Jpad-Journal of Prevention of Alzheimers Disease最新文献

{"title":"Preferences about Future Alzheimer’s Disease Treatments Elicited through an Online Survey Using the Threshold Technique","authors":"Sonia Roldan Munoz, S. T. de Vries, G. Lankester, F. Pignatti, B. C. van Munster, I. Radford, L. Guizzaro, P. G. M. Mol, H. Hillege, D. Postmus","doi":"10.14283/jpad.2023.84","DOIUrl":"https://doi.org/10.14283/jpad.2023.84","url":null,"abstract":"Treatments aiming at slowing down the progression of Alzheimer’s disease (AD) may soon become available. However, information about the risks that people are willing to accept in order to delay the progression of the disease is limited. To determine the trade-offs that individuals are willing to make between the benefits and risks of hypothetical treatments for AD, and the extent to which these trade-offs depend on individuals’ characteristics and beliefs about medicines. Online, cross-sectional survey study. Population in the UK. Public link to the survey available at the websites of Alzheimer’s Research UK and Join Dementia Research. Everyone self-reported ≥18 years old was eligible to participate. A total of 4384 people entered the survey and 3658 completed it. The maximum acceptable risks (MARs) of participants for moderate and severe adverse events in exchange for a 2-year delay in disease progression. The risks were expressed on ordinal scales, from <10% to ≥50%, above a pre-existing risk of 30% for moderate adverse events and 10% for severe adverse events. We obtained the population median MARs using log-normal survival models and quantified the effects of individuals’ characteristics and beliefs about medicines in terms of acceleration factors. For the moderate adverse events, 26% of the participants had a MAR ≥50%, followed by 25% of the participants with a MAR of 10 to <20%, giving an estimated median MAR of 25.4% (95% confidence interval [CI] 24.5 to 26.3). For the severe adverse events, 43% of the participants had a MAR <10%, followed by 25% of the participants with a MAR of 10 to <20%, resulting in an estimated median MAR of 12.1% (95%CI 11.6 to 12.5). Factors that were associated with the individuals’ MARs for one or both adverse events were age, gender, educational level, living alone, and beliefs about medicines. Whether or not individuals were living with memory problems or had experience as a caregiver had no effect on the MARs for any of the adverse events. Trade-offs between benefits and risks of AD treatments are heterogeneous and influenced by individuals’ characteristics and beliefs about medicines. This heterogeneity should be acknowledged during the medicinal product decision-making in order to fulfil the needs of the various subpopulations.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"756 - 764"},"PeriodicalIF":6.4,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing the Effects of Ageing on Cognition with Therapeutic Intervention of an Oral Multi-Nutrient: The REACTION Pilot Trial Study Design","authors":"Christian J. Camargo, S. Merritt, M. Modjeski, D. S. Counotte, K. Fernández McInerney","doi":"10.14283/jpad.2023.81","DOIUrl":"https://doi.org/10.14283/jpad.2023.81","url":null,"abstract":"Clinical benefits have been reported with a specific multinutrient intervention (Souvenaid) in Alzheimer’s disease and mild cognitive impairment due to Alzheimer’s disease. The effects of Souvenaid in age-related cognitive decline are not established. To assess the feasibility of using virtual assessments to study the effects of a multinutrient on cognitive ageing. This is a randomized, double-blind, placebo-controlled, parallel group virtual pilot trial performed over 6 months in a single-centre. Participants are randomly allocated (1:1) to receive the specific multinutrient (Souvenaid) or an isocaloric, same tasting, placebo. Trial visits are done virtually using secure online video communication. English or Spanish speaking people aged 55–89 years from all ethnic groups and considered to have age-related cognitive decline are eligible. Neuropyschological tests are done at baseline and after 6 months of intervention. Participants are contacted monthly by telephone to monitor safety, assess motivation and promote compliance. The primary outcome is feasibility determined by assessing recruitment rate, recruitment time, adherence rate and retention rate. A comprehensive set of neuropyschological measures will provide a broad assessment of cognitive function, including verbal memory, processing speed, and attention and executive function. Self-reported questionnaires are used to assess quality of life. This pilot trial will provide data to guide inform selection of participants and outcome measures in future studies in age-related cognitive decline.","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"821 - 827"},"PeriodicalIF":6.4,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Dietary Cholesterol and Dementia Risk.","authors":"L T Middleton, E Riboli","doi":"10.14283/jpad.2023.66","DOIUrl":"10.14283/jpad.2023.66","url":null,"abstract":"","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"746-747"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocol of a Phase II Randomized, Multi-Center, Double-Blind, Placebo-Controlled Trial of S-Adenosyl Methionine in Participants with Mild Cognitive Impairment or Dementia Due to Alzheimer's Disease.","authors":"S Holper, R Watson, L Churilov, P Yates, Y Y Lim, K J Barnham, N Yassi","doi":"10.14283/jpad.2023.55","DOIUrl":"10.14283/jpad.2023.55","url":null,"abstract":"<p><strong>Background: </strong>S-adenosyl methionine (SAMe) is a pivotal metabolite in multiple pathways required for neuronal homeostasis, several of which are compromised in Alzheimer's disease (AD). Correction of the SAMe deficiency that is characteristic of the AD brain may attenuate or prevent pathological processes driving AD-associated neurodegeneration including aberrant tau hyperphosphorylation and DNA hypomethylation.</p><p><strong>Objectives: </strong>The primary aim is to test the hypothesis that daily treatment with 400 mg oral SAMe for 180 days will lead to a greater reduction from baseline in plasma levels of p-tau181 compared to placebo in patients with mild cognitive impairment or dementia due to AD.</p><p><strong>Design, setting, participants: </strong>This is a phase II, randomized, multi-center, double-blind, placebo-controlled trial among 60 participants with mild cognitive impairment or dementia due to AD. Participants will be randomized in a 1:1 ratio to receive either SAMe or matching placebo, to be taken as an adjunct to their AD standard of care.</p><p><strong>Measurements and results: </strong>The primary outcome is change in plasma p-tau181 concentration between baseline and following 180 days of treatment, which will be compared between the active and placebo group. Secondary outcomes are the safety of SAMe administration (incidence of serious adverse events), change from baseline in cognitive performance (as measured by the Repeatable Battery for the Assessment of Neuropsychological Status), and epigenetic changes in DNA methylation.</p><p><strong>Conclusion: </strong>Demonstration of effective and safe lowering of plasma p-tau181 with SAMe in this phase II trial would pave the way for an exciting field of translational research and a larger phase III trial.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"800-809"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47271564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Findings of PreventE4: A Double-Blind Placebo Controlled Clinical Trial Testing High Dose DHA in APOE4 Carriers before the Onset of Dementia.","authors":"H N Yassine, I C Arellanes, A Mazmanian, L De La Cruz, J Martinez, L Contreras, N Kono, B S Liu, D Badie, M A Bantugan, A Grindon, T Urich, L D'Orazio, B A Emmanuel, H C Chui, W J Mack, M G Harrington, M N Braskie, L S Schneider","doi":"10.14283/jpad.2023.77","DOIUrl":"10.14283/jpad.2023.77","url":null,"abstract":"<p><strong>Introduction: </strong>Lower blood levels of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) are correlated with worse cognitive functions, particularly among APOE ε4 carriers. Whether DHA supplementation in APOE ε4 carriers with limited DHA consumption and dementia risk factors can delay or slow down disease progression when started before the onset of clinical dementia is not known.</p><p><strong>Methods: </strong>PreventE4 is a double-blind, single site, randomized, placebo-controlled trial in cognitively unimpaired individuals with limited omega-3 consumption and dementia risk factors (n=368). Its objectives are to determine (1) whether carrying the APOE ε4 allele is associated with lower delivery of DHA to the brain; and (2) whether high dose DHA supplementation affects brain imaging biomarkers of AD and cognitive function.</p><p><strong>Results: </strong>365 cognitively unimpaired individuals between 55 and 80 (mean age 66) were randomized to 2 grams of DHA per day or identically appearing placebo for a period of 2 years. Half the participants were asked to complete lumbar punctures at baseline and 6-month visits to obtain cerebrospinal fluid (CSF). The primary trial outcome measure is the change in CSF DHA to arachidonic acid ratio after 6 months of the intervention (n=181). Secondary trial outcomes include the change in functional and structural connectivity using resting state functional MRI at 24 months (n=365). Exploratory outcomes include the change in Repeatable Battery of the Assessment of Neuropsychological Status at 24 months (n=365).</p><p><strong>Conclusions: </strong>Findings from PreventE4 will clarify the brain delivery of DHA in individuals carrying the APOE ε4 allele with implications for dementia prevention strategies. Trial was registered as NCT03613844.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"810-820"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Oligomer β-Amyloid and White Matter Microstructural Integrity in Cognitively Normal Older Adults According to Cerebral Amyloid Deposition.","authors":"Sheng-Min Wang, Dong Woo Kang, Yoo Hyun Um, Sunghwan Kim, Chang Uk Lee, Philip Scheltens, Hyun Kook Lim","doi":"10.14283/jpad.2023.87","DOIUrl":"10.14283/jpad.2023.87","url":null,"abstract":"<p><strong>Background: </strong>Multimer detection system-oligomeric amyloid-β (MDS-OAβ) measure plasma OAβ level, which is associated with earlier Alzheimer's disease (AD) pathology. However, no study has investigated MDS-OAβ differences in cognitive normal older adults (CN) with or without cerebral Aβ burden and its correlation with Aβ deposition and white matter (WM) integrity.</p><p><strong>Objective: </strong>To investigate associations among cerebral Aβ burden, MDS-OAβ, and WM integrity in CN.</p><p><strong>Design: </strong>This is a single center, cross-sectional study which used data from Catholic Aging Brain Imaging (CABI) database.</p><p><strong>Setting: </strong>CABI database contains brain scans of patients who visited the outpatient clinic at Catholic Brain Health Center, Yeouido St. Mary's Hospital, The Catholic University of Korea, between 2017 and 2022.</p><p><strong>Participants: </strong>A total 34 amyloid-PET negative CN and 23 amyloid-PET positive CN were included.</p><p><strong>Measurements: </strong>Plasma Aβ level using MDS-OAβ, cerebral Aβ deposition level using global standardized uptake value ratio (SUVR) values, WM integrity using fractional anisotropy (FA) and mean diffusivity (MD), and cortical thickness from structural MRI were utilized.</p><p><strong>Restuls: </strong>The amyloid-PET positive group showed higher MDS-OAβ level than the amyloid-PET negative group (0.997 ± 0.19 vs. 0.79 ± 0.28, P <0.005), but they did not differ in WM integrity or cortical thickness. The MDS-OAβ positive group showed higher global cerebral Aβ deposition or mean global SUVR values (0.609 ± 0.135 vs. 0.533 ± 0.121 vs. P <0.05), lower regional FA of left forceps minor and the right superior longitudinal fasciculus (family-wise error rate, p <0.05), and lower cortical thickness of left fusiform (p <0.05, Monte Carlo simulation) than the MDS-OAβ negative group. MDS-OAβ was positively associated with global cerebral Aβ deposition (r=0.278, P <0.05) and negatively associated (r = - 0.324, P < 0.05) with regional WM integrity.</p><p><strong>Conclusions: </strong>In this study, MDS-OAβ value demonstrated earlier and different AD pathology than cerebral Aβ retention according to amyloid-PET. Longitudinal studies are needed to elucidate the causal relationships of plasma OAβ and cerebral Aβ with WM integrity disturbance and cortical atrophy during the AD trajectory.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"837-846"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotypic Effects of the TOMM40'523 Variant and APOE on Longitudinal Cognitive Change over 4 Years: The TOMMORROW Study.","authors":"H Zou, S Luo, H Liu, M W Lutz, D A Bennett, B L Plassman, K A Welsh-Bohmer","doi":"10.14283/jpad.2023.115","DOIUrl":"10.14283/jpad.2023.115","url":null,"abstract":"<p><strong>Background: </strong>The 523 poly-T length polymorphism (rs10524523) in TOMM40 has been reported to influence longitudinal cognitive test performance within APOE ε3/3 carriers. The results from prior studies are inconsistent. It is also unclear whether specific APOE and TOMM40 genotypes contribute to heterogeneity in longitudinal cognitive performance during the preclinical stages of AD.</p><p><strong>Objectives: </strong>To determine the effects of these genes on longitudinal cognitive change in early preclinical stages of AD, we used the clinical trial data from the recently concluded TOMMORROW study to examine the effects of APOE and TOMM40 genotypes on neuropsychological test performance.</p><p><strong>Design: </strong>A phase 3, double-blind, placebo-controlled, randomized clinical trial.</p><p><strong>Setting: </strong>Academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA.</p><p><strong>Participants: </strong>Cognitively normal older adults aged 65 to 83.</p><p><strong>Intervention: </strong>Pioglitazone tablet.</p><p><strong>Measurements: </strong>Participants from the TOMMORROW trial were stratified based on APOE genotype (APOE ε3/3, APOE ε3/4, APOE ε4/4). APOE ε3/3 carriers were further stratified by TOMM40'523 genotype. The final analysis dataset consists of 1,330 APOE ε3/3 carriers and 7,001 visits. Linear mixed models were used to compare the rates of decline in cognition across APOE groups and the APOE ε3/3 carriers with different TOMM40'523 genotypes.</p><p><strong>Results: </strong>APOE ε3/4 and APOE ε4/4 genotypes compared with the APOE ε3/3 genotype were associated with worse performance on measures of global cognition, episodic memory, and expressive language. Further, over the four years of observation, the APOE ε3/3 carriers with the TOMM40'523-S/S genotype showed better global cognition and accelerated rates of cognitive decline on tests of global cognition, executive function, and attentional processing compared to APOE ε3/3 carriers with TOMM40'523-S/VL and VL/VL genotypes and compared to the APOE ε3/4 and APOE ε4/4 carriers.</p><p><strong>Conclusions: </strong>We suggest that both APOE and TOMM40 genotypes may independently contribute to cognitive heterogeneity in the pre-MCI stages of AD. Controlling for this genetic variability will be important in clinical trials designed to slow the rate of cognitive decline and/or prevent symptom onset in preclinical AD.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"886-894"},"PeriodicalIF":6.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10734664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Determinants of Health among Older Adults with Dementia in Urban and Rural Areas.","authors":"M M Bartley, H Baer-Benson, D R Schroeder, J L St Sauver, N Khera, J M Griffin","doi":"10.1007/s42414-023-0002-2","DOIUrl":"10.1007/s42414-023-0002-2","url":null,"abstract":"<p><strong>Background: </strong>Social determinants of health (SDOH) may influence health in people living with dementia. Little is known about SDOH differences in urban compared to rural dwelling people living with dementia.</p><p><strong>Objectives: </strong>To explore urban-rural differences in SDOH in people living with mild cognitive impairment (MCI) and dementia.</p><p><strong>Design: </strong>Descriptive study.</p><p><strong>Setting/participants: </strong>People ≥55 years with MCI or dementia empaneled to Community Internal Medicine at Mayo Clinic (Rochester, MN, USA) who completed SDOH questions between June 1, 2019 and June 30, 2021 were included.</p><p><strong>Measurements: </strong>SDOH questions addressed education, depression, alcohol use, financial strain, food insecurity, physical activity, social connections, stress and transportation. SDOH data were compared by location based on Rural-Urban Commuting Areas Codes.</p><p><strong>Results: </strong>Of 3552 persons with MCI (n=1495) or dementia (n=2057), 62% lived in urban areas, 19% in large rural, 10% in small rural and 9% in isolated areas. Approximately 60% were physically inactive, 20% socially isolated and 30% had stress concerns. Rural patients experienced greater financial strain (p=0.003).</p><p><strong>Conclusion: </strong>Social isolation, stress and physical inactivity are common in people living with MCI and dementia across urban and rural areas. Targeted interventions to improve physical and psychosocial health could have great impact in this population.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"1 1","pages":"895-902"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45013586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Mobile-First Registry to Recruit Healthy Volunteers and Members of Underrepresented Communities for Alzheimer's Disease Prevention Studies.","authors":"R Aggarwal, E Sidnam-Mauch, D Neffa-Creech, A Plant, E Williams, E Shami, U Menon, S George, J B Langbaum","doi":"10.14283/jpad.2023.86","DOIUrl":"10.14283/jpad.2023.86","url":null,"abstract":"<p><strong>Background: </strong>Web-based participant recruitment registries can be useful tools for accelerating enrollment into studies, but existing Alzheimer's disease (AD)-focused recruitment registries have had limited success enrolling individuals from underrepresented racial and ethnic groups. Designing these registries to meet the needs of individuals from these communities, including designing mobile-first, may facilitate improvement in the enrollment of underrepresented groups.</p><p><strong>Objectives: </strong>Evaluate the usability of a prototype mobile-first participant recruitment registry for AD prevention studies; assess users' perceptions of and willingness to sign up for the registry.</p><p><strong>Design and setting: </strong>Quantitative usability testing and an online survey; online setting.</p><p><strong>Participants: </strong>We recruited 1,358 adults ages 45-75 who self-reported not having a diagnosis of mild cognitive impairment, AD, or other forms of dementia (Study 1: n=589, Study 2: n=769). Black/African American and Hispanic/Latino participants were specifically recruited, including those with lower health literacy.</p><p><strong>Methods and measurements: </strong>Study 1 measures the prototype's usability through observed task success rates, task completion times, and responses to the System Usability Scale. Study 2 uses an online survey to collect data on perceptions of and willingness to sign up for the mobile-first registry.</p><p><strong>Results: </strong>Study 1 findings show the prototype mobile-first recruitment registry website demonstrates high usability and is equally usable for Black / African American, Hispanic/Latino, and White user groups. Survey results from Study 2 indicate that users from underrepresented communities understand the registry's purpose and content and express willingness to sign up for the registry on a mobile device.</p><p><strong>Conclusions: </strong>Designing mobile-first participant recruitment registries based on feedback from underrepresented communities may result in more sign-ups by individuals from minoritized communities.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"857-864"},"PeriodicalIF":6.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-Year Prognostic Utility of Plasma p217+tau across the Alzheimer's Continuum.","authors":"A Feizpour, V Doré, J D Doecke, Z S Saad, G Triana-Baltzer, R Slemmon, P Maruff, N Krishnadas, P Bourgeat, K Huang, C Fowler, S R Rainey-Smith, A I Bush, L Ward, J Robertson, R N Martins, C L Masters, V L Villemagne, J Fripp, H C Kolb, C C Rowe","doi":"10.14283/jpad.2023.83","DOIUrl":"10.14283/jpad.2023.83","url":null,"abstract":"<p><strong>Background: </strong>Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-β (Aβ) and tau in Alzheimer's Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aβ and tau in predicting cognitive decline are unknown.</p><p><strong>Objectives: </strong>To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aβ (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aβ (A+) and tau (T+) with and without p217+tau pre-screening.</p><p><strong>Design: </strong>A prospective observational cohort study.</p><p><strong>Setting: </strong>Participants of the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT).</p><p><strong>Participants: </strong>153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) individuals.</p><p><strong>Measurements: </strong>Baseline p217+tau Simoa® assay, 18F-MK6240 tau-PET and 18F-NAV4694 Aβ-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years.</p><p><strong>Results: </strong>In CI, p217+tau was a significant predictor of change in MMSE (β = -0.55, p < 0.001) and CDR-SB (β =0.61, p < 0.001) with an effect size similar to Aβ Centiloid (MMSE β = -0.48, p = 0.002; CDR-SB β = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: β = -0.62, p < 0.001; CDR-SB: β = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (β = -0.22, p = 0.008). Screening pT+ CI participants into a trial could lead to 24% reduction in sample size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26-38% biomarker test cost-saving in the CU.</p><p><strong>Conclusions: </strong>Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":"10 1","pages":"828-836"},"PeriodicalIF":8.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}