Pick's Disease
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Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of
dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
involving the progressive degeneration of the brain's frontal and
temporal lobe The temporal lobe is one of the four 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 is involved in pr ...
s. Men and women appear to be equally affected. FTD generally presents as a behavioral or language disorder with gradual onset. Signs and symptoms tend to appear in late adulthood, typically between the ages of 45 and 65, although it can affect people younger or older than this. There is currently no cure or approved symptomatic treatment for FTD, although some
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...
drugs and behavioral methods are prescribed. Features of FTD were first described by Arnold Pick between 1892 and 1906. The name ''Pick's disease'' was coined in 1922. This term is now reserved only for the behavioral variant of FTD, in which characteristic Pick bodies and Pick cells are present. These were first described by
Alois Alzheimer Alois Alzheimer ( , , ; 14 June 1864 – 19 December 1915) was a German psychiatrist, neuropathologist and colleague of Emil Kraepelin. He is credited with identifying the first published case of "presenile dementia", which Kraepelin later ide ...
in 1911. Common signs and symptoms include significant changes in social and personal behavior, disinhibition, apathy, blunting and dysregulation of emotions, and deficits in both expressive and receptive language. Each FTD subtype is relatively rare. FTDs are mostly early onset syndromes 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. Com ...
(FTLD), which is characterized by progressive
neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
al loss predominantly involving the frontal or temporal lobes, and a typical loss of more than 70% of spindle neurons, while other neuron types remain intact. 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 In neurology, 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 ...
(PPA):
semantic Semantics is the study of linguistic Meaning (philosophy), meaning. It examines what meaning is, how words get their meaning, and how the meaning of a complex expression depends on its parts. Part of this process involves the distinction betwee ...
(svPPA) and nonfluent (nfvPPA). Two rare distinct subtypes of FTD are neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease (BIBD). Other related disorders include corticobasal syndrome (CBS or CBD), and FTD with
amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
(ALS).


Signs and symptoms

Frontotemporal dementia (FTD) is an early onset disorder that mostly occurs between the ages of 45 and 65, but can begin earlier, and in 20–25% of cases onset is later. Men and women appear to be equally affected. It is the most common early presenting dementia. FTD is the second most prevalent type of early onset dementia after
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
. The
International Classification of Diseases The International Classification of Diseases (ICD) is a globally used medical classification that is used in epidemiology, health management and clinical diagnosis. The ICD is maintained by the World Health Organization (WHO), which is the dir ...
recognizes the disease as causative to disorders affecting mental and
behavioural Behavior (American English) or behaviour (British English) is the range of actions of individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as well as the inanimate ph ...
aspects in humans. Dissociation from family, compulsive buying disorder (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 (bvFTD), two variants of
primary progressive aphasia In neurology, 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 ...
semantic dementia (svPPA) and progressive nonfluent aphasia (nfvPPA) – as well as FTD associated with amyotrophic lateral sclerosis (
FTD–ALS Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and low ...
or FTD-MND). Two distinct rare subtypes are neuronal intermediate filament inclusion disease (NIFID), and basophilic inclusion body disease (BIBD). Related disorders are corticobasal syndrome (CBS or CBD), and
progressive supranuclear palsy Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain, linked to 4-repeat tau pathology. The condition leads to symptoms including Balance di ...
(PSP).


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—in the United States—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and low ...
. The Pick bodies which are present in behavioral variant FTD are spherical inclusion bodies found in the
cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
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 19 ...
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 cytosk ...
.


Semantic dementia

Semantic dementia (SD) is characterized by the loss of
semantic Semantics is the study of linguistic Meaning (philosophy), meaning. It examines what meaning is, how words get their meaning, and how the meaning of a complex expression depends on its parts. Part of this process involves the distinction betwee ...
understanding, resulting in impaired word comprehension. However, speech remains fluent and grammatical.


Progressive nonfluent aphasia

Progressive nonfluent aphasia (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 that are present in NIFID are
cytoplasmic The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell and ...
and made up of type IV
intermediate filament Intermediate filaments (IFs) are cytoskeleton, 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' ...
s. NIFID has an early age of onset between 23 and 56. Symptoms can include behavioral and personality changes, memory and cognitive impairments, language difficulties, motor weakness, and
extrapyramidal symptoms Extrapyramidal symptoms (EPS) are signs and symptoms, symptoms that are wikt:archetypical, archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they ...
. NIFID is one of the
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. Com ...
(FTLD)- FUS proteopathies.
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 (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
in the
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
. 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 part of the basal ganglia in the human brain. Although the caudate nucleus has long been associated with motor processes because of its relation to Parkinso ...
of the striatum; frontotemporal
gyri In neuroanatomy, a gyrus (: gyri) is a ridge on the cerebral cortex. It is generally surrounded by one or more sulcus (neuroanatomy), sulci (depressions or furrows; : sulcus). Gyri and sulci create the folded appearance of the brain in huma ...
are narrowed, with widened intervening
sulci Sulci or Sulki (in Greek , Stephanus of Byzantium, Steph. B., Ptolemy, Ptol.; , Strabo; , Pausanias (geographer), Paus.), was one of the most considerable cities of ancient Sardinia, situated in the southwest corner of the island, on a small isla ...
, 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 (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
, 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, 1 ...
. People with FTD show marked deficiencies in executive functioning and
working memory Working memory is a cognitive system with a limited capacity that can Memory, hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term m ...
. Most become unable to perform skills that require complex planning or sequencing. 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. In rare cases, FTD can occur in people with
amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
(ALS), a
motor neuron disease Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and low ...
. , the prognosis for people with ALS was worse when combined with FTD, shortening survival by about a year. Cerebrospinal fluid leaks are a known cause of reversible frontotemporal dementia.


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 neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
. More and more mutations and genetic variants are being identified all the time, needing constant updating of genetic influences. * Tau-positive
frontotemporal dementia and parkinsonism linked to chromosome 17 Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant neurodegenerative tauopathy and Parkinson plus syndrome. FTDP-17 is caused by mutations in the MAPT (microtubule associated protein tau) gene l ...
(FTDP-17) is caused by mutations in the
MAP A map is a symbolic depiction of interrelationships, commonly spatial, between things within a space. A map may be annotated with text and graphics. Like any graphic, a map may be fixed to paper or other durable media, or may be displayed on ...
T gene on chromosome 17 that encodes the tau protein. 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 Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...
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 that can include
amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...
, inclusion body myopathy,
Paget's disease of bone Paget's disease of bone (commonly known as Paget's disease or, historically, osteitis deformans) is a condition involving Bone remodeling, cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone ...
, and FTD. The most recent addition to the list () was a hexanucleotide repeat expansion in intron 1 of C9ORF72. Only one or two cases have been reported describing TARDBP (the TDP-43 gene) mutations in a clinically pure FTD (FTD without ALS). * Several other genes have been linked to this condition. These include CYLD, OPTN, SQSTM1 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 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 on
autopsy An autopsy (also referred to as 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 deat ...
. The most severe brain atrophy appears to be associated with behavioral variant FTD, and corticobasal degeneration. With regard to the genetic defects that have been found, repeat expansion in the C9orf72 gene is considered a major contribution to FTLD, although defects in the GRN and
MAPT The tau proteins (abbreviated from tubulin associated unit) form 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. DNA damage and the defective repair of such damages have been etiologically linked to various neurodegenerative diseases including FTD.


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 and
temporal lobe The temporal lobe is one of the four 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 is involved in pr ...
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 Functional imaging (or physiological imaging) is a medical imaging technique of detecting or measuring changes in metabolism, blood flow, regional chemical composition, and absorption. As opposed to structural imaging, functional imaging center ...
, and cortical thickness measurements in an attempt to offer an earlier diagnosis to the FTD patient. Fluorine-18-fluorodeoxyglucose positron emission tomography scans classically show frontal and/or anterior temporal hypometabolism, which helps differentiate the disease from
Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
, as 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/ cute appearances, inte ...
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 and philosophy, theory of mind (often abbreviated to ToM) refers to the capacity to understand other individuals by ascribing mental states to them. A theory of mind includes the understanding that others' beliefs, desires, intent ...
". This is entirely in keeping with the notion that on the basis of cognitive neuropsychological evidence, the
ventromedial prefrontal cortex The ventromedial prefrontal cortex (vmPFC) is a part of the prefrontal cortex in the mammalian brain. The ventral medial prefrontal is located in the frontal lobe at the bottom of the cerebral hemispheres and is implicated in the processing of ...
is a major locus of dysfunction early on in the course of the behavioural variant of frontotemporal degeneration. The language subtypes of FTLD (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 affect 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 #
Apathy Apathy, also referred to as indifference, 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 i ...
/ Inertia # Loss of
Sympathy Sympathy is the perception of, understanding of, and reaction to the Mental distress, distress or need of another life form. According to philosopher David Hume, this sympathetic concern is driven by a switch in viewpoint from a personal perspe ...
/
Empathy Empathy is generally described as the ability to take on another person's perspective, to understand, feel, and possibly share and respond to their experience. There are more (sometimes conflicting) definitions of empathy that include but are ...
# Perseverative /
Compulsive behavior Compulsive behavior (or compulsion) is defined as performing an action persistently and repetitively. Compulsive behaviors could be an attempt to make obsessions go away. Compulsive behaviors are a need to reduce apprehension caused by internal ...
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 criteria allow for a diagnostic hierarchy distinguished possible, probable, and definite bvFTD based on the number of symptoms present. A 2021 study, determined that using
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
(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 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, 1 ...
and medial aspects such as
ventromedial prefrontal cortex The ventromedial prefrontal cortex (vmPFC) is a part of the prefrontal cortex in the mammalian brain. The ventral medial prefrontal is located in the frontal lobe at the bottom of the cerebral hemispheres and is implicated in the processing of ...
. In later stages, it gradually expands its area to the
dorsolateral prefrontal cortex The dorsolateral prefrontal cortex (DLPFC or DL-PFC) is an area in the prefrontal cortex of the primate brain. It is one of the most recently derived parts of the human brain. It undergoes a prolonged period of maturation which lasts into adulthoo ...
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 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. The Faux Pas Recognition test is intended to measure one's ability to detect faux pas types of social blunders (accidentally making 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 own behavior to make sure that their behavior 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 alert the individual to adapt social behavior 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 behavior, because they fail to generate social emotions that promote adaptive social behavior. 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. 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 markers) are associated with their outcomes, and this 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 behaviors while avoiding others. It is thought that somatic markers are processed in the 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 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 are 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 have combined neuropsychological tests which detect the dysfunction of orbitofrontal cortex into one grouping, so that it increases its specificity to the degeneration of the frontal lobe, in order to detect early-stage bvFTD. They invented the ''Executive and Social Cognition Battery'' which comprises five neuropsychological tests: * Faux Pas test * Hotel task * Iowa gambling 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. Rehabilitiation services supporting every day functioning have demonstrated some positive results, in particular the Tailored Activity Programme, which is occupational therapy based. Positive behavior support (PBS) has also been identified as potentially beneficial for people with bvFTD. 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 primarily work by blo ...
(SSRIs). Agitation can be controlled with small doses of atypical antipsychotics. Although Alzheimer's and FTD share certain symptoms, they cannot be treated with the same pharmacological agents because the cholinergic systems are not affected in FTD. Because FTD often occurs in relatively younger adults (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.


History

Features of FTD were first described by the Czech psychiatrist Arnold Pick between 1892 and 1906. The name ''Pick's disease'' was coined in 1922. This term is now reserved only for behavioral variant FTD which shows the presence of the characteristic Pick bodies and Pick cells, which were first described by
Alois Alzheimer Alois Alzheimer ( , , ; 14 June 1864 – 19 December 1915) was a German psychiatrist, neuropathologist and colleague of Emil Kraepelin. He is credited with identifying the first published case of "presenile dementia", which Kraepelin later ide ...
in 1911. 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 the International Behavioural Variant FTD Criteria Consortium in 2011.


Notable cases

People who have been diagnosed as having FTD (often referred to as ''Pick's disease'' in cases of the behavioral variant) include: * John Berry (1963–2016), American
hardcore punk Hardcore punk (commonly abbreviated to hardcore or hXc) is a punk rock music genre#subtypes, subgenre and subculture that originated in the late 1970s. It is generally faster, harder, and more aggressive than other forms of punk rock. Its roots ...
musician and founding member of the
Beastie Boys The Beastie Boys were an American Hip-hop, hip hop and Rap rock, rap rock group formed in New York City in 1979. They were composed of Ad-Rock, Adam "Ad-Rock" Horovitz (vocals, guitar), Adam Yauch, Adam "MCA" Yauch (vocals, bass), and Mike D, ...
* Clancy Blair (born 1960), American developmental psychologist and professor * Don Cardwell (1935–2008), Major League Baseball pitcher * Charmian Carr (1942–2016), who played Liesl, from the ''Sound of Music'', born Charmian Anne Farnon * Jerry Corbetta (1947–2016), frontman, organist and keyboardist of American psychedelic rock band
Sugarloaf A sugarloaf was the usual form in which refined sugar was produced and sold until the late 19th century, when granulated and cube sugars were introduced. A tall cone with a rounded top was the end product of a process in which dark molasses, ...
* Ted Darling (1935–1996),
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television Television (TV) is a telecommunication medium for transmitting moving images and sound. Additionally, the term can refer to a physical television set rather than the medium of transmission. Television is a mass medium for advertising, ...
announcer * Robert W. Floyd (1936–2001), computer scientist * Lee Holloway (born 1982), computer scientist, co-founder of
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* Colleen Howe (1933–2009), sports agent and ice hockey team manager, known as "Mrs. Hockey" *
Kazi Nazrul Islam Kazi Nazrul Islam (24 May 1899 – 29 August 1976) was a Bengalis, Bengali poet, short story writer, journalist, lyricist and musician. He is the national poet of Bangladesh. Nazrul produced a List of works by Kazi Nazrul Islam, large body of ...
(1899–1976) national poet of Bangladesh *
Terry Jones Terence Graham Parry Jones (1 February 1942 – 21 January 2020) was a Welsh actor, comedian, director, historian, writer and member of the Monty Python comedy troupe. After graduating from Oxford University with a degree in English, Jones a ...
(1942–2020), Welsh comedian (Monty Python) and director * Ralph Klein (1942–2013), former premier of Alberta, Canada * Kevin Moore (1958–2013), English footballer * Ernie Moss (1949–2021), English footballer *
Nic Potter Nic Potter (18 October 1951 – 16 January 2013) was a British bassist, composer and painter, best known for his work with the group Van der Graaf Generator in the 1970s. Biography Nic Potter was born in Wiltshire and left school at 15, origin ...
(1951–2013), British bassist for
Van der Graaf Generator Van der Graaf Generator are an English progressive rock band, formed in 1967 in Manchester by singer-songwriters Peter Hammill and Judge Smith, Chris Judge Smith. They were the first act signed by Charisma Records. They did not experience much ...
* Christina Ramberg (1946–1995), American painter associated with the Chicago Imagists *
David Rumelhart David Everett Rumelhart (June 12, 1942 – March 13, 2011) was an American psychologist who made many contributions to the formal analysis of cognition, human cognition, working primarily within the frameworks of mathematical psychology, symbo ...
(1942–2011), American
cognitive psychologist Cognitive psychology is the scientific study of human mental processes such as attention, language use, memory, perception, problem solving, creativity, and reasoning. Cognitive psychology originated in the 1960s in a break from behaviorism, whi ...
* Sir Nicholas Wall (1945–2017), English judge * Wendy Williams (born 1964), American broadcaster *
Bruce Willis Walter Bruce Willis (born March 19, 1955) is a retired American actor. He achieved fame with a leading role on the comedy-drama series ''Moonlighting (TV series), Moonlighting'' (1985–1989) and has appeared in over one hundred films, gaining ...
(born 1955), American actor * Mark Wirtz (1943–2020), pop musician, composer and producer


See also

* Alcoholic dementia *
Lewy body dementia Lewy body dementia (LBD) is an umbrella term for 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 ...
*
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 ...
* Mini-SEA * Proteopathy * Transportin 1 *
Vascular dementia Vascular dementia is dementia caused by a series of strokes. Restricted blood flow due to strokes reduces oxygen and glucose delivery to the brain, causing cell injury and neurological deficits in the affected region. Subtypes of vascular dement ...


References


Further reading

* * * * *


External links

* Patient group {{CNS diseases of the nervous system Cognitive disorders Dementia Frontal lobe Temporal lobe de:Frontotemporale Demenz