What is the approach to diagnose different types of dementias?

Diagnostic Approach to Different Types of Dementia

Diagnose dementia through a structured, tiered approach that begins with establishing core diagnostic criteria through patient and informant history, followed by objective cognitive testing, laboratory workup to exclude reversible causes, and neuroimaging, then differentiate dementia subtypes based on specific clinical phenotypes and, when needed, advanced biomarker testing. 1

Step 1: Establish Core Dementia Diagnosis

Essential Diagnostic Criteria

Dementia requires all three of the following 1, 2, 3:

• Cognitive or behavioral symptoms that interfere with ability to function at work or usual activities
• Decline from previous levels of functioning and performing
• Not explained by delirium or major psychiatric disorder

Critical History Components

Never rely solely on patient self-report—always obtain corroborative history from a reliable informant, as patients with dementia lack insight into their deficits 4, 1. Document the following domains 4, 3:

• Onset and progression pattern (gradual vs. sudden, stepwise vs. progressive)
• Specific cognitive changes in memory, language, visuospatial abilities, executive function
• Functional decline in instrumental activities of daily living (managing finances, medications, transportation, household tasks)
• Behavioral and neuropsychiatric symptoms (personality changes, apathy, disinhibition, mood fluctuations)
• Risk factors (vascular disease, family history, head trauma, medications)

Structured Assessment Tools for Informants

Use validated informant-based instruments 1, 4:

• For cognitive/functional changes: AD8, IQCODE, ECog, Quick Dementia Rating System
• For functional assessment: Lawton-Brody IADL Scale, FAQ, 4-item IADL scale
• For behavioral symptoms: NPI-Q, MBI-C

Step 2: Objective Cognitive Assessment

Cognitive Screening Tools

The MoCA is superior to MMSE for detecting mild cognitive impairment and early dementia, while MMSE remains valuable for moderate dementia and longitudinal tracking 4, 1. Specific recommendations 1, 3:

• MoCA: More sensitive for MCI and mild dementia, offers strong normative data
• MMSE: High sensitivity and specificity (>80%) for moderate dementia, validated for longitudinal tracking
• Clock Drawing Test: Useful supplementary screening tool
• DCQ (Dementia Cognitive Questionnaire): Specifically designed for atypical syndromes (behavioral variant frontotemporal dementia, primary progressive aphasia, AD variants)

When to Order Neuropsychological Testing

Consider formal neuropsychological evaluation when 3, 5:

• Routine history and bedside examination cannot provide confident diagnosis
• Patient presentation is complex or symptoms are mild/unusual
• Educational extremes or language/cultural considerations exist
• Age of onset younger than 65 years
• Rapid symptom onset or atypical cognitive profile

Step 3: Core Laboratory Testing to Exclude Reversible Causes

Perform the following core laboratory tests in all patients 4, 3, 6:

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

These tests identify treatable conditions including hypothyroidism, metabolic encephalopathies (hyponatremia, hyperparathyroidism, hypoglycemia), and vitamin deficiencies 6.

Step 4: Neuroimaging

MRI is preferred over CT, especially for detecting vascular lesions, atrophy patterns, and structural abnormalities 4, 3. Neuroimaging is particularly important when 3:

• Onset of cognitive symptoms within the past 2 years
• Unexpected decline in cognition or function
• Recent significant head trauma
• Unexplained neurological manifestations (focal deficits, gait disturbance, seizures)
• Significant vascular risk factors
• Age younger than 65 years

Step 5: Differentiate Dementia Subtypes Based on Clinical Phenotypes

Alzheimer's Disease (Most Common)

Typical presentation 1:

• Amnestic presentation: Prominent impairment in acquiring and remembering new information (repetitive questions, misplacing belongings, forgetting appointments), plus dysfunction in at least one other cognitive domain
• Nonamnestic presentations:
  • Language variant: Word-finding difficulties as most prominent deficit
  • Visuospatial variant: Spatial cognition deficits, object agnosia, impaired face recognition
  • Executive dysfunction variant: Impaired reasoning, judgment, problem-solving as primary features

Exclude probable AD when 1:

• Substantial cerebrovascular disease (stroke temporally related to cognitive decline, multiple infarcts, severe white matter disease)
• Core features of other dementias are prominent (see below)

Dementia with Lewy Bodies/Parkinson's Disease Dementia

Key distinguishing features 1:

• Core clinical features: Visual hallucinations, fluctuating cognition, parkinsonism (rigidity, bradykinesia, tremor)
• Supportive features: REM sleep behavior disorder, severe neuroleptic sensitivity
• Timing: In DLB, cognitive symptoms precede or occur within 1 year of motor symptoms; in PDD, parkinsonism precedes dementia by >1 year

Frontotemporal Dementia (Behavioral Variant)

Characteristic presentation 1, 7:

• Early behavioral changes: Disinhibition, apathy, loss of empathy, compulsive behaviors, hyperorality
• Personality changes: Socially inappropriate behaviors, loss of insight
• Relative preservation of memory and visuospatial function early in disease
• Age of onset: Typically 35-75 years, often younger than AD
• Neuroimaging: Focal atrophy of frontal and anterior temporal regions

Primary Progressive Aphasia

Three main variants 1:

• Logopenic variant: Word-finding difficulties, impaired sentence repetition (often due to AD pathology)
• Semantic variant: Loss of word meaning, impaired object knowledge, surface dyslexia
• Nonfluent/agrammatic variant: Effortful speech, agrammatism, apraxia of speech

Vascular Dementia/Vascular Cognitive Impairment

Diagnostic features 1:

• Temporal relationship: Cognitive decline temporally related to stroke or vascular event
• Neuroimaging evidence: Multiple or strategic infarcts, extensive white matter hyperintensities, microbleeds
• Stepwise progression: Often (but not always) stepwise decline rather than gradual
• Vascular risk factors: Hypertension, diabetes, hyperlipidemia, atrial fibrillation

Other Important Dementia Types

Refer to established diagnostic criteria for 1:

• LATE (Limbic-predominant Age-related TDP-43 encephalopathy): Often mimics AD, common in those >80 years
• Progressive supranuclear palsy: Vertical gaze palsy, axial rigidity, frequent falls
• Corticobasal degeneration: Asymmetric parkinsonism, apraxia, alien limb phenomenon
• Creutzfeldt-Jakob disease: Rapid progression, myoclonus, periodic sharp waves on EEG
• Huntington's disease: Chorea, psychiatric symptoms, positive family history

Step 6: Advanced Biomarker Testing (When Indicated)

Current Biomarker Framework

The 2025 Alzheimer's Association guidelines introduce a biological staging system 1:

Core AD biomarkers 1:

• Core 1 (A/T1): Amyloid-beta (PET, CSF, plasma) and phosphorylated tau (p-tau 217, p-tau 181, p-tau 231)
• Core 2 (T2): AD tau proteinopathy (p-tau 205, tau PET)

Non-specific AD-related biomarkers 1:

• N (neurodegeneration): CSF/plasma neurofilament-light, MRI volumetrics, FDG-PET hypometabolism
• I (astrocytic activation): CSF/plasma GFAP

Non-AD pathology biomarkers 1:

• Vascular injury: MRI white matter hyperintensities, infarcts
• Alpha-synuclein: CSF alpha-synuclein seed amplification assay

When to Consider Biomarker Testing

Consider advanced testing in 1, 5:

• Atypical presentations (age <65 years, rapid progression, unusual cognitive profile)
• Diagnostic uncertainty after standard evaluation
• When disease-modifying therapies are being considered
• Research settings or clinical trials

Critical Pitfalls to Avoid

Common diagnostic errors 4, 3:

• Failing to obtain informant history: Patient self-report is unreliable
• Overlooking reversible causes: Depression, medication effects, metabolic disturbances, sleep disorders can mimic or coexist with dementia 1, 2
• Relying solely on cognitive screening scores: Diagnosis requires functional impairment, not just test scores 1
• Missing mixed etiology: Most patients >80 years have multiple pathologies contributing to cognitive impairment 1
• Confusing depression with dementia: Depression can cause cognitive symptoms ("pseudodementia"), but mood changes are also early symptoms of neurodegenerative disease 1

Longitudinal Monitoring After Diagnosis

Schedule follow-up visits every 6-12 months for stable patients to track disease progression using a multi-dimensional approach 4, 3:

• Cognition: Repeat standardized cognitive testing (same instrument for comparison)
• Functional autonomy: Reassess IADLs and basic ADLs
• Behavioral symptoms: Monitor neuropsychiatric symptoms
• Caregiver burden: Assess caregiver stress and support needs
• Safety concerns: Driving, wandering, medication management