An expert workgroup reviewed 7,374 publications to develop updated clinical practice guidelines for diagnosing Alzheimer’s disease and related dementias. Published in Alzheimer’s & Dementia, these guidelines outline a structured, patient-centered diagnostic framework that includes recommendations for minimizing unnecessary testing.

A Three-Step Framework

The guidelines outline a structured diagnostic process:

1. Cognitive Functional Status: Evaluate overall impairment levels.
2. Cognitive-Behavioral Syndrome: Identify symptom patterns to refine differential diagnoses.
3. Underlying Brain Diseases: Determine likely contributing pathologies.

This framework provides a systematic and individualized approach for clinicians.

Key Diagnostic Tools

Diagnostic tools were assessed for their accuracy:

• FDG-PET Imaging: Sensitivity of 80–99% and specificity of 63–98% for distinguishing Alzheimer’s disease (AD) from frontotemporal dementia.
• CSF Biomarkers: Sensitivity of 85–90% and specificity of 80–84% compared to autopsy findings.
• Amyloid PET Scans: Sensitivity of 89–98% and specificity of 88–100% for detecting amyloid plaques.

These tools, integrated into the diagnostic process, enhance confidence in identifying Alzheimer’s disease and related dementias.

Tiered Diagnostic Recommendations

The 19 recommendations provide a stepwise evaluation strategy:

Initial Steps (Recommendations 1–3):

• Initiate multitiered evaluations for cognitive, behavioral, or functional changes.
• Establish shared goals with patients and care partners.
• Use individualized assessments to determine cognitive status, behavioral syndromes, and underlying causes.

History and Testing Basics (Recommendations 4–7):

• Using structured tools, gather detailed history from informants about cognition, daily function, mood, and sensorimotor changes.
• Evaluate patient-specific risk factors for cognitive decline, such as family history or vascular risks.
• Perform a mental status and dementia-focused neurological examination to characterize the cognitive-behavioral syndrome.
• Use validated tools to assess cognition comprehensively.

Foundational Testing (Recommendations 8–11):

• Conduct Tier 1 laboratory tests (e.g., TSH, vitamin B12).
• Perform structural imaging, prioritizing MRI when feasible.
• Use structured methods for diagnostic disclosure, including prognosis and treatment options.

Advanced Testing (Recommendations 12–14):

• Refer patients with atypical findings or diagnostic uncertainty to specialists for further evaluation.
• Specialists should perform comprehensive cognitive, neuropsychiatric, and neurological evaluations.
• Neuropsychological evaluation is recommended when office-based cognitive assessments are insufficient or patient presentations are complex.

Specialized Testing (Recommendations 15–19):

• Apply FDG-PET and amyloid PET imaging selectively for intermediate diagnostic confidence.
• Utilize CSF biomarkers to confirm amyloid or tau pathology.
• Conduct genetic counseling and testing for suspected autosomal dominant inheritance or early-onset dementia.

Emerging Tools and Personalized Care

Emerging plasma-based biomarkers show promise for future diagnostic integration. The guidelines also emphasize addressing mixed pathologies, such as vascular disease and Lewy body disease, to develop comprehensive and personalized care plans.

Key Considerations

The guidelines highlight limitations, such as the need for improved insurance coverage and access to diagnostic tools like PET imaging and advanced biomarker tests. They also emphasize the importance of shared decision-making and patient-centered communication throughout the diagnostic process.

Disclosures for all contributors are detailed in the original guidelines.