What Is Frontotemporal Dementia?

Disease Name: Frontotemporal Dementia

Frontotemporal dementia

Frontotemporaldementia refers to middle-aged and elderly patients who are slowly experiencing personality changes, speech disorders, and behavioral abnormalities. Neuroimaging shows atrophy of the frontotemporal lobe, and pathological examination does not find Pick bodies and Pick cell dementia syndrome. Frontotemporal dementia is a group of dementia syndromes characterized by frontotemporal atrophy, including Pick's disease and Pick's syndrome with similar clinical manifestations, which in turn includes frontal dementia and primary progressive aphasia. Clinically, it is characterized by obvious personality, behavioral changes, and cognitive impairment.

Chinese name: Frontotemporal dementia
Foreign name: frontotemporaldementia

Cause: Frontotemporal atrophy
Clinical manifestation: Personality, behavior change, and cognitive impairment

Basic information on frontotemporal dementia

Disease Name: Frontotemporal Dementia

Disease Classification: Neurology

Overview of the disease: Frontotemporal dementia is a group of dementia syndromes characterized by frontotemporal atrophy, including Pick's disease and Pick syndrome with similar clinical manifestations, which in turn includes frontal dementia and primary progressive aphasia. Clinically, it is characterized by obvious personality, behavioral changes, and cognitive impairment.

Overview of frontotemporal dementia

Frontotemporal dementia Frontotemporal dementia is a dementia syndrome characterized by frontotemporal atrophy. It is a more common cause of neurodegenerative dementia, accounting for about a quarter of all dementia patients. Pick bodies are present in about a quarter of patients with frontotemporal dementia and can be diagnosed as Pick's disease. Frontotemporal dementia actually includes Pick disease and Pick syndrome with similar clinical manifestations, such as frontal dementia and progressive aphasia. The peak incidence is 60 years old, and there are many females.

Pick (1892) first described a group of patients with frontal-temporal atrophy as a pathological feature, showing slowly progressing behavioral abnormalities, cognitive impairment, and aphasia, which are rare clinically. Histological observation by Alzheimer (1911) revealed that the neurons were diffusely swollen and loose chromatin, called Pick cells. There were silver inclusions (Pick bodies) in the cytoplasm, no neurofibrillary tangles and senile plaques, which was significantly different from AD Onari and Spatz (1926) named Pick's disease. It is difficult to distinguish Pick disease from frontotemporal dementia without pathological evidence. At present, it is advocated to classify Pick disease as frontotemporal dementia. Clinical studies have found that frontotemporal dementia is probably the most common neurodegenerative dementia syndrome after Alzheimer's disease, accounting for about a quarter of all dementia patients. Some people think that frontotemporal dementia actually includes Pick disease with pathological Pick bodies and other Pick syndromes with similar clinical manifestations without Pick bodies, the latter including frontaldementia and primary progressive aphasia ( primaryprogressiveaphasia) etc.

Frontotemporal dementia (FTD) progresses and eventually progresses to fatal neurological diseases. About 10% of ALS cases and about 30% of FTD cases are familial. The genetic characteristics are usually autosomal dominant and have different penetrances. The overlap between ALS and FTD phenotypes can be in the same family Happen within. Copper or zinc superoxide dismutase 1 (SOD1) mutations are found in approximately 20% of familial ALS and approximately 3% of sporadic ALS cases, but are not associated with dementia. Microtubule-associated protein tau (MAPT) mutations were detected in approximately 30% of familial FTD families. Dominant ALS with FTD was previously thought to be associated with 9q21, and pure ALS was associated with 16q21, 18q21, and 20p13 loci. In this study, Affymetrix 10K gene chip microarray analysis was used to report the results of extensive genomic linkage studies of an ALS combined FTD family. Single nucleotide polymorphism (SNP) linkage analysis data showed that the log of dominance (LOD) score of autosome 9p continued to be positive (the highest LOD score was 2.4).

Frontotemporal dementia symptoms and signs

1. Hidden attacks start slowly and progress slowly. Early personality and emotional changes such as irritability, violence

Frontotemporal dementia (2) Anger, stubbornness, indifference, and depression; gradually appear abnormal behaviors, such as improper behavior, unmotivated, indifferent and impulsive behaviors, etc., can appear Kluver-Bucy syndrome, slow performance, indifference, recognition and rapid changes in thinking, Excessive oral activity, good muscles, gluttony, obesity, put everything in the mouth to try, with forgetfulness, aphasia, etc. Can't think, few words, poor vocabulary, stereotypes and imitating language to silence, somatosensory and fragmented delusions.

2. In the early stages of the nervous system, sucking reflexes and strong grip reflexes can be seen, and myoclonus, pyramidal tract signs, and Parkinson's syndrome appear later.

3. Primary progressive aphasia Mesulam (1982) first reported 6 cases of chronic progressive aphasia without dementia. Weintraub et al. (1990) named it PPA. Usually onset before the age of 65, the course of disease is longer, up to 10 years. The main clinical feature is that slow progressive language disorder is not accompanied by other cognitive dysfunction. It develops into severe aphasia or silence in 6-7 years, which is the difference from AD or frontotemporal dementia. There may be visual loss or spatial damage, but life can still take care of itself, and eventually dementia occurs without signs of the nervous system. MRI showed significant atrophy of the frontal, temporal, and parietal hemispheres. Pathology showed atrophy of the frontotemporal lobe without Pick bodies.

Causes of frontotemporal dementia

The etiology and pathogenesis of frontotemporal dementia and Pick's disease are unclear, which may be idiopathic degeneration of neuronal soma

Frontotemporal dementia (3) Changes, or secondary somatic changes following axonal injury. Familial frontotemporal dementia with autosomal dominant inheritance has been demonstrated in about half of cases, and Wilhelmsen et al. (1994) mapped the disease gene to chromosome 17 (17q21). Neurons and glial cells contain microtubule-associated tau protein inclusion bodies. About 20% of patients with frontotemporal dementia have this gene mutation. Therefore, frontotemporal dementia is classified as tau proteinopathy. Cause:

The etiology may be idiopathic degenerative changes of neuronal soma or secondary somatic changes of axonal injury. Wilhelmsen (1994) et al. Located a gene of this disease on chromosome 17 in a large family with frontotemporal dementia and extrapyramidal symptoms, and confirmed that it is related to the mutation of the tau protein gene. About 20% of patients with frontotemporal dementia have been found. There is a mutation in this gene.

Frontotemporal dementia pathophysiology

The histopathological features of frontotemporal dementia and Pick's disease are characteristically limited frontotemporal atrophy, involving the amygdala, hippocampus, substantia nigra, and basal ganglia; Pick's disease can show Pick cells and Pick inclusions, lacking the characteristics of Alzheimer's disease Neurofibrillary tangles and amyloid plaques. Nerve cells in atrophic brain lobe cortex were significantly reduced under the microscope, and and layers were obvious; diffuse proliferation of glial cells with sponge-like changes.

Frontal-temporal dementia diagnosis

(A) auxiliary inspection:

1. The EEG is normal in the early stage, the minority wave amplitude is reduced, and the alpha wave is reduced; in the late stage, there is little or no alpha wave.

Frontotemporal dementia (4) Irregular medium-amplitude delta waves are present. A few patients see sharp waves, sleep spindle waves are reduced, comprehensive waves are difficult to appear, and slow waves are reduced.

2. CT or MRI shows limited frontal or anterior temporal lobe atrophy, widening of the sulcus, balloon-like enlargement of the forehead angle, thinning of the frontal pole and anterior temporal pole cortex, enlargement of the temporal angle, widening of the lateral cleft cistern, and more asymmetry. Can appear early. SPECT showed asymmetrical frontotemporal blood flow reduction, PET showed asymmetrical frontotemporal metabolism, which was more sensitive than MRI and could be diagnosed early.

3, genetic examination found a variety of tau protein gene mutations to help confirm the diagnosis.

(Two) diagnosis and differential diagnosis

1.Diagnosis

Frontotemporal dementia, including Pick's disease, is diagnosed based on early onset (50-60 years old) and may have a family history. Behavioral disorders are more obvious than cognitive impairments. CT and MRI showed frontal and anterior temporal lobe atrophy. Diagnosis is usually not confirmed before birth and depends on histopathological evidence, such as localized frontotemporal atrophy, tau protein inclusions in neurons and glial cells, Pick bodies and cells found in Pick disease, and lack of AD-specific neurofibrillary entanglement Knots and amyloid plaques.

2.Differential diagnosis

This disease should be distinguished from Alzheimer's disease. AD usually has early cognitive dysfunction, such as amnesia, visual spatial orientation, and computational impairment, and relative retention of social and etiquette. Pick disease or frontotemporal dementia has early personality changes, behavioral abnormalities, and speech disorders. Kluver-Bucy's most significant sign appears in typical cases, with better spatial orientation and near-memory preservation. Neuroimaging showed atrophy of the frontotemporal lobe of Pick disease and extensive brain atrophy of Alzheimer disease. The prognosis is poor, the course of disease is 5-12 years, and most of them die from complications such as pulmonary and urinary tract infections and bedsores.

Frontotemporal dementia treatment options

There is currently no cure. Acetylcholinesterase inhibitors are usually ineffective. People with behavioral disorders such as aggressive behavior, irritability, and aggressiveness may use small amounts of diazepam, selective serotonin reuptake inhibitors or tips. If possible, appropriate care and behavioral guidance can be given by the caregivers who pass by.

Frontotemporal dementia epidemiology

Incidence and prevalence of dementia increase with age. Foreign surveys show that the prevalence of dementia ranges from 85 years of age.

Frontotemporal dementia (5) Up to 40% of the above population, of which Alzheimer's disease (AD) accounts for 50%; multifocal infarct dementia (also known as vascular dementia VaD) accounts for 12% to 20%; other types of dementia account for 15% to 20% . For people over 60 years of age, the prevalence of dementia is 0.75% to 4.69%. Frontotemporal dementia and Pick's disease are also frequently reported in cases, but no statistical data on categorical incidence is available.

Pathogenesis of frontotemporal dementia

Frontotemporal dementia

The pathogenesis is unclear. It is reported in the literature that the tau protein is composed of 6 subunits formed by different splicing of the tau gene. The carboxy terminus of the amino acid polypeptide of the tau protein can have an insertion peptide consisting of 35 amino acids, which can be combined with other polypeptides to form microtubules, including insertions. Increased tau (4R) of peptide or point mutation of exon 10 can lead to increase of free tau protein and cell death. The pathological features are similar to those of Pick's disease. The general pathology is that about 1/3 of patients with frontal and / or temporal lobe atrophy show bilateral symmetrical atrophy, severe cerebral cortex involvement, and mild to moderate magnification of the temporal angle of the anterior horn of the lateral ventricle. It can be seen that the number of neurons in each layer of the atrophic cerebral cortex is significantly reduced, the neurons in layer and III are lost, and the proliferation of glial cells is diffused. The residual neurons have different degrees of degeneration. Pick bodies and Pick cells are the main causes of this disease and Pick disease. Pathological identification point.

Clinical manifestations of frontotemporal dementia

Frontotemporal dementia

1. The clinical manifestations of this disease are the same as those of Pick's disease. They are more than 50-60 years old and have an onset of insidious attack. Progress is slow. Personality changes and speech disorders and behavioral abnormalities appear early, such as Klüver-Bucy syndrome. If there is a family history, CT and MRI showed that frontal-temporal atrophy genetics found a variety of tau protein gene coding regions or intron-related mutations in No. 10, and pathological examination without Pick bodies and Pick cells can be diagnosed. 2, Primary progressive aphasia (primary progressive aphasiaPPA) is a progressive decline in language function for 2 years or more, other cognitive functions remain normal, and AD and other frontotemporal dementia are significantly different. Pathologically, the atrophy of the frontal and temporal lobes was the main body without Pick.

Mesulam (1982) first reported 6 cases of chronic progressive aphasia without dementia, and Weintraub et al. (1990) named it as primary progressive aphasia. The main clinical features are:

(1) Usually onset before the age of 65, slowly progressing aphasia, without other cognitive dysfunction can be combined with visual impairment of spatial impairment or apraxia, etc., and daily life ability can be preserved intact.

(2) The course of disease can be as long as more than 10 years, and the language disorder can exist for several years alone. It develops into severe aphasia or silence in 6 to 7 years, and can still maintain self-care. Eventually, some cases of dementia appear as progressive aphasia in the early stage. In a short period of time, it develops into Pick disease, motor neuron disease, or degeneration of cortical basal nucleus.

(3) There were no positive signs on neurological examination. MRI showed significant atrophy of the frontal and temporal lobe and parietal lobe of the dominant hemisphere. SPECT showed reduced blood flow in the left temporal and frontal or bilateral frontal lobe.

Frontotemporal dementia complications

With the development of the disease, in addition to the obvious dementia (cognitive disorder), patients often have aphasia, depression, and severe mental and behavioral abnormalities. In addition, attention should be paid to secondary pulmonary infections and urinary tract infections.

Frontotemporal dementia diagnosis

Frontal-temporal dementia image analysis

At present, there is no unified diagnostic standard for frontotemporal dementia and Pick's disease. The following criteria can be used as a reference: 1. Middle-aged and elderly people (usually 50 to 60 years old) have early personality changes, emotional changes, and improper behavior, and gradually behave abnormally, such as Klüver- Bucy syndrome.

2. Early onset of speech disorders such as reduced speech, poor vocabulary, stereotyped language, and imitation of language followed by obvious aphasia. Early computational power preservation. Memory impairment.

3. In the late stage, there is intelligent decline, forgetting urinary incontinence and mutism.

4. CT and MRI showed asymmetric atrophy of frontal and / or temporal lobe.

5. Pathological examination revealed Pick bodies and Pick cells.

1 to 4 items can be diagnosed and clinical diagnosis of frontotemporal dementia can be diagnosed if other dementia diseases are excluded. If a family history genetic examination reveals a tau protein gene mutation, the diagnosis can be confirmed; 1 to 5 items can be diagnosed as Pick's disease. Pick-free bodies and Pick cells are the main pathological identification points of frontotemporal dementia and Pick disease.

A research team at the University of London's Wellcome Trust Neuroimaging Centre has shown the results of scanning the brains of patients with frontotemporal dementia. Computers can identify brain-specific injuries in patients with Alzheimer's disease. "Computer scans are faster, more accurate, and cheaper than current diagnostic methods," explains Professor Richard Frackowiak of the center. "The new method avoids human intervention and makes the diagnosis more objective. The new method was found by using a computer to scan and compare the brains of patients with frontotemporal dementia and healthy people. Both cases can be done with a single clinical MRI scan To highly precise distinctions. "

The computer can accurately find the difference between normal people and patients with frontotemporal dementia through a set of scans, and then scan other cases based on the correct diagnosis. Its accuracy rate is better than 86% accuracy rate of current best clinical practice diagnosis. Frontotemporal dementia is misdiagnosed as dementia in many cases.

Professor Frackowiak emphasized that after a considerable amount of damage to the human brain can cause symptoms of a disease in the brain, it is very important to make an accurate diagnosis early to improve the effective prevention of brain degradation. "The next step is to see if we can use a technology to determine how sick a patient is," said Professor Frackowiak. "This allows a quick test with a non-invasive tool that reflects the efficacy of the new drug treatment."

Differential diagnosis of frontotemporal dementia

It should be mainly distinguished from Alzheimer's disease, both of which are insidious attacks, and have slow progress and have many common points in clinical. The most discriminative is the chronological sequence of progressive dementia symptoms during the course of AD. Early cognitive impairments such as impaired visual spatial orientation and computing power, relative retention of social skills and personal etiquette; early manifestations of personality in frontotemporal dementia Klüver-Bucy syndrome, such as altered speech and behavioral disorders, better preservation of spatial orientation and memory, and intelligent decline and forgetfulness only in the later stages, are early manifestations of behavioral changes in frontotemporal dementia. CT and MRI are helpful in distinguishing the two. AD shows extensive cerebral atrophy, frontotemporal dementia, and frontal and / or temporal lobe atrophy; clinical diagnosis requires histopathological examination.

Frontotemporal dementia

Laboratory examination: determination of ApoE polymorphism Tau protein quantification and amyloid fragments in cerebrospinal fluid and serum, which have diagnostic or differential diagnostic significance.

Other auxiliary examinations: 1. In the early stage of the EEG examination, most of them are normal and the visible amplitude is reduced. The alpha wave is reduced; the late background activity is low or there is little or no irregular mid-amplitude delta wave. A few patients have sharp waves during sleep. Fewer and fewer kappa complex waves, slow wave reduction 2, CT and MRI examinations show characteristic limitations of frontal and / or temporal atrophy, narrowing of the brain gyrus, widening of the sulcus and forehead with balloon-like expansion of the frontal pole and anterior The polar cortex is thinned and the temporal angle is enlarged and the lateral cleft pool is widened. Many asymmetries and few can be symmetrical, which can appear early in the disease. SPECT showed asymmetric frontal and decreased temporal blood flow. PET showed that asymmetric frontal and temporal lobular metabolism was more sensitive than MRI, which is helpful for early diagnosis.

Frontotemporal dementia treatment

There is no effective treatment similar to Pick's disease, and the main symptomatic treatment of acetylcholinesterase inhibitors is usually ineffective. For people with behavioral disorders such as aggressive behavior, irritability and combativeness, it is advisable to use small amounts of benzodiazepines, selective 5-HT reuptake inhibitors, neuroleptics and propranolol (propranolol). Patients can be hospitalized, or given appropriate life, behavioral guidance, and symptomatic treatment by trained caregivers.

Frontotemporal dementia prevention

Prognosis: The course of disease rarely exceeds 10 years, and the poor prognosis is mostly due to lung infection, urinary tract infection, and bedsores.

Prevention: There is no effective preventive method. Symptomatic treatment is an important part of clinical medical care. Early diagnosis and early treatment may slow down the irreversible process of dementia.