Frontotemporal dementia
Encyclopedia
Frontotemporal dementia (FTD) is a clinical syndrome
caused by degeneration of the frontal lobe
of the brain
and may extend back to the temporal lobe
. It is one of three syndromes caused by frontotemporal lobar degeneration
, and the second most common early-onset dementia after Alzheimer's disease
.
Language skills can be affected in a number of ways with two broad patterns. Some patients remain fluent with normal phonology and syntax but increasing difficulty with naming and word comprehension, known as semantic dementia
in which there is atrophy of the anterior temporal lobes, typically with an asymmetric pattern. Other patients, by contrast, present with a breakdown in speech fluency due to articulation difficulty, phonological and/or syntactic errors but preservation of word comprehension, referred to as progressive nonfluent aphasia
.
In addition to the characteristic cognitive dysfunction, a number of primitive reflexes
known as frontal release signs are often able to be elicited. Usually the first of these frontal release signs to appear is the palmomental reflex
which appears relatively early in the disease course whereas the palmar grasp reflex and rooting reflex appear late in the disease course.
FTD can occur in patients with motor neuron disease (also known as amyotrophic lateral sclerosis
) in a small number of cases. The prognosis for people with MND is worse when combined with FTD, shortening survival by about a year.
Structural MRI scans often reveal frontal lobe and/or anterior temporal lobe atrophy but in early cases the scan may seem normal. Atrophy is often asymmetric. Registration of images at different time points (e.g. one year apart) can show evidence of atrophy in two cross-sectional images that may be reported as normal. This is a useful diagnostic technique. However, many research groups are currently looking at ways of making an early diagnosis of FTD using other techniques (magnetic resonance spectroscopy, functional imaging, cortical thickness
measurements etc.). FDG-PET scans classically show frontal and/or anterior temporal hypometabolism, which helps differentiate from Alzheimer's disease. The PET scan in Alzheimer's disease classically shows biparietal hypometabolism.
Meta-analyses based on imaging methods have shown that frontotemporal dementia mainly affects a frontomedian network discussed in the context of social cognition or 'theory of mind'. This is entirely in keeping with the notion that, on the basis of cognitive neuropsychological evidence, the ventromedial prefrontal cortex is a major locus of dysfunction early on in the course of the behavioural variant of frontotemporal degeneration. The language subtypes of frontotemporal lobar degeneration (semantic dementia and progressive nonfluent aphasia) can be regionally dissociated by imaging approaches in vivo.
However, it is estimated that each of these two genes only accounts for about 5–10% of all cases of FTD, thus other genes or heritable components are likely responsible for the high degree of heritability in FTD.
Because FTD often occurs in younger people (i.e. in their 40's or 50's), it can severely affect families. Patients often still have children living in the home. Financially, it can be devastating as the disease strikes at the time of life that is often the top wage-earning years.
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
caused by degeneration of the frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
of the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
and may extend back to the temporal lobe
Temporal lobe
The temporal lobe is a region of the cerebral cortex that is located beneath the Sylvian fissure on both cerebral hemispheres of the mammalian brain....
. It is one of three syndromes caused by frontotemporal lobar degeneration
Frontotemporal lobar degeneration
-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
, and the second most common early-onset dementia after Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
Signs and symptoms
Symptoms can be classified (roughly) into two groups which underlie the functions of the frontal lobe: behavioural symptoms (and/or personality change) and symptoms related to problems with executive function.- Behavioural symptoms include lethargy and aspontaneity or oppositely disinhibitionDisinhibitionDisinhibition is a term in psychology used to describe a lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive and perceptual aspects with signs and symptoms...
. Apathetic patients may become socially withdrawn and stay in bed all day or no longer take care of themselves. Disinhibited patients can make inappropriate (sometimes sexual) comments or perform inappropriate acts. Patients with FTD can sometimes get into trouble with the policePoliceThe police is a personification of the state designated to put in practice the enforced law, protect property and reduce civil disorder in civilian matters. Their powers include the legitimized use of force...
because of inappropriate behaviour such as stealing. Recent findings indicate that psychotic symptoms are rare in FTD, possibly due to limited temporal-limbic involvement in this disorder. Among FTD patients, only approximately 2% have delusions, sometimes with paranoid ideation; hallucinations are rare. This is significantly less than AD patientsAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, where approximately 20% have delusions and paranoia. See ref. "Psychotic symptoms."
- Executive function is the cognitive skill of planning and organizing. Patients become unable to perform skills that require complex planning or sequencing.
Language skills can be affected in a number of ways with two broad patterns. Some patients remain fluent with normal phonology and syntax but increasing difficulty with naming and word comprehension, known as semantic dementia
Semantic dementia
Semantic dementia is a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains...
in which there is atrophy of the anterior temporal lobes, typically with an asymmetric pattern. Other patients, by contrast, present with a breakdown in speech fluency due to articulation difficulty, phonological and/or syntactic errors but preservation of word comprehension, referred to as progressive nonfluent aphasia
Progressive nonfluent aphasia
Progressive nonfluent aphasia is one of three clinical syndromes associated with frontotemporal lobar degeneration. The major symptom is progressive difficulties with the production of speech.-Clinical features:...
.
In addition to the characteristic cognitive dysfunction, a number of primitive reflexes
Primitive reflexes
Primitive reflexes are reflex actions originating in the central nervous system that are exhibited by normal infants but not neurologically intact adults, in response to particular stimuli. These reflexes disappear or are inhibited by the frontal lobes as a child moves through normal child...
known as frontal release signs are often able to be elicited. Usually the first of these frontal release signs to appear is the palmomental reflex
Palmomental reflex
The palmomental reflex is a primitive reflex consisting of a twitch of the chin muscle elicited by stroking a specific part of the palm. It is present in infancy and disappears as the brain matures during childhood but may reappear due to processes that disrupt the normal cortical inhibitory...
which appears relatively early in the disease course whereas the palmar grasp reflex and rooting reflex appear late in the disease course.
FTD can occur in patients with motor neuron disease (also known as amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
) in a small number of cases. The prognosis for people with MND is worse when combined with FTD, shortening survival by about a year.
Pathology
A number of case series have now been published looking at the pathological basis of frontotemporal dementia. As with other syndromes associated with FTLD, a number of different pathologies are associated with FTD:- Pick's diseasePick's diseasePick's disease, is a rare neurodegenerative disease that causes progressive destruction of nerve cells in the brain. Symptoms include loss of speech , and dementia. While some of the symptoms can initially be alleviated, the disease progresses and patients often die within two to ten years...
(3-repeat Tau inclusions) - Other tau-positive pathology including FTDP-17Frontotemporal dementia and parkinsonism linked to chromosome 17Frontotemporal dementia and parkinsonism linked to chromosome 17 is an autosomal dominant neurodegenerative disorder, which has three cardinal features: behavioral and personality changes, cognitive impairment, and motor symptoms. FTDP-17 was defined during the International Consensus Conference...
, corticobasal degenerationCorticobasal degenerationCorticobasal degeneration or Corticobasal Ganglionic Degeneration is a rare progressive neurodegenerative disease involving the cerebral cortex and the basal ganglia. It is characterized by marked disorders in movement and cognitive dysfunction...
, progressive supranuclear palsyProgressive supranuclear palsyProgressive supranuclear palsy is a degenerative disease involving the gradual deterioration and death of specific areas of the brain.... - Frontotemporal lobar degenerationFrontotemporal lobar degeneration-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...
with ubiquitin positive, tau- and alpha-synuclein negative inclusions with and without motor neuron degeneration (recently characterized by nuclear and cytoplasmic staining of TDP-43 protein) - DementiaDementiaDementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
lacking distinctive histologyHistologyHistology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope... - In rare cases, patients with clinical FTD were found to have changes consistent with Alzheimer's diseaseAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
on autopsyAutopsyAn autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present... - Evidence suggests that FTD selectively impairs spindle neuronSpindle neuronSpindle neurons, also called von Economo neurons , are a specific class of neurons that are characterized by a large spindle-shaped soma, gradually tapering into a single apical axon in one direction, with only a single dendrite facing opposite. Whereas other types of neurons tend to have many...
s, a type of neuron which has only been found in the brains of humans, great apes, and whales.
Diagnosis
According to DSM-IV diagnosis is mainly clinical including changed behaviors, changes in language and others, using also image exams and neuropsychological tests.Structural MRI scans often reveal frontal lobe and/or anterior temporal lobe atrophy but in early cases the scan may seem normal. Atrophy is often asymmetric. Registration of images at different time points (e.g. one year apart) can show evidence of atrophy in two cross-sectional images that may be reported as normal. This is a useful diagnostic technique. However, many research groups are currently looking at ways of making an early diagnosis of FTD using other techniques (magnetic resonance spectroscopy, functional imaging, cortical thickness
measurements etc.). FDG-PET scans classically show frontal and/or anterior temporal hypometabolism, which helps differentiate from Alzheimer's disease. The PET scan in Alzheimer's disease classically shows biparietal hypometabolism.
Meta-analyses based on imaging methods have shown that frontotemporal dementia mainly affects a frontomedian network discussed in the context of social cognition or 'theory of mind'. This is entirely in keeping with the notion that, on the basis of cognitive neuropsychological evidence, the ventromedial prefrontal cortex is a major locus of dysfunction early on in the course of the behavioural variant of frontotemporal degeneration. The language subtypes of frontotemporal lobar degeneration (semantic dementia and progressive nonfluent aphasia) can be regionally dissociated by imaging approaches in vivo.
Genetics
A higher proportion of FTD cases seem to have a familial component (perhaps more so than Alzheimer's disease). Two known mutations are associated with familial FTD:- tau-positive frontotemporal dementia with parkinsonism (FTDP-17) with mutations in the MAPT gene on chromosome 17
- tau-negative frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U; positive for TDP-43) with progranulin mutations (also on chromosome 17)
However, it is estimated that each of these two genes only accounts for about 5–10% of all cases of FTD, thus other genes or heritable components are likely responsible for the high degree of heritability in FTD.
Management
There is no known curative treatment for FTD. Supportive care is essential. Management of behavioural symptoms may be necessary (e.g. SSRIs for depression; atypical neuroleptics etc.).Because FTD often occurs in younger people (i.e. in their 40's or 50's), it can severely affect families. Patients often still have children living in the home. Financially, it can be devastating as the disease strikes at the time of life that is often the top wage-earning years.
External links
- The Association for Frontotemporal Dementias
- The Bluefield Project to Cure Frontotemporal Dementia
- Columbia University Update
- A collection of articles about Frontotemporal dementia in the journal Neurology
- UCSF Memory and Aging Center
- UCSF Memory and Aging Center YouTube channel with films about FTD
- Conference 6th International Conference on Frontotemporal Dementia in Rotterdam, September 2008
- New York Times article 4/8/2008 suggesting that scientist Anne Adams and composer Maurice Ravel had frontotemporal dementia
- FRONTIER - Frontotemporal Dementia Research Group - at POWMRI, Sydney, Australia
- GeneReview/NIH/UW entry on Frontotemporal Dementia with Parkinsonism-17
- GeneReview/NIH/UW entry on GRN-Related Frontotemporal Dementia