Overview
A type of dementia caused by lesions and atrophy of the frontal lobe, temporal lobe, or both lobes of the brain.
It is characterized by persistently worsening mental and behavioral abnormalities and impairment of cognitive and language abilities.
The cause of the disease is unknown, and some patients have a family history of the disease.
It is mainly treated with non-pharmacologic and pharmacologic therapies
Definition
Frontotemporal lobar degeneration (FTLD) is a common clinical disorder.
The pathology of frontotemporal lobe dementia is characterized by atrophy of the frontal lobe, temporal lobe, or both lobes of the brain, and patients exhibit progressively worsening mental behavioral abnormalities, impairment of executive function, and impairment of language function [1].
Currently, it is customary to use the term frontal lobe dementia (FTD) to describe the clinical signs and symptoms of the disease and FTLD to describe the pathological features of the disease.
In addition, the disease often overlaps with three neurodegenerative diseases, corticobasal ganglia degeneration (CBD), progressive supranuclear palsy (PSP) and motor neuron disease (MND) [2].
Typology.
There are three main subtypes of frontotemporal lobe dementia [1]:
Behavioral variant frontotemporal dementia (bvFTD)
Primary progressive aphasia (PPA)
Semantic variant (svPPA)
Non-fluent variant (nfvPPA)
Morbidity
There is no detailed epidemiologic data in China, and only data from Europe and the United States and other countries can be referred to at present.
The general age of onset is between 45 and 65 years old, accounting for about 60% or more of the total incidence [3].
The incidence is about 30% at age greater than 65 years, and less than 10% at age less than 45 years [3].
There is no significant gender difference.
Etiology
Pathogenesis
The pathology of frontotemporal dementia is characterized by degenerative atrophy of the frontal and/or temporal lobes of the brain, but the exact cause of the degenerative atrophy is not fully understood.
Studies have shown that patients have reduced frontal and temporal cortical 5-hydroxytryptaminergic transmitters, and some patients have significantly reduced numbers of temporal muscarinic acetylcholinergic receptors [4].
Approximately 30% to 50% of patients with frontotemporal dementia have a familial genetic component [5].
Risk factors
People with a family history of the disease are at higher risk of developing it.
Pathogenesis
Degenerative atrophy of the frontal and/or temporal lobes is the direct cause of the appearance of clinical symptoms, but the pathogenesis leading to atrophy is not fully understood and may be related to alterations in the 5-hydroxytryptamine and cholinergic neurotransmitter systems.
Approximately 30% to 50% of patients with frontotemporal dementia have at least one relative with similar symptoms, and 10% to 15% have a family history of the disease, which shows an autosomal dominant pattern of inheritance. To date, more than 10 gene mutations have been found to be associated with this disease, including MAPT, PGRN, and C9ORF72 gene variants in approximately 40% of patients with familial frontotemporal dementia [2].
Other gene mutations may also be involved in this disease CHMP2B, VCP, TARDBP, SQSTM1, FUS, UBQLN, OPTN, TREM2, CHCHD10 and BK1 [2].
Thirty-two rare genetic variants have been identified in patients with this disease, including 25 disease-causing mutations and seven mutations of uncertain significance.
Symptoms
Main symptoms
bvFTD
bvFTD is the most common subtype and is mainly characterized by personality changes and behavioral abnormalities [6].
Patients may present early with behavioral inability to control themselves, apathy, stereotypic behavior, altered eating preferences and eating behavior, decreased empathy, and executive dysfunction.
More than 80% of bvFTD may present with abnormal eating behaviors, which are mainly characterized by strong preference for carbohydrates and sucrose, changes in appetite and eating habits, binge eating, and severe dysphagia, which is one of the symptomatic hallmarks of bvFTD.
Memory loss and psychiatric symptoms such as hallucinations and delusions are less common.
svPPA
is centrally characterized by naming deficits and word comprehension deficits [7].
In the early stages of the disease patients are fluent and grammatically correct, but may have abnormalities in understanding words, inability to name objects, difficulty finding words, and inability to have their language understood by others, accompanied by varying degrees of impairment in recognizing objects and faces.
The disease may progress to loss of reading, writing, and expressive skills.
As the disease progresses, the patient gradually develops abnormal behavior similar to behavioral variant dementia.
nfvPPA
is characterized by an inability to speak fluently and a lack of grammar in speech.
Patients have impaired expressive language, decreased conversational skills, slurred speech, phonological and grammatical errors, reluctance to talk, preferring to listen rather than speak, and eventually becoming reticent [8].
Patients have difficulty reading and writing, but have relatively preserved comprehension, preserved ability to perform activities of daily living, and extremely rare behavioral and personality changes.
Medical treatment
Department of Medicine
Neurology
Prompt consultation in the department of neurology is recommended if the patient presents with psychobehavioral, language, and cognitive dysfunction.
Psychiatry may also be consulted when mental behavioral abnormalities occur.
Preparation
Preparing for the consultation: registration, preparation of documents, and frequently asked questions.
Tips
Be accompanied by a family member to avoid the diagnosis being affected by unclear description of the patient’s medical history and symptoms.
Preparation List
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Has the patient become stubborn, apathetic and lazy?
Has the patient become passive and lacks spontaneous initiative?
Does the patient engage in behavior that violates social norms, such as stealing, urinating and defecating, or even loitering naked?
Has the patient become unsympathetic and lost the ability to express feelings for others?
Does the patient exhibit obsessive-compulsive behaviors, such as repeated counting, pacing, clapping, etc.?
Does the patient have changes in eating habits, such as binge eating, preference for certain foods, changes in eating patterns, etc.?
Does the patient have cognitive impairment, e.g., decreased executive ability, judgment?
Does the patient have naming impairment and inability to understand the meaning of certain words?
Does the patient have expressive language impairment, decreased conversational ability, slurred speech, etc.?
Can others understand what the patient says?
Has the patient become reluctant to talk, preferring to listen rather than speak, or even silent?
Has the patient’s ability to read and write declined significantly?
Medical History Checklist
Any history of intracranial tumors, intracranial vascular malformations, cerebrovascular disease, head trauma, etc.?
Are there any infectious, toxic, or metabolic diseases? For example, history of encephalitis, neurosyphilis, HIV infection, carbon monoxide poisoning, alcoholism, vitamin B12 deficiency, hypothyroidism, heavy metal poisoning, etc.
Any family history of dementia?
Checklist
Test results in the last six months, which can be brought to the doctor’s office
Imaging tests: cranial CT, cranial MRI, etc.
Other tests: blood routine, blood biochemistry (liver and kidney function, blood lipids and glucose, blood electrolytes, etc.), thyroid function, folic acid, vitamin B12, blood homocysteine, tumor series, autoantibody profile, syphilis spirochete, HIV viral test, electrocardiogram, etc.
Medication List
Medication use in the last 3 months, if available in a box or package, bring it with you to the doctor’s office
Medications to improve cognitive and language disorders: e.g., memantine, sodium glycolate, etc.
Antidepressant and anxiety medications: e.g. citalopram, sertraline, etc.
Atypical antipsychotic medications: e.g., risperidone, olanzapine, and quetiapine.
Other medications being taken.
Diagnosis
Diagnosis is based on
Medical history
History of psychotic behavioral abnormalities, executive dysfunction, and language impairment.
Some patients may have a family history of dementia.
Symptoms
Stubbornness, irritability or emotional indifference, abnormal behavior, inappropriate mannerisms, stereotyped behavior, indifference to the outside world, lack of empathy, and impulsive behavior.
Easy hunger, hyperphagia and changes in eating behavior, binge eating, changes in eating preferences, etc.
Cognitive dysfunction, such as decreased executive ability and judgment, loss of self-awareness, and deterioration of memory.
Language disorders, such as naming disorders and word comprehension deficits, or expressive language disorders, decreased conversational skills, slowness of speech, and phonological and grammatical errors.
Physical Examination
The doctor will talk and interact with the patient to observe any emotional disorders, behavioral abnormalities and language disorders, such as apathy, depression, euphoria, excitability and restlessness, poor word understanding, and naming difficulties.
The doctor will have the patient complete a number of psycho-psychological scales and cognitive functioning scales to further quantify and refine the patient’s mental disorders and cognitive impairment.
The doctor will ask the patient to do movements such as shaking hands, stretching the upper limbs, and kicking the legs against resistance to determine whether there is any limb weakness and to clarify whether there is any overlap with diseases such as motor neuron disease, which leads to the patient’s motor dysfunction.
Doctors will use needling, swabbing, and temperature stimulation on both sides of the face and limbs to compare and examine whether there are sensory abnormalities on the side of the face and limbs, which will be used for differential diagnosis to rule out other diseases.
Tests
Laboratory Tests
Including blood routine, urine routine, blood biochemistry (liver and kidney function, blood lipids and glucose, blood electrolytes, etc.), thyroid function, folic acid, vitamin B12, blood homocysteine, tumor series, autoantibody profile, syphilis spirochete, HIV virus test, etc..
The purpose is to assess the overall body condition and to detect the presence of metabolic abnormalities, infections and other causes of dementia.
Some of the programs may need to be reviewed periodically during the course of treatment for side effects of medications.
Neuropsychological Assessment
Comprehensive impairment assessment scales such as the FTLD Modified Clinical Dementia Rating Scale (FTLD-CDR).
Cognitive domain scales such as the Brief Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA).
Neuropsychiatric symptom assessment scales such as the Frontal Behavioral Inventory (FBI) and the Neuropsychiatric Inventory (NPI).
Executive functioning, such as the Frontal Assessment Battery (FAB).
Linguistic function assessment scales, such as the Boston Naming Test (BNT), Word Fluency Test, Token Test, Chinese Aphasia Bundle Test (ABC) of the First Hospital of Beijing Medical University (BMU), and Chinese Standardized Aphasia Checklist of the Chinese Rehabilitation Research Center (CRRCAE).
Eating behavior assessment scales, such as the Cambridge Behavioral Inventory (CBI), Appetite and Eating Habits Questionnaire (APEHQ).
Clinical assessment scales for motor symptoms, e.g., World Movement Disorder Society Parkinson’s Disease Rating Scale (MDS-UPDRS) and Progressive Supranuclear Palsy Rating Scale (PSPRS).
Ability to perform activities of daily living, e.g.:Ability to perform activities of daily living (ADL).
Multi-modality neuroimaging evaluation
Cranial CT scan is mainly used to rule out dementia caused by other treatable diseases.
Cranial MRI can observe the degree of brain atrophy in patients with frontotemporal lobe dementia of different clinical phenotypes, clearly show abnormal changes in the gray matter regions of the frontal and temporal lobes and the associated white matter tracts, and track the pattern of brain damage and disease severity [9].
Currently, the commonly used examination techniques are:Structural Magnetic Resonance (sMRI), Functional Magnetic Resonance (fMRI), Diffusion Tensor Imaging (DTI).
Molecular imaging imaging techniques [10], such as 18-fluoro-2-deoxy-D-glucose (18F-FDG), and positron emission tomography (PET). The latter is considered to be an effective test for obtaining the earliest biomarkers of FTLD.
Precautions:
Avoid wearing metal jewelry on the head and neck or clothing with metal buttons zippers, etc. during CT/MRI.
Check with your doctor if you can have a head MRI when you wear metal dentures or have metal implants such as heart stents in your body.
Neurobiomarkers
Our expert consensus recommends cerebrospinal fluid examination as a routine examination for patients with frontotemporal lobe dementia, and cerebrospinal fluid t-tau, p-tau181, p-tau199, p-tau231, Aβ42, and neurofilament (NfL) combined testing for patients with a proposed diagnosis of frontotemporal lobe dementia, in order to improve the diagnostic sensitivity and specificity [1].
There are no specific markers that can be directly used to diagnose frontotemporal dementia.
Genetic and neuropathologic testing
Frontotemporal lobe dementia has a clear genetic component, and genetic testing is performed as early as possible in patients with a clear family history of dementia, early-onset sporadic cases, and patients with specific clinical phenotypes and superimposed syndromes to aid in the diagnosis and subtype classification [1].
Diagnostic criteria
According to the 2022 Chinese Expert Consensus on the Diagnosis and Treatment of Frontotemporal Lobar Degeneration, the diagnostic criteria for this disease are briefly summarized as follows [1].
Diagnostic criteria for bvFTD
I Neurodegenerative disease
There must be progressively worsening behavioral and cognitive dysfunction.
II Suspected bvFTD
At least 3 of the following abnormal manifestations must be present and symptoms persist or recur.
Inappropriate social behavior, lack of decorum or social respect, impulsive recklessness or carelessness early onset of apathy, retardation within 3 years of symptom onset.
Lack of sympathy, empathy, including lack of responsiveness to the needs and feelings of others, lack of interest, interpersonal relationships, or emotions.
Presence of persistent, compulsive, stereotyped behaviors such as simple repetitive actions, doing the same thing over and over again, and saying the same thing.
Hyperphagia, changes in eating habits, such as changes in favor or dislike of food, overeating, excessive smoking and drinking, eating non-foods such as chalk and cinders (xerophagia).
Abnormal neuropsychological manifestations, including inability to perform tasks properly, memory loss, but ability to remember scenes of what happened.
II Probable bvFTD
On the basis of meeting the suspected diagnosis, the condition significantly affects the patient’s life, socialization, and is supported by some imaging, such as frontal or anterior temporal lobe rhomboid contraction, or the presence of hypoperfusion or hypometabolism.
IV pathologically confirmed diagnosis of bvFTD
Pathologic findings confirming the presence of frontotemporal lobe degeneration, or genetic testing identifying an associated pathogenic mutation, based on meeting the suspected or probable diagnosis.
Exclusion criteria for bvFTD
The following conditions are the standard symptoms for exclusion of bvFTD.
Behavioral and cognitive abnormalities are more likely to be due to other disorders, and behavioral abnormalities are more consistent with a psychiatric disorder.
Biomarkers are very consistent with Alzheimer’s disease or other neurodegenerative diseases.
Diagnostic criteria for svPPA
Clinical diagnosis
Must have both naming disorder, and vocabulary comprehension disorder. Must meet at least 3 diagnostic features:
Difficulty with verbal content, especially infrequently used or less familiar items.
Difficulty in reading or dysgraphia.
Retelling function preserved.
Preserved oral or grammatical functioning.
Diagnosis supported by imaging findings
At least one abnormality on imaging based on compliance with the clinical diagnosis.
This includes significant atrophy, hypoperfusion, or hypometabolism of the anterior temporal lobe.
Diagnosis with clear pathologic evidence
Pathologic examination reveals specific changes on the basis of compliance with the clinical diagnosis.
For example, FTLD-tau, FTLD, TDP or other related changes, genetic testing reveals related pathogenic gene mutations.
Diagnostic criteria for PNFA
Clinical diagnosis
At least 1 focal feature, including:
Lack of grammar in speech.
Speech is labored, intermittent, and marked by inconsistent speech errors and distortions (speech disuse).
Meets ≥2 of the following features.
Difficulty understanding sentences with more complex grammar.
Can understand vocabulary.
Preserved semantic knowledge of objects.
Diagnosis supported by imaging findings
Imaging abnormalities based on compliance with clinical diagnosis.
Includes marked atrophy of the left frontal gyrus, superior temporal gyrus and frontoparietal junction, hypoperfusion or hypometabolism.
Diagnosis with clear pathologic evidence
Pathologic examination reveals specific changes on the basis of a clinical diagnosis consistent with PNFA.
For example, FTLD-tau, FTLD, TDP or other related changes, genetic testing found relevant pathogenic gene mutations.
Differential diagnosis
Alzheimer’s disease
Similarities: Both manifest dementia symptoms such as cognitive decline and behavioral abnormalities.
Differences: Temporal lobe dementia usually presents early with symptoms such as mental behavioral abnormalities, decreased executive ability, and changes in eating habits, while memory, visuospatial ability, and computational deficits appear later, whereas Alzheimer’s disease is just the opposite.
Parkinson’s disease dementia
Similarities: Both can manifest as cognitive decline and motor impairment.
Differences: Parkinson’s disease dementia develops dementia symptoms 10 or more years after the onset of Parkinson’s motor symptoms. Frontotemporal lobe dementia generally does not have the stiffness, slowness, and involuntary movements of Parkinson’s disease; patients with frontotemporal lobe dementia have significant frontal and/or temporal lobe atrophy visible on cranial MRI.
Vascular dementia
Similarities: Both can present with dementia symptoms of cognitive decline.
Differences: vascular dementia often has a clear history of cerebrovascular disease, with focal neurological symptoms and signs, such as abnormal sensory-motor function of the lateral side, etc., while frontotemporal lobe dementia usually does not have the above conditions; cranial MRI can be used for differentiation.
Treatment
Aims of treatment: There is no treatment that can stop or reverse the course of the disease. The aim of treatment at this stage is to reduce cognitive and mental symptoms associated with dementia, minimize complications, improve the quality of life, and prolong life expectancy.
Treatment principle: Detailed and comprehensive life care, nutritional support and other general treatments are supplemented with certain drug treatments.
Non-pharmacological treatment
Non-pharmacological treatments are considered to be the preferred intervention prior to the use of pharmacological treatments, which are aimed at alleviating symptoms of aggression, disinhibition and dyskinesia in order to reduce the risk of accidents and caregiver distress.
Reducing noise stimuli and improving the surrounding environment can alleviate the irritability, aggression and anxiety that patients experience due to difficulties in processing information around them.
Wearing hearing aids and increasing sensory stimulation as appropriate to reduce the patient’s discomfort with the environment.
Medication
Improvement of cognitive and language functions
Therapeutic aim: N-methyl-D-aspartate receptor antagonists may help to improve cognitive and language function [2].
Commonly used drugs: memantine.
Precautions: Observe the improvement of cognitive and language function and the change of mental behavioral symptoms of the patients, if there is no improvement of cognitive impairment symptoms or worsening of mental behavioral abnormalities, it is necessary to go to the hospital for follow-up in time.
Improvement of mental behavioral symptoms
Treatment objective: to reduce the severity of anxiety, impulsivity, aggression, abnormal eating behavior and obsessive-compulsive behavior.
Commonly used drugs: citalopram, trazodone, risperidone, olanzapine and quetiapine.
Precautions: Regularly review the blood routine, liver and kidney functions, and closely monitor the patient’s clinical symptoms.
Regulating intestinal flora treatment
Some studies have shown that mannitna can remodel the intestinal flora and inhibit neuroinflammation and tau protein production through the microbiota-gut-brain axis, which can help in the treatment of this disease, but it is still in the research stage [2].
Prognosis
Cure.
There are no drugs approved for the treatment of FTD, and there are no treatments that can stop or reverse the course of the disease, so the disease cannot be cured.
Prognostic factors
Frontotemporal dementia has a poor prognosis, with an average time from dementia diagnosis to death of about 3 to 4 years [3].
Harmful effects
Frontotemporal lobe dementia leads to mental behavioral abnormalities, language and cognitive deficits, which brings great pain to patients and seriously affects their quality of life.
Frontotemporal lobe dementia brings heavy mental pressure, medical burden and care burden to the family and society.
The prognosis of frontotemporal lobe dementia is poor, the average time from the diagnosis of dementia to death is about 3 to 4 years, and death often occurs due to complications such as severe lung infection, deep vein thrombosis, and urinary tract infection.
Questions you may be concerned about
Can frontotemporal lobe dementia be cured?
Frontotemporal lobar dementia is usually not curable, but aggressive treatment can reduce symptoms and slow disease progression.
Frontotemporal lobar dementia is a type of degenerative dementia, the pathogenesis of which is not entirely clear and for which there are no specific drugs. As the disease progresses, progressive neurological damage occurs, leading to a wide range of high-level cortical hypoplasia.
The cognitive dysfunction caused by frontotemporal lobe dementia cannot be reversed, such as memory impairment, reduced learning ability, reduced ability to perform daily life, personality changes, mental abnormalities, etc., and can only be treated symptomatically.
If diagnosed with frontotemporal lobe dementia, it should be treated aggressively. Treating the disease as soon as possible can control its progression or slow down its development, and improve the patient’s quality of life.
Daily
Daily Management
Dietary management
Balanced nutrition with high quality protein, low fat, low salt, low oil, high fiber diet (e.g. eggs, fish and poultry, fresh fruits and vegetables, etc.).
For patients with dysphagia, positional adjustment (e.g., upright), combined with dietary modification can be performed.
For abnormal eating behaviors, it is important to reduce the patient’s access to large portions of food, monitor the patient’s food-seeking or stealing behaviors, provide healthy alternatives to sweets, and supervise the slowing down of the eating rate [11].
Life management
For patients who are bedridden for a long period of time in the late stages of dementia, attention should be paid to turning and cleaning to avoid lung infections, urinary tract infections, and bedsores.
For patients with urinary incontinence, a urinary catcher or diapers can be used, and they should be changed and washed frequently to keep the perineum clean and dry.
Exercise management
Exercise can reduce behavioral symptoms and contribute to the patient’s mood, cognition, and overall health. Appropriate forms of exercise workouts, such as walking and tai chi, can be selected on the advice of a physician.
Family members or caregivers should accompany the patient when exercising to prevent accidents such as falls and injuries.
Psychological support
Patients often have depression, anxiety, euphoria, behavioral disinhibition, impulsivity, aggressiveness, etc. It is necessary for family members or caregivers to understand the patient’s condition and strengthen psychological care and nursing.
Cultivate hobbies and interests to reduce inappropriate behaviors. Encourage the patient to do what he/she can do to strengthen the patient’s integration with family and society and self-confidence.
When the patient’s mental behavioral abnormalities are serious, he/she should go to the hospital in time and be given appropriate medication.
Disease monitoring
Monitor the patient’s cognitive impairment, mental behavioral abnormality changes, according to the situation, adjust the treatment plan.
Monitor the patient’s diet and nutritional status to ensure nutritional intake while preventing overfeeding leading to other nutritional metabolic diseases.
After the patient is bedridden in the late stage of the disease, the skin changes should be monitored to avoid the occurrence of pressure ulcers, and attention should be paid to any changes such as redness, blisters, and purpling of the skin.
Regularly follow up in the hospital for review, to understand the patient’s condition changes to adjust the treatment program.
Prevention
People with a clear family history are advised to undergo genetic testing as early as possible for early intervention.