinical Alzheimer’s disease
Authors: Blennow Kaj , Heeman Fiona , Kern Silke , Moscoso Alexis , Zetterberg Henrik , Schöll Michael 
Published: December 2023

AbstractBackgroundFor disease‐modifying treatments to be successful in Alzheimer’s disease (AD), it is essential to identify individuals in the early phases of the disease, characterised by first biomarker abnormalities. At present, most AD diagnoses in Sweden are made within primary care which is not equipped for detecting individuals who are at risk of developing AD dementia. Considering current treatment developments, it will be essential to have access to biomarkers to aid an informed diagnosis already in primary care. REAL AD will evaluate the feasibility of a screening approach for preclinical AD using remote cognitive testing and blood‐based biomarkers in a naturalistic setting.MethodREAL AD is a collaborative initiative between the Swedish Västra Götaland County Council (VGR), VGR Primary Care, the Sahlgrenska University Hospital, the University of Gothenburg and pharmaceutical industry partners. A targeted PR‐campaign will facilitate reaching a recruitment goal of a minimum of 3000 socioeconomically and ethnically diverse individuals aged 50‐80 years without AD dementia. All participants will perform remote cognitive testing at home and undergo blood sampling at a local primary care unit on two occasions. Based on baseline blood biomarker profiles, a subgroup of participants will be enrolled into a validation study and further undergo CSF sampling, neuroimaging and clinical and neuropsychological assessment, also on two occasions.ResultLongitudinal remote cognitive assessment and blood sampling will be conducted at baseline and after 18 months, the blood samples will be analysed for a range of established and novel biomarkers. Within the validation study, results of the screening approach will be validated against established neuropsychological, CSF, MRI and [18F]RO948 tau PET assessments, and the feasibility of implementing this approach in the existing primary care infrastructure will be evaluated. We plan to present first data on recruitment and implementation at AAIC.ConclusionREAL AD aims to evaluate the applicability of a population‐based screening method to detect preclinical AD in a naturalistic setting and to inform the implementation of recent biomarker developments in clinical routine.
Effect of COVID‐19 and telehealth implementation on Patient Centered Outcome Measures completion by patients with Alzheimer’s and related disorders in an academic memory center
Authors: Gubler Boston , Finch Kelly , Holden Samantha K. , Mullen Rebecca , Matlock Daniel D , Pressman Peter S. 
Published: December 2023

AbstractBackgroundPatient Centered Outcome Measures (PCOMs) are increasingly recognized as a means of improving clinical efficiency, particularly when completed electronically ahead of clinic visits. However, PCOM completion is often far from consistent. The shift to telehealth introduced by the Covid‐19 pandemic changed how patients and caregivers engaged with medical care, possibly encouraging increased participation in electronic assessments. We questioned how the pandemic influenced electronic PCOM completion by our patients with Alzheimer’s disease (AD) and their caregivers.MethodsPatients and caregivers were routinely invited to fill electronic PCOM questionnaires prior to visits both before and during the Covid‐19 pandemic. PCOMs assessed the predominant cognitive domain of concern, other diagnostically useful symptoms, disease severity, neuropsychiatric symptoms, and caregiver wellbeing. A date of 3/15/2020 was set as the onset of the pandemic for this study, after which time our clinic converted to telehealth visits only. We tallied rates of completion of electronic surveys by patients and/or caregivers three and a half months before and after that time, comparing completion rates by two proportion Z‐test.ResultsDuring this timeframe, across a total of 402 visits (total: 333 individuals, 69 returns; AD: 73 individuals, 6 returns), caregivers and/or patients were offered an opportunity to fill PCOMs ahead of the visit. Across all clinical diagnoses combined, the probability of a visit being associated with filled PCOMS was greater after switching to only telehealth (caregivers: P = 0.005,patients: P = 0.016). Additionally,after the shift to telehealth, AD‐related visits were twice as likely to have completed preclinical electronic PCOMs (caregivers: P = 0.002, patients: P = 0.008). Approximately 33.3% of PCOMS to be filled by AD caregivers were completed before the telehealth shift, and 67.5% were afterwards. Approximately 26.7% of patient PCOMs were filled before the change, and afterwards this percentage rose to 55.0%.ConclusionThe beginning of the Covid‐19 pandemic and subsequent shift towards telehealth‐only practice was associated with greater use of electronic PCOMs by all patients, including those with AD and their caregivers. Increased acceptance of electronic PCOMs seems to offer promising opportunities for remote assessment in the future of dementia diagnosis and care.
Comparison of Event‐Related Potential Markers in Amyloid Positive vs. Amyloid Negative Patients with Mild Cognitive Impairment (MCI) and Dementia in a general neurological clinic
Authors: Levy Igor 
Published: December 2023

AbstractBackgroundWe used an automated Event Related Potentials (ERP) technique to compare ERP responses in amyloid positive and negative group of 75 patients with Mild Cognitive Impairment (MCI) and Dementia in a general neurological outpatient clinic. Over the years, research labs have repeatedly reported abnormal ERP markers in patients with MCI and dementia. Recent advances in technology have made ERP testing safe, easy to use and low cost, thus rendering it suitable for clinical use. Indeed, ERPs have become more routinely used in clinical assessment of neurological patients with cognitive changes. The possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers.MethodPatients with a history of cognitive complains underwent an auditory oddball ERP paradigm in conjunction with routine neurological evaluation and imaging studies. Standard neuropsychological testing were available in most cases. Amyloid PET imaging was done as part of the IDEAS (Imaging Dementia ‐Evidence for Amyloid Scanning) study and provided the readings for amyloid load.ERP responses were analyzed in the context of beta amyloid readings, and in relation to the patients’ degree of cognitive deficits.ResultFinal data analysis will be presented at the time of the conferenceConclusionThe possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers. possibility that ERP could help identify amyloid status in MCI and dementia patients adds to the potential clinical utility of these biomarkers.