Frontotemporal Dementia

Background

• Frontotemporal dementias are a group of neurodegenerative conditions caused by progressive and relatively selective degeneration of frontal and/or temporal lobes. Frontotemporal dementia is characterized by deterioration in behavior and personality or in language abilities, culminating in dementia, usually with onset age < 65 years.
• It presents as either behavioral variant frontotemporal dementia (bvFTD) or primary progressive aphasia (semantic variant [svPPA] or nonfluent/agrammatic variant [nfvPPA]).
• It often affects people at a younger age than Alzheimer disease, accounting for up to one-quarter of cases of early-onset dementia (onset < 65 years).

Evaluation

• Consider frontotemporal dementia as a possible diagnosis in adults with slowly progressing behavioral problems and/or language impairments that represent a change from baseline.
• Frontotemporal dementia is classified into 3 clinical variants based on the predominant presenting symptoms, although some patient exhibit a mixed or overlapping initial presentation.
  • Behavioral variant is characterized by early personality changes, behavioral disinhibition, apathy, loss of empathy or interpersonal warmth, and other deficits in executive function.
  • Primary progressive aphasia (PPA) is characterized by prominent language deficits, most commonly aphasia in early disease stage, which interferes with daily functioning
    • Semantic variant PPA involves early deficits in semantic knowledge including anomia (especially for nouns) and impaired single-word comprehension.
    • Nonfluent variant PPA is characterized by slow or halting speech production and agrammatism (omitting or missing grammar).
• Initial diagnosis is made clinically using diagnostic criteria to document the presence of behavioral, psychiatric, and/or language symptoms.
  • Clinical diagnosis is based on careful clinician observation and extensive history from a knowledgeable informant.
  • Refer patient to a psychiatrist and for detailed neuropsychological assessment to evaluate symptoms and help rule out primary psychiatric disorders, especially in cases of suspected behavioral variant frontotemporal dementia.
• Perform structural brain imaging to support clinical diagnosis of frontotemporal dementia.
• Perform genetic testing in select patients, such as those with a clinical diagnosis of probable behavioral-variant frontotemporal dementia (bvFTD) and first-degree relatives with either bvFTD, early-onset dementia, Parkinson disease, amyotrophic lateral sclerosis, or unexplained late-onset psychiatric disorder.
• There are no cerebrospinal fluid (CSF) biomarkers that can reliably identify frontotemporal dementia; however, CSF analysis of beta-amyloid-42, total tau, and phosphorylated tau biomarkers may be considered to assess for the presence of Alzheimer pathology.

Management

• There are no effective disease-modifying treatments, so treatment is directed at managing the associated symptoms and helping patients and caregivers cope with the disease impact.
• Offer multidisciplinary nonpharmacologic management to help mitigate the disease impact, such as with speech and language therapy, occupational therapy, psychological counseling, and/or social support.
• Provide caregiver support, including education, counseling, psychological support, and programmed respite.
• Evidence for medications is limited and pharmacotherapy is primarily focused on managing associated psychiatric and behavioral symptoms.
  • Neither cholinesterase inhibitors nor memantine appear to improve symptoms of frontotemporal dementia.
  • Antidepressants such as citalopram and trazodone might help address some frontotemporal dementia symptoms but evidence is limited. Antidepressants in general may be considered for other symptoms such as depression, anxiety, sexually inappropriate or compulsive behaviors, and/or sleep disturbance.
  • Only consider antipsychotic medications for frontotemporal dementia if symptoms such as agitation, aggression, hallucinations, or delusions present a danger to the patient or others, and symptoms cannot be managed by other strategies. If deemed necessary, consider low-dose risperidone or quetiapine with close clinical monitoring.
• Neurostimulation such as transcranial direct current stimulation (tDCS) might slow cognitive decline in patients with primary progressive aphasia, but evidence is limited.