Glossary of FTD Terms

Aggregation — Accumulation or clumping; used to refer to the abnormal build-up of certain proteins that occurs in FTD and other neurodegenerative disorders.

Agnosia — A common symptom of FTD disorders that literally means “loss of knowing,” and which refers to the loss of the ability to process sensory information. There are different kinds; visual agnosia, for example, is the inability to recognize objects or familiar people by sight.

Agrammatism — Inability to form grammatically correct sentences. For example, an affected individual may omit words, use incorrect verb tenses, form plurals incorrectly, or make mistakes in word order. Agrammatism is a common symptom of nonfluent/agrammatic primary progressive aphasia (nfvPPA).

Akinesia — Absence or loss of voluntary movements.

Alien limb phenomenon —Sensation that an arm or leg is no longer part of the body, often accompanied by the inability to control movement of the affected limb. Alien limb phenomenon is a symptom of the FTD disorder known as corticobasal syndrome.

Allele — One of the two copies of a gene (one from each parent) found in every cell of the human body.

Alzheimer’s disease (AD) — Neurodegenerative brain disorder and the most common form of dementia. In contrast to FTD, which affects brain regions that play key roles in behavior, personality, language, and movement, AD affects brain regions important for memory and cognition. Like FTD, AD is characterized by the abnormal accumulation of the protein beta-amyloid, in structures called plaques, and the protein tau, in structures known as neurofibrillary tangles. Over time, affected brain cells die, resulting in progressive loss of function.

Amyloid — General term for accumulations of proteins that are folded incorrectly, producing three-dimensional structures that stick to one another to form clumps. Beta-amyloid, a protein fragment derived from a larger precursor protein, forms such clumps in Alzheimer’s disease. These clumps can be visualized using a brain imaging technique known as amyloid PET scanning, helping to differentiate AD from FTD.

Amyotrophic lateral sclerosis (ALS) — Also known as Lou Gehrig’s disease, ALS is a neurodegenerative disease that results from the death of nerve cells in the brain and spinal cord responsible for controlling voluntary muscle movement. Up to 30% of people diagnosed with FTD also have symptoms of ALS; this form of FTD is called FTD-ALS or FTD-MND (motor neuron disease).

Anomia — Inability to recall the names of familiar objects. Anomia is a common symptom of semantic variant primary progressive aphasia (svPPA)

Apathy — Lack of interest in previously meaningful activities or self-care. Apathy is a common early symptom of behavioral variant FTD (bvFTD)

Aphasia — An acquired (i.e., not present from birth) brain disorder characterized by the loss of the ability to speak, write or understand what others are saying. Language-predominant FTD disorders are known collectively as primary progressive aphasia (PPA).

Apraxia — Inability to carry out purposeful activities, even if the person still has the muscle strength needed to do so. Apraxia of speech, in which the affected person has difficulty producing the movement of the lips and tongue needed to talk, is a symptom of nonfluent/agrammmatic PPA. Limb apraxia is a symptom of corticobasal syndrome.

Atrophy — Degeneration of an organ or body part due to the death of the cells that make up that tissue. FTD is characterized by atrophy of the frontal and temporal lobes of the brain.

Augmentative and alternative communication — Strategies used to assist or replace verbal communication for people with language disorders, such as PPA. Examples include flash cards, gestures, or electronic devices.

Autosomal dominant — Pattern of inheritance in which a mutation in only one of the two copies of an FTD-associated gene is needed to cause FTD and there are no differences in inheritance between boys and girls; i.e., both are equally affected.

Axon — The part of a brain cell that sends messages to another brain cell. The axon is typically a long process that extends from the body of the cell and resembles the taproot of a plant.

Basal ganglia — Group of brain regions located deep in the brain (hence “basal” – at the base) that collectively play a key role in the regulation of voluntary movements, cognition, and emotion. Degeneration of structures within the basal ganglia occurs in progressive supranuclear palsy and corticobasal syndrome.

Behavioral neurology — Subspecialty of neurology devoted to the neural basis of behavior and cognition. Behavioral neurologists are trained in the diagnosis and treatment of neurodegenerative disorders, including FTD.

Behavioral variant FTD (bvFTD) — Form of FTD characterized by changes in personality, apathy, disinhibition, and a decline in judgment, self-control, and empathy. bvFTD is the most common form of FTD.

Biomarker — Physiological characteristic that can be objectively measured as an indicator of underlying biological or pathological process. Blood pressure – an indicator of heart disease – is an example of a biomarker. The identification of FTD biomarkers to guide diagnosis and drug development is a critical research priority; such a biomarker could be a protein or other factor measured in the blood or cerebrospinal fluid (CSF) or features detected by brain imaging.

Bradykinesia — Abnormally slow movement. Bradykinesia is a symptom of CBS and PSP.

C9ORF72 — A specific mutation of this gene on chromosome 9, known as a hexanucleotide repeat, is the most common genetic cause of both FTD and ALS. The C9ORF72 mutation is associated with an abnormal accumulation of the protein TDP-43, which is involved in RNA metabolism.

CHMP2B — Rare mutations in this gene are one cause of genetic FTD. The protein encoded by the CHMP2B gene is thought to play a role in recycling or breaking down certain proteins.

Cerebellum — Large structure located at the back of the brain below the cerebral cortex, which plays an important role in coordination and balance.

Cerebral cortex — The wrinkled outer layer of the brain. The largest part of the brain, the cerebral cortex is divided into four main regions, or lobes: frontal, temporal, parietal, and occipital. The cerebral cortex plays key roles in many important brain functions, including thinking, perception, memory, voluntary movement, language, and the regulation of emotional and social behavior.

Cerebrospinal fluid (CSF) — Clear fluid that surrounds the brain and also fills the hollow spaces within the brain (known as ventricles) and the spinal cord. In a lumbar puncture, a sample of this fluid is extracted and analyzed.

Chromosome — Threadlike structure composed of DNA and protein located in the nucleus of cells, including brain cells. The DNA of chromosomes contains the genes – segments that are “recipes” for proteins and are the basis of inherited characteristics. Human cells typically contain 23 pairs of chromosomes.

Clinical diagnosis — A diagnosis based on signs, symptoms, and medical history, in conjunction with laboratory tests or imaging procedures, but without confirmatory pathology. A clinical diagnosis of FTD can only be confirmed post-mortem by examining brain tissue for characteristic pathological features.

Clinical trial — Type of research study designed to evaluate the safety and effectiveness of a new medication or other type of treatment. Every clinical trial follows a protocol that includes clear criteria for participation, the dosage and duration of treatment, the methods that will be used to measure the effects of the treatment, and the statistical procedures that will be used to analyze the data.

Cognition — Term that collectively refers to complex mental processes, including perception, memory, reasoning, problem-solving, judgment, imagination, and self-awareness.

Community-based care — Model of FTD care that emphasizes care delivered at home or locations within a patient’s community, rather than in the hospital or a residential care facility.

Computed tomography (CT) scan — Brain-imaging procedure in which a series of X-rays is taken from multiple angles; computer analysis of these X-rays is used to construct a cross-sectional image of a thin segment or “slice” of the brain. CT scans cannot diagnose FTD, but can be used to rule out other causes of behavioral, language, or motor symptoms.

Connectivity — Refers to brain networks or circuits made up of regions linked anatomically or indirectly by virtue of the fact that they are activated at the same time in the course of carrying out a specific function.

Corticobasal degeneration (CBD) — The pattern of brain degeneration associated with the clinical symptoms of corticobasal syndrome (CBS). The affected brain regions include the frontal and temporal lobes as well as the brain stem, cerebellum, and substantia nigra. These regions play important roles in initiating, controlling, and coordinating movement.

Corticobasal syndrome (CBS)—The clinical diagnosis given to the symptoms associated with CBD. One of the movement-predominant FTD disorders, CBS is characterized by limb apraxia, akinesia or bradykinesia, rigidity, and uncontrollable muscle contractions. People with CBS may also exhibit behavioral and language symptoms common to other forms of FTD.

Delusion —A belief that is strongly held despite convincing evidence that it is untrue. Delusions are a behavioral symptom that is sometimes observed in people with FTD due to mutation of the C9ORF72 gene.

Dementia — Often used incorrectly as a synonym for Alzheimer’s disease, “dementia” is a general term that indicates significant impairment in multiple aspects of cognition (e.g., memory, language, visuospatial function, attention, executive function, social understanding) severe enough to restrict the ability to carry out typical daily activities. FTD is a form of dementia that is distinct from the dementia of Alzheimer’s disease.

Dendrite — The part of a brain cell that receives messages from other brain cells. Collectively, the many dendrites extending from the cell resemble the branches of a tree.

Deoxyribonucleic acid (DNA) — A double-stranded molecule containing the genetic information passed down from one generation to the next.  This information is encoded in the sequence of the 4 types of chemical “building blocks,” or bases (adenine, thymine, guanine, and cytosine) that make up each chain. The bases pair up – adenine to thymine and guanine to cytosine – joining the two chains to form a helix.

Differential diagnosis — A physician’s “short list” of the likely causes of a patient’s symptoms. Additional observation and diagnostic tests are used to rule out disorders on this list and arrive at a specific diagnosis.

Diffusion tensor imaging (DTI) — Type of magnetic resonance imaging (MRI) that allows doctors and researchers to visualize the connections between brain regions.

Disease-modifying treatment — Medication or other form of treatment aimed at slowing or reversing the underlying disease process. Because no disease-modifying treatments are currently available for any of the FTD disorders, identifying such treatments is a high priority for FTD researchers.

Disinhibition — Inability to control or suppress an immediate, impulsive response to a situation. For example, the affected person may blurt out a rude comment or engage in risky, even dangerous, behavior.

Dysarthria — Slurred or slowed speech that is difficult to understand, caused by difficulty moving and coordinating the muscles that control the lips, tongue and jaw.

Dysphagia — Difficulty swallowing, which can lead to gagging or choking.

Dystonia — Uncontrollable muscle contractions that cause involuntary twisting, writhing, or abnormal postures.

Electroencephalography (EEG) — Noninvasive diagnostic technique that uses electrodes placed on the scalp to record the electrical activity of the brain, similar to electrocardiography (ECG), used to monitor heart rhythm and detect heart disorders.

Exclusion criteria — Factors that disqualify an individual from participating in a clinical trial. For example, a potential participant may have other medical conditions, have an FTD disorder other than the one being investigated, or fall outside of the specified age range. Being excluded from a trial on the basis of these criteria does not mean there is anything wrong with that person – he or she may meet the criteria for a different trial.

Executive function — Refers to a set of advanced cognitive skills that control and regulate behavior, including planning, strategizing, self-monitoring, judgment, reasoning, attention, and abstract thinking.

Familial — Indicates that a disease has been documented in multiple family members. While a familial pattern of occurrence often occurs because of a gene mutation passed down from generation to generation, it can also be caused by common exposure to an environmental factor.

Fasciculations — Brief, spontaneous, uncontrolled muscle twitches.

FTD/ALS — Form of FTD that includes symptoms of the motor disorder ALS, including muscle weakness and atrophy, fasciculations, spasticity, and difficulty speaking or swallowing in addition to changes in behavior, personality or language. Also referred to as FTD with motor neuron disease (FTD-MND).

Frontal lobe — One of the four major subdivisions of the brain’s outer layer or cerebral cortex, located at the front of the brain near the forehead. The frontal lobe plays important roles in executive function, voluntary movement, and emotional regulation.

Frontotemporal spectrum disorder — Comprehensive term that places FTD without motor symptoms, FTD-ALS, and ALS on a disease continuum that accounts for the clinical, pathological, and genetic overlap between FTD and ALS.

Functional magnetic resonance imaging (fMRI) — Form of brain imaging that utilizes changes in blood flow and oxygen utilization to detect brain activity related to behavior or cognition.

Fused in sarcoma (FUS) — The least common of the proteins found in the abnormal accumulations that are a characteristic pathological feature of FTD. Mutations of the FUS gene are also a rare cause of genetic FTD.

GRN — The gene that encodes the protein progranulin, which plays a role in several important cellular functions, including the regulation of inflammation. Mutations in the GRN gene, one of the most common causes of hereditary FTD, lead to a reduction in progranulin referred to as progranulin haploinsufficiency.

Gene — A segment of DNA that constitutes a “recipe” for making a specific protein.

Gene sequencing — Process of determining the sequence of the chemical building blocks (bases) that make up a segment of DNA. When the complete DNA sequence of the entire genome is established in a single effort, the process is known as whole genome sequencing.

Genetic testing — The analysis of an individual’s DNA to identify gene mutations associated with a disease.

Hereditary — Describes a disease genetically inherited by a child from an affected parent.

Inclusion — A term used by pathologists for an abnormal accumulation or clump of protein within brain cells.

Inclusion criteria — Factors that define whether or not an individual can be enrolled in a clinical trial. For example, the trial protocol may specify that participants must be within a certain age range, be diagnosed with a specific FTD disorder, or be capable of completing neuropsychological tests.

Induced pluripotent stem cells (iPSCs) — Stem cells – cells capable of developing into multiple body tissues, typically present only early in development – engineered in the laboratory by “reprogramming” adult cells (e.g. skin cells). iPSCs can subsequently be treated to generate specific cell types, such as neurons (nerve cells). Laboratory-derived neurons developed from iPSCs made by reprogramming cells from individuals with FTD-causing gene mutations are an important research tool.

Inflammation — One of the immune system’s responses to unfamiliar and potentially harmful organisms or substances, including bacteria, viruses, toxins, debris from damaged cells, or allergens. Inflammation involves the activation and movement of white blood cells and changes in blood vessels, coordinated by multiple chemical signals. Although inflammation is usually a self-protective response, it can also damage tissues, particularly if it continues for a prolonged period. Recent research points to destructive inflammation as a possible cause of neurodegenerative disorders like FTD.

Informed consent — An important protection required in all research involving human participants. Researchers conducting the study provide information about the study’s purpose and the procedures involved as well as the risks and potential benefits in a written document that is clear and easy to understand. In addition, they answer any questions a potential participant may have. If participants then choose to enroll in the study, they sign the informed consent document to indicate that they understand and agree to comply with the experimental protocol.

Logopenic variant primary progressive aphasia (lvPPA) — A form of PPA (the term encompassing the language-predominant FTD disorders) characterized by difficulty recalling words and omission or substitution of sounds in words, making it difficult for listeners to understand what the affected person is saying.

Lumbar puncture — Also known as a spinal tap, this diagnostic procedure involves the insertion of a thin needle into the lower back to collect cerebrospinal fluid. The fluid is then analyzed for abnormalities, such as changes in disease-associated biomarkers or pathogens.

MAPT — The gene that encodes the microtubule-associated protein tau. Mutations in the MAPT gene are one of the more common causes of inherited FTD and result in abnormal accumulations of tau.

Magnetic resonance imaging (MRI) — Form of brain imaging that uses radio waves and magnets to visualize brain structure or function. While MRI scans cannot provide a definitive diagnosis of FTD, they can, in conjunction with other evidence from a neurological exam, medical history, laboratory or neuropsychological tests, and procedures such lumbar puncture, support the diagnosis. MRI is also an important research tool.

Microglia — Type of immune cell specific to the brain. Microglia play a key role in defending the brain from infection, inflammation, and the response to brain injury.

Microtubules — Hollow, fibrous rods that make up the brain cell’s internal scaffolding and facilitate the movement of cellular components. The tau protein, which accumulates in some cases of FTD, helps to stabilize microtubules.

Mutation — Alteration in DNA that changes a gene and the protein it encodes. Many mutations are harmful, resulting in an abnormality or disease.

Mutism — Inability to speak.

Natural history study — Type of observational research study in which participants who have a disease or are at risk of developing a disease are observed and evaluated repeatedly over a period of time to document changes in their health that define the typical course of the disorder. Two natural history studies of FTD funded by the National Institutes of Health, Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS), are currently ongoing and recruiting participants.

Neuroimaging — A collective term for procedures that enable visualization of the structure or function of the brain and spinal cord, including changes associated with FTD and other brain disorders. Examples include CT, PET and MRI scanning. Advances in neuroimaging are fueling important advances in our understanding of FTD disease mechanisms as well as biomarker discovery and development.

Neuron — The type of brain cell responsible for transmitting information. The degeneration of neurons in the frontal and temporal lobes is a defining feature of FTD.

Neuropathologist — A physician who specializes in the examination of brain tissue to identify changes characteristic of disease. Only a neuropathologist can confirm an FTD diagnosis.

Neuropsychological testing — Diagnostic procedures that utilize pencil-and-paper-type questionnaires and activities to test cognitive functions, such as memory, concentration, attention, and problem solving as well as visuospatial, math, and language skills.

Neuropsychologist — Health care professional who administers and interprets neuropsychological tests.

Neurotransmitters — Chemical signals used by neurons to communicate; examples include serotonin, dopamine, and acetylcholine.

Neurotransmission — Process of converting the electrical signals generated by neurons into chemical signals that can cross the gap between cells, known as a synapse, to relay information.

Nonfluent/agrammatic primary progressive aphasia (nfvPPA) — Language-predominant FTD disorder characterized by progressive difficulty in forming speech sounds, using words incorrectly, and constructing grammatically correct sentences.

Nonpharmacologic therapies — Treatments that are not medications. Transcranial direct current stimulation (tDCS) is an example of a nonpharmacologic treatment currently being tested in FTD.

Outcome measure — A physiological or anatomical feature, behavior, biomarker, test parameter, or other disease indicator monitored during a clinical trial to evaluate the effectiveness of a medication or nonpharmacologic intervention.

Parkinsonism — Motor symptoms commonly observed in Parkinson’s disease, such as tremors, rigidity, abnormally slow movement, and difficulty maintaining balance. These symptoms (but not other symptoms of Parkinson’s disease) are also observed in two movement-dominant FTD disorders, corticobasal syndrome and progressive supranuclear palsy. As a result, these diseases are sometimes referred to as atypical parkinsonism.

Pathology — The medical specialty that focuses on the study of organs and tissues to determine the specific changes characteristic of diseases.

Pathological diagnosis — A diagnosis made by examining affected tissues under a microscope to identify characteristic changes. Post-mortem pathological diagnosis confirming the presence of abnormal aggregation of FTD-associated proteins (tau, TDP-43, FUS) is currently the only way to know for certain that the affected individual had FTD.

Pedigree — A family history showing family members and their relationships to one another. A pedigree can include details of each member’s health that reveal patterns suggestive of a heritable disorder. Between 30% and 50% of people diagnosed with FTD have a family history of FTD disorders that can be observed in their pedigrees.

Phonological paraphrasias — Substitution of a similar-sounding nonword for a legitimate word; e.g., “ped” instead of “bed” or “efelant” instead of “elephant.”

Pick body — Specific type of inclusion containing a form of the tau protein known as “3R tau.” Pick bodies have a unique appearance in post-mortem brain tissue and are found in a small proportion of people with FTD-tau.

Pick’s disease — Originally another name for FTD, the term “Pick’s disease” is now reserved for the subset of individuals with FTD-tau in whom Pick bodies are present on post-mortem pathological examination.

Positron emission tomography (PET) — A type of brain imaging that utilizes a short-lived radioactive tracer to visualize specific brain components (e.g., tau) or monitor brain activity.

Primary progressive aphasia —The umbrella term for FTD syndromes characterized by the progressive loss of the ability to speak, read, write, or understand spoken language. Three types, or variants, of PPA can be differentiated:

Semantic variant PPA (svPPA), in which the affected individual loses the ability to recall the names of objects and the meanings of words

Nonfluent/agrammatic PPA (nfvPPA), in which the individual retains the meanings of word but loses the ability to produce speech, use words correctly, or construct grammatically correct sentences

Logopenic variant PPA (lvPPA), in which the affected individual experiences difficulty recalling words and omits or substitutes sounds in words, making it difficult for listeners to understand what they are saying

Progressive supranuclear palsy (PSP) — A movement-predominant FTD disorder characterized by a progressive inability to move the eyes, especially vertically, as well as difficulties with balance, coordination, and movement of the muscles controlling the mouth and throat. People with PSP can also exhibit symptoms common to individuals with Parkinson’s disease, such as rigidity and abnormally slow movement. As a result, PSP is sometimes referred to as an example of atypical parkinsonism. All individuals with PSP have abnormal accumulations of the protein tau.

Progranulin — A protein that plays an important role in the regulation of inflammation and other cellular functions. Mutations in the progranulin gene (GRN) are one of the more common mutations in hereditary FTD. The brains of people with GRN mutations contain abnormal accumulations of the protein TDP-43.

Protein — Type of molecule made up of chains of chemical building blocks known as amino acids. The sequence of amino acids is specified by the order of bases in the DNA of the gene encoding that protein. Proteins are critical to the structure and function of all cells, including brain cells.

Protocol — Written description of the objectives, study design, methods, and outcome measures for a clinical trial. In a trial that involves researchers in multiple locations, all sites utilize the same protocol to avoid site-specific variations in the way data are collected that could introduce bias and raise questions about the results.

Radiologist — Physician who specializes in carrying out and interpreting the results of imaging procedures, such as PET and MRI brain scans.

Rigidity — Stiffness; resistance to movement.

Semantic variant primary progressive aphasia (svPPA) — A form of primary progressive aphasia characterized by loss of the ability to recall the names of objects, their uses, and the meanings of words. People with svPPA remain able to speak and to repeat words or sentences. Sometimes referred to as semantic dementia.

Spasticity — Prolonged, uncontrollable contraction of a muscle, resulting in tightness and stiffness.

Speech-language pathologist — A healthcare professional who specializes in the evaluation of a person’s ability to produce and understand spoken and written speech.

Sporadic — Refers to FTD cases in which the affected individual has no known family history of FTD disorders.

Supranuclear gaze palsy — Impaired ability to move the eyes, especially in the vertical direction; may be experienced as blurry vision, trouble going down stairs, or difficulty reading.

Surface dyslexia/dysgraphia — Difficulty reading or writing words that do not follow pronunciation or spelling rules; these words are spelled or spoken “as if” they followed the rules (e.g., “no” substituted for “know”).

Symptomatic treatment — Medication or other form of treatment aimed at relieving symptoms, without affecting the process causing the disease. For example, medications are sometimes prescribed for people with FTD to decrease agitation and other behavioral symptoms, while speech-language therapy can preserve language skills in people with PPA.

TAR DNA binding protein 43 (TDP-43) — One of the proteins in the brain that forms abnormal accumulations in FTD. Approximately half of people with FTD have FTD-TDP-43; it is also the protein that accumulates in the majority of ALS cases. Mutations in the gene encoding TDP-43, TARDBP, are a rare cause of hereditary FTD and also cause hereditary ALS.

Tau —One of the brain proteins that forms abnormal accumulations in FTD; approximately 40% of people with FTD have FTD-tau. In healthy brain cells, tau stabilizes microtubules that maintain the internal structure of axons.

Tauopathy — General term for neurodegenerative disorders associated with the abnormal accumulation of tau; FTD is one example.

Temporal lobe — One of the four major subdivisions of the brain’s outer layer or cerebral cortex, located on either side of the brain behind the ear. The temporal lobes play important roles in language, hearing, memory, and emotion.

Transcranial direct current stimulation (tDCS) — Nonpharmacologic, noninvasive form of treatment for brain disorders that applies a weak electrical current to the scalp to stimulate an increase or decrease in brain activity. Research to evaluate the effectiveness of tDCS in FTD is currently underway.

Valosin-containing protein (VCP) — Mutations in the VCP gene are a rare cause of hereditary FTD. Such mutations are also responsible for a rare disorder known as inclusion body myopathy with Paget disease of bone, characterized by muscle weakness and abnormalities of the bones of the spine, arms, and legs, which can occur in conjunction with FTD.

Additional Online Resources

As you learn more about FTD, you may encounter additional terms and concepts that are unfamiliar or you may want to learn more about the brain or the role of genes in health and disease. The online resources below are excellent general sources of neuroscientific and genetic background information, particularly for people who are not scientists or physicians.

Neuroscience Resources

Brain Facts: www.brainfacts.org

The Brain From Top to Bottom: thebrain.mcgill.ca

Genes to Cognition Online: www.g2conline.org

The Dana Foundation:  www.dana.org

Society for Neuroscience: www.sfn.org

Genetics Resources

Learn. Genetics – Genetic Science Learning Center: learn.genetics.utah.edu