From the Guidelines
Alzheimer's disease (AD) can be diagnosed based on a combination of clinical criteria and biomarker evidence.
Diagnostic Criteria
The diagnostic criteria for AD include:
- Core clinical criteria:
- Cognitive decline
- Interference with daily life
- Biomarker evidence:
- Low CSF Aβ42
- Positive PET amyloid imaging
- Elevated CSF tau and phosphorylated tau (p-tau)
- Decreased 18fluorodeoxyglucose (FDG) uptake on PET in temporo–parietal cortex
- Disproportionate atrophy on structural magnetic resonance imaging in medial, basal, and lateral temporal lobe, and medial parietal cortex
Biomarker Use
Biomarkers can be used to increase the certainty of the diagnosis, but are not recommended for routine diagnostic purposes due to limited standardization and access 1.
Clinical Application
The use of biomarkers may be useful in investigational studies, clinical trials, and as optional clinical tools where available and deemed appropriate by the clinician 1.
Interpretation of Biomarker Results
Biomarker test results can be clearly positive, clearly negative, or indeterminate, and the application of biomarkers should operate as outlined in the diagnostic guidelines 1. The National Institute on Aging and the Alzheimer’s Association recommend the use of biomarkers to support the diagnosis of AD dementia, but also emphasize that AD dementia is fundamentally a clinical diagnosis 1.
From the Research
Diagnostic Criteria for Alzheimer's Disease (AD)
The diagnostic criteria for Alzheimer's disease (AD) have undergone significant revisions in recent years, incorporating advances in biomarkers and a better understanding of the disease's biological processes 2, 3, 4. The key elements of the diagnostic criteria include:
- The presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology 3
- The use of biomarkers such as amyloid positron emission tomography (PET), cerebrospinal fluid biomarkers, and plasma biomarkers to establish a diagnosis of AD 2
- The integration of biological and clinical staging schemes to accommodate the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages 2
- The consideration of downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, for the measurement and monitoring of the course of disease 3
Biomarkers for AD Diagnosis
Biomarkers play a crucial role in the diagnosis of AD, with different types of biomarkers providing information on different aspects of the disease. These include:
- Core 1 biomarkers (amyloid PET, approved cerebrospinal fluid biomarkers, and accurate plasma biomarkers) that reflect the presence of AD neuropathologic change (ADNPC) 2
- Core 2 biomarkers (biofluid and tau PET) that provide prognostic information and increase confidence that AD is contributing to symptoms 2
- Structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid beta or tau proteins that can be used to support a diagnosis of AD 4
Clinical Application of Diagnostic Criteria
The revised diagnostic criteria for AD have important implications for clinical practice, providing more accurate and specific guidelines for the diagnosis of AD dementia and mild cognitive impairment (MCI) due to AD 5. The use of biomarkers and integrated biological and clinical staging schemes can help clinicians to diagnose AD more accurately and provide better care for patients with the disease 2, 6.