Primary progressive aphasia

Title

Other Names:

Aphasia, primary progressive; Primary progressive aphasia syndrome; PPA

Categories:

Nervous System Diseases

Subtypes:

Logopenic progressive aphasia; Progressive non-fluent aphasia

This disease is grouped under:

Frontotemporal dementia

Summary Summary

Primary progressive aphasia (PPA) affects a person's ability to use language to communicate. This includes difficulty making or understanding speech (aphasia).^[1] PPA is a specific type of a more general disease called frontotemporal dementia.^[2] PPA can be classified into three distinct types which include:^[1]

PPA is caused by a loss of tissue (atrophy) in the area of the brain that is responsible for producing language.^[1] In some cases, this loss of tissue is caused by genetic changes (mutations or pathogenic variants) in the GRN gene. In these cases, the disease is inherited in an autosomal dominant manner.^[3] Diagnosis of PPA is suspected when a doctor observes signs and symptoms such as progressive loss of language abilities. Imaging of the brain with a CT scan or MRI can confirm the diagnosis.^[1] Although there is no cure for the disease, treatment options include speech therapy and medication to manage behavioral changes.^[1]^[3]

Last updated: 4/7/2018

Symptoms Symptoms

Symptoms of primary progressive aphasia (PPA) usually begin gradually. The age that symptoms begin is typically between 50-70 years.^[4] The first symptoms of the disease may include speech problems and behavioral changes.^[3] Speech problems may include difficulty naming objects, difficulty forming words, frequent pauses in speech, slow speech, difficulty comprehending speech, and problems with grammar.^[1]^[3] In general, speech problems are the primary symptom of PPA for the first couple of years. Eventually some people may develop problems with judgement and other cognitive skills.^[5]

PPA is a progressive disease, meaning the symptoms generally worsen over time. People who have PPA may become unable to speak (mute) and completely lose the ability to understand written or spoken language.^[3] Some people develop symptoms of depression as the disease progresses.^[5] In some cases, progressive language loss may be the initial symptom of another neurodegenerative disease, such as Alzheimer disease.^[1]

Last updated: 4/7/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 23 |

Medical Terms	Other Names	Learn More: HPO ID
Percent of people who have these symptoms is not available through HPO
Agitation		0000713
Apathy		0000741
Aphasia	Difficulty finding words Losing words Loss of words [ more ]	0002381
Apraxia		0002186
Autosomal dominant inheritance		0000006
Cerebral cortical atrophy	Decrease in size of the outer layer of the brain due to loss of brain cells	0002120
Dilation of lateral ventricles		0006956
Disinhibition		0000734
Dysphasia		0002357
Frontotemporal dementia		0002145
Gliosis		0002171
Hallucinations	Hallucination Sensory hallucination [ more ]	0000738
Hyperorality		0000710
Hypersexuality	Sex addiction	0030214
Memory impairment	Forgetfulness Memory loss Memory problems Poor memory [ more ]	0002354
Mutism	Inability to speak Muteness [ more ]	0002300
Neuronal loss in central nervous system		0002529
Parkinsonism		0001300
Perseveration		0030223
Personality changes	Personality change	0000751
Polyphagia	Voracious appetite	0002591
Progressive language deterioration		0007064
Repetitive compulsive behavior		0008762

Showing of 23 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2018

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Primary progressive aphasia (PPA) is caused by a loss of tissue (atrophy) in the area of the brain that is responsible for language. This loss of brain tissue causes people with PPA to slowly lose their ability to find the right words they want to say or to understand words that other people say.^[1]

In some cases, PPA is caused by genetic changes (mutations or pathogenic variants) in the GRN gene.^[2] However, most cases of PPA are thought to be caused by a combination of genetic and environmental factors.^[5] People who have learning disabilities may be more likely to develop PPA.^[1]

Last updated: 4/7/2018

Inheritance Inheritance

About 40-50% of people with primary progressive aphasia (PPA) have other family members who are also affected by the disease.^[5] When PPA is caused by a genetic change (mutations or pathogenic variants) in the GRN gene, it is inherited in an autosomal dominant manner.^[3] Like most genes, the GRN gene comes in a pair. One copy of the gene comes from the mother and the other copy from the father. Autosomal dominant means that only one copy of the GRN gene needs to have a pathogenic variant for a person to develop PPA.

When a person who has a pathogenic variant in the GRN gene has children, each child has a:

50% chance to inherit the changed copy of the GRN gene, meaning he or she is at an increased risk to develop PPA
50% chance to inherit the working copy of the GRN gene, meaning he or she is not at an increased risk to develop PPA

Most cases of PPA are not caused by a pathogenic variants in the GRN gene, but PPA can still run in families. In these situations, the disease is likely more common in the family because of shared genetic and environmental factors.^[5]

Last updated: 4/7/2018

Diagnosis Diagnosis

Primary progressive aphasia (PPA) may be suspected when a person has signs and symptoms of the disease including behavioral changes and progressive loss of language abilities. A doctor may then take a thorough personal medical history and family history to look for other signs of the disease. Most people who have PPA begin to develop symptoms suddenly, and they experience a progressive loss of language skills for two years without other loss of cognitive function.^[4] Imaging of the brain using a CT scan or MRI may confirm the diagnosis.^[1] In some cases, the exact type of disease that a person has cannot be determined until after he or she has passed away.^[6]

Last updated: 4/7/2018

Treatment Treatment

Unfortunately, there is no cure for primary progressive aphasia (PPA). Treatment is focused on slowing the progression of the disease and helping the person to adapt to the loss of language skills in everyday life. For example, speech therapy may be a helpful tool for people with PPA to maintain language skills for as long as possible.^[1] Some people benefit from learning sign language or other ways to communicate.^[3]^[7]

Selective serotonin reuptake inhibitors (SSRIs) can be used to treat behavioral changes that may be associated with PPA. These medications may also help treat symptoms of anxiety or depression, which can impact people who have PPA.^[2] Clinical trials are ongoing to try to determine more effective treatments for PPA.^[8]

Last updated: 4/7/2018

Prognosis Prognosis

Primary progressive aphasia (PPA) is typically a progressive disease, meaning that people who have the disease tend to continue to lose language skills. Many people who have the disease eventually completely lose the ability to use language to communicate.^[1]

People who have the disease typically live about 3-12 years after they are originally diagnosed. In some people, difficulty with language remains the primary symptom, while others may develop additional problems including cognitive or behavioral changes or difficulty coordinating movements.^[3] Many people with PPA eventually require care and monitoring at home to help them in daily life.^[8] People who have PPA may be more likely to experience complications such as an injury or infections such as pneumonia.^[9]

Last updated: 4/7/2018

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Primary progressive aphasia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

The Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL) is an integrated group of academic medical centers, patient support organizations, and clinical research resources dedicated to conducting clinical research on conditions that occur in association with frontotemporal lobar degeneration. The ARTFL has a contact registry for patients who wish to be contacted about clinical research opportunities and updates on the progress of the ARTFL research projects.

For more information on the registry see: http://www.rarediseasesnetwork.org/cms/artfl/Get-Involved/Contact-Registry

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Aphasia Center of Maine
6027 Village on the Green #130
Carrabassett Valley, ME 04947
Telephone: 207.237.2123
E-mail: info@aphasiacenterofmaine.org
Website: http://www.aphasiacenterofmaine.org/
Aphasia Hope Foundation
750 Woodlands Pkwy
Ridgeland, MS 39157
Telephone: (913)-484-8302
E-mail: jstradinger.2007@comcast.net
Website: http://aphasiahope.wpengine.com/
Association for Frontotemporal Degeneration (AFTD)
Radnor Station Building 2
Suite 320
290 King of Prussia Road
Radnor, PA 19087
Toll-free: 866-507-7222
Telephone: 267-514-7221
E-mail: info@theaftd.org
Website: http://www.theaftd.org/
Frontotemporal Dementia Caregiver Support Center
E-mail: jeffbrauer@cableone.net
Website: http://www.ftdsupport.com
Frontotemporal Lobar Degeneration Association (FTLDA)
21019 U.S. Hwy. 281
Suite 830-27
San Antonio, TX 78258
Telephone: 210-824-9510
E-mail: oxford@ftlda.org
Website: http://www.ftlda.org/
National Aphasia Association
P.O. Box 87
Scarsdale, NY 10583
Toll-free: 800-922-4622
E-mail: naa@aphasia.org
Website: http://www.aphasia.org

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The MayoClinic.com provides information about Primary progressive aphasia. Click on the above link to access this information.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Primary progressive aphasia. Click on the link to view a sample search on this topic.

Selected Full-Text Journal Articles

Rogalski EJ, Rademaker A, Wieneke C, Bigio EH, Weintraub S, Mesulam MM. The prevalence of learning disabilities in primary progressive aphasia is not segregated by pathology or subtype. JAMA Neurol. 2014 Dec; 71(12):1576-7.
Mesulam MM, Rogalski EJ, Wieneke C, Hurley RS, Geula C, Bigio EH, Thompson CK, Weintraub S. Primary progressive aphasia and the evolving neurology of the language network. Nat Rev Neurol. 2014 Oct; 10(10):554-69.
Rogalski E, Weintraub S, Mesulam MM. Are there susceptibility factors for primary progressive aphasia? Brain Lang. 2013 Nov; 127(2):135-8.
Mesulam M. Primary progressive aphasia: A dementia of the language network. Dement Neuropsychol. 2013 Jan 1; 7(1):2-9.

News & Events News & Events

News

NCATS Rare Diseases Are Not Rare! Challenge
October 9, 2018
The NIH Undiagnosed Diseases Network Expands
September 26, 2018

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

What are the causes of death related to PPA? I see lots of information about life expectancy, but nothing indicating what it is that eventually causes death. See answer
Do you have any information on the stages of progressive primary aphasia (PPA) semantic variant? See answer

Have a question? Contact a GARD Information Specialist.

References References

Ratnavalli E. Progress in the last decade in our understanding of primary progressive aphasia. Ann Indian Acad Neurol. December 2010; 13(Suppl2):S109-S115. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039160/.
Primary progressive aphasia. Orphanet. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=95432. Accessed 3/27/2018.
Hsiung GYR and Feldman HH. GRN-Related Frontotemporal Dementia. GeneReviews. March 14, 2013; http://www.ncbi.nlm.nih.gov/books/NBK1371/.
Matías-Guiu JA and García-Ramos R. Primary progressive aphasia: from syndrome to disease. Neurologia. July-August 2013; 28(6):366-374. https://www.ncbi.nlm.nih.gov/pubmed/22703637.
Léger GC and Johnson N. A review on primary progressive aphasia. Neuropsychiatric Disease and Treatment. December 2007; 3(6):745-752. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656316/.
Utianski RL, Duffy JR, Savica R, Whitwell JL, Machulda MM, and Josephs KA. Molecular neuroimaging in primary progressive aphasia with predominant agraphia. Neurocase. March 2018; 23:1-3. https://www.ncbi.nlm.nih.gov/pubmed/29569990.
Jokel R, Meltzer J, D.R.J., D.M.L., J.C.J., A.N.E., and D.T.C. Group intervention for individuals with primary progressive aphasia and their spouses: Who comes first?. Journal of Communication Disorders. March 2017; 66:51-64. https://www.ncbi.nlm.nih.gov/pubmed/28412599.
Frontotemporal Dementia Information Page. National Institute of Neurological Disorders and Stroke (NINDS). June 21, 2018; https://www.ninds.nih.gov/Disorders/All-Disorders/Frontotemporal-Dementia-Information-Page.
Disease Overview. The Association for Frontotemporal Degeneration. http://www.theaftd.org/understandingftd/ftd-overview. Accessed 3/27/2018.