JournalTOCs

Journal of Prevention of Alzheimer's Disease
Number of Followers: 1

Hybrid journal (It can contain Open Access articles)
ISSN (Online) 2426-0266
Published by Springer-Verlag

[2469 journals]

Association of a MIND Diet with Brain Structure and Dementia in a French
Population
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Background Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines higher consumption of vegetables, berries, nuts, whole grains, olive oil, fish, beans and poultry, with lower consumption of meat, sugars and saturated fats, is a promising strategy to prevent dementia. However, evidence in populations with non-US food culture, especially from Europe, is limited. OBJECTIVES: To evaluate the association of a French-adapted MIND diet score with gray matter volumes, white matter microstructure and incident dementia. Design and Setting This longitudinal study included participants from the population-based Three-City Bordeaux cohort (≥65 years), with a follow-up from June 2001 to February 2018. Participants Dementia-free participants at dietary assessment, in 2001–2002, who underwent systematic detection of incident dementia (over up to 7 visits). A subset of the cohort was included in an ancillary MRI study in 2010–2011. Measurements A French-adapted MIND diet score (range, 0–15) was computed from a 148-item Food Frequency Questionnaire and a 24-hour recall administered at home. Incident dementia and its subtypes were adjudicated by an expert committee; and gray matter volumes and white matter microstructure were assessed by 3D-T1 MRI and diffusion-MRI. RESULTS: Among 1,412 participants (mean age, 75.8 [SD, 4.8]; 63% women), followed for a median of 9.7 years (maximum 16.3 years), 356 (25.2%) developed incident dementia. In multivariable-adjusted Cox model, a higher French MIND diet score was associated with lower risks of dementia and AD (hazard ratios for 1-point of score = 0.89 [95% confidence interval, 0.83–0.95] and 0.88 [0.81–0.96], respectively). In Tract-Based Spatial Statistics analysis of 175 participants included in the MRI sub-study, a higher MIND diet score was associated with lower diffusivity values in the splenium of the corpus callosum (P <.05 after Family-Wise Error-correction). In contrast, there was no significant association of the adapted MIND diet score with gray matter volumes in Voxel-Based Morphometry analysis. Conclusion In this cohort of French older adults, higher adherence to the French MIND diet was associated with a lower dementia risk and with preserved white matter microstructure. These results provide further evidence for a role of the MIND diet in the prevention of dementia.
  PubDate: 2022-08-09
Cognitive Digital Biomarkers from Automated Transcription of Spoken
Language
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Background Although patients with Alzheimer’s disease and other cognitive-related neurodegenerative disorders may benefit from early detection, development of a reliable diagnostic test has remained elusive. The penetration of digital voice-recording technologies and multiple cognitive processes deployed when constructing spoken responses might offer an opportunity to predict cognitive status. Objective To determine whether cognitive status might be predicted from voice recordings of neuropsychological testing Design Comparison of acoustic and (para)linguistic variables from low-quality automated transcriptions of neuropsychological testing (n = 200) versus variables from high-quality manual transcriptions (n = 127). We trained a logistic regression classifier to predict cognitive status, which was tested against actual diagnoses. Setting Observational cohort study. Participants 146 participants in the Framingham Heart Study. Measurements Acoustic and either paralinguistic variables (e.g., speaking time) from automated transcriptions or linguistic variables (e.g., phrase complexity) from manual transcriptions. Results Models based on demographic features alone were not robust (area under the receiver-operator characteristic curve [AUROC] 0.60). Addition of clinical and standard acoustic features boosted the AUROC to 0.81. Additional inclusion of transcription-related features yielded an AUROC of 0.90. Conclusions The use of voice-based digital biomarkers derived from automated processing methods, combined with standard patient screening, might constitute a scalable way to enable early detection of dementia.
  PubDate: 2022-07-13
The Clinical Trials Alzheimer’s Disease (CTAD) Meeting in San Francisco,
Fall 2022, Will Be a Very Exciting Event!
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  PubDate: 2022-07-04
Reply to Letter to the Editor: “Early-Onset Type 2 Diabetes and Risk
of Dementia”
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  PubDate: 2022-07-01
Clinical Trial Endpoints and Their Clinical Meaningfulness in Early Stages
of Alzheimer’s Disease
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Abstract As the focus of Alzheimer’s disease (AD) therapeutic development shifts to the early stages of the disease, the clinical endpoints used in drug trials, and how these might translate into clinical practice, are of increasing importance. The clinical meaningfulness of trial outcome measures is often unclear, with a lack of conclusive evidence as to how these measures correlate to changes in disease progression and treatment response. Clarifying this would benefit all, including patients, care partners, primary care providers, regulators, and payers, and would enhance our understanding of the relationship between clinical trial endpoints and assessments used in everyday practice. At present, there is a wide range of assessment tools used in clinical trials for AD and substantial variability in measures selected as endpoints across these trials. The aim of this review is to summarize the most commonly used assessment tools for early stages of AD, describe their use in clinical trials and clinical practice, and discuss what might constitute clinically meaningful change in these measures in relation to disease progression and treatment response.
  PubDate: 2022-07-01
Association between Dietary Theobromine and Cognitive Function in a
Representative American Population: A Cross-Sectional Study
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Background Despite reports on neuroprotective effects of dietary theobromine intake, whether dietary theobromine has beneficial effects on cognitive function is unclear. Objectives To investigate the association between dietary theobromine and cognitive function. Design A cross-sectional study. Setting Data were collected from the 2011–2014 cycles of the National Health and Nutrition Examination Survey conducted by the Centers for Disease Control and Prevention of the USA. Participants A representative American population aged ≥60 years. Measurements L-theobromine was treated as a log transform and dichotomous form (the highest quantile vs. others). Cognitive function was measured using four tests Consortium to Establish a Registry for Alzheimer’s Disease Word Learning tests, Consortium to Establish a Registry for Alzheimer’s Disease delayed recall test, animal fluency test, and digit symbol substitution test. We conducted multiple regression analyses and subgroup analyses to study the association between theobromine and cognitive performance. Basic characteristics, lifestyle factors, disease history, and nutritional intake were adjusted for in these models. Results A total of 2,845 participants were included in the study. The highest quantile of L-theobromine intake was positively associated with sores of delayed recall, animal fluency, and digit symbol substitution tests (β, 95% confidence interval, P 0.11, −0.00–0.30, 0.049; 0.50, 0.02–0.99, 0.043; 1.55, 0.33–2.77, 0.015; respectively) in the fully adjusted model, but not with immediate recall score (β=0.13, 95% confidence interval −0.16–0.43, P=0.361). Subgroup analyses showed that L-theobromine intake was associated with cognitive performance in the highest quantile of caffeine intake. Conclusions Daily theobromine intake was associated with cognitive performance in a large nationally representative population. However, further research is needed to corroborate our findings.
  PubDate: 2022-07-01
Cerebral Phospho-Tau Acts Synergistically with Soluble Aβ42 Leading to
Mild Cognitive Impairment in AAV-AD Rats
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Background Alzheimer’s disease (AD) is a continuum of events beginning with an increase in brain soluble Aβ342 followed by the appearance of hyperphosphorylated tau (P-tau, asymptomatic stage). Mild Cognitive Impairment (MCI) then appears (prodromal stage). However, the individual contribution of these two soluble proteins in the onset of the first cognitive symptoms remains unclear. Objectives We sought to understand the specific impact of p-tau on the development of MCI in the AAV-AD rat model, a model of late-onset Alzheimer’s disease (LOAD) predementia. Methods We specifically reduced the phosphorylation level of tau while leaving Aβ342 levels unchanged using a DYRK1A protein kinase inhibitor, Leucettine L41, in an adeno-associated virus-based Alzheimer’s disease (AAV-AD) rat model. Leucettine L41 was administered by intraperitoneal injection at 20 mg/kg per day in AAV-AD rats from 9 (late asymptomatic phase) to 10 (prodromal phase) months of age. Results Decreased soluble forms of P-tau induced by chronic administration of Leucettine L41 did not change soluble Aβ342 levels but prevented MCI onset in 10-month-old AAV-AD rats. Conclusions The present study argues that P-tau is required to induce the development of MCI. Consistent with our previous findings that soluble Aβ342 is also required for MCI onset, the data obtained in the AAV-AD rat model confirm that the transition from the asymptomatic to the prodromal stage may be caused by the combined presence of both soluble brain forms of Aβ342 and p-tau, suggesting that the development of MCI may be the consequence of their synergistic action.
  PubDate: 2022-07-01
What Matters to Patients with Alzheimer’s Disease and Their Care
Partners' Implications for Understanding the Value of Future
Interventions
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Abstract Alzheimer’s Disease (AD) is the most common cause of dementia. Recent thinking portrays AD as a continuum consisting of three stages: an asymptomatic preclinical period, a mild cognitive impairment phase, and dementia, which can be further classified as mild, moderate or severe. While many studies explore the cognitive and functional aspects of AD, fully understanding AD pathophysiology, as well as the potential value of pharmacological and psycho-social interventions, requires a deeper understanding of patient and care partner priorities, particularly in the early stages where such interventions may have the greatest impact in slowing or delaying progression. Available studies highlight a diverse range of patient and care partner priorities, including impacts on their emotions, moods, and social lives. These priorities have not been systematically incorporated in the clinical and value assessments of potential interventions. We propose approaches to better understand the humanistic impact of AD including conducting additional research into the impacts of interventions from the point of view of patients and care partners, expanding notions of ‘value’ and improving health system capacity for diagnosis.
  PubDate: 2022-07-01
Decreased Gray—White Matter Contrast of [11C]-PiB Uptake in Cognitively
Unimpaired Subjects with Severe Obstructive Sleep Apnea
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Background Very recently, cognitively normal, middle-aged adults with severe obstructive sleep apnea (OSA) were shown to have regional cortical amyloid-β deposits. In the normal brain, amyloid tracer (e.g., [11C]-PiB) uptake is observed in white matter (WM) but not in cortical gray matter (GM), resulting in clear GM—WM contrast. There are no reports on possible changes in this contrast in severe OSA. Objectives Evaluate changes in the global [11C]-PiB GM—WM contrast and study if factors reflecting clinical and imaging characteristics are associated with them. Design and Setting Cross-sectional imaging study. Participants 19 cognitively intact middle-aged (mean 44 years) patients with severe OSA (Apnea—Hypopnea Index >30/h), carefully selected to exclude any other possible factors that could alter brain health. Measurements Detailed neuroimaging (amyloid PET, MRI). Signs of possible alterations in amyloid tracer GM—WM contrast and kinetics were studied with static and dynamic [11C]-PiB PET and WM structures with detailed 3.0T MRI. Results Static [11C]-PiB PET uptake showed significantly decreased GM—WM contrast in 5 out of 19 patients. This was already clearly seen in visual evaluation and also detected quantitatively using retention indexes. Dynamic imaging revealed decreased contrast due to alterations in trace accumulation in the late phase of [11C]-PiB kinetics. Decreased GM—WM contrast in the late phase was global in nature. MRI revealed no corresponding alterations in WM structures. Importantly, decreased GM—WM contrast was associated with smoking (p = 0.007) and higher Apnea—Hypopnea Index (p = 0.001). Conclusions Severe OSA was associated with decreased GM—WM contrast in amyloid tracer uptake, with significant correlation with clinical parameters of smoking and AHI. The results support and further extend the current understanding of the deleterious effect of severe OSA on proper amyloid clearance, possibly reflecting dysfunction of the brain glymphatic system.
  PubDate: 2022-07-01
Mesenchymal Stem Cells Modulate SIRT1/MiR-134/GSK3β Signaling Pathway in
a Rat Model of Alzheimer’s Disease
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Abstract Prolonged exposure to environmental aluminum-containing substances is associated with the development of Alzheimer’s disease (AD). AD is a brain disorder associated with a gradual weakening in neurocognitive functions. Mesenchymal stem cells (MSCs) transplant as a promising and safe approach is used to treat AD through countless mechanisms. Therefore, this study aims to elucidate how MSCs improve biochemical and histopathological approaches associated with the AD model in rats. MSCs treatment restores the redox status impairment through a notable decline in the malondialdehyde (MDA) levels along with antioxidant enrichment. The anti-inflammatory effect of MSCs through conversion of microglial cells from M1 to M2 and inhibition of pro-inflammatory mediator’s release work in with de-activated GSK-3β. Additionally, the alleviation of autophagy and lysosomal clearance of Aβ and tau aggregates was accompanied by a down-regulation of the mTOR. Moreover, MSCs upregulate the expression of SIRT1 together with a limited expression of miR-134 thereby, improve neurite outgrowth and synaptic loss. Overall, the obtained data confirm the novelty of MSCs in the treatment of AD not only by their antioxidant, anti-inflammatory effect but also by restoring the neural integrity, neurogenesis, improving the neurocognitive function, and modulation of the signal pathways linked to the Aβ hypothesis.
  PubDate: 2022-07-01
Site Readiness Framework to Improve Health System Preparedness for a
Potential New Alzheimer’s Disease Treatment Paradigm
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Abstract New therapies that address the underlying pathophysiology of Alzheimer’s Disease (AD), coupled with the growth of the AD population, will transform the AD care pathway and present significant challenges to health systems. We explored real-world challenges health systems may face in delivering potential new AD therapies with diverse stakeholders. Key challenges in care included integrating primary care providers into assessment and management, availability of memory care specialists, understanding payment and coverage issues and training mid-level providers to help coordinate care and serve as a shared resource across the system. This input informed a novel Site Readiness Framework for AD, comprising self-assessment exercises to identify health system capabilities and gaps and a framework of core strategies and responsive tools to help prepare to integrate new AD therapies. These resources may help health systems improve readiness to modify care pathways to integrate new therapies for AD.
  PubDate: 2022-07-01
Effects of Non-Invasive Brain Stimulation on Alzheimer’s Disease
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Background Previous meta-analyses did not explore the immediate and long-term effect of non-invasive brain stimulation (NIBS) on different cognitive domains in Alzheimer’s disease (AD). The meta-analysis aimed to assess the therapy effect of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on different cognitive domains in AD in randomized controlled trials (RCTs). Methods Studies published before December 2021 and exploring therapy effect of rTMS, tDCS on different cognitive domains in AD were searched in the following databases: PubMed and Web of Science. We used STATA 12.0 software to compute the standard mean difference (SMD) and a 95% confidence interval (CI). Results The present study included 16 articles (including 372 AD patients treated with rTMS and 310 treated with sham rTMS) for rTMS and 11 articles (including 152 AD patients treated with tDCS and 134 treated with sham tDCS) for tDCS. The present study showed better immediate and long-term general cognitive function increase effects in AD given rTMS, compared to those given sham rTMS with random effects models (immediate effect: SMD = 2.07, 95% CI = 0.37 to 3.77, I2 = 97.8%, p < 0.001; long-term effect: SMD = 5.04, 95% CI = 2.25 to 7.84, I2 = 97.8%, p < 0.001). The present study showed no significant immediate and long-term effects of rTMS on attention, executive, language and memory functions. In addition, the present study showed no significant difference in immediate or long-term effects of tDCS on general cognitive function, attention, language or memory functions between tDCS group and sham tDCS group. Conclusions RTMS was an effective treatment technique for general cognitive function in AD, whereas tDCS showed no significant therapy effect on cognitive function in AD. More large-scale studies were essential to explore the effect of NIBS on various cognitive function in AD.
  PubDate: 2022-07-01
Evaluation of the Feasibility, Safety and Efficacy of the Use of
Intravenous Infusions of Adenosine Triphosphate (ATP) in People Affected
by Moderate to Severe Alzheimer’s Disease: A Double-Blind Masked
Clinical Trial for Dose Finding
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Background There are currently no drug therapies modifying the natural history of patients suffering Alzheimer’s disease (AD). Most recent clinical trials in the field include only subjects in early stage of the disease, while patients with advanced AD are usually not represented. Objectives To evaluate the feasibility, safety and efficacy of systemic infusions of adenosine triphosphate (ATP) in patients with moderate to severe AD, and to select the minimum effective dose of infusion. Design A phase IIb, randomized, double-blind, placebo-controlled clinical trial investigates. Participants A total of 20 subjects with moderate or severe AD were included, 16 in the treatment group and 4 in the placebo group (4:1 randomization) at two dosage regimens, 6-hour or 24-hour infusions. Results The proof-of-concept study was successfully conducted, with no significant deviations from the study protocol and no serious adverse events reported. Regarding efficacy, only marginal differences were observed between ATP and placebo arms for H-MRS and MMSE variables. Conclusions Our study demonstrates that the use of ATP infusion as therapy is feasible and safe. Larger studies are however needed to assess the efficacy of ATP in moderate to severe AD.
  PubDate: 2022-07-01
Aging, Senescence, and Dementia
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Abstract The underlying processes occurring in aging are complex, involving numerous biological changes that result in chronic cellular stress and sterile inflammation. One of the main hallmarks of aging is senescence. While originally the term senescence was defined in the field of oncology further research has established that also microglia, astrocytes and neurons become senescent. Since age is the main risk factor for neurodegenerative diseases, it is reasonable to argue that cellular senescence might play a major role in Alzheimer’s disease. Specific cellular changes seen during Alzheimer’s disease are similar to those observed during senescence across all resident brain cell types. Furthermore, increased levels of senescence-associated secretory phenotype proteins such as IL-6, IGFBP, TGF-β and MMP-10 have been found in both CSF and plasma samples from Alzheimer’s disease patients. In addition, genome-wide association studies have identified that individuals with Alzheimer’s disease carry a high burden of genetic risk variants in genes known to be involved in senescence, including ADAMIO, ADAMTS4, and BIN1. Thus, cellular senescence is emerging as a potential underlying disease process operating in Alzheimer’s disease. This has also attracted more attention to exploiting cellular senescence as a therapeutic target. Several senolytic compounds with the capability to eliminate senescent cells have been examined in vivo and in vitro with notable results, suggesting they may provide a novel therapeutic avenue. Here, we reviewed the current knowledge of cellular senescence and discussed the evidence of senescence in various brain cell types and its putative role in inflammaging and neurodegenerative processes.
  PubDate: 2022-07-01
Clinical Research Investigating Alzheimer’s Disease in China: Current
Status and Future Perspectives Toward Prevention
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Abstract Based on the background of research investigating brain aging and neurodegenerative diseases in China, the present review addresses Alzheimer’s disease (AD), one of the most common types of neurodegenerative diseases, clinical research progress, and prospects for future development in China.
  PubDate: 2022-07-01
The Dawn of a New Era of Alzheimer’s Research and Drug Development
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  PubDate: 2022-07-01
Tackling a Major Deficiency of Diversity in Alzheimer’s Disease
Therapeutic Trials: An CTAD Task Force Report
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Abstract As the last opportunity to assess treatment effect modification in a controlled setting prior to formal approval, clinical trials are a critical tool for understanding the safety and efficacy of new treatments in diverse populations. Recruitment of diverse participants in Alzheimer’s Disease (AD) clinical trials are therefore essential to increase the generalizability of study results, with diversity broadly described to be representative and inclusive. This representation of study participants is equally critical in longitudinal cohort (observational) studies, which will be key to understanding disease disparities and are often used to design adequately powered AD clinical trials. New and innovative recruitment initiatives and enhanced infrastructure facilitate increased participant diversity in AD clinical studies.
  PubDate: 2022-05-13
  DOI: 10.14283/jpad.2022.50
Prediction of Cognitive Decline for Enrichment of Alzheimer’s
Disease Clinical Trials
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Background A key issue to Alzheimer’s disease clinical trial failures is poor participant selection. Participants have heterogeneous cognitive trajectories and many do not decline during trials, which reduces a study’s power to detect treatment effects. Trials need enrichment strategies to enroll individuals who are more likely to decline. Objectives To develop machine learning models to predict cognitive trajectories in participants with early Alzheimer’s disease and presymptomatic individuals over 24 and 48 months respectively. Design Prognostic machine learning models were trained from a combination of demographics, cognitive tests, APOE genotype, and brain imaging data. Setting Data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), National Alzheimer’s Coordinating Center (NACC), Open Access Series of Imaging Studies (OASIS-3), PharmaCog, and a Phase 3 clinical trial in early Alzheimer’s disease were used for this study. Participants A total of 2098 participants who had demographics, cognitive tests, APOE genotype, and brain imaging data, as well as follow-up visits for 24–48 months were included. Measurements Baseline magnetic resonance imaging, cognitive tests, demographics, and APOE genotype were used to separate decliners, defined as individuals whose CDR-Sum of Boxes scores increased during a predefined time window, from stable individuals. A prognostic model to predict decline at 24 months in early Alzheimer’s disease was trained on 1151 individuals who had baseline diagnoses of mild cognitive impairment and Alzheimer’s dementia from ADNI and NACC. This model was validated on 115 individuals from a placebo arm of a Phase 3 clinical trial and 76 individuals from the PharmaCog dataset. A second prognostic model to predict decline at 48 months in presymptomatic populations was trained on 628 individuals from ADNI and NACC who were cognitively unimpaired at baseline. This model was validated on 128 individuals from OASIS-3. Results The models achieved up to 79% area under the curve (cross-validated and out-of-sample). Power analyses showed that using prognostic models to recruit enriched cohorts of predicted decliners can reduce clinical trial sample sizes by as much as 51% while maintaining the same detection power. Conclusions Prognostic tools for predicting cognitive decline and enriching clinical trials with participants at the highest risk of decline can improve trial quality, derisk endpoint failures, and accelerate therapeutic development in Alzheimer’s disease.
  PubDate: 2022-05-05
  DOI: 10.14283/jpad.2022.49
Standardizing Electronic Health Record Data on AD/ADRD to Accelerate
Health Equity in Prevention, Detection, and Treatment
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  Abstract: Abstract Improving the prevention, detection, and treatment of Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) across racial, ethnic, and other diverse populations is a national priority. To this end, this paper proposes the development of the Standard Health Record for Dementia (SHRD, pronounced “shared”) for collecting and sharing AD/ADRD real-world data (RWD). SHRD would replace the current unstandardized, fragmented, or missing state of key RWD with an open source, consensus-based, and interoperable common data standard. This paper describes how SHRD could leverage the best practices of the Minimal Common Oncology Data Elements (mCODE™) initiative to advance prevention, detection, and treatment; gain adoption by clinicians and electronic health record (EHR) vendors; and establish sustainable business and governance models. It describes a range of potential use cases to advance equity, including strengthening public health surveillance by facilitating AD/ADRD registry reporting; improving case detection and staging; and diversifying participation in clinical trials.
  PubDate: 2022-05-02
  DOI: 10.14283/jpad.2022.47
Early-Onset Type 2 Diabetes and Risk of Dementia
- Free pre-print version: Loading...
  Rate this result: What is this?
  
  Please help us test our new pre-print finding feature by giving the pre-print link a rating.
  A 5 star rating indicates the linked pre-print has the exact same content as the published article.
  
  PubDate: 2022-04-28
  DOI: 10.14283/jpad.2022.43