Introduction to the DETeCD‐ADRD special issue

[Audio] Received: 23 November 2024 Accepted: 25 November 2024 DOI: 10.1002/alz.14483 P E R S P E C T I V E Introduction to the DETeCD-ADRD special issue Bradford C. Dickerson1 Alireza Atri2,3 1Frontotemporal Disorders Unit and Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 2Banner Sun Health Research Institute and Banner Alzheimer's Institute, Banner Health, Sun City, Arizona, USA 3Center for Brain/Mind Medicine, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA KEY WO RDS Alzheimer's disease, cerebrospinal fluid, dementia, diagnosis, frontotemporal dementia, Lewy body dementia, magnetic resonance imaging, mild cognitive impairment, molecular biomarkers, positron emission tomography, vascular cognitive impairment Correspondence Bradford C. Dickerson, Frontotemporal Disorders Unit, Massachusetts General Hospital & Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA. Email: brad.dickerson@mgh.harvard.edu Highlight Alireza Atri, Banner Sun Health Research Institute, Bldg A, 10515 W Santa Fe Drive, Sun City, AZ 85351, USA. Email: alireza.atri@bannerhealth.com ∙ This special issue contains multiple articles related to the DETeCD-ADRD guideline. We have entered a new era of improved and emerging biologicallymild cognitive impairment (MCI)3 and dementia,4 and then by the 2018 AAN practice guideline on MCI5 (now retired). Similar sets of based diagnostic biomarkers for Alzheimer's disease (AD) and ADrecommendations have been published globally.6–8 Most are aimed at related dementias (ADRD) that are rapidly impacting evaluation and specialists or dementia subspecialists. This CPG expands the scope of care paradigms in every clinical setting: primary care, specialty care, prior guidelines by providing recommendations for practicing clinicians and dementia subspecialty care. The integration of biomarkers— on shared goal-setting for a person-centered clinical evaluation and on following appropriate use guidelines—into a person-centered assessthe diagnostic disclosure process. The DETeCD-ADRD CPG does not ment of each person's risk profile for various types of dementia (taking propose diagnostic or staging criteria for diseases such as AD, LBD, and into account both modifiable and non-modifiable risk factors)1, symptoms, and signs will add critical value to the diagnostic formulation and FTLD, which continue to evolve.9–18 Rather, it provides an overarching care plan for persons in whom there is a clinical concern for AD or framework for a high-quality process that aims to enable clinicians to an ADRD. This special issue highlights the new Diagnostic Evaluation, establish etiology and contributing factors for any syndromic diagnoTesting, Counseling, and Disclosure of suspected Alzheimer's Disease sis, emphasizing the importance of a three-step diagnostic formulation and Related Disorders (DETeCD-ADRD) Clinical Practice Guideline including cognitive functional status, cognitive-behavioral syndrome, (CPG) that summarizes the process of diagnostic evaluation and discloand likely etiology(-ies). The CPG also does not provide guidance on sure for persons suspected of potentially having cognitive-behavioral diagnostic studies or testing obtained for treatment purposes—for impairment due to AD or ADRD, which includes Lewy body disease example, it provides guidance regarding apolipoprotein E (APOE) test(LBD), frontotemporal lobar degeneration (FTLD), vascular cognitive ing for diagnostic evaluation purposes (not recommended) but does impairment and dementia (VCID), and a host of other diseases and not address the role of.

[Audio] 2 DICKERSON AND ATRI clinicians' confidence in effectively communicating diagnostic findings for specialists and subspecialists. In this special issue of Alzheimer's & and a plan of care. The authors discuss many of the nuances required Dementia, the three executive summaries by the DETeCD-ADRD workto compassionately and clearly deliver a summary of the patient's group distill these recommendations, briefly summarize the evidence diagnosis, including the need to assess the patient's understanding supporting them, and attempt to operationalize them as a series of and appreciation of symptoms, goals for the evaluation, and desire for steps in an evaluation process—starting with patient-centered goalinformation. setting and ending with compassionate disclosure of results. A comprehensive report hosted online provides extensive details about the "Precision Diagnosis of Cognitive Impairment Due to Alzheimer Disease guideline development methodology, evidence review process, peer for Therapeutic Interventions" is focused on the increasingly targeted diagnostic assessments that are necessary in our current era of amyreview process, rationale and recommendations for implementation, loid plaque–lowering monoclonal antibody therapies that call for a and specific narratives with evidence supporting each recommennew paradigm of care which currently contains substantial real-world dation. This 2024 CPG provides a comprehensive foundation for a proficiency, resource, access, health equity, and implementation gaps. person-centered diagnostic evaluation and disclosure process within Of course, biomarker evidence of cerebral amyloid is necessary, which some details will likely require modification as new clinical tools moving our clinical practices squarely into the 21st century. Yet not and biomarkers transition from research settings and become sufall biomarkers are created equal, and Dr. Knopman astutely advocates ficiently validated, approved, accessible, and covered by payors for for (and we each agree with) quantitative amyloid PET as well as appropriate clinical use in real-world practice. For example, we expect fluorodeoxyglucose (FDG)–PET in some (or many) cases in specialist that in the next 12–18 months some AD blood-based biomarkers settings. He also discusses the challenges of trying to dissociate (BBMs) (e.g., phosphorylated tau-217 [p-tau217] and related ratios multiple etiologies in some patients to better understand the primary and multiplex tests) may be sufficiently validated, U.S. Food and Drug drivers of symptoms—a critically important gap that still exists in Administration (FDA) approved, reimbursed, and will have appropriour knowledge and expanding arsenal of AD/ADRD biomarkers and ate use recommendations (AURs) available to support their inclusion which further highlights the importance of a thorough, holistic and as part of another DETeCD-ADRD CPG formal recommendation and to person-centered clinical evaluation process to best care for persons be slotted into the evaluation process pathways in primary, specialty, living with AD/ADRD and related conditions. and subspecialty settings. Other tools and biomarkers that will likely sufficiently mature soon and have AURs to be considered for more forIn "Clinical Use of Biomarkers in the Era of Alzheimer Disease Treatmal inclusion as CPG recommendations and in the process pathways ments," Drs. Vandevrede and Schindler provide a broad overview of molecular biomarkers focused largely on AD, including PET, CSF, and include tau positron emission tomography (PET) and alpha-synuclein emerging BBMs. They adeptly discuss not only the evidence base for assays (e.g., skin biopsy or cerebrospinal fluid (CSF)–based seed amplithese tests, but also factors that influence accessibility, the possibilities fication assays), whereas biomarkers of inflammatory pathways (e.g., of false-positive or false-negative results, and challenges in interpretglial fibrillary acidic protein or GFAP) and TAR DNA-binding protein 43 ing results. They.

[Audio] DICKERSON AND ATRI 3 JOMDD, Lundbeck, Life Molecular Imaging, Merck, ONO, Prothena, further develop comprehensive and standardized guidelines for counRoche/Genentech, Novo Nordisk, Qynapse, and Vaxinnity. Indepenseling, disclosure, and post-disclosure follow-up in the context of AD dent DSMB: Roche/Genentech. Royalties: Oxford University Press. biomarker testing. Author disclosures are available in the Supporting Information. In "Paving the Way for Alzheimer's Blood-Based Biomarkers in Primary Care," Drs. Erickson, Largent, and O'Brien prudently echo many REFERENCES points made by Dr. Bolton and colleagues and explain some steps they view as necessary to prepare for the incorporation of AD BBMs into primary care. They thoughtfully emphasize four immediate challenges: (1) preparing primary care providers to order and disclose AD BBMs (primarily the need for education and training as well as support resources), (2) expanding the dementia-capable workforce (including by making nurse practitioners fully independent and by adding more social work resources), (3) ensuring equitable uptake of AD BBM testing (by addressing a variety of factors contributing to health disparities), and (4) securing access to AD treatment (by developing primary care-specialty care collaborations to facilitate efficient access to disease-modifying therapies). The remaining article in this special issue is a summary of a workshop led by Drs. Wolk and Schneider: the "Clinical Criteria for LimbicPredominant Age-Related TDP-43 Encephalopathy." Limbic Predominant Age-related TDP-43 Encephalopathy Neuropathologic Change (LATENC) is highly prevalent in late life and a common co-neuropathological change observed in conjunction with AD neuropathologic change. LATE-NC is usually observed along with a slowly progressive, amnestic clinical syndrome. With the emergence of amyloid plaque–lowering therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. This expert work group proposes criteria for clinical diagnosis of LATE as an initial framework with the need for further validation. ACKNOWLEDGMENTS We are extremely grateful to our colleagues who wrote the very thoughtful perspective papers in this special issue; to the DETeCDADRD CPG Workgroup Members for 7 years of diligent and gratis service to this endeavor; to the dozens of internal and external reviewers and stakeholders of the CPG documents and manuscripts who reviewed, critiqued, and helped refine and broaden the perspectives, quality, and consensus of this CPG; to the Alzheimer's Association and the numerous key staff members of the Association and of other organizations who supported the CPG; and, most importantly, to all persons and communities affected by and advocating for AD/ADRD, including our colleagues and multiple stakeholders, who serve as the inspiration for this CPG and for us to do better to improve autonomy, justice, and the care and lives of persons impacted by AD/ADRD. CONFLICT OF INTEREST STATEMENT Bradford C. Dickerson: Consulting: Acadia, Alector, Arkuda, Biogen, Denali, Eisai, Genentech, Ilios, and Takeda, WaveLifeSciences. Data Safety and Monitoring Board (DSMB): Lilly, Merck. Royalties: Cambridge University Press, Elsevier, Oxford University Press, and Up To Date. Alireza Atri: Consulting: Acadia, Alzheimer's 1. Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024;404:572-628. 2. Practice parameter for diagnosis and evaluation of dementia (summary statement). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1994;44:22032206. 3. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter:.

[Audio] 4 DICKERSON AND ATRI How to cite this article: Dickerson BC, Atri A. Introduction to 18. Wolk DA, Nelson PT, Apostolova L, et al. Clinical criteria for Limbic- Predominant age-related TDP-43 encephalopathy. Alzheimer's Dement. 2024; In press. the DETeCD-ADRD special issue. Alzheimer's Dement. 2024;1-4. https://doi.org/10.1002/alz.14483 SUPPORTING INFORMATION Additional supporting information can be found online in the Supporting Information section at the end of this article. 15525279, 0, Downloaded from https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14483 by Test, Wiley Online Library on [17/01/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License.