What are the diagnostic criteria for subtypes of dementia?

Diagnostic Criteria for Dementia Subtypes

Alzheimer's Disease Dementia

The diagnosis of Alzheimer's disease dementia requires meeting core clinical criteria: cognitive or behavioral symptoms that interfere with daily function, represent documented decline from previous levels, are not explained by delirium or psychiatric disorder, and involve impairment in at least two cognitive domains (memory, executive function, visuospatial ability, language, or behavior/personality). 1, 2

Core Clinical Diagnostic Framework

• Functional impairment is mandatory: Cognitive symptoms must interfere with ability to function at work or usual activities, distinguishing dementia from mild cognitive impairment 2
• Documented decline is essential: Symptoms must represent decline from previous functioning, obtained through history from both patient AND a knowledgeable informant 2
• Minimum two cognitive domains must be impaired: Memory, executive function, visuospatial ability, language dysfunction, or behavioral/personality changes 2
• Objective cognitive assessment is required: Use bedside mental status examination or neuropsychological testing in addition to history-taking 2

Biomarker-Enhanced Diagnosis (Research and Specialized Settings)

The 2025 Alzheimer's Association guidelines provide a contemporary biomarker framework that significantly enhances diagnostic specificity 1:

• Core AD biomarkers include two categories: Core 1 consists of Aβ (amyloid beta via PET, CSF, or plasma) and hyperphosphorylated tau species (p-tau 217, p-tau 181, p-tau 231); Core 2 consists of AD tau proteinopathy markers (p-tau 205, MTBR-243, non-phosphorylated tau fragments, tau PET) 1
• Biological staging by PET follows a progression: Stage A (amyloid-positive), Stage B (amyloid and tau positive in medial temporal lobe), Stage C (amyloid and tau positive with moderate neocortical involvement), Stage D (amyloid and tau positive with high neocortical involvement) 1
• Biomarkers are NOT recommended for routine clinical diagnosis: The core clinical criteria provide excellent diagnostic accuracy in most patients, and biomarker standardization remains limited across locales 1
• Biomarkers increase diagnostic certainty in three specific circumstances: Investigational studies, clinical trials, and as optional tools when available and deemed appropriate by specialists 1

Important Clinical Nuances

• Memory impairment is NOT always the primary deficit: Nonamnestic presentations occur, particularly with onset before age 65, including language-predominant, visuospatial-predominant, or executive dysfunction-predominant presentations 2
• Probable AD dementia requires: Meeting core clinical criteria with insidious onset and clear history of progressive cognitive worsening 1
• Possible AD dementia applies when: Clinical criteria are met but there is atypical course, mixed etiology with cerebrovascular disease, or insufficient information for probable diagnosis 1

Dementia with Lewy Bodies and Parkinson's Disease Dementia

Dementia with Lewy bodies and Parkinson's disease dementia are distinguished by specific clinical features including visual hallucinations, parkinsonism, fluctuating cognition, and REM sleep behavior disorder, with dopaminergic imaging assisting diagnosis. 1, 3

• Established diagnostic criteria exist: Specific consensus criteria differentiate DLB from Parkinson's disease dementia based on timing of cognitive and motor symptoms 1
• Dopaminergic PET or SPECT imaging can assist diagnosis: These functional imaging techniques demonstrate reduced dopamine transporter uptake in the striatum 3
• Alpha-synuclein biomarkers are emerging: CSF alpha-synuclein seed amplification assays are now recognized as biomarkers of non-AD pathology 1

Frontotemporal Dementia Subtypes

Frontotemporal dementia encompasses behavioral variant frontotemporal dementia and primary progressive aphasia variants, each with distinct diagnostic criteria focusing on behavioral changes or language dysfunction as primary features. 1

• Behavioral variant FTD has specific diagnostic criteria: Characterized by progressive behavioral and personality changes, with relative preservation of memory early in disease course 1
• Primary progressive aphasia includes three variants: Nonfluent/agrammatic, semantic, and logopenic variants, each with distinct language profiles 1
• Logopenic variant PPA can be an atypical presentation of AD: When characteristics are consistent with logopenic variant, underlying AD pathology should be considered 1
• 18F-fluorodeoxyglucose PET has high sensitivity and specificity: FDG-PET demonstrates characteristic patterns distinguishing AD from FTD 3

Vascular Dementia/Vascular Cognitive Impairment

Vascular dementia diagnosis requires evidence of cognitive impairment temporally related to cerebrovascular disease, with MRI demonstrating infarcts and/or white matter hyperintensities. 1

• MRI indicators of vascular brain injury are key biomarkers: Infarcts and white matter hyperintensities provide objective evidence of cerebrovascular pathology 1
• Temporal relationship between stroke and cognitive decline supports diagnosis: Onset of cognitive symptoms should correlate with vascular events 4

Other Neurodegenerative Dementias

The 2025 Alzheimer's Association guidelines reference established diagnostic criteria for additional dementia subtypes 1:

• LATE (limbic-predominant age-related TDP-43 encephalopathy): Has specific diagnostic criteria, though validated TDP-43 imaging tracers remain a notable gap 1, 3
• Progressive supranuclear palsy: Distinct clinical criteria focusing on vertical gaze palsy and axial rigidity 1
• Corticobasal degeneration: Characterized by asymmetric motor and cognitive features 1
• ALS-FTD: Combined motor neuron disease and frontotemporal dementia features 1
• Huntington's disease: Genetic testing confirms diagnosis in presence of characteristic motor, cognitive, and psychiatric features 1
• Creutzfeldt-Jakob disease: Rapidly progressive dementia with specific EEG and MRI findings 1

Mixed Etiology Dementia

Mixed etiology dementia is common in older adults, particularly those over age 80, where multiple pathologies contribute to cognitive impairment, most commonly AD with cerebrovascular disease. 1, 4

• Patients with mixed etiology are more likely to present with atypical symptoms: Non-amnestic presentations should raise suspicion for multiple contributing pathologies 1
• Contributing conditions must be identified: Obstructive sleep apnea, cognitively impairing medications, excessive alcohol consumption, and psychiatric disorders can exacerbate symptoms 1
• Identification provides opportunities for risk mitigation: Particularly when cardiac, cerebrovascular, sleep, medication, or substance-related factors are present 1

Critical Diagnostic Pitfalls

• Do not rely solely on memory impairment: Many dementia subtypes present with non-memory cognitive deficits as the primary feature 2
• Biomarker results can be indeterminate: All biomarkers are continuous measures requiring cutoff values, and ambiguous results are inevitable 1
• Standardization of biomarkers remains limited: Quantitative analysis must rely on local laboratory-specific standards until full standardization is achieved 1
• Psychiatric disorders can mimic or coexist with dementia: Differentiation from emerging neurodegenerative disease may be difficult 1