What are the diagnostic criteria for frontotemporal dementia?

Frontotemporal Dementia Diagnostic Criteria

The diagnosis of frontotemporal dementia (FTD) requires a comprehensive neuropsychological assessment focusing on behavioral changes, social cognition deficits, and specific cognitive patterns, with neuroimaging showing frontal or anterior temporal atrophy. 1

Clinical Subtypes of FTD

FTD encompasses several clinical syndromes, with behavioral variant FTD (bvFTD) being the most common:

Behavioral Variant FTD (bvFTD)

• Characterized by progressive deterioration in behavior, personality, and social cognition 2
• Early symptoms include disinhibition, apathy, loss of empathy, and hyperorality 1, 2
• Insidious onset with progressive course is a key diagnostic feature 2
• Typically presents between ages 40-70 years 2

Language Variants (Primary Progressive Aphasia)

• Non-fluent/agrammatic variant PPA: characterized by effortful speech and grammatical errors 1
• Semantic variant PPA: impaired word finding and loss of meaning of words and objects 1

Diagnostic Criteria for Behavioral Variant FTD

Core Clinical Features (at least 3 must be present)

• Early behavioral disinhibition 1
• Early apathy or inertia 1
• Early loss of sympathy or empathy 1
• Early perseverative, stereotyped, or compulsive behaviors 1
• Hyperorality and dietary changes 1
• Executive dysfunction with relative sparing of memory and visuospatial functions 1

Diagnostic Categories

1. Possible bvFTD: Meets core clinical criteria
2. Probable bvFTD: Meets clinical criteria plus shows functional decline and imaging abnormalities
3. Definite bvFTD: Meets clinical criteria with either histopathological confirmation or known pathogenic mutation 2

Neuropsychological Assessment

A comprehensive neuropsychological examination is essential and should include:

• Assessment of multiple cognitive domains, not just executive function 1
• At least one structured test of social cognition (e.g., Ekman 60 Faces Test, SEA or Mini-SEA) 1
• Language testing including assessment of semantic associations 1
• Executive tasks (e.g., Stroop Test, Trail Making Test Part B, Hayling Sentence Completion Test) 1
• Memory assessment (episodic verbal and non-verbal) 1
• Working memory evaluation (e.g., Digits Backwards) 1
• Visuoperceptual tasks (e.g., VOSP) 1

Important Considerations in Assessment

• Executive dysfunction is not always the most prominent deficit in early bvFTD 1
• 10% of pathologically-confirmed bvFTD cases show marked episodic memory deficits at initial presentation 1
• Action naming is more affected in bvFTD, while object naming is more disturbed in Alzheimer's disease 1
• Qualitative aspects of test performance are crucial (e.g., stereotypies of speech, impulsivity, rigidity) 1

Neuroimaging and Biomarkers

• Brain MRI with T1 and FLAIR sequences including coronal cuts is essential 2
• Look for pathological atrophy in frontal or anterior temporal areas 2
• FDG-PET can be used in ambiguous cases without clear CT/MRI fronto-temporal atrophy 2
• CSF analysis of amyloid-β42, tau, and p-tau can help rule out Alzheimer's disease 2
• Consider serum or CSF neurofilament light chain (NfL) to differentiate bvFTD from psychiatric disorders 2

Genetic Testing

• Genetic testing for C9orf72, MAPT, and GRN mutations should be considered, especially with family history 2
• C9orf72 mutation screening should be strongly considered in all possible/probable bvFTD cases and suspected cases with strong psychiatric features 1

Differential Diagnosis

Psychiatric Disorders

• Careful differentiation from psychiatric disorders is crucial, as behavioral symptoms can overlap 1
• Neuropsychological testing, particularly language tests and picture naming, can help differentiate bvFTD from psychiatric disorders 1
• Plasma NfL has shown elevation in bvFTD compared to schizophrenia, depression, and bipolar disorder 2

Other Dementias

• Alzheimer's disease typically presents with more pronounced episodic memory impairment 3
• Dementia with Lewy bodies/Parkinson's disease dementia has distinct features 1
• Vascular cognitive impairment requires evidence of cerebrovascular disease 1

Common Pitfalls in Diagnosis

• Relying solely on executive dysfunction for diagnosis, as it may not be present in early stages 1
• Overlooking the importance of social cognition assessment 1
• Failing to obtain detailed caregiver history (essential due to impaired insight in bvFTD patients) 2
• Missing cases of non-progressive bvFTD phenocopies, which can be challenging to diagnose 1
• Standard visual neuroradiological review may be insufficient in early stages 2

Longitudinal Follow-up

• In ambiguous cases, longitudinal follow-up often becomes the diagnostic arbiter until pathology is available 1
• Cases of non-progressive bvFTD phenocopies require careful monitoring and specialized psychiatric assessment 1