Alzheimer's Disease: Diagnosis Step by Step in 4 Points

4 Fundamental Changes After 30 Years

Diagnostic criteria for treating Alzheimer's disease (AD) are not frequently updated. However, in 2011, the criteria that had been valid for nearly 30 years were revised. The main changes included the following points:

• Introduction of 3 stages of Alzheimer's disease: preclinical phase, mild cognitive impairment stage, dementia stage.
• Unlike the previous version, memory impairment is not strictly required; the new concept includes behavioral and personality disorders on par with cognitive domains.
• Recognition of the interplay between Alzheimer's disease and vascular dementia.
• Incorporation of biomarkers into diagnostic methods.

4 Stages of the Diagnostic Process

According to the latest criteria, the diagnostic process for Alzheimer's disease can be divided into 4 stages.

1. Determining the presence of dementia: A newly developed long-lasting cognitive deterioration in at least 2 cognitive domains leading to impaired self-sufficiency (memory impairment is not strictly required).

2. Identifying AD as the cause of dementia using common clinical methods. Within this, the following diagnoses can be defined:

• “Probable dementia due to AD”: presence of dementia + history of gradual onset and worsening.
• “Dominant memory impairment”, potentially “non-amnestic forms” (anomia, visuospatial form, executive dysfunction).
• “Possible dementia due to AD”: with typical clinical presentation but atypical course (rapid onset / unknown course / mixed etiology).

3. Determining the probability of increased presence of AD: The newly defined category “probable dementia due to AD with increased diagnostic certainty” applies to patients with clinically documented deterioration over time at repeated check-ups or with proven autosomal dominant mutations causing AD.

4. Determining the probability of AD pathology presence in the brain based on biomarker evaluation (reduced amyloid β42 in cerebrospinal fluid, positive PET scan with amyloid β binding ligands, increased tau and phospho tau in cerebrospinal fluid, hypometabolism in the temporal and parietal cortex on FDG-PET, temporal and parietal atrophy on MRI brain scan).

Basic and Extended Examinations

Standard examination for suspected Alzheimer's disease should unequivocally include a detailed medical history (gradual onset and worsening of cognitive deficit, dominant memory impairment), neurological examination (positive topical finding suggesting the probable contribution of other pathologies), cognitive examination – neuropsychological (dominant memory impairment, presence of other domain impairments; possibility of atypical forms – anomic, visuospatial), brain imaging (atrophy primarily in the mediotemporal and parietal regions, absence of other changes), laboratory tests including thyroid hormone levels, potentially vitamin B₁₂ levels, infection serology (typically normal findings).

In indicated cases, for example, to exclude CNS inflammation or frontotemporal lobar degeneration (and in clinical studies), a cerebrospinal fluid examination, including biomarkers for neurodegeneration – beta-amyloid, tau, and phospho tau (normal cytological findings, decreased beta-amyloid, and increased tau and phospho tau), or functional imaging methods – FDG-PET, perfusion SPECT (regional hypoperfusion or hypometabolism in the mediotemporal and parietal regions).

Conclusion

Current diagnostic methods allow for relatively early detection of AD and earlier initiation of therapy. Thus, there is potential for treatment during the early stages, where it achieves the most significant effects.

(dos)

Sources:
1. McKhann G. M., Knopman D. S., Chertkow H. et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging – Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7 (3): 263–269, doi: 10.1016/j.jalz.2011.03.005.
2. Vyhnálek M., Láczó J., Nikolai T. et al. Early diagnosis of Alzheimer’s disease in light of the new diagnostic criteria. Neurologie pro praxi 2012; 13 (6): 325–329.