scholarly journals Impaired perfusion and capillary dysfunction in prodromal Alzheimer's disease

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Rune B. Nielsen ◽  
Peter Parbo ◽  
Rola Ismail ◽  
Rikke Dalby ◽  
Anna Tietze ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prodromal Alzheimer’S Disease ◽  
Capillary Dysfunction

scholarly journals On the design of early-phase Alzheimer’s disease clinical trials with cerebrospinal fluid tau outcomes

2021 ◽  
pp. 174077452110344
Author(s):  
Michelle M Nuño ◽  
Joshua D Grill ◽  
Daniel L Gillen ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cerebrospinal Fluid ◽  
Phosphorylated Tau ◽  
Inclusion Criteria ◽  
Eligibility Criteria ◽  
Total Tau ◽  
Prodromal Alzheimer’S Disease ◽  
Study Power

Background/Aims: The focus of Alzheimer’s disease studies has shifted to earlier disease stages, including mild cognitive impairment. Biomarker inclusion criteria are often incorporated into mild cognitive impairment clinical trials to identify individuals with “prodromal Alzheimer’s disease” to ensure appropriate drug targets and enrich for participants likely to develop Alzheimer’s disease dementia. The use of these eligibility criteria may affect study power. Methods: We investigated outcome variability and study power in the setting of proof-of-concept prodromal Alzheimer’s disease trials that incorporate cerebrospinal fluid levels of total tau (t-tau) and phosphorylated (p-tau) as primary outcomes and how differing biomarker inclusion criteria affect power. We used data from the Alzheimer’s Disease Neuroimaging Initiative to model trial scenarios and to estimate the variance and within-subject correlation of total and phosphorylated tau. These estimates were then used to investigate the differences in study power for trials considering these two surrogate outcomes. Results: Patient characteristics were similar for all eligibility criteria. The lowest outcome variance and highest within-subject correlation were obtained when phosphorylated tau was used as an eligibility criterion, compared to amyloid beta or total tau, regardless of whether total tau or phosphorylated tau were used as primary outcomes. Power increased when eligibility criteria were broadened to allow for enrollment of subjects with either low amyloid beta or high phosphorylated tau. Conclusion: Specific biomarker inclusion criteria may impact statistical power in trials using total tau or phosphorylated tau as the primary outcome. In concert with other important considerations such as treatment target and population of clinical interest, these results may have implications to the integrity and efficiency of prodromal Alzheimer’s disease trial designs.

scholarly journals Event-related potential and EEG oscillatory predictors of verbal memory in mild cognitive impairment

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Jiangyi Xia ◽  
Ali Mazaheri ◽  
Katrien Segaert ◽  
David P Salmon ◽  
Danielle Harvey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Verbal Memory ◽  
Verbal Learning ◽  
Event Related Potential ◽  
Single Trial ◽  
Prodromal Alzheimer’S Disease ◽  
Alpha Beta

Abstract Reliable biomarkers of memory decline are critical for the early detection of Alzheimer’s disease. Previous work has found three EEG measures, namely the event-related brain potential P600, suppression of oscillatory activity in the alpha frequency range (∼10 Hz) and cross-frequency coupling between low theta/high delta and alpha/beta activity, each of which correlates strongly with verbal learning and memory abilities in healthy elderly and patients with mild cognitive impairment or prodromal Alzheimer’s disease. In the present study, we address the question of whether event-related or oscillatory measures, or a combination thereof, best predict the decline of verbal memory in mild cognitive impairment and Alzheimer’s disease. Single-trial correlation analyses show that despite a similarity in their time courses and sensitivities to word repetition, the P600 and the alpha suppression components are minimally correlated with each other on a trial-by-trial basis (generally |rs| < 0.10). This suggests that they are unlikely to stem from the same neural mechanism. Furthermore, event-related brain potentials constructed from bandpass filtered (delta, theta, alpha, beta or gamma bands) single-trial data indicate that only delta band activity (1–4 Hz) is strongly correlated (r = 0.94, P < 0.001) with the canonical P600 repetition effect; event-related potentials in higher frequency bands are not. Importantly, stepwise multiple regression analyses reveal that the three event-related brain potential/oscillatory measures are complementary in predicting California Verbal Learning Test scores (overall R2’s in 0.45–0.63 range). The present study highlights the importance of combining EEG event-related potential and oscillatory measures to better characterize the multiple mechanisms of memory failure in individuals with mild cognitive impairment or prodromal Alzheimer’s disease.

O1-07-08: Resting brain metabolic connectivity in prodromal Alzheimer's disease: Evidence for early functional disconnection-An EADC joint project.

2011 ◽  
Vol 7 ◽  
pp. S111-S112 ◽  
Author(s):  
Flavio Nobili ◽  
Rik Ossenkoppele ◽  
Alexander Drzezga ◽  
Bart van Berckel ◽  
Giovanni Frisoni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Joint Project ◽  
Prodromal Alzheimer’S Disease ◽  
Metabolic Connectivity

scholarly journals The use of genetic risk prediction to study prodromal Alzheimer’s disease in the PISA study

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Michelle K. Lupton ◽  
Amir Fazlollahi ◽  
Amelia Ceslis ◽  
Jurgen Fripp ◽  
Stephen Rose ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Prediction ◽  
Genetic Risk ◽  
Genetic Risk Prediction ◽  
Prodromal Alzheimer’S Disease

scholarly journals RECRUITMENT INTO THE ALZHEIMER PREVENTION TRIALS (APT) WEBSTUDY FOR A TRIAL-READY COHORT FOR PRECLINICAL AND PRODROMAL ALZHEIMER’S DISEASE (TRCPAD)

2020 ◽  
pp. 1-7
Author(s):  
S. Walter ◽  
T.B. Clanton ◽  
O.G. Langford ◽  
M.S. Rafii ◽  
E.J. Shaffer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Effective Means ◽  
Web Based ◽  
The Us ◽  
Study Team ◽  
Prodromal Alzheimer’S Disease ◽  
Prevention Trials ◽  
Study Participants ◽  
The Impact

BACKGROUND: The Alzheimer Prevention Trials (APT) Webstudy is the first stage in establishing a Trial-ready Cohort for Preclinical and Prodromal Alzheimer’s disease (TRC-PAD). This paper describes recruitment approaches for the APT Webstudy. Objectives: To remotely enroll a cohort of individuals into a web-based longitudinal observational study. Participants are followed quarterly with brief cognitive and functional assessments, and referred to Sites for in-clinic testing and biomarker confirmation prior to enrolling in the Trial-ready Cohort (TRC). Design: Participants are referred to the APT Webstudy from existing registries of individuals interested in brain health and Alzheimer’s disease research, as well as through central and site recruitment efforts. The study team utilizes Urchin Tracking Modules (UTM) codes to better understand the impact of electronic recruitment methods. Setting: A remotely enrolled online study. Participants: Volunteers who are at least 50 years old and interested in Alzheimer’s research. Measurements: Demographics and recruitment source of participant where measured by UTM. Results: 30,650 participants consented to the APT Webstudy as of April 2020, with 69.7% resulting from referrals from online registries. Emails sent by the registry to participants were the most effective means of recruitment. Participants are distributed across the US, and the demographics of the APT Webstudy reflect the referral registries, with 73.1% female, 85.0% highly educated, and 92.5% Caucasian. Conclusions: We have demonstrated the feasibility of enrolling a remote web-based study utilizing existing registries as a primary referral source. The next priority of the study team is to engage in recruitment initiatives that will improve the diversity of the cohort, towards the goal of clinical trials that better represent the US population.

scholarly journals The frequency and influence of dementia risk factors in prodromal Alzheimer's disease

2017 ◽  
Vol 56 ◽  
pp. 33-40 ◽  
Author(s):  
Isabelle Bos ◽  
Stephanie J. Vos ◽  
Lutz Frölich ◽  
Johannes Kornhuber ◽  
Jens Wiltfang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dementia Risk ◽  
Prodromal Alzheimer’S Disease
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