Our newest research-advisor Prof. Randall J. Bateman, MD.
New Criteria Issued for Diagnosis of AD
Pat & Dennis Bender Early Dementia Diagnosis & Prognosis Fund
J. Dennis Bender
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We support the development of improved diagnostic methods for the early detection and diagnosis of MCI, Alzheimer’s, vascular and other dementias, their likely prognosis, and best treatment options. We focus on the development of Bayesian-based, medical-decision-support systems, comparative-effectiveness research, and the better utilization of these for the above. (After incorporating in KY as a 501(c)3 in 2002, we dissolved that entity in favor of a simplified form of two entirely self-financed, private philanthropies utilizing a Vanguard Charitable Trust for making annual-research-grants for early-dementia-detection and its correct differential-diagnosis and likely-prognosis. They will continue on, after I am long gone, either mentally or physically, with annual grants. Scripps Foundation, Profs. Randall Bateman, James Brewer and others will be our fund’s future research grant advisors. KMK Law is my legal advisor and Elizabeth Dunn is my Estate Administrator & Executor. (See: https://www.alz.org/alzheimers-dementia/research_progress/earlier-diagnosis)
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July 2, 2024
““This is a forward-looking document based on current scientific evidence that provides a common framework for AD diagnostic and staging criteria to inform both research and clinical care," wrote lead author Clifford R. Jack Jr., MD, of the Department of Radiology at the Mayo Clinic in Rochester, MN. “We do not provide detailed guidance on clinical workflow or treatment protocols; formal clinical practice guidelines will appear in a subsequent document. The criteria we describe are presently operationalizable at some but by no means all centers even among major medical institutions in high-income countries. We therefore view these criteria as a bridge between research and clinical care."”
This is exactly what we are focused on helping to promote with our annual research grants of $365,000 allocated for this year.
New Criteria Issued for Diagnosis of Alzheimer's-Disease
By Caitlin Heaney West - June 28, 2024 - https://journals.lww.com/neurotodayonline/blog/breakingnews/pages/post.aspx?PostID=1478
The National Institute on Aging and the Alzheimer's Association have released updated recommendations for the diagnosis and characterization of Alzheimer’s-disease (AD) based on recent developments in biomarker research.
The recommendations, published online June 27 in Alzheimer's & Dementia, update the research frameworks issued in 2018 that came after the organizations convened work groups in 2011, 2012, and 2018. The authors of the new document emphasized that their criteria “serve as general principles to inform diagnosis and staging of AD that reflect current science."
They updated the document because of three recent major developments, including regulatory approval of treatments targeting core disease pathology; the development of blood-based markers, with some assays capable of accurate diagnoses; and the recognition that imaging, cerebrospinal fluid, and blood-based biomarkers in “a pathobiological AT(N) (amyloid/tau/neurodegeneration) category are interchangeable for some, but not all, intended uses."
The authors considered these principles developed by past workgroups foundation for updating the 2018 guidelines. Among them is the idea that clinical syndrome, orclinically identified impairmentmust be separated from biology (etiology).
The authors described AD as “a biological process that begins with the appearance of AD neuropathologic change ADNPC) while people are asymptomatic," with progression of neuropathologic burden eventually leading to the appearance and progression of clinical symptoms.
“AD is defined by its unique neuropathologic findings; therefore, detection of AD neuropathologic change by biomarkers is equivalent to diagnosing the disease," they said.
The authors also noted that AD “exists on a continuum," with disease-specific core biomarkers emerging when patients are asymptomatic.
“Pathophysiologic mechanisms involved with processing and clearance of protein fragments may be involved very early in the disease process, but these are not yet well understood," they said.
The authors also noted that symptoms result from the disease process but are not necessary for clinicians to diagnose AD. Patients with abnormal biomarker test results are at risk of developing symptoms from AD even if they are unimpaired, they said.
“Clinical syndromes commonly seen with AD may also be caused by disorders other than AD, and therefore clinical presentation alone is not diagnostic of AD," the authors wrote. “The same AD biology may result in different phenotypic presentations."
The authors identified three broad categories for biomarkers: “core biomarkers of AD neuropathologic change (ADNPC), non-specific biomarkers that are important in AD pathogenesis but are also involved in other brain diseases, and biomarkers of common non-AD copathologies." Subcategories focused on which proteinopathy pathway or pathogenic process each biomarker measures.
The authors split tau fragments into two categories: T1 comprised early changing phosphorylated mid-region tau fragments (p-tau 217, 181, and 231), while T2 included later-changing biofluid tau fragments, such as MTBR-tau243, plus tau PET.
They divided the pathology into two categories—Core 1 and Core 2 biomarkers—which differ according to when abnormalities begin and their intended use.
“Early-changing Core 1 biomarkers (amyloid positron emission tomography [PET], approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers [especially phosphorylated tau 217]) map onto either the amyloid beta or AD tauopathy pathway," the authors wrote.
These biomarkers become abnormal at approximately the same time as amyloid PET, the authors said, and with that category representing “ADNPC more generally (i.e., both neuritic plaques and tangles."
“Core 1 biomarkers define the initial stage of AD that is detectable in vivo and can identify the presence of AD in both symptomatic and asymptomatic individuals," they added.
Core 2 biomarkers “include tau PET and certain soluble tau fragments associated with tau proteinopathy (e.g., MTBR-tau243), but also pT205 and nonphosphorylated mid-region tau fragments." These biomarkers do not become abnormal until later in the course of the disease and are linked more closely with the beginning of symptoms than the Core 1 biomarkers, according to the document.
“An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making throughout the disease continuum," the authors wrote. “Later-changing Core 2 biomarkers (biofluid and tau PET) can provide prognostic information, and when abnormal, will increase confidence that AD is contributing to symptoms."
The authors also provided what they described as “an integrated biological and clinical staging scheme … that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages." They based the four-stage scheme (A through D) on the sequence of events seen in natural history research: stage A, initial changing biomarkers; stage B, early changing; stage C, intermediate changing; and stage D, advanced changing.
“Staging by amyloid and tau PET or with a combination of T1 fluid markers and tau PET is clinically viable at the present time and is our focus for biological staging," the authors wrote. “We also describe a conceptual staging scheme based on fluid biomarkers alone. We do not attempt to link PET and fluid biomarker stages but do use the same naming convention within each modality."
The authors also issued several recommendations for the future, including that observational studies and clinical trials be more diverse and that biofluid assays, tau PET quantification methods, and cut points be standardized.
Disclosures Dr. Jack received grant funding from the National Institutes of Health, the Alexander family professorship, and the GHR Foundation; received funding from the Alzheimer's Association for travel; has served on a data safety monitoring board for Roche pro bono; and holds index funds.
Link Up for More Information Jack CR Jr., Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s-disease: Alzheimer's Association Workgroup. Alzheimers Dement 2024; Epub 2024 Jun 27.
Draft - 7/2/2024 10:54 AM
{New Criteria Issued for Diagnosis of AD}
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