What are the diagnostic criteria and treatment options for Alzheimer's disease?

Diagnostic Criteria and Treatment Options for Alzheimer's Disease

The diagnosis of Alzheimer's disease requires a structured approach using clinical criteria, cognitive assessments, and biomarker testing, with treatment focused on cholinesterase inhibitors like donepezil for symptomatic relief alongside non-pharmacological interventions. 1, 2

Diagnostic Criteria

Core Clinical Criteria for Alzheimer's Dementia

1. Cognitive or behavioral symptoms that:

   • Interfere with ability to function at work or usual activities
   • Represent a decline from previous functioning
   • Are not explained by delirium or psychiatric disorder
   • Are detected through history and objective cognitive assessment 1

2. Cognitive impairment involving at least two of the following domains:

   • Amnestic presentation (most common): Impaired learning and recall of recently learned information
   • Language presentation: Word-finding difficulties
   • Visuospatial presentation: Deficits in spatial cognition, object recognition
   • Executive dysfunction: Impaired reasoning, judgment, and problem-solving 1

3. Insidious onset and clear history of worsening over months to years, not sudden onset 1

Diagnostic Exclusion Criteria

The diagnosis of probable AD should not be applied when there is:

• Substantial cerebrovascular disease temporally related to cognitive decline
• Core features of Lewy body dementia
• Prominent features of frontotemporal dementia
• Evidence of another neurological disease affecting cognition 1

Diagnostic Testing Algorithm

Step 1: Initial Assessment

• Obtain detailed collateral history from reliable informants
• Administer validated cognitive screening tools (MoCA, Mini-Cog, or GPCOG)
• Screen for depression using Geriatric Depression Scale or PHQ-9 2

Step 2: Basic Laboratory Testing

• Complete blood count
• Comprehensive metabolic panel
• Thyroid function tests
• Vitamin B12 and folate levels
• These tests help identify reversible causes of cognitive impairment 2

Step 3: Neuroimaging

• Brain MRI (preferred) or CT to assess:
  • Structural causes
  • Vascular disease
  • Patterns of atrophy characteristic of AD 2

Step 4: Advanced Diagnostic Testing (for uncertain cases)

• Biomarker Testing:

  • Core AD biomarkers:
    • Amyloid-β (PET, CSF, or plasma)
    • Hyperphosphorylated tau (specific CSF or plasma tau species)
  • Neurodegeneration markers:
    • CSF or plasma neurofilament light
    • MRI anatomic measures
    • FDG PET hypometabolism 1

• Biomarker-based likelihood of AD:

  • High: Both amyloid and neuronal injury biomarkers positive
  • Intermediate: One biomarker positive, one negative or untested
  • Low: Both biomarkers negative 1

Treatment Options

Pharmacological Treatments

1. Cholinesterase Inhibitors:

   • Donepezil: FDA-approved for mild to severe AD
     • Starting dose: 5 mg daily
     • May increase to 10 mg daily after 4-6 weeks
     • For moderate to severe AD, 23 mg daily dose provides additional benefit 3
   • Rivastigmine: Particularly useful for Parkinson's disease dementia 4

2. NMDA Receptor Antagonist:

   • Memantine: For moderate to severe AD
     • Can be used alone or as add-on therapy to cholinesterase inhibitors 4

Non-Pharmacological Approaches

1. Cognitive Engagement:

   • Reading, puzzles, and other mentally stimulating activities 4

2. Physical Exercise:

   • Regular physical activity, particularly walking 4

3. Social Engagement:

   • Family gatherings and other social activities 4

4. Environmental Modifications:

   • Structured routine
   • Simplified environment to reduce confusion 2

Clinical Staging and Monitoring

Clinical Staging for AD Continuum

• Stage 0: Asymptomatic with genetic abnormality, no biomarker abnormality
• Stage 1: Asymptomatic with biomarker evidence
• Stage 2: Transitional cognitive/behavioral decline
• Stage 3: Mild Cognitive Impairment (MCI)
• Stage 4: Mild dementia
• Stage 5: Moderate dementia
• Stage 6: Severe dementia 1

Follow-up and Monitoring

• Schedule follow-up visits every 3-6 months
• Use consistent cognitive assessment tools to monitor progression
• Document functional changes reported by patient and informants 2

Common Pitfalls to Avoid

1. Misdiagnosis: Remember that AD is often accompanied by other neuropathologies, particularly cerebrovascular disease. Mixed etiology dementia is common, especially in older individuals 1

2. Overlooking Reversible Causes: Always rule out conditions that can mimic dementia, such as depression, medication side effects, thyroid disorders, and vitamin deficiencies 2

3. Delayed Diagnosis: Early recognition allows time for planning and treating patients before marked deterioration occurs 5

4. Relying Solely on Clinical Criteria: The accuracy of clinical diagnosis without biomarkers is limited (approximately 77% even among experts) 6

5. Neglecting Caregiver Support: Caregiver education and support are essential components of comprehensive management 5