Frontotemporal dementia (FTD) refers to sporadic and hereditary disorders that affect the frontal and temporal lobes, including Pick disease.
(See also Overview of Delirium and Dementia and Dementia.)
Dementia is chronic, global, usually irreversible deterioration of cognition. Frontotemporal dementia accounts for up to 10% of dementias. Age at onset is typically younger (age 55 to 65) than in Alzheimer disease. FTDs affect men and women about equally.
Pick disease is a term used to describe pathologic changes in FTD, including severe atrophy, neuronal loss, gliosis, and presence of abnormal neurons (Pick cells) containing inclusions (Pick bodies).
About half of FTDs are inherited; most mutations involve chromosome 17q21-22 and result in abnormalities of the microtubule-binding tau protein; thus, FTDs are generally considered tauopathies. Some experts classify supranuclear palsy and corticobasal degeneration with FTDs because they share similar pathology and gene mutations affecting the tau protein. Symptoms, gene mutations, and pathologic changes may not correspond to each other. For example, the same mutation causes FTD symptoms in one family member but symptoms of corticobasal degeneration in another.
Dementia should not be confused with delirium, although cognition is disordered in both. The following helps distinguish them:
Dementia affects mainly memory, is typically caused by anatomic changes in the brain, has slower onset, and is generally irreversible.
Delirium affects mainly attention, is typically caused by acute illness or drug toxicity (sometimes life threatening), and is often reversible.
Other specific characteristics also help distinguish the dementia and delirium (see table Differences Between Delirium and Dementia).
Symptoms and Signs of Frontotemporal Dementia
Generally, frontotemporal dementia affects personality, behavior, and usually language function (syntax and fluency) more and memory less than does Alzheimer disease. Abstract thinking and attention (maintaining and shifting) are impaired; responses are disorganized. Orientation is preserved, but retrieval of information may be impaired. Motor skills are generally preserved. Patients have difficulty sequencing tasks, although visuospatial and constructional tasks are affected less.
Frontal release signs (grasp, rooting, suck, snout, and palmomental reflexes and glabellar sign [pathologic reflexes]) appear late in the disease but also occur in other dementias.
Some patients develop motor neuron disease with generalized muscle atrophy, weakness, fasciculations, bulbar symptoms (eg, dysphagia, dysphonia, difficulty chewing), and increased risk of aspiration pneumonia and early death.
There are different types of frontotemporal dementias, depending on which part of the brain is affected.
Behavioral (frontal) variant FTD
Social behavior and personality change because the orbitobasal frontal lobe is affected. Patients become impulsive and lose their social inhibitions (eg, they may shoplift); they neglect personal hygiene. Impersistence (impaired concentration), inertia, and mental rigidity may appear. Some have Klüver-Bucy syndrome, which involves emotional blunting, hypersexual activity, hyperorality (eg, bulimia, sucking and smacking of lips), and visual agnosias.
Behavior becomes repetitive and stereotyped (eg, patients may walk to the same location every day). Patients may pick up and manipulate random objects for no reason (called utilization behavior).
Verbal output is reduced; echolalia, perseveration (inappropriate repetition of a response), and eventually mutism occur.
Primary progressive aphasia
Language function deteriorates because of asymmetric (worse on left) anterolateral temporal lobe atrophy; the hippocampus and memory are relatively spared. Most patients present with difficulty finding words. Attention (eg, digit span) may be severely impaired. Many patients have aphasia, with decreased fluency and difficulty comprehending language; hesitancy in speech production and dysarthria are also common. In some patients, aphasia is the only symptom for ≥ 10 years; in others, global cognitive deficits develop within a few years.
Semantic dementia is a type of primary progressive aphasia. When the left side of the brain is affected most, the ability to comprehend words is progressively lost. Speech is fluent but lacks meaning; a generic or related term may be used instead of the specific name of an object. When the right side is affected most, patients have progressive anomia (inability to name objects) and prosopagnosia (inability to recognize familiar faces). They cannot remember topographic relationships. Some patients with semantic dementia also have Alzheimer disease.
Diagnosis of Frontotemporal Dementia
Generally similar to diagnosis of other dementias
Additional clinical evaluation to differentiate from some other dementias
A general diagnosis of dementia requires all of the following:
Cognitive or behavioral (neuropsychiatric) symptoms interfere with the ability to function at work or do usual daily activities.
These symptoms represent a decline from previous levels of functioning.
These symptoms are not explained by delirium or a major psychiatric disorder.
Diagnosis of frontotemporal dementia is suggested by typical clinical findings (eg, social disinhibition or impaired language function with relative sparing of memory).
As for other dementias, cognitive deficits are evaluated. Evaluation involves taking a history from the patient and from someone who knows the patient plus doing a bedside mental status examination or, if bedside testing is inconclusive, formal neuropsychologic testing.
CT and MRI are done to determine location and extent of brain atrophy and to exclude other possible causes (eg, brain tumors, abscesses, stroke). FTDs are characterized by severely atrophic, sometimes paper-thin gyri in the temporal and frontal lobes. However, MRI or CT may not show these changes until late in FTD. Thus, FTDs and Alzheimer disease can usually be differentiated more easily by clinical criteria. For example, primary progressive aphasia differs from Alzheimer disease in that memory and visuospatial function are preserved and syntax and fluency are impaired.
Positron emission tomography (PET) with fluorine-18 (18F)–labeled deoxyglucose (fluorodeoxyglucose, or FDG) may help differentiate Alzheimer disease from FTD by showing differences in location of hypometabolic areas. In Alzheimer disease, these areas are located in the posterior temporoparietal association cortex and posterior cingulate cortex; in FTD, they are located in the anterior regions—in the frontal lobes, anterior temporal cortex, and anterior cingulate cortex.
Treatment of Frontotemporal Dementia
Supportive measures
There is no specific treatment for frontotemporal dementia. Treatment is generally supportive. For example, the environment should be bright, cheerful, and familiar, and it should be designed to reinforce orientation (eg, placement of large clocks and calendars in the room). Measures to ensure patient safety (eg, signal monitoring systems for patients who wander) should be implemented.
Symptoms are treated as needed.
Prognosis for Frontotemporal Dementia
Frontotemporal dementias usually progress gradually, but progression rate varies; if symptoms are limited to speech and language, progression to general dementia may be slower.
End-of-life issues
Because insight and judgment deteriorate in patients with dementia, appointment of a family member, guardian, or lawyer to oversee finances may be necessary. Early in dementia, before the patient is incapacitated, the patient’s wishes about care should be clarified, and financial and legal arrangements (eg, durable power of attorney, durable power of attorney for health care) should be made. When these documents are signed, the patient’s capacity should be evaluated, and evaluation results recorded. Decisions about artificial feeding and treatment of acute disorders are best made before the need develops.
In advanced dementia, palliative measures may be more appropriate than highly aggressive interventions or hospital care.
