What are the features of frontotemporal dementia (FTD)?

Features of Frontotemporal Dementia

Frontotemporal dementia (FTD) is characterized by progressive behavioral changes, personality alterations, and executive dysfunction, with three distinct clinical subtypes: behavioral variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA), and non-fluent variant primary progressive aphasia (nfvPPA). 1, 2

Core Clinical Features by Subtype

Behavioral Variant FTD (bvFTD)

The behavioral variant represents the most common presentation and manifests with:

• Progressive personality changes including apathy, disinhibition, and loss of social awareness as the hallmark features 2, 3
• Loss of empathy and emotional blunting, which distinguishes it from primary psychiatric disorders 4
• Executive dysfunction manifesting as poor planning, organization, and decision-making abilities 3
• Compulsive and stereotyped behaviors, including ritualistic activities and dietary changes 4, 5
• Insidious onset with gradual progression, typically affecting individuals between 40-70 years of age 2, 6

Language Variants (Primary Progressive Aphasia)

Semantic Variant PPA (svPPA)/Semantic Dementia:

• Focal atrophy in anterior temporal lobes disrupting semantic processing 7
• Progressive loss of word meaning and object knowledge while speech remains fluent 8
• Surface dyslexia and impaired naming as early features 8

Non-Fluent Variant PPA (nfvPPA):

• Effortful, halting speech with agrammatism due to degeneration in speech production networks 7
• Apraxia of speech affecting motor planning for speech 4
• Preserved comprehension in early stages, distinguishing it from other variants 8

Neuropsychiatric Symptom Progression

• Disinhibition and depression become common across all FTD subtypes over the course of illness 5
• Apathy occurs significantly more in behavioral presentations compared to language variants 5
• Language presentations eventually converge with behavioral phenotypes, though with longer latency to onset of neuropsychiatric changes 5
• Visual hallucinations are uncommon in FTD and should prompt consideration of dementia with Lewy bodies or specific genetic mutations like GRN 6

Distinguishing Features from Psychiatric Disorders

Critical differentiating features between bvFTD and primary psychiatric disorders include:

• Age of onset typically after 40 years with insidious, progressive course rather than episodic presentation 1, 2
• Impaired insight is almost always present in bvFTD, whereas psychiatric patients often retain awareness 2
• Family history of FTD, ALS, or early-onset neurodegenerative disease in 20-40% of cases 1, 2
• Absence of response to psychiatric medications and lack of premorbid psychiatric history 1

Neuroanatomical Patterns

• BvFTD shows prominent degeneration in frontal and medial temporal lobes, insula, cingulate cortex, and limbic system 7
• Widespread brain abnormalities encompass frontal, temporal, and parietal lobes, as well as subcortical structures including basal ganglia and thalamus 7
• Right frontal parietal atrophy presents with behavioral changes, loss of empathy, executive dysfunction, and visuospatial deficits 3
• Asymmetric hemispheric atrophy with parietal involvement suggests possible GRN genetic mutations 3

Genetic Considerations

• 20-40% of cases have autosomal-dominant inheritance with C9orf72, GRN, and MAPT being the most common causative genes 1, 9
• C9orf72 mutation carriers can present with prominent psychiatric symptoms and form a diagnostic challenge given their slow progressive course 1, 2
• GRN mutations are associated with visual hallucinations and delusions in up to 25% of patients, an atypical feature for FTD 6

Common Diagnostic Pitfalls

• Average diagnostic delay is 5-6 years from symptom onset, with approximately 50% of patients receiving a prior psychiatric diagnosis (most frequently major depression) 1
• Current diagnostic criteria for possible bvFTD have poor specificity (27%) in mixed neuropsychiatric cohorts 1
• Standard MRI sensitivity is only 70% for detecting early frontotemporal degeneration, and may appear normal in early disease stages 3
• Up to 40% of primary psychiatric disorder patients show abnormal FDG-PET findings, limiting specificity 3
• Some patients present with non-progressive "phenocopy" FTD, which requires different management approaches 2

Disease Course

• Progressive clinicopathological deterioration with mortality typically within 6-8 years from diagnosis 9
• Symptoms often follow a pattern of remission and exacerbation, requiring flexible management approaches 2
• Language variants eventually develop behavioral symptoms, converging with the behavioral phenotype over time 5