What is the diagnostic approach for different types of dementia?

Diagnostic Approach to Different Types of Dementia

Diagnose dementia through a systematic three-step approach: establish cognitive decline with informant corroboration, perform targeted neuroimaging and laboratory testing to identify etiology, and apply specific clinical criteria to differentiate dementia subtypes. 1

Step 1: Establish the Diagnosis of Dementia

Core Clinical Criteria

• Dementia requires cognitive or behavioral symptoms that interfere with work or usual activities, represent decline from previous functioning, and are not explained by delirium or major psychiatric disorder. 1, 2, 3
• Obtain corroborative history from a reliable informant about changes in cognition, function, and behavior—this is mandatory and has prognostic significance. 2, 3, 4

Cognitive Domain Assessment

Systematically evaluate five specific domains: 1, 2

• Memory: Forgetting recent events, misplacing belongings, repeating questions 1
• Executive function: Poor judgment, inability to manage finances, poor decision-making 1
• Visuospatial abilities: Inability to recognize faces/objects, difficulty operating implements 1
• Language: Word-finding difficulty, speech hesitations, writing errors 1
• Personality/behavior: Mood fluctuations, apathy, social withdrawal, loss of empathy 1

Structured Assessment Tools

• Use Mini-Mental State Examination (MMSE) as the primary tool for initial assessment and longitudinal tracking—it has high sensitivity for moderate dementia. 2, 4
• Montreal Cognitive Assessment (MoCA) is more sensitive for mild cognitive impairment and early dementia. 2, 3, 4
• Supplement with Clock Drawing Test for visuospatial and executive function screening. 2, 3, 4
• Use informant-based scales: IQCODE, ECog, or Lawton IADL Scale for functional assessment. 2, 4

Functional Impact Documentation

Document specific impairments in instrumental activities of daily living: 2, 4

• Managing finances
• Medication management
• Transportation abilities
• Household management
• Cooking and shopping abilities

Step 2: Identify Etiology Through Targeted Testing

Mandatory Laboratory Tests

Core laboratory workup includes: 2, 3, 5

• Complete blood count
• Comprehensive metabolic panel (especially sodium, calcium, glucose)
• Thyroid function tests (TSH, free T4)
• Vitamin B12 and folate levels
• HIV testing if risk factors present 2, 3

Neuroimaging Strategy

MRI is preferred over CT, especially for detecting vascular lesions and atrophy patterns. 1, 2, 3

Specific indications for anatomical neuroimaging: 1, 2

• Onset of cognitive symptoms within past 2 years
• Unexpected and unexplained decline in cognition/function
• Recent significant head trauma
• Unexplained neurological manifestations (new severe headache, seizures, Babinski sign)
• History of cancer (risk for brain metastases)
• Subject at risk for intracranial bleeding
• Symptoms compatible with normal pressure hydrocephalus
• Significant vascular risk factors

Recommended MRI sequences: 1

• 3D T1 volumetric sequence (with coronal reformations for hippocampal assessment)
• Fluid-attenuated inversion recovery (FLAIR)
• T2 or susceptibility-weighted imaging (SWI)
• Diffusion-weighted imaging (DWI)

Use semi-quantitative scales for interpretation: 1

• Medial temporal lobe atrophy (MTA) scale
• Fazekas scale for white matter changes
• Global cortical atrophy (GCA) scale

Step 3: Differentiate Dementia Subtypes

Alzheimer's Disease (Probable AD Dementia)

Diagnose probable AD when: 1

• Insidious onset over months to years
• Clear history of worsening cognition by report or observation
• Initial and most prominent deficits in one of these presentations:
  • Amnestic: Memory impairment plus dysfunction in at least one other cognitive domain
  • Language: Word-finding deficits with other cognitive domain involvement
  • Visuospatial: Spatial cognition deficits, object agnosia, impaired face recognition
  • Executive dysfunction: Impaired reasoning, judgment, problem-solving

Exclude probable AD if: 1

• Substantial cerebrovascular disease (stroke temporally related to cognitive onset, multiple/extensive infarcts, severe white matter hyperintensity)
• Core features of Dementia with Lewy bodies
• Prominent features of behavioral variant frontotemporal dementia
• Prominent features of primary progressive aphasia variants

Biomarker-Enhanced Diagnosis (Specialty Setting)

Core AD biomarkers include: 1

• Amyloid-beta ("A"): PET, CSF, or plasma
• Phosphorylated tau ("T1"): CSF or plasma p-tau 217, p-tau 181, p-tau 231
• Neurodegeneration ("N"): CSF/plasma neurofilament-light, MRI anatomic measures, FDG PET hypometabolism

Likelihood of AD pathophysiology: 1

• High: Both amyloid-beta and neuronal injury biomarkers present
• Intermediate: One biomarker positive, other untested or negative
• Low: Both biomarkers absent

Non-AD Dementias

Apply established diagnostic criteria for: 1

• Behavioral variant frontotemporal dementia: Early behavioral disinhibition, apathy, loss of empathy, compulsive behaviors
• Primary progressive aphasia: Progressive language impairment (can be atypical AD presentation if logopenic variant)
• Dementia with Lewy bodies/Parkinson's disease dementia: Visual hallucinations, parkinsonism, fluctuating cognition, REM sleep behavior disorder
• Vascular dementia/vascular cognitive impairment: Temporal relationship to stroke, stepwise decline, focal neurological signs
• Creutzfeldt-Jakob disease: Rapid progression, myoclonus, characteristic EEG/MRI findings

Advanced Imaging for Uncertain Cases

When underlying pathological process remains unclear after standard evaluation by a specialist: 1

• First-line: FDG PET for differential diagnosis (high accuracy for AD vs FTD)
• Alternative: SPECT rCBF if FDG PET unavailable
• Amyloid PET imaging: Limited to dementia experts following appropriate use criteria—obtain FDG PET first due to cost considerations
• DaTscan (123I-Ioflupane SPECT): Useful for suspected Lewy Body Disease when diagnosis remains unconfirmed after specialist evaluation

CSF Biomarkers (Selective Use)

Consider CSF analysis in: 1

• Diagnostic uncertainty with onset at early age (<65 years) to rule out AD pathophysiology
• Diagnostic uncertainty with predominance of language, visuospatial, dysexecutive, or behavioral features

Common Diagnostic Pitfalls

Critical errors to avoid: 2, 3, 4

• Failing to obtain corroborative informant history—patient self-report alone misses diagnoses due to lack of insight
• Overlooking reversible causes: medication effects, depression, hypothyroidism, B12 deficiency, normal pressure hydrocephalus
• Not recognizing that psychiatric symptoms (depression, irritability) often precede cognitive impairment in dementia—over half of patients developing MCI or dementia had mood symptoms first 1
• Assuming single pathology in patients over 80—most harbor multiple neuropathological changes (AD plus cerebrovascular disease most common) 1

Longitudinal Monitoring

Schedule follow-up every 6-12 months to assess: 2, 3, 4

• Cognition using MMSE for tracking
• Functional autonomy with structured scales
• Behavioral symptoms using NPI-Q or similar tools
• Caregiver burden using Zarit Burden Interview

All domains must be evaluated at least annually. 1, 2, 4