Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder,
encompasses several types of
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
involving the progressive degeneration of
frontal
Front may refer to:
Arts, entertainment, and media Films
* ''The Front'' (1943 film), a 1943 Soviet drama film
* ''The Front'', 1976 film
Music
* The Front (band), an American rock band signed to Columbia Records and active in the 1980s and e ...
and
temporal lobe
The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain.
The temporal lobe ...
s.
FTDs broadly present as behavioral or language disorders with gradual onsets.
The three main subtypes or variant syndromes are a behavioral variant (bvFTD) previously known as ''Pick's disease'',
and two variants of
primary progressive aphasia
Primary progressive aphasia (PPA) is a type of neurological syndrome in which language capabilities slowly and progressively become impaired. As with other types of aphasia, the symptoms that accompany PPA depend on what parts of the left hemisphe ...
–
semantic variant (svPPA), and
nonfluent variant (nfvPPA).
Two rare distinct subtypes of FTD are neuronal intermediate filament inclusion disease (NIFID), and basophilic inclusion body disease. Other related disorders include
corticobasal syndrome Corticobasal syndrome (CBS) is a rare, progressive disease, progressive Parkinson plus syndrome, atypical Parkinsonism syndrome and is a tauopathy related to frontotemporal dementia. CBS is typically caused by the deposit of tau proteins forming in ...
and FTD with
amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
(ALS) ''FTD-ALS'' also called ''FTD-
MND''.
Frontotemporal dementias are mostly early-onset syndromes that are linked to
frontotemporal lobar degeneration
Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.
Common ...
(FTLD),
which is characterized by progressive
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
al loss predominantly involving the
frontal
Front may refer to:
Arts, entertainment, and media Films
* ''The Front'' (1943 film), a 1943 Soviet drama film
* ''The Front'', 1976 film
Music
* The Front (band), an American rock band signed to Columbia Records and active in the 1980s and e ...
or
temporal lobe
The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain.
The temporal lobe ...
s, and a typical loss of more than 70% of
spindle neuron
Von Economo neurons (VENs), also called spindle neurons, are a specific class of mammalian cortical neurons characterized by a large spindle-shaped soma (or body) gradually tapering into a single apical axon (the ramification that ''transmits' ...
s, while other neuron types remain intact.
FTD was first described by
Arnold Pick
Arnold Pick (20 July 18514 April 1924) was a Jewish Czech psychiatrist. He is known for identifying the clinical syndrome of Pick's disease and the Pick bodies that are characteristic of the disorder. He was the first to name reduplicative param ...
in 1892 and was originally called ''Pick's disease'', a term now reserved only for behavioral variant FTD which shows the presence of Pick bodies and Pick cells.
Second only to
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
(AD) in
prevalence
In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
,
FTD accounts for less than, or actually, 20% (''number is perhaps rounded'') of degenerative dementia cases found at autopsy.
Signs and symptoms typically manifest in late adulthood, more commonly between the ages of 45 and 65, approximately equally affecting men and women.
Common signs and symptoms include significant changes in social and personal behavior, apathy, blunting of emotions, and deficits in both expressive and receptive language. Currently, there is no cure for FTD, but there are treatments that help alleviate symptoms.
Signs and symptoms
Frontotemporal dementia (FTD) is an early-onset disorder that mostly occurs before the age of 65, but can begin earlier, and in 20–25% of cases onset is later.
It is the most common early presenting dementia.
The
International Classification of Diseases
The International Classification of Diseases (ICD) is a globally used diagnostic tool for epidemiology, health management and clinical purposes. The ICD is maintained by the World Health Organization (WHO), which is the directing and coordinating ...
recognizes the disease as causative to disorder affecting
mental and
behavioural
Behavior (American English) or behaviour (British English) is the range of actions and mannerisms made by individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as wel ...
aspects of the human organism. Dissociation from family, extreme
oniomania, vulgar speech characteristics, screaming, inability to control emotions, behavior, personality, and temperament are characteristic social display patterns. A gradual onset and progression of changes in behavior or language deficits are reported to have begun several years prior to presentation to a neurologist.
Subtypes and related disorders
The main subtypes of frontotemporal dementia are behavioral variant FTD, semantic dementia, progressive nonfluent aphasia, and FTD associated with amyotrophic lateral sclerosis (
FTD–ALS
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most commo ...
). Two distinct rare subtypes are neuronal intermediate filament inclusion disease, and basophilic inclusion body disease. Related disorders are
corticobasal syndrome Corticobasal syndrome (CBS) is a rare, progressive disease, progressive Parkinson plus syndrome, atypical Parkinsonism syndrome and is a tauopathy related to frontotemporal dementia. CBS is typically caused by the deposit of tau proteins forming in ...
, and
progressive supranuclear palsy
Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty ...
.
Behavioral variant frontotemporal dementia
Behavioral variant frontotemporal dementia (BvFTD) was previously known as ''Pick's disease'', and is the most common of the FTD types.
BvFTD is diagnosed four times as often as the PPA variants.
Behavior can change in BvFTD in either of two ways—it can change to being impulsive and disinhibited, acting in socially unacceptable ways; or it can change to being listless and apathetic.
About 12–13% of people with bvFTD develop
motor neuron disease
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
.
The Pick bodies in behavioral variant FTD are spherical
inclusion bodies
Inclusion bodies are aggregates of specific types of protein found in neurons, a number of tissue cells including red blood cells, bacteria, viruses, and plants. Inclusion bodies of aggregations of multiple proteins are also found in muscle cells ...
found in the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
of affected cells. They consist of tau fibrils as a major component together with a number of other protein products including
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
and
tubulin
Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...
.
Semantic dementia
Semantic dementia
Semantic dementia (SD), also known as semantic variant primary progressive aphasia (svPPA), is a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains. However, the most common p ...
(SD) is characterized by the loss of
semantic
Semantics (from grc, σημαντικός ''sēmantikós'', "significant") is the study of reference, meaning, or truth. The term can be used to refer to subfields of several distinct disciplines, including philosophy, linguistics and comput ...
understanding, resulting in impaired word comprehension. However, speech remains fluent and grammatical.
[
]
Progressive nonfluent aphasia
Progressive nonfluent aphasia
Progressive nonfluent aphasia (PNFA) is one of three clinical syndromes associated with frontotemporal lobar degeneration. PNFA has an insidious onset of language deficits over time as opposed to other stroke-based aphasias, which occur acutely fol ...
(PNFA) is characterized by progressive difficulties in speech production.[
]
Neuronal intermediate filament inclusion disease
Neuronal intermediate filament inclusion disease (NIFID) is a rare distinct variant. The inclusion bodies
Inclusion bodies are aggregates of specific types of protein found in neurons, a number of tissue cells including red blood cells, bacteria, viruses, and plants. Inclusion bodies of aggregations of multiple proteins are also found in muscle cells ...
that are present in NIFID are cytoplasmic
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. Th ...
and made up of type IV intermediate filament
Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''.
Intermedia ...
s. NIFID has an early age of onset between 23 and 56. Symptoms can include behavioural, and personality changes, memory and cognitive impairments, language difficulties, motor weakness, and extrapyramidal symptoms
Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...
. NIFID is one of the FTLD -FUS proteopathies
In medicine, proteinopathy (; 'pref''. protein -pathy 'suff''. disease proteinopathies ''pl''.; proteinopathic ''adj''), or proteopathy, protein conformational disorder, or protein misfolding disease refers to a class of diseases in which ...
. Imaging
Imaging is the representation or reproduction of an object's form; especially a visual representation (i.e., the formation of an image).
Imaging technology is the application of materials and methods to create, preserve, or duplicate images.
...
commonly shows atrophy in the frontotemporal region, and in part of the striatum
The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...
in the basal ganglia
The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...
. Post-mortem studies show a marked reduction in the caudate nucleus
The caudate nucleus is one of the structures that make up the corpus striatum, which is a component of the basal ganglia in the human brain. While the caudate nucleus has long been associated with motor processes due to its role in Parkinson's di ...
of the striatum; frontal temporal gyri are narrowed with widened intervening sulci, and the lateral ventricles are enlarged.
Basophilic inclusion body disease
Another rare FTD variant, also a FTLD-FUS proteopathy, is basophilic inclusion body disease (BIBD).
Other characteristics
In later stages of FTD, the clinical phenotypes may overlap.[ People with FTD tend to struggle with ]binge eating
Binge eating is a pattern of disordered eating which consists of episodes of uncontrollable eating. It is a common symptom of eating disorders such as binge eating disorder and bulimia nervosa. During such binges, a person rapidly consumes an exc ...
and compulsive behaviors. Binge eating habits are often associated with changes in food preferences (cravings for more sweets, carbohydrates), eating inedible objects and snatching food from others. Recent findings from structural MRI research have indicated that eating changes in FTD are associated with atrophy (wasting) in the right ventral insula, striatum
The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...
, and orbitofrontal cortex
The orbitofrontal cortex (OFC) is a prefrontal cortex region in the frontal lobes of the brain which is involved in the cognitive process of decision-making. In non-human primates it consists of the association cortex areas Brodmann area 11, 12 ...
.
People with FTD show marked deficiencies in executive functioning and working memory. Most become unable to perform skills that require complex planning or sequencing. In addition to the characteristic cognitive dysfunction, a number of 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 are suppressed by the development of the f ...
known as frontal release signs
Frontal release signs are primitive reflexes traditionally held to be a sign of disorders that affect the frontal lobes. The appearance of such signs reflects the area of brain dysfunction rather than a specific disorder which may be diffuse, such ...
are often able to be elicited. Usually the first of these frontal release signs to appear is the palmomental reflex The palmomental reflex (PMR) or Marinesco-Radovici Sign or Kinn reflex or Marinesco 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 t ...
which appears relatively early in the disease course whereas the palmar grasp
Palmar grasp reflex (or grasp reflex) is a primitive and involuntary reflex found in infants of humans and most primates. When an object, such as an adult finger, is placed in an infant's palm, the infant's fingers reflexively grasp the object. ...
reflex and rooting reflex
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 are suppressed by the development of the f ...
appear late in the disease course.
In rare cases, FTD can occur in people with amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
(ALS) a motor neuron disease
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
. The prognosis for people with ALS is worse when combined with FTD, shortening survival by about a year.
Genetics
A higher proportion of frontotemporal dementias seem to have a familial component than other neurodegenerative diseases such as Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. More and more mutations and genetic variants are being identified all the time, needing constant updating of genetic influences.
* Tau-positive (FTDP-17) is caused by mutations in the MAP
A map is a symbolic depiction emphasizing relationships between elements of some space, such as objects, regions, or themes.
Many maps are static, fixed to paper or some other durable medium, while others are dynamic or interactive. Although ...
T gene on chromosome 17 that encodes the tau protein
The tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintaining ...
. It has been determined that there is a direct relationship between the type of tau mutation and the neuropathology of gene mutations. The mutations at the splice junction of exon 10 of tau lead to the selective deposition of the repetitive tau in neurons and glia. The pathological phenotype associated with mutations elsewhere in tau is less predictable with both typical neurofibrillary tangles (consisting of both 3 repeat and 4 repeat tau) and Pick bodies (consisting of 3 repeat tau) having been described. The presence of tau deposits within glia is also variable in families with mutations outside of exon 10. This disease is now informally designated FTDP-17T. FTD shows a linkage to the region of the tau locus on chromosome 17, but it is believed that there are two loci leading to FTD within megabases of each other on chromosome 17. The only other known autosomal dominant genetic cause of FTLD-tau is a hypomorphic mutation in VCP which is associated with a unique neuropathology called vacuolar tauopathy.
* FTD caused by FTLD-TDP43 has numerous genetic causes. Some cases are due to mutations in the GRN gene, also located on chromosome 17. Others are caused by hypomorphic VCP mutations, although these patients present with a complex picture of multisystem proteinopathy
Multisystem proteinopathy (MSP) is a dominantly inherited, pleiotropic, degenerative disorder of humans that can affect muscle, bone, and/or the central nervous system. MSP can manifest clinically as classical amyotrophic lateral sclerosis (ALS), ...
that can include amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
, inclusion body myopathy
Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body m ...
, Paget's disease of bone
Paget's disease of bone (commonly known as Paget's disease or, historically, osteitis deformans) is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the ...
, and FTD. The most recent addition to the list is a hexanucleotide repeat expansion in intron 1 of C9ORF72
C9orf72 (chromosome 9 open reading frame 72) is a protein which in humans is encoded by the gene ''C9orf72''.
The human ''C9orf72'' gene is located on the short (p) arm of chromosome 9 open reading frame 72, from base pair 27,546,546 to base pai ...
. Only one or two cases have been reported describing TARDBP
TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa) is a protein that in humans is encoded by the ''TARDBP'' gene.
Structure
TDP-43 is 414 amino acid residues long. It consists of 4 domains: an N-terminal d ...
(the TDP-43
TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa) is a protein that in humans is encoded by the ''TARDBP'' gene.
Structure
TDP-43 is 414 amino acid residues long. It consists of 4 domains: an N-terminal d ...
gene) mutations in a clinically pure FTD (FTD without MND).
* Several other genes have been linked to this condition. These include CYLD, OPTN, SQSTM1
Sequestosome-1 is a protein that in humans is encoded by the ''SQSTM1'' gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacti ...
and TBK1. These genes have been implicated in the autophagy pathway.
* No genetic causes of FUS pathology in FTD have yet been reported.
* Major alleles of TMEM106B Transmembrane protein 106B is a protein that is encoded by the ''TMEM106B'' gene. It is found primarily within Neuron, neurons and Oligodendrocyte, oligodendrocytes in the central nervous system with its subcellular location being in Lysosome, lysos ...
SNPs have been found to be associated with risk of FTLD.
Pathology
There are three main histological subtypes found at post-mortem: FTLD-tau, FTLD-TDP, and FTLD-FUS. In rare cases, patients with clinical FTD were found to have changes consistent with Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
on autopsy
An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any di ...
. The most severe brain atrophy appears to be associated with behavioral variant FTD, and corticobasal degeneration
Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is chara ...
.
With regard to the genetic defects that have been found, repeat expansion in the C9orf72
C9orf72 (chromosome 9 open reading frame 72) is a protein which in humans is encoded by the gene ''C9orf72''.
The human ''C9orf72'' gene is located on the short (p) arm of chromosome 9 open reading frame 72, from base pair 27,546,546 to base pai ...
gene is considered a major contribution to frontotemporal lobar degeneration
Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.
Common ...
, although defects in the GRN and MAPT
The tau proteins (abbreviated from tubulin associated unit) are a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintainin ...
genes are also associated with it.
Diagnosis
FTD is traditionally difficult to diagnose owing to the diverse nature of the associated symptoms. Signs and symptoms are classified into three groups based on the affected functions of the frontal
Front may refer to:
Arts, entertainment, and media Films
* ''The Front'' (1943 film), a 1943 Soviet drama film
* ''The Front'', 1976 film
Music
* The Front (band), an American rock band signed to Columbia Records and active in the 1980s and e ...
and temporal lobe
The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain.
The temporal lobe ...
s: These are behavioural variant frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. An overlap between symptoms can occur as the disease progresses and spreads through the brain regions.
Structural MRI scans often reveal frontal lobe and/or anterior temporal lobe atrophy but in early cases the scan may seem normal. Atrophy can be either bilateral or asymmetric. Registration of images at different points of time (e.g., one year apart) can show evidence of atrophy that otherwise (at individual time points) may be reported as normal. Many research groups have begun using techniques such as magnetic resonance spectroscopy, functional imaging and cortical thickness measurements in an attempt to offer an earlier diagnosis to the FTD patient. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) scans classically show frontal and/or anterior temporal hypometabolism, which helps differentiate the disease from Alzheimer's disease. The PET
A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence, ...
scan in Alzheimer's disease classically shows biparietal hypometabolism. Meta-analyses based on imaging methods have shown that frontotemporal dementia mainly affects a frontomedial network discussed in the context of social cognition or 'theory of mind
In psychology, theory of mind refers to the capacity to understand other people by ascribing mental states to them (that is, surmising what is happening in their mind). This includes the knowledge that others' mental states may be different fro ...
'. 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''.
The confusion between Alzheimer's and FTD is justifiable due to the similarities between their initial symptoms. Patients do not have difficulty with movement and other motor tasks. As FTD symptoms appear, it is difficult to differentiate between a diagnosis of Alzheimer's disease and FTD. There are distinct differences in the behavioral and emotional symptoms of the two dementias, notably, the blunting of emotions seen in FTD patients. In the early stages of FTD, anxiety and depression are common, which may result in an ambiguous diagnosis. However, over time, these ambiguities fade away as this dementia progresses and defining symptoms of apathy, unique to FTD, start to appear.
Recent studies over several years have developed new criteria for the diagnosis of behavioral variant frontotemporal dementia (bvFTD).The confirmatory diagnosis is made by brain biopsy, but other tests can be used to help, such as MRI, EEG, CT, and physical examination and history. Six distinct clinical features have been identified as symptoms of bvFTD.
# Disinhibition
In psychology, disinhibition is a lack of restraint manifested in disregard of social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive, and perceptual aspects with signs and symptom ...
# Apathy
Apathy is a lack of feeling, emotion, interest, or concern about something. It is a state of indifference, or the suppression of emotions such as concern, excitement, motivation, or passion. An apathetic individual has an absence of intere ...
/Inertia
# Loss of Sympathy
Sympathy is the perception of, understanding of, and reaction to the distress or need of another life form. According to David Hume, this sympathetic concern is driven by a switch in viewpoint from a personal perspective to the perspective of ano ...
/Empathy
Empathy is the capacity to understand or feel what another person is experiencing from within their frame of reference, that is, the capacity to place oneself in another's position. Definitions of empathy encompass a broad range of social, co ...
# Perseverative/compulsive behavior
Compulsive behavior is defined as performing an action persistently and repetitively. Compulsive behaviors could be an attempt to make obsessions go away. The act is usually a small, restricted and repetitive behavior, yet not disturbing in a pa ...
s
# Hyperorality
# Dysexecutive neuropsychological profile
Of the six features, three must be present in a patient to diagnose one with possible bvFTD. Similar to standard FTD, the primary diagnosis stems from clinical trials that identify the associated symptoms, instead of imaging studies. The above criteria are used to distinguish bvFTD from disorders such as Alzheimer's and other causes of dementia. In addition, the new criteria allow for a diagnostic hierarchy distinguished possible, probable, and definite bvFTD based on the number of symptoms present.
A 2021 study, led by researchers at the University of Pennsylvania, determined that using cerebrospinal fluid (CSF) biomarkers of pathologic amyloid plaques, tangles, and neurodegeneration, collectively called ATN, can be useful in diagnosing FTD.
Neuropsychological tests
The progression of the degeneration caused by bvFTD may follow a predictable course. The degeneration begins in the orbitofrontal cortex and medial aspects such as ventromedial cortex. In later stages, it gradually expands its area to the dorsolateral cortex and the temporal lobe. Thus, the detection of dysfunction of the orbitofrontal cortex and ventromedial cortex is important in the detection of early stage bvFTD. As stated above, a behavioural change may occur before the appearance of any atrophy in the brain in the course of the disease. Because of that, image scanning such as MRI can be insensitive to the early degeneration and it is difficult to detect early-stage bvFTD.
In neuropsychology, there is an increasing interest in using neuropsychological tests such as the Iowa gambling task
The Iowa gambling task (IGT) is a psychological task thought to simulate real-life decision making.
It was introduced by Antoine Bechara, Antonio Damasio, Hanna Damasio and Steven Anderson, then researchers at the University of Iowa. It has been ...
or Faux Pas Recognition test as an alternative to imaging for the diagnosis of bvFTD. Both the Iowa gambling task and the Faux Pas test are known to be sensitive to dysfunction of the orbitofrontal cortex.
Faux Pas Recognition test is intended to measure one's ability to detect faux pas types of social blunders (accidentally make a statement or an action that offends others). It is suggested that people with orbitofrontal cortex dysfunction show a tendency to make social blunders due to a deficit in self-monitoring. Self-monitoring is the ability of individuals to evaluate their behaviour to make sure that their behaviour is appropriate in particular situations. The impairment in self-monitoring leads to a lack of social emotion signals. The social emotions such as embarrassment are important in the way that they signal the individual to adapt social behaviour in an appropriate manner to maintain relationships with others. Though patients with damage to the OFC retain intact knowledge of social norms, they fail to apply it to actual behaviour because they fail to generate social emotions that promote adaptive social behaviour.
The other test, the Iowa gambling task, is a psychological test intended to simulate real-life decision making. The underlying concept of this test is the somatic marker hypothesis
The somatic marker hypothesis, formulated by Antonio Damasio and associated researchers, proposes that emotional processes guide (or bias) behavior, particularly decision-making. '' Descartes' Error''
"Somatic markers" are feelings in the body t ...
. This hypothesis argues that when people have to make complex uncertain decisions, they employ both cognitive and emotional processes to assess the values of the choices available to them. Each time a person makes a decision, both physiological signals and evoked emotion (somatic marker) are associated with their outcomes and it accumulates as experience. People tend to choose the choice which might produce the outcome reinforced with positive stimuli, thus it biases decision-making towards certain behaviours while avoiding others. It is thought that somatic marker is processed in orbitofrontal cortex.
The symptoms observed in bvFTD are caused by dysfunction of the orbitofrontal cortex, thus these two neuropsychological tests might be useful in detecting the early stage bvFTD. However, as self-monitoring and somatic marker processes are so complex, it likely involves other brain regions. Therefore, neuropsychological tests are sensitive to the dysfunction of orbitofrontal cortex, yet not specific to it. The weakness of these tests is that they do not necessarily show dysfunction of the orbitofrontal cortex.
In order to solve this problem, some researchers combined neuropsychological tests which detect the dysfunction of orbitofrontal cortex into one so that it increases its specificity to the degeneration of the frontal lobe in order to detect the early-stage bvFTD. They invented the ''Executive and Social Cognition Battery'' which comprises five neuropsychological tests.
* Iowa gambling task
The Iowa gambling task (IGT) is a psychological task thought to simulate real-life decision making.
It was introduced by Antoine Bechara, Antonio Damasio, Hanna Damasio and Steven Anderson, then researchers at the University of Iowa. It has been ...
* Faux Pas test
* Hotel task
* Mind in the Eyes
* Multiple Errands Task
The result has shown that this combined test is more sensitive in detecting the deficits in early bvFTD.
Management
Currently, there is no cure for FTD. Treatments are available to manage the behavioral symptoms. Disinhibition and compulsive behaviors can be controlled by selective serotonin reuptake inhibitors
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracell ...
(SSRIs). Although Alzheimer's and FTD share certain symptoms, they cannot be treated with the same pharmacological agents because the cholinergic
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...
systems are not affected in FTD.
Because FTD often occurs in younger people (i.e. in their 40s or 50s), it can severely affect families. Patients often still have children living in the home.
Prognosis
Symptoms of frontotemporal dementia progress at a rapid, steady rate. Patients with the disease can survive for 2–20 years. Eventually patients will need 24-hour care for daily function.
CSF leaks are a known cause of reversible frontotemporal dementia.
History
Frontotemporal dementia was first described by Pick in 1892. In 1989, Snowden suggested the term “semantic dementia” to describe the patient with predominant left temporal atrophy and aphasia that Pick described. The first research criteria for FTD “Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups,” was developed in 1994. The clinical diagnostic criteria were revised in the late 1990s, when the FTD spectrum was divided into a behavioral variant, a nonfluent aphasia variant and a semantic dementia variant. The most recent revision of the clinical research criteria was by International Behavioural Variant FTD Criteria Consortium (FTDC) in 2011.
Notable cases
Notable cases of bvFTD when mostly were referred to as ''Pick's disease''.
* John Berry (1963-2016), American hardcore punk
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.
* Clancy Blair
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* Don Cardwell
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* Charmian Carr
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* Jerry Corbetta
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* Ted Darling
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(1935–1996), Buffalo Sabres
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television
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announcer
* Robert W. Floyd
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* Lee Holloway
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(born 1981), co-founder of Cloudflare
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* Colleen Howe
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(1933–2009), sports agent and hockey team manager, known as "Mrs. Hockey"
* Kazi Nazrul Islam
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(1899–1976), notable Bengali poet and National Poet of Bangladesh
* Ralph Klein
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(1942–2013), former premier of Alberta
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, Canada
* Terry Jones
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(1942-2020), Welsh comedian (Monty Python) and director.
* Kevin Moore
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(1958–2013), English footballer
* Pat Moran (1947–2011), British record producer, singer and Mellotron player with progressive rock band Spring
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* Ernie Moss
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* Nic Potter
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(1951–2013), British bassist for Van der Graaf Generator
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* Christina Ramberg
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* David Rumelhart
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Cognitive psychology is the scientific study of mental processes such as attention, language use, memory, perception, problem solving, creativity, and reasoning.
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* Colin Savage, father of footballer Robbie Savage
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* Sir Nicholas Wall (1945–2017), English judge
* Mark Wirtz
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‘’The Daily Telegraph’’, 13 Aug 2020
See also
* Alcoholic dementia
Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomina ...
* Lewy body dementia
Lewy body dementias are two similar and common subtypes of dementia—dementia with Lewy bodies (DLB) and
Parkinson's disease dementia (PDD). Both are characterized by changes in thinking, movement, behavior, and mood. The two conditions have sim ...
* Logopenic progressive aphasia
Logopenic progressive aphasia (LPA) is a variant of primary progressive aphasia. It is defined clinically by impairments in naming and sentence repetition. It is similar to conduction aphasia and is associated with atrophy to the left posterior tem ...
* Mini-SEA
The mini-SEA (mini-Social cognition & Emotional Assessment) is a neuropsychological battery aiming to evaluate the impairment of the social and emotional cognition. Developed by Maxime Bertoux in 2012, the mini-SEA has been preferentially design ...
* Proteopathy
In medicine, proteinopathy (; 'pref''. protein -pathy 'suff''. disease proteinopathies ''pl''.; proteinopathic ''adj''), or proteopathy, protein conformational disorder, or protein misfolding disease refers to a class of diseases in which certa ...
* Transportin 1
Transportin-1 (or Importin-β 2) is a protein that in humans is encoded by the ''TNPO1'' gene.
Function
This protein is a karyopherin which interacts with nuclear localization sequence to target nuclear proteins to the nucleus. The classical ka ...
* Vascular dementia
Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisting ...
References
Further reading
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External links
OMIM on Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis and Chromosome 9 Open Reading Frame 72; C9ORF72
{{CNS diseases of the nervous system
Cognitive disorders
Dementia
Frontal lobe
Temporal lobe
de:Frontotemporale Demenz