Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(8), С. 5143 - 5169

Опубликована: Июнь 27, 2024

Abstract The National Institute on Aging and the Alzheimer's Association convened three separate work groups in 2011 single 2012 2018 to create recommendations for diagnosis characterization of disease (AD). present document updates research framework response several recent developments. Defining diseases biologically, rather than based syndromic presentation, has long been standard many areas medicine (e.g., oncology), is becoming a unifying concept common all neurodegenerative diseases, not just AD. consistent with this principle. Our intent objective criteria staging AD, incorporating advances biomarkers, serve as bridge between clinical care. These are intended provide step‐by‐step practice guidelines workflow or specific treatment protocols, but general principles inform AD that reflect current science. Highlights We define (AD) be biological process begins appearance neuropathologic change (ADNPC) while people asymptomatic. Progression burden leads later progression symptoms. Early‐changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid accurate plasma [especially phosphorylated tau 217]) map onto either amyloid beta tauopathy pathway; however, these presence ADNPC more generally (i.e., both neuritic plaques tangles). An abnormal biomarker result sufficient establish decision making throughout continuum. Later‐changing 2 (biofluid PET) can prognostic information, when abnormal, will increase confidence contributing integrated scheme described accommodates fact copathologies, cognitive reserve, resistance may modify relationships stages.

Язык: Английский

---

Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

JAMA Neurology, Год журнала: 2024, Номер 81(3), С. 255 - 255

Опубликована: Янв. 22, 2024

Importance Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of tests research and clinical use has been limited. Expanding access this highly accurate AD crucial wider evaluation implementation tests. Objective To determine utility novel commercially available immunoassay plasma detect pathology evaluate reference ranges abnormal amyloid β (Aβ) longitudinal change across 3 selected cohorts. Design, Setting, Participants This cohort study examined data from single-center observational cohorts: cross-sectional Translational Biomarkers in Aging Dementia (TRIAD) (visits October 2017–August 2021) Wisconsin Registry Alzheimer’s Prevention (WRAP) February 2007–November 2020) Sant Pau Initiative on Neurodegeneration (SPIN) (baseline visits March 2009–November 2021). included individuals without cognitive impairment grouped by (AT) status using PET or CSF biomarkers. Data were analyzed June 2023. Exposures Magnetic resonance imaging, Aβ positron emission tomography (PET), PET, cerebrospinal fluid (CSF) biomarkers (Aβ42/40 p-tau immunoassays), (ALZpath pTau217 assay). Main Outcomes Measures Accuracy detecting according baseline status. Results The 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] 282 males [35.9%]). High accuracy was observed identifying elevated (area under curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) (AUC, 0.93-0.97; 0.84-0.99) all These accuracies comparable determining signal. detection 3-range yielded reproducible results reduced confirmatory testing approximately 80%. Longitudinally, values showed an annual increase only Aβ-positive individuals, highest those positivity. Conclusions Relevance found that accurately identified biological AD, biomarkers, cut-offs It detected changes, including at preclinical stage.

Язык: Английский

---

Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests

Nature Medicine, Год журнала: 2024, Номер 30(4), С. 1085 - 1095

Опубликована: Фев. 21, 2024

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test perform as well established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry Swedish BioFINDER-2 cohort (n = 1,422) US Charles F. Joanne Knight Alzheimer Disease Research Center (Knight ADRC) 337). Matched CSF samples were with clinically used FDA-approved automated immunoassays for Aβ42/40 p-tau181/Aβ42. The primary secondary outcomes detection brain Aβ or pathology, respectively, using positron emission tomography (PET) imaging reference standard. Main analyses focused on individuals cognitive impairment (mild mild dementia), which is target population available treatments. equivalent classifying PET status, an area under curve (AUC) both between 0.95 0.97. generally superior classification tau-PET AUCs 0.95-0.98. cognitively impaired subcohorts (BioFINDER-2: n 720; ADRC: 50), plasma had accuracy, positive predictive value negative 89-90% 87-88% tests, further improving 95% two-cutoffs approach. Blood demonstrated performance that AD pathology. Use high-performance clinical practice can improve access accurate diagnosis AD-specific

Язык: Английский

---

Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care

JAMA, Год журнала: 2024, Номер 332(15), С. 1245 - 1245

Опубликована: Июль 28, 2024

Importance An accurate blood test for Alzheimer disease (AD) could streamline the diagnostic workup and treatment of AD. Objective To prospectively evaluate a clinically available AD in primary care secondary using predefined biomarker cutoff values. Design, Setting, Participants There were 1213 patients undergoing clinical evaluation due to cognitive symptoms who examined between February 2020 January 2024 Sweden. The values had been established an independent cohort applied (n = 307) 300); 1 plasma sample per patient was analyzed as part single batch each cohort. then evaluated 208) 398); sent analysis within 2 weeks collection. Exposure Blood tests based on analyses by mass spectrometry determine ratio phosphorylated tau 217 (p-tau217) non–p-tau217 (expressed percentage p-tau217) alone when combined with amyloid-β 42 40 (Aβ42:Aβ40) (the amyloid probability score [APS2]). Main Outcomes Measures outcome pathology (determined abnormal cerebrospinal fluid Aβ42:Aβ40 p-tau217). positive predictive value (PPV), negative (NPV), accuracy, area under curve (AUC) calculated. Results mean age 74.2 years (SD, 8.3 years), 48% women, 23% subjective decline, 44% mild impairment, 33% dementia. In both assessments, 50% pathology. When samples cohort, AUC 0.97 (95% CI, 0.95-0.99) APS2 used, PPV 91% 87%-96%), NPV 92% 87%-96%); 0.96 0.94-0.98) 88% 83%-93%), 87% 82%-93%). (biweekly) 81%-94%), 90% 84%-96%); 0.95-0.98) 87%-95%), 87%-95%). accuracy high 4 cohorts (range, 88%-92%). Primary physicians 61% 53%-69%) identifying after examination, testing, computed tomographic scan vs 86%-96%) APS2. Dementia specialists 73% 68%-79%) 88%-95%) overall population, (90% [95% 88%-92%]) not different from p-tau217 88%-91%]). Conclusions Relevance among individuals Future studies should how use these biomarkers influences care.

Язык: Английский

---

Acceptable performance of blood biomarker tests of amyloid pathology — recommendations from the Global CEO Initiative on Alzheimer’s Disease

Nature Reviews Neurology, Год журнала: 2024, Номер 20(7), С. 426 - 439

Опубликована: Июнь 12, 2024

Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need biomarker confirmation of amyloid pathology. Blood (BBM) tests pathology are more acceptable, accessible and scalable than PET or cerebrospinal fluid (CSF) tests, but highly variable levels performance. The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to consider minimum acceptable performance clinical use. Amyloid status was identified as reference standard. For use triaging test before subsequent confirmatory such CSF recommends that sensitivity ≥90% with specificity ≥85% primary care ≥75–85% secondary depending availability follow-up testing. without should equivalent — ~90%. Importantly, predictive values all vary according pre-test probability must be interpreted complete context. Use meet these standards could enable people receive an accurate timely diagnosis potentially benefit from new treatments. blood offer test. This Consensus Statement provides recommendations

Язык: Английский

---

Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies

JAMA Neurology, Год журнала: 2023, Номер 81(1), С. 69 - 69

Опубликована: Дек. 4, 2023

Antiamyloid immunotherapies against Alzheimer disease (AD) are emerging. Scalable, cost-effective tools will be needed to identify amyloid β (Aβ)-positive patients without an advanced stage of tau pathology who most likely benefit from these therapies. Blood-based biomarkers might reduce the need use cerebrospinal fluid (CSF) or positron emission tomography (PET) for this.

Язык: Английский

---

Timing of lifespan influences on brain and cognition

Trends in Cognitive Sciences, Год журнала: 2023, Номер 27(10), С. 901 - 915

Опубликована: Авг. 8, 2023

Modifiable risk and protective factors for boosting brain cognitive development preventing neurodegeneration decline are embraced in neuroimaging studies. We call sobriety regarding the timing quantity of such influences on cognition. Individual differences level cognition, many which present already at birth early development, appear stable, larger, more pervasive than change across lifespan. Incorporating early-life factors, including genetics, investigating both will reduce ascribing undue importance causality to proximate adulthood older age. This has implications mechanistic understanding prevention.

Язык: Английский

---

Alzheimer Disease as a Clinical-Biological Construct—An International Working Group Recommendation

JAMA Neurology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Importance Since 2018, a movement has emerged to define Alzheimer disease (AD) as purely biological entity based on biomarker findings. The recent revision of the Association (AA) criteria for AD furthers this direction. However, concerns about definition being applied clinically, understanding by society at large, and translation blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations. Objective To consider revised AA offer an alternative definitional view clinical-biological construct use. recommendations 2021 IWG diagnostic are further elaborating at-risk presymptomatic states. Evidence Review PubMed was searched articles published between July 1, 2020, March 2024, using terms “biomarker” OR “amyloid” “tau” “neurodegeneration” “preclinical” “CSF” “PET” “plasma” AND “Alzheimer’s disease.” references relevant were also searched. Findings In new criteria, can be defined clinically encompassing cognitively normal people having core 1 biomarker. literature shows that majority biomarker-positive individuals will not become symptomatic along proximate timeline. setting, disclosing diagnosis with only represents most problematic implication disease. Conclusions Relevance ultimate aim field foster effective treatments, including preventing symptoms dementia. approach diagnosing without would unwarranted potentially concerning clear knowledge when or whether ever develop. It is recommended those who amyloid-positive and, more generally, individuals, should labeled AD. Rather, they considered risk expansion viewed better specific pattern biomarkers, indicating expression in near future.

Язык: Английский

---

Artificial intelligence for biomarker discovery in Alzheimer's disease and dementia

Alzheimer s & Dementia, Год журнала: 2023, Номер 19(12), С. 5860 - 5871

Опубликована: Авг. 31, 2023

Abstract With the increase in large multimodal cohorts and high‐throughput technologies, potential for discovering novel biomarkers is no longer limited by data set size. Artificial intelligence (AI) machine learning approaches have been developed to detect interactions complex sets. We discuss exemplar uses evaluate current applications limitations of AI discover biomarkers. Remaining challenges include a lack diversity sets available, sheer complexity investigating interactions, invasiveness cost some biomarkers, poor reporting studies. Overcoming these will involve collecting from underrepresented populations, developing more powerful approaches, validating use noninvasive adhering guidelines. By harnessing rich through international collaborative innovation, we are well positioned identify clinically useful that accurate, generalizable, unbiased, acceptable clinical practice. Highlights may accelerate dementia biomarker discovery. suitability due size bias cohort selection. Multimodal data, diverse sets, improved real‐world validation, interdisciplinary collaboration required.

Язык: Английский

---

Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 13900 - 13900

Опубликована: Сен. 9, 2023

In an ever-increasing aged world, Alzheimer’s disease (AD) represents the first cause of dementia and one chronic diseases in elderly people. With 55 million people affected, WHO considers AD to be a with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies aimed mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, best approaches managing seem combine pharmacological non-pharmacological therapies stimulate cognitive reserve. Over last twenty years, number drugs have been discovered acting on well-established biological hallmarks AD, deposition β-amyloid aggregates accumulation hyperphosphorylated tau protein cells. Although previous efforts disappointed expectations, new era treating has working its way recently. The Food Drug Administration (FDA) gave conditional approval disease-modifying therapy (DMT) treatment aducanumab, monoclonal antibody (mAb) designed against Aβ plaques oligomers 2021, January 2023, FDA granted accelerated second antibody, Lecanemab. This review describes ongoing clinical trials DMTs therapies. We will also present future scenario based biomarkers that can detect preclinical or prodromal stages, identify at risk developing allow early curative treatment.

Язык: Английский

---