What are the symptoms and treatment options for frontotemporal dementia?

Frontotemporal Dementia: Clinical Symptoms

Frontotemporal dementia presents with progressive behavioral changes, personality alterations, and/or language deficits, typically beginning between ages 40-70 years, with behavioral disinhibition, apathy, loss of empathy, and social cognition deficits as hallmark features. 1, 2

Core Behavioral Symptoms

The behavioral variant of frontotemporal dementia (bvFTD) manifests with six cardinal features, requiring at least three for diagnosis: 1

• Disinhibition: Socially inappropriate behaviors, impulsive actions, and loss of social tact 1, 3
• Apathy/inertia: Profound loss of motivation and initiative, distinct from depression 1, 3
• Loss of sympathy/empathy: Reduced emotional responsiveness to others' distress, a defining feature that distinguishes FTD from psychiatric disorders 1, 2
• Perseverative/compulsive behaviors: Rigid routines, repetitive actions, and stereotyped behaviors 1
• Hyperorality: Excessive eating, dietary changes, oral exploration of objects 1, 3
• Dysexecutive profile: Impaired planning, organization, and problem-solving 1

Language Deficits

Two distinct language variants exist: 4

• Progressive non-fluent aphasia: Effortful, halting speech with grammatical errors and impaired sentence construction 4, 3
• Semantic variant: Impaired word-finding, loss of word meaning, and inability to recognize objects (action naming is more affected than object naming, the reverse of Alzheimer's disease) 2, 4

Social Cognition Impairments

Social cognition deficits represent the neuropsychological hallmark: 2

• Impaired emotion recognition: Inability to identify facial expressions of emotion 2
• Theory of mind deficits: Failure to understand others' mental states and intentions 2
• Impaired moral reasoning: Loss of ethical judgment and social norms 2

Critical Distinguishing Features from Psychiatric Disorders

Emotional blunting with absence of subjective distress is the key differentiator—patients lack the emotional distress characteristic of psychiatric disorders and show marked lack of insight: 5

• Insidious, progressive course: Gradual worsening over months to years, not episodic 1, 2
• Profound lack of insight: Patients typically deny problems; caregivers initiate consultations 5, 2
• Age of onset 40-70 years: Earlier than typical Alzheimer's disease 1, 2
• Family history: 20-40% have family history of FTD, ALS, or early-onset neurodegeneration 6, 2

Associated Neurological Signs

Motor features may develop: 1

• Parkinsonism: Rigidity, bradykinesia, postural instability 1
• Motor neuron disease features: Muscle weakness, fasciculations, bulbar symptoms (10-15% of cases) 1
• Alien limb phenomenon: Involuntary limb movements 1
• Vertical gaze palsy with falls: Suggests progressive supranuclear palsy overlap 1

Cognitive Profile

Memory is relatively preserved early in the disease, distinguishing FTD from Alzheimer's disease, though approximately 10% show episodic memory deficits at presentation: 2

• Executive dysfunction: Impaired planning, set-shifting, and abstract reasoning dominate 1
• Preserved visuospatial abilities: Unlike Alzheimer's disease 2
• Attention and orientation: Often intact until later stages 2

Common Diagnostic Pitfalls

Approximately 50% of FTD patients receive initial psychiatric misdiagnosis, with diagnostic delays averaging 5-6 years: 2

• Do not dismiss FTD due to psychiatric history: Psychiatric symptoms can be the initial presentation, especially in C9orf72 mutation carriers 6, 2
• Do not rely on patient self-report: Impaired insight is characteristic; always obtain caregiver history 6, 2
• Do not miss diagnosis due to family psychiatric history: Genetic FTD can present with psychiatric phenotypes 2
• Recognize phenocopy FTD: Some patients present with non-progressive behavioral changes requiring different management 6, 1

Treatment Approaches

No disease-modifying treatments exist; management focuses on behavioral interventions and symptomatic support: 5, 7

Non-Pharmacological Management (First-Line)

• Structured routines: Compensate for executive dysfunction through environmental adaptations 6
• Behavioral management techniques: Exploit preserved functions and redirect attention from maladaptive behaviors 6, 7
• Speech and language therapy: For communication and swallowing difficulties, focusing on regaining voluntary control 6
• Caregiver education and support: Essential component given behavioral burden 6, 7

Pharmacological Considerations

• Selective serotonin reuptake inhibitors (SSRIs): May improve behavioral symptoms, particularly disinhibition and compulsions 3, 8
• Avoid cholinesterase inhibitors and memantine: No consistent benefit in FTD, unlike Alzheimer's disease 5, 3, 8
• Antipsychotics: Use with extreme caution only for severe agitation; increased risk of falls, stroke, and death 5, 3

Essential Diagnostic Workup

• Brain MRI with 3D T1 and FLAIR sequences: Shows frontal and anterior temporal atrophy (70% sensitivity in early stages) 6, 2
• FDG-PET: Recommended in diagnostically ambiguous cases 6
• Genetic testing for C9orf72: Should be performed in all possible/probable cases, especially with psychiatric features 6, 2
• Structured social cognition testing: Ekman 60 faces test for emotion recognition 6
• Frontal Behavioral Inventory (FBI): Score ≥12 on positive subscale indicates bvFTD 1