Digital Commons Network^™

A Protocol For The Inclusion Of Minoritized Persons In Alzheimer Disease Research From The Adni3 Diversity Taskforce, Ozioma C Okonkwo, Beau M Ances, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.

OBJECTIVE: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from a longitudinal, multisite, …

Naturalistic Assessment Of Reaction Time Variability In Older Adults At Risk For Alzheimer's Disease, Matthew S Welhaf, Hannah Wilks, Andrew J Aschenbrenner, David A Balota, Suzanne E Schindler, Tammie L S Benzinger, Brian A Gordon, Carlos Cruchaga, Chengjie Xiong, John C Morris, Jason Hassenstab

2020-Current year OA Pubs

OBJECTIVE: Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer's disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD.

METHOD: Three hundred and seventy older adults (aged 75.8 +/- 5.8 years) completed a week of remote daily testing on the …

Human Whole-Exome Genotype Data For Alzheimer's Disease, Yuk Yee Leung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to a joint analysis. Here we present a bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen sequencing centers in the Alzheimer's Disease Sequencing Project. The joint-genotype called variant-called format (VCF) file contains only positions within the union of capture kits. The VCF was then processed specifically to account for the batch effects arising from the use of different capture kits from different studies. We identified 8.2 million autosomal variants. 96.82% of the variants are high-quality, and …

A Blood Biomarker Test For Brain Amyloid Impacts The Clinical Evaluation Of Cognitive Impairment, Mark Monane, B Joy Snider, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline.

METHODS: The Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single-arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result …

Evaluation Of The Electronic Clinical Dementia Rating For Dementia Screening, Rachel L Nosheny, Daniel Yen, Krista Moulder, Connie Mayo, Maureen Mcmillan, John C Morris, Yan Li, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The Clinical Dementia Rating (CDR) is a well-validated instrument widely used to detect and stage dementia due to Alzheimer disease. The digital Electronic Clinical Dementia Rating (eCDR) can be remotely self-administered and automatically scored, with potential to facilitate efficient dementia screening and staging.

OBJECTIVE: To evaluate the association of the eCDR with the CDR and other in-clinic assessments for screening older adults for cognitive impairment.

DESIGN, SETTING, AND PARTICIPANTS: This multisite, cross-sectional study used baseline data from a longitudinal, observational study from 2020 to 2023, including up to 3 years of follow-up. Participants were enrolled from 3 Alzheimer Disease …

Novel Vaccine Against Pathological Pyroglutamate-Modified Amyloid Beta For Prevention Of Alzheimer's Disease, Karen Zagorski, Olga King, Armine Hovakimyan, Irina Petrushina, Tatevik Antonyan, Gor Chailyan, Manush Ghazaryan, Krzysztof L Hyrc, Jean Paul Chadarevian, Hayk Davtyan, Mathew Blurton-Jones, David H Cribbs, Michael G Agadjanyan, Anahit Ghochikyan

2020-Current year OA Pubs

Post-translationally modified N-terminally truncated amyloid beta peptide with a cyclized form of glutamate at position 3 (pE

Brain Aerobic Glycolysis And Resilience In Alzheimer Disease, Manu S Goyal, Tyler Blazey, Nicholas V Metcalf, Mark P Mcavoy, Jeremy F Strain, Maryam Rahmani, Tony J Durbin, Chengjie Xiong, Tammie L-S Benzinger, John C Morris, Marcus E Raichle, Andrei G Vlassenko

2020-Current year OA Pubs

The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood. Using PET measurements of regional blood flow, oxygen consumption, and glucose utilization-from which we derive AG-we find that cognitive impairment is strongly associated with loss of the typical youthful pattern of AG. In contrast, amyloid positivity without cognitive impairment was associated with preservation of youthful brain AG, which was even higher …

Effect Of Race On Prediction Of Brain Amyloidosis By Plasma Aβ42/Aβ40, Phosphorylated Tau, And Neurofilament Light, Suzanne E Schindler, Rachel L Henson, Yan Li, Benjamin Saef, Krista L Moulder, David Bradford, Anne M Fagan, Brian A Gordon, Tammie L S Benzinger, Joyce Balls-Berry, Randall J Bateman, Chengjie Xiong, John C Morris, Et Al

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: To evaluate whether plasma biomarkers of amyloid (Aβ42/Aβ40), tau (p-tau181 and p-tau231), and neuroaxonal injury (neurofilament light chain [NfL]) detect brain amyloidosis consistently across racial groups.

METHODS: Individuals enrolled in studies of memory and aging who self-identified as African American (AA) were matched 1:1 to self-identified non-Hispanic White (NHW) individuals by age,

RESULTS: There were 76 matched pairs of AA and NHW participants (n = 152 total). For both AA and NHW groups, the median age was 68.4 years, 42% were

DISCUSSION: Models predicting brain amyloidosis using a high-performance plasma Aβ42/Aβ40 assay may provide an accurate and …

A Conformational Variant Of P53 (U-P53az) As Blood-Based Biomarker For The Prediction Of The Onset Of Symptomatic Alzheimer's Disease, S Piccirella, L Van Neste, C Fowler, C L Masters, J Fripp, J D Doecke, C Xiong, D Uberti, P Kinnon

2020-Current year OA Pubs

BACKGROUND: Ongoing research seeks to identify blood-based biomarkers able to predict onset and progression of Alzheimer's disease (AD).

OBJECTIVE: The unfolded conformational variant of p53 (U-p53AZ), previously observed in AD individuals, was evaluated in plasma samples from individuals participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) cohort for diagnostic and prognostic assessment, validated on a neuropsychological-based diagnosis, over the course of six years.

DESIGN: Retrospective Longitudinal Prognostic biomarker study.

SETTING: Single-center study based on the AIBL cohort.

PARTICIPANTS: 482 participants of the AIBL cohort, aged 60-85 years, without uncontrolled diabetes, vascular disease, severe depression or psychiatric illnesses.

MEASUREMENTS: The …

Is Comprehensiveness Critical? Comparing Short And Long Format Cognitive Assessments In Preclinical Alzheimer Disease, Jason Hassenstab, Jessica Nicosia, Megan Larose, Andrew J Aschenbrenner, Brian A Gordon, Tammie L S Benzinger, Chengjie Xiong, John C Morris

2020-Current year OA Pubs

BACKGROUND: Comprehensive testing of cognitive functioning is standard practice in studies of Alzheimer disease (AD). Short-form tests like the Montreal Cognitive Assessment (MoCA) use a "sampling" of measures, administering key items in a shortened format to efficiently assess cognition while reducing time requirements, participant burden, and administrative costs. We compared the MoCA to a commonly used long-form cognitive battery in predicting AD symptom onset and sensitivity to AD neuroimaging biomarkers.

METHODS: Survival, area under the receiver operating characteristic (ROC) curve (AUC), and multiple regression analyses compared the MoCA and long-form measures in predicting time to symptom onset in cognitively normal …

25-Hydroxycholesterol Amplifies Microglial Il-1Β Production In An Apoe Isoform-Dependent Manner, Man Ying Wong, Michael Lewis, James J Doherty, Yang Shi, Anil G Cashikar, Anna Amelianchik, Svitlana Tymchuk, Patrick M Sullivan, Mingxing Qian, Douglas F Covey, Gregory A Petsko, David M Holtzman, Steven M Paul, Wenjie Luo

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies of Alzheimer's disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling and innate immunity. Cholesterol 25-hydroxylase (CH25H), the enzyme responsible for 25-HC production, has also been found to be one of the disease-associated microglial (DAM) genes that are upregulated in the brain of AD and AD transgenic mouse models.

METHODS: We used real-time PCR and immunoblotting to examine …

White Matter Diffusion Alterations Precede Symptom Onset In Autosomal Dominant Alzheimer's Disease, Miguel Ángel Araque Caballero, Tammie Benzinger, Anne M Fagan, Randall J Bateman, Celeste Karch, John C Morris, Jason Hassenstab, Et Al.

2010-2019 OA Pubs

White matter alterations are present in the majority of patients with Alzheimer's disease type dementia. However, the spatiotemporal pattern of white matter changes preceding dementia symptoms in Alzheimer's disease remains unclear, largely due to the inherent diagnostic uncertainty in the preclinical phase and increased risk of confounding age-related vascular disease and stroke in late-onset Alzheimer's disease. In early-onset autosomal-dominantly inherited Alzheimer's disease, participants are destined to develop dementia, which provides the opportunity to assess brain changes years before the onset of symptoms, and in the absence of ageing-related vascular disease. Here, we assessed mean diffusivity alterations in the white matter …

Left Frontal Hub Connectivity Delays Cognitive Impairment In Autosomal-Dominant And Sporadic Alzheimer's Disease, Nicolai Franzmeier, Anne M Fagan, Katrina Paumier, Tammie Benzinger, John C Morris, Randall J Bateman, Et Al.

2010-2019 OA Pubs

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left …