Newly Published Guideline on Diagnosing Alzheimer and Related Cognitive Disorders for Clinical Practice

Brad Dickerson, MD
(Credit: Harvard Medical School)

A workgroup of experts from multiple disciplines and multiple care settings, including primary care and specialty care, summarized the process of diagnostic evaluation and disclosure for patients suspected of potentially having cognitive-behavioral impairment because of Alzheimer disease (AD) or AD-related neurodegenerative disorders (ADRD) in a new guideline. Published in Alzheimer's & Dementia, the belief is that the recommendations provided in the guideline should help improve outcomes in most patients in practice and health care systems.^1,2

This guideline does not establish diagnostic or staging criteria for AD or ADRD but provides a framework for a personalized, high-quality diagnostic process. Developed through a modified-Delphi approach and guideline-development process—reviewing 7374 publications, of which 133 met inclusion criteria—an expert workgroup outlined a 3-step patient-centered evaluation process. This includes assessing cognitive functional status, identifying the cognitive-behavioral syndrome based on specific symptoms, and determining the likely brain diseases or conditions causing the symptoms.

"With this guideline, we expand the scope of prior guidelines by providing recommendations for practicing clinicians on the process from start to finish," coauthor Brad Dickerson, MD, director of the Massachusetts General Hospital Frontotemporal Disorders Unit and professor of neurology at Harvard Medical School, said in a statement.¹ "We recommend that medical professionals begin by making sure their thinking about the goals of the evaluation aligns with that of the patient, which usually requires a discussion to educate the patient on the specific steps of the process. Then we outline the steps involved in obtaining information about symptoms and examination, followed by a variety of diagnostic tests tailored to the patient, and summarize best practices regarding the diagnostic disclosure process."

"We emphasize the importance of the involvement of a care partner throughout this process for most patients, since cognitive symptoms often compromise a person's ability to process all of this information by themselves," Dickerson added in the statement.¹

READ MORE: CT1812 Meets Primary End Point in Phase 2 SHIMMER Study for Dementia with Lewy Bodies

The following is a summary of the recommendations for clinicians that aim to provide a structured yet flexible approach to diagnosing and managing cognitive-behavioral syndromes with patient-centered care:

• Initial Evaluation: For patients reporting or showing cognitive, behavioral, or functional changes, initiate a multi-tiered evaluation tailored to the specific problem.
• Patient-Centered Approach: Use clear communication to establish a partnership with the patient and care partner, define shared evaluation goals, and assess the patient’s capacity to engage in goal-setting.
• Diagnostic Formulation: Utilize tiered assessments to determine:
  • Cognitive functional status (e.g., mild cognitive impairment or dementia).
  • Cognitive-behavioral syndrome based on symptoms (e.g., memory loss, mood changes).
  • Likely cause(s) or contributing factors.
• Comprehensive History: Collect reliable informant-reported data on:
  • Cognitive changes.
  • Activities of daily living (ADLs/IADLs).
  • Mood and neuropsychiatric symptoms.
  • Sensory and motor function.
• Risk Factors: Evaluate individualized risk factors for cognitive decline during history-taking.
• Examination: Conduct a dementia-focused neurologic exam, mental status evaluation, and use validated tools to assess cognition, mood, and behavior.
• Laboratory Tests: Follow a multi-tiered approach, performing routine Tier 1 tests for all patients and additional tests (Tier 2–4) based on clinical findings.
• Imaging: Obtain structural brain imaging (MRI or CT) to identify potential causes of cognitive-behavioral syndromes. Advanced molecular imaging (e.g., FDG PET) can be used for persistent diagnostic uncertainty.
• Communication: Use a structured and compassionate approach to explain diagnostic findings, including:
  • Syndrome characteristics and severity.
  • Likely cause(s) and disease stage.
  • Prognosis, treatment options, and safety concerns.
  • Resources for care planning and support.
• Specialist Referral: Refer patients with atypical findings, early-onset, or rapidly progressive conditions to a specialist for further evaluation.
• Neuropsychological Testing: Recommended for cases with diagnostic uncertainty or complex clinical profiles, covering memory, executive function, visuospatial skills, and language.
• Advanced Diagnostics: In cases with unresolved uncertainty:
  • Obtain CSF analysis for amyloid beta and tau markers.
  • Perform amyloid PET scans if warranted by appropriate use criteria.
• Genetic Testing: Consider genetic testing for patients with autosomal dominant family histories, involving a genetic counselor throughout the process.

"The workgroup provides rigorous, evidence- and practice-informed foundational steps that capture the core elements of a high-quality evaluation and disclosure process," Dickerson said in a statement.¹ "The guidelines are formulated into 19 practical recommendations that are applicable to any practice setting, including primary care, along with additional guidance for specialists and subspecialists."

This guideline encourages clinicians from all specialties and practice settings to work closely with patients and care partners, adopting a systematic, patient-centered approach for the timely evaluation of cognitive or behavioral symptoms suggestive of AD or ADRD. The authors noted that evaluation may result in an AD or ADRD diagnosis, or it may identify opportunities to promote brain-healthy strategies, manage comorbid conditions, and reduce the risk of cognitive and functional decline.

"The AD/ADRD field has entered a new era and is moving rapidly, which is very exciting," coauthor Alireza Atri, MD, PhD, chief medical officer of Banner Research, and director of the Banner Sun Health Research Institute at Banner Health, and lecturer on neurology at Brigham and Women's Hospital and Harvard Medical School, said in a statement.¹ "This first U.S. interdisciplinary national evaluation guideline, designed for broad clinical settings, provides a comprehensive foundation summarizing a high-quality and personalized process within which specific tests are slotted and can be updated as the field evolves."

"Some details of the guideline will likely require modification as new tools and biomarkers become sufficiently validated for appropriate clinical use in real-world practice. The workgroup leveraged best evidence and practices to empower persons with memory or thinking symptoms or concerns and their loved ones, clinicians, and health systems, to engage in a person-centered process that will enhance knowledge, appreciation and autonomy for the person with a potential illness — and facilitate doing what is right for them," Atri said in a statement.¹

Regardless of the outcome, authors noted that the process should lead to a clear and compassionate diagnostic explanation, including discussions about management and prognosis. Additionally, experts recommended that a comprehensive plan should be developed to address symptoms affecting quality of life, health, and important life decisions, such as care needs, finances, and safety, through treatment, risk reduction, education, psychosocial support, and monitoring.

"We encourage clinicians to review these guidelines and incorporate them into their practice," Maria C. Carrillo, PhD, chief science officer and medical affairs lead at Alzheimer's Association, said in a statement.¹ "These guidelines are important because they guide clinicians in the evaluation of memory complaints, which could have many underlying causes. That is the necessary start for an early and accurate Alzheimer's diagnosis. In addition, these guidelines provide clinicians information about other underlying causes that may contribute to the memory complaints."

REFERENCES
1. New Clinical Practice Guideline on the Process for Diagnosing Alzheimer's Disease or a Related Form of Cognitive Impairment or Dementia. News Release. Alzheimer's Association. Published December 23, 2024. Accessed December 23, 2024. https://www.prnewswire.com/news-releases/new-clinical-practice-guideline-on-the-process-for-diagnosing-alzheimers-disease-or-a-related-form-of-cognitive-impairment-or-dementia-302337811.html
2. Atri A, Dickerson BC, Clevenger C, et al. Alzheimer's Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD): Executive summary of recommendations for primary care. Alzheimers Dement. Published December 23, 2024. doi:10.1002/alz.14333.