The Basics of Dementia and Cognitive Impairment
Dementias Associated with Aging and Neurodegeneration
Neuropathology of Neurodegenerative Disorders
Reversible Dementia-like Disorders and Conditions
Other Neurodegenerative Diseases and Conditions that Include Dementia or Dementia-like Symptoms
Risk Factors for Dementia and Vascular Cognitive Impairment
Treatment and Management
Where can I get more information?
A diagnosis of dementia can be frightening for those affected by the syndrome, their family members, and caretakers. Unfortunately, there is a stigma associated with this term. Learning more about this medical condition can help. This booklet provides a general overview of various types of dementia, describes how the disorders are diagnosed and treated, and offers highlights of research supported by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), both part of the National Institutes of Health (NIH).
Alzheimer’s disease and related dementias have a high impact on public health and are a priority for NIH-supported research.
*A Glossary of terms is found at the end of this document.
Dementia is the loss of cognitive functioning—the ability to think, remember, or reason—to such an extent that it interferes with a person’s daily life and activities. These functions include memory, language skills, visual perception, problem solving, self-management, and the ability to focus and pay attention. Some people with dementia cannot control their emotions, and their personalities may change. Dementia ranges in severity from the mildest stage, when it is just beginning to affect a person’s functioning, to the most severe stage, when the person must depend completely on others for basic activities of daily living.
Age is the primary risk factor for developing dementia. For that reason, the number of people living with dementia could double in the next 40 years as the number of Americans age 65 and older increases from 48 million today to more than 88 million in 2050. Regardless of the form of dementia, the personal, economic, and societal demands can be devastating.
Dementia is not the same as age-related cognitive decline—when certain areas of thinking, memory, and information processing slow with age, but intelligence remains unchanged. Unlike dementia, age-related memory loss isn’t disabling. Occasional lapses of forgetfulness are normal in elderly adults. While dementia is more common with advanced age (as many as half of all people age 85 or older may have some form of dementia), it is not an inevitable part of aging. Many people live into their 90s and beyond without any signs of dementia.
Dementia is also not the same as delirium, which is usually a short-term complication of a medical condition and most often can be treated successfully. Signs and symptoms of dementia result when once-healthy neurons (nerve cells) in the brain stop working, lose connections with other brain cells, and die. While everyone loses some neurons as they age, people with dementia experience far greater loss.
Mild cognitive impairment (MCI) is a stage between normal cognitive changes that may occur with age and more serious symptoms that indicate dementia. Symptoms of MCI can include problems with thinking, judgment, memory, and language, but the loss doesn’t significantly interfere with the ability to handle everyday activities. Symptoms of MCI include mild memory loss; difficulty with planning or organization; trouble finding words; frequently losing or misplacing things; and forgetting names, conversations, and events. Someone who has MCI may be at greater risk of eventually developing Alzheimer’s or another type of dementia, particularly if the degree of memory impairment is significant, but MCI does not always progress to dementia. Symptoms may remain stable for several years, and even improve over time in some people.
It is common to have more than one cause of dementia. Many people with dementia have both Alzheimer’s disease and one or more closely related disorders that share brain scanning or clinical features (and sometimes both) with Alzheimer’s disease. When a person is affected by more than one dementia disorder, the dementia can be referred to as a mixed dementia.
Autopsy studies of the brains of people who had dementia suggest that a majority of those age 80 and older probably had mixed dementia caused by Alzheimer’s-related neurodegenerative processes, vascular disease-related processes, or another neurodegenerative condition. In fact, some studies indicate that mixed vascular-degenerative dementia is the most common cause of dementia in the elderly.
Researchers are still trying to understand the underlying disease processes involved in dementia. Scientists have some theories about mechanisms that may lead to different forms of dementia, but more research is needed to better understand if and how these mechanisms are involved.
Various disorders and factors contribute to dementia, resulting in a progressive and irreversible loss of neurons and brain functions. Currently, there are no cures for these neurodegenerative disorders.
Some specific causes of dementia disorders are explained below.
Alzheimer’s disease (AD) is the most common cause of dementia in older adults. As many as 5 million Americans age 65 and older may have the disease. In most neurodegenerative diseases, certain proteins abnormally clump together and are thought to damage healthy neurons, causing them to stop functioning and die. In Alzheimer’s, fragments of a protein called amyloid form abnormal clusters called plaques between brain cells, and a protein called tau forms tangles inside nerve cells.
It seems likely that damage to the brain starts a decade or more before memory and other cognitive problems appear. The damage often initially appears in the hippocampus, the part of the brain essential in forming memories. Ultimately, the abnormal plaques and tangles spread throughout the brain, and brain tissue significantly shrinks.
As Alzheimer’s disease progresses, people experience greater memory loss and other cognitive difficulties. Problems can include wandering and getting lost, trouble handling money and paying bills, repeating questions, taking longer to complete normal daily tasks, and personality and behavior changes.
People are often diagnosed in this stage. Memory loss and confusion worsen, and people begin to have problems recognizing family and friends. They may be unable to learn new things, carry out multi-step tasks such as getting dressed, or cope with new situations. In addition, people at this stage may have hallucinations, delusions, and paranoia and may behave impulsively.
People with severe Alzheimer’s cannot communicate and are completely dependent on others for their care. Near the end, the person may be in bed most or all of the time as body functions shut down. Certain drugs can temporarily slow some symptoms of Alzheimer’s from getting worse, but currently there are no treatments that stop the progression of the disease. For more information on Alzheimer’s disease, visit the Alzheimer’s and related Dementias Education and Referral (ADEAR) Center at www.alzheimers.gov.
Researchers have not found a single gene solely responsible for Alzheimer’s disease; rather, multiple genes are likely involved. One genetic risk factor— having one form of the apolipoprotein E (APOE) gene on chromosome 19—does increase a person’s risk for developing Alzheimer’s. People who inherit one copy of this APOE ε4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. (An allele is a variant form of a pair of genes that are located on a particular chromosome and control the same trait.) The APOE ε4 allele may also be associated with an earlier onset of memory loss and other symptoms. Researchers have found that this allele is associated with an increased number of amyloid plaques in the brain tissue of affected people.
Frontotemporal disorders are forms of dementia caused by a family of neurodegenerative brain diseases collectively called frontotemporal lobar degeneration. They primarily affect the frontal and temporal lobes of the brain, rather than the widespread shrinking and wasting away (atrophy) of brain tissue seen in Alzheimer’s disease. In these disorders, changes to nerve cells in the brain’s frontal lobes affect the ability to reason and make decisions, prioritize and multitask, act appropriately, and control movement. Changes to the temporal lobes affect memory and how people understand words, recognize objects, and recognize and respond to emotions. Some people decline rapidly over 2 to 3 years, while others show only minimal changes for many years. People can live with frontotemporal disorders for 2 to 10 years, sometimes longer, but it is difficult to predict the time course for an affected individual. The signs and symptoms may vary greatly among individuals as different parts of the brain are affected. No treatment that can cure or reverse frontotemporal disorders is currently available.
Clinically, FTD is classified into two main types of syndromes:
Other types of frontotemporal disorders include:
Lewy body dementia (LBD) is one of the most common causes of dementia after Alzheimer’s disease and vascular disease. It typically begins after age 50, but can occur earlier. It involves abnormal protein deposits called Lewy bodies, which are balloon-like structures that form inside nerve cells. The abnormal buildup of the protein alpha-synuclein and other proteins causes neurons to work less effectively and die. Initial symptoms may vary, but over time, people with these disorders develop similar cognitive, behavioral, physical, and sleep-related symptoms.
Lewy body dementia includes two related conditions—dementia with Lewy bodies and Parkinson’s disease dementia. In dementia with Lewy bodies, the cognitive symptoms are seen within a year of movement symptoms called parkinsonism (including tremor, difficulty with walking and posture, and rigid muscles). In Parkinson’s disease dementia, the cognitive symptoms develop more than a year after movement problems begin.
Vascular contributions to cognitive impairment and dementia (VCID) cause significant changes to memory, thinking, and behavior. Cognition and brain function can be significantly affected by the size, location, and number of brain injuries. Vascular dementia and vascular cognitive impairment arise as a result of risk factors that similarly increase the risk for cerebrovascular disease (stroke), including atrial fibrillation, hypertension, diabetes, and high cholesterol. Symptoms of VCID can begin suddenly and progress or subside during one’s lifetime. VCID can occur along with Alzheimer’s disease. Persons with VCID almost always have abnormalities in the brain on magnetic resonance imaging scans. These include evidence of prior strokes, often small and asymptomatic, as well as diffuse changes in the brain’s “white matter”—the connecting “wires” of the brain that are critical for relaying messages between brain regions. Microscopic brain examination shows thickening of blood vessel walls called arteriosclerosis and thinning or loss of components of the white matter.
Forms of VCID include:
The different forms of age-related dementia, as well as many age-related neurodegenerative diseases, are thought to be caused by changes in various proteins. These diseases are called proteinopathies because they involve the abnormal buildup of specific proteins in the brain. Mutations in genes that provide instructions for making these proteins have been found to cause dementia in families. However, in the vast majority of affected individuals, dementia is not inherited, and the cause is unknown. Alzheimer’s disease, frontotemporal disorders, and Lewy body dementia are proteinopathies.
In some dementias, changes in the protein tau cause it to form clumps inside nerve cells in the brain, which is believed to make the cells stop functioning properly and die. Disorders that are associated with the abnormal buildup of tau are called tauopathies.
In Alzheimer’s disease, the tau protein aggregates (accumulates into abnormal clumps) and becomes twisted and tangled, forming fibers— called neurofibrillary or tau tangles—inside neurons. Abnormal clumps (plaques) of another protein, called beta-amyloid, are prominent in spaces between brain cells. Both plaques and tangles are thought to contribute to reduced function and nerve-cell death in Alzheimer’s and are the hallmarks of the disease.
Beta-amyloid plaques are also seen in some forms of LBD, cerebral amyloid angiopathy, and Parkinson’s disease dementia. They are also common in elderly individuals who do not have dementia.
Some, but not all, forms of frontotemporal disorders are tauopathies. Other forms of these disorders are associated with the buildup of the protein TDP-43. A mutation in a gene called progranulin, and another in a gene called C9orf72, can cause frontotemporal disorders with accumulation of TDP-43 in nerve cells.
In other dementias and some brain disorders, the protein synuclein becomes misshapen and forms harmful clumps inside neurons in different brain regions. Disorders in which synuclein builds up inside neurons are called synucleinopathies. Changes in synuclein and/or its function are the basis of LBD and other disorders such as multiple system atrophy. Multiple system atrophy is a progressive neurodegenerative disorder characterized by a combination of symptoms that affect both the autonomic nervous system (the part of the nervous system that controls involuntary action such as blood pressure or digestion) and movement. These changes cause parkinsonism, a condition resembling Parkinson’s disease.
Many conditions that cause dementia-like symptoms can be halted or even reversed with the appropriate treatment.
Doctors have identified many other conditions that can cause dementia or dementia-like symptoms. The diseases have different symptoms that involve body and brain functions, and affect mental health and cognition.
Argyrophilic grain disease is a common, late-onset degenerative disease that affects brain regions involved in memory and emotion. It causes cognitive decline and changes in memory and behavior, with difficulty finding words. The disease’s signs and symptoms are indistinguishable from late-onset AD. Confirmation of the diagnosis can be made only at autopsy.
Creutzfeldt-Jakob disease is a rare brain disorder that is characterized by rapidly progressing dementia. Scientists found that infectious proteins called prions become misfolded and tend to clump together, causing the brain damage. Initial symptoms include impaired memory, judgment, and thinking, along with loss of muscle coordination and impaired vision. Some symptoms of CJD can be similar to symptoms of other progressive neurological disorders, such as Alzheimer’s disease.
Chronic traumatic encephalopathy (CTE) is caused by repeated traumatic brain injury (TBI) in some people who suffered multiple concussions. People with CTE may develop dementia, poor coordination, slurred speech, and other symptoms similar to those seen in Parkinson’s disease 20 years or more after the injury. Late-stage CTE is also characterized by brain atrophy and widespread deposits of tau in nerve cells. In some people, even just 5 to 10 years beyond the traumatic brain injury, behavioral and mood changes may occur. Dementia may not yet be present and the brain may not have started to shrink, but small deposits of tau are seen in specific brain regions at autopsy.
Huntington’s disease is an inherited, progressive brain disease that affects a person’s judgment, memory, ability to plan and organize, and other cognitive functions. Symptoms typically begin around age 30 or 40 years and include abnormal and uncontrollable movements called chorea, as well as problems with walking and lack of coordination. Cognitive problems worsen as the disease progresses, and problems controlling movement lead to complete loss of ability for self-care.
HIV-associated dementia (HAD) can occur in people who have human immunodeficiency virus, the virus that causes AIDS. HAD damages the brain’s white matter and leads to a type of dementia associated with memory problems, social withdrawal, and trouble concentrating. People with HAD may develop movement problems as well. The incidence of HAD has dropped dramatically with the availability of effective antiviral therapies for managing the underlying HIV infections.
Secondary dementias occur in people with disorders that damage brain tissue. Such disorders may include multiple sclerosis, meningitis, and encephalitis, as well as Wilson’s disease (in which excessive amounts of copper build up to cause brain damage). People with malignant brain tumors may develop dementia or dementia-like symptoms because of damage to their brain circuits or a buildup of pressure inside the skull.
The following risk factors may increase a person’s chance of developing one or more kinds of dementia. Some of these factors can be modified, while others cannot.
The National Academies of Sciences, Engineering, and Medicine recently released a report of the evidence on preventing dementia: www.ncbi.nlm.nih.gov/books/NBK436397.
To diagnose dementia, doctors first assess whether an individual has an underlying treatable condition such as abnormal thyroid function, vitamin deficiency, or normal pressure hydrocephalus that may relate to cognitive difficulties. Early detection of symptoms is important, as some causes can be treated. In many cases, the specific type of dementia may not be confirmed until after the person has died and the brain is examined.
An assessment generally includes:
Guidelines prepared by the National Institute on Aging and the Alzheimer’s Association focus on three stages of Alzheimer's disease: (1) dementia due to Alzheimer's, (2) mild cognitive impairment (MCI) due to Alzheimer's, and (3) preclinical (presymptomatic) Alzheimer's. (Presymptomatic identification is exclusively used as a research diagnosis at this point and has no relevance to routine clinical practice.) The guidelines also include biomarker tests used in studies to measure biological changes in the brain associated with Alzheimer’s disease and criteria for documenting and reporting Alzheimer’s-related changes observed during an autopsy.
There are currently no treatments to stop or slow dementia in neurodegenerative diseases. Some diseases that occur at the same time as dementia (such as diabetes and depression) can be treated. Other symptoms that may occur in dementia-like conditions can also be treated, although some symptoms may only respond to treatment for a period of time. A team of specialists—doctors, nurses, and speech, physical, and other therapists—familiar with these disorders can help guide patient care.
Medications are available to treat certain behavioral symptoms, as well as delusions, depression, muscle stiffness, and risk factors for vascular cognitive impairment such as high blood pressure. Always consult with a doctor, as some medications may make symptoms worse.
Alzheimer’s disease. Most drugs for dementia are used to treat symptoms in AD. One class of drugs, called cholinesterase inhibitors, can temporarily improve or stabilize memory and thinking skills in some people by increasing the activity of the cholinergic brain network—a subsystem in the brain that is highly involved with memory and learning. These drugs include donepezil, rivastigmine, and galantamine. The drug memantine is in another class of medications called NMDA receptor antagonists, which prevent declines in learning and memory. Memantine may be combined with a cholinesterase inhibitor for added benefits. In June 2021 the U.S. Food and Drug Administration approved the drug educanumab (Adulhelm) to reduce the building up harmful amyloid beta plaques.
Frontotemporal disorders. There are no medications approved to treat or prevent FTD and most other types of progressive dementia. Sedatives, antidepressants, and other drugs used to treat Parkinson’s and Alzheimer’s symptoms may help manage certain symptoms and behavioral problems associated with the disorders.
Dementia with Lewy bodies. Medicines available for managing DLB are aimed at relieving symptoms such as gait and balance disturbances, stiffness, hallucinations, and delusions. Studies suggest that the cholinesterase inhibitor drugs for Alzheimer’s disease may offer some benefit to people with DLB.
Parkinson’s disease dementia. Some studies suggest that the cholinesterase inhibitors used to treat people with AD might improve cognitive, behavioral, and psychotic symptoms in people with Parkinson’s disease dementia. Unfortunately, many of the medications used to treat the motor symptoms of PD worsen the cognitive problems. The U.S. Food and Drug Administration has approved rivastigmine (an Alzheimer’s drug) to treat cognitive symptoms in PDD.
Vascular contributions to cognitive impairment and dementia. This type of dementia is often managed with drugs to prevent strokes or reduce the risk of additional brain damage. Some studies suggest that drugs that improve memory in AD might benefit people with early vascular dementia. Treating the modifiable risk factors can help prevent additional stroke.
A team of therapists can help with maintaining physical movement, address speech and swallowing issues, and help people learn new ways to handle loss of skills with everyday tasks such as feeding oneself.
It is important to educate family, friends, and caregivers about a loved one’s medical issues. Also, in-person and online support groups available through many disease awareness and caregiver advocacy organizations can give families and other caregivers additional resources, as well as opportunities to share experiences and express concerns. (See Resources section at the end of this document).
The National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH), is the leading federal funder of research on nervous system disorders, including dementia. Another NIH Institute, the National Institute on Aging (NIA), is the leading federal funder of research on Alzheimer’s disease and Alzheimer’s disease related dementias. Together, these Institutes are world leaders in supporting research on the dementias, including Lewy body dementia, frontotemporal disorders, and vascular contributions to cognitive impairment and dementia.
Although scientists have some understanding of the dementias and the mechanisms involved, ongoing research may lead to new ways to understand the cause(s) of the disease, diagnose, treat, or perhaps prevent or block disease development.
The National Alzheimer’s Project Act (NAPA) is a coordinated national plan to attack Alzheimer’s disease (AD) and improve care and services. The Project calls for increased collaboration between scientists, the federal government, and public organizations while improving patient care. The NAPA National Plan to Address Alzheimer’s Disease is designed to expand research in Alzheimer’s disease and related dementias prevention and treatment and to move the most promising drugs from discovery into clinical trials. The National Plan also calls for increased Federal funding for AD research, as well as support for those affected by AD and their families, increased public awareness about AD, and improved data collection and analysis. These goals also apply to dementia with Lewy bodies as well as frontotemporal, mixed, and vascular dementias. The Plan’s overarching research goal is to “prevent or effectively treat Alzheimer’s disease by 2025.” For more information, see http://aspe.hhs.gov/national-alzheimers-project-act.
Accelerating Medicine Partnership® – Alzheimer’s Disease (AMP® -AD) is a multi-sector partnership among the NIH, 10 biopharmaceutical companies, and several nonprofit organizations to develop new clinically relevant therapeutics and biomarkers to confirm existing therapies. The goal is to speed up the process of bringing new medicines to people either with or at risk of AD. For more information, see https://www.nia.nih.gov/research/amp-ad.
ACCELERATING MEDICINES PARTNERSHIP and AMP are registered service marks of the U.S. Department of Health and Human Services.
M2OVE-AD (Molecular Mechanisms of the Vascular Etiology of Alzheimer’s Disease) allows scientists from diverse fields to work collaboratively to understand the complex molecular mechanisms by which vascular risk factors influence AD. The work also will identify new targets for treatment and prevention. M2OVE-AD builds on the open-science approach and the big data infrastructure established by the AMP-AD.
The Tau Center Without Walls program is designed to increase collaboration and sharing of data and resources among researchers to better understand the protein tau and its involvement in such disorders as frontotemporal degeneration (FTD). These efforts may lead to advances in prevention, diagnosis, or treatment of tau toxicity associated with FTD, and contribute to tool development that can be applied in FTD clinical trials and other tau-related disorders.
The Dementia with Lewy Body Biomarkers Consortium is designed to expand the collection of clinical data and biological specimens in the NINDS Parkinson’s Disease Biomarkers Program to include data from people with Lewy body dementias. Standardized research and data collection and reporting systems will make it easier for researchers to share and confirm their research. For more information, see https://pdbp.ninds.nih.gov/dementia_with_lewy_bodies_consortium_U01.
Researchers in The Small Vessel Vascular Contributions to Cognitive Impairment and Dementia (VCID) Biomarkers Program hope to develop biomarkers of key vascular processes related to VCID in Alzheimer’s disease. Identifying biomarkers may improve the efficiency and outcome of trials designed to test drug effectiveness and safety in humans, and speed the development of therapies for the dementias.
Clinical studies. Clinical studies offer an opportunity to help researchers find better ways to safely detect, treat, or prevent dementias. Various NIH Institutes support clinical studies on AD and related dementias at the NIH research campus in Bethesda, Maryland, and at medical research centers throughout the U.S. For information about participating in clinical studies for AD, related dementias, and other disorders, visit “NIH Clinical Research Trials and You” at www.nih.gov/health/clinicaltrials. For a list of AD and related dementias clinical trials and studies, see www.nia.nih.gov/alzheimers/clinical-trials. For a comprehensive list of all trials, go to www.clinicaltrials.gov and type in the name of the dementia, such as “Lewy Body dementia” or “vascular dementia.”
Biomarkers. Several research projects hope to identify biomarkers (measurable biological signs that may indicate disease risk and progression or confirm diagnosis) for the dementias. Such biomarkers could be detected through imaging or even blood tests. Research projects include the study of possible biomarkers to predict cognitive decline in people with Parkinson’s disease, the Alzheimer’s Biomarkers Consortium in Down Syndrome (many people with Down syndrome have Alzheimer’s-related brain changes in their 30s that can lead to dementia in their 50s and 60s), and genetic and biomarker studies that may lead to promising treatments for FTD. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a longitudinal study to validate the use of biomarkers for Alzheimer’s disease clinical trials and diagnosis (see www.adni-info.org).
Drugs and compounds. A number of drugs and compounds that might slow the progression of AD and other dementias are in various stages of testing. A NINDS study found that tau antisense oligonucleotides—compounds that are genetically engineered to block a cell’s assembly line production of the toxic form of the protein tau—could prevent and reverse some of the brain injury in animal models of the disease. NIH-supported prevention trials are testing promising drugs that target amyloid proteins that form plaques in the brain. Other NIH studies include the use of drugs being developed to treat autism spectrum disorders to see if they can improve cognitive functions in people with age-related cognitive decline.
Exercise. Physical activity can benefit mental well-being and improve daily functioning and quality of life in people with dementia. Researchers are assessing the combined approach of aerobic and cognitive exercise to see if it can delay or slow the progression of Alzheimer’s disease in at-risk older adults. Other research is assessing the benefit of exercise to delay mild cognitive impairment in older individuals, and to improve brain function in older adults who may be at risk for developing AD.
Genetics. NIH scientists continue to look for new genes that may be responsible for the development of AD and other forms of dementia. One approach is using genome-wide association studies which can rapidly scan the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Identifying new genetic associations for neurodegenerative diseases may lead to better strategies to detect, treat, and prevent the dementias.
Imaging. Clinical imaging may help researchers better understand changes in the brains of people with dementia, as well as help diagnose these disorders. For example, research hopes to enhance brain imaging techniques to make it possible to detect, and therefore try to stop, the earliest changes in the protective blood-brain barrier that may contribute to vascular contributions to cognitive impairment and dementia. The Alzheimer’s Disease Neuroimaging Initiative has identified and developed imaging techniques and biomarker measures in blood and cerebrospinal fluid being used in research to track changes in the living brains of older people who are cognitively normal, have mild cognitive impairment, or have mild Alzheimer’s disease.
International efforts. The International Alzheimer’s Disease Research Portfolio (IADRP) helps individuals learn about both AD research and research into Alzheimer’s disease-related dementias at public and private organizations in the U.S. and abroad. It also helps organizations leverage resources and avoid duplication of effort. The Common Alzheimer’s Disease Research Ontology—a classification system that allows organizations to integrate and compare research portfolios—was developed by NIA, NIH, and the Alzheimer’s Association. For more information about IADRP, see https://iadrp.nia.nih.gov.
Natural history studies. Studying groups of people over time may lead to ways to identify those at risk of developing dementia or cognitive impairment. Three NIH-funded research teams, for example, are conducting longitudinal studies of individuals in which frontotemporal disorders run in families and appear on their own (sporadic) to understand the progression of FTD both before and after symptom onset; identify genes; discover biomarkers for diagnosis, progression, and prognosis; and establish a clinical research consortium to support FTD therapy development.
Proteins. A number of proteins—including tau, alpha-synuclein, TDP-43, and amyloid-beta—are involved with various cellular processes. When there is a change in the genes that direct the production or rate of clearance (degradation) of these proteins, the proteins can build into abnormal amounts and form abnormal clumps that damage nerve cells in the brain, causing dementia and other symptoms such as motor function disorders. NIH-funded research projects are aimed at better understanding the toxic effects of protein buildup and how it is related to the development of dementia. For example, a number of studies are targeting the buildup of amyloid, which forms plaques that are characteristic in Alzheimer’s disease. Other research hopes to better understand how proteins misfold and become harmful in frontotemporal disorders and Lewy body dementia.
Stem cells. Stem cells are unique in that they have the potential to develop into many different cell types in the body, including brain cells. Scientists are exploring various types of cells, including stem cells, to discover nerve cell mechanisms that lead to the onset and progression of AD and other forms of dementia. For example, scientists converted human skin cells into a model of human neurons. Such neurons, when created from individuals with familial forms of Alzheimer's, show biochemical changes that typify the disease. Researchers are investigating the mechanism by which human Alzheimer neurons develop cellular and molecular defects in protein production and degradation.
Additional NIH research projects. More information about dementias research supported by NIA, NINDS, and other NIH Institutes and Centers can be found using NIH RePORTER (www.projectreporter.nih.gov), a searchable database of current and past research projects supported by NIH and other Federal agencies. RePORTER also includes links to publications and resources from these projects.
Currently, there are no cures for the common dementias caused by progressive neurodegeneration, including AD, frontotemporal disorders, and Lewy body dementia. There is some evidence suggesting that controlling vascular risk factors such as high blood pressure may reduce the risk of developing dementia decades later. Some symptoms of dementia and conditions that cause dementia or have dementia-like symptoms are treatable. A better understanding of dementia disorders, as well as their diagnosis and treatment, will make it possible for affected individuals and their caretakers to live their lives more fully and meet daily challenges. NIH, primarily through research activities funded by NIA and NINDS, continues to improve diagnosis, design therapeutic approaches to dementias, and create tools and resources to help speed the development of treatments that can be used in practice. These discoveries may eventually lead to ways to slow disease progression or even cure and prevent the dementias.
For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:
P.O. Box 5801
Bethesda, MD 20824
Information also is available from the following organizations:
National Institute on Aging
Alzheimer's and related Dementias Education and Referral (ADEAR) Center
National Institute on Aging
P.O. Box 8250
Silver Spring, MD 20907-8250
Association for Frontotemporal Degeneration (AFTD)
Radnor Station Building #2 Suite 320
290 King of Prussia Road
Radnor, PA 19087
Tel: 267-514-7221; 866-507-7222
The Bluefield Project to Cure Frontotemporal Dementia
637 Carolina Street
San Francisco, CA 94107
John Douglas French Alzheimer's Foundation
11620 Wilshire Blvd.
Los Angeles, CA 90025
National Institute of Mental Health (NIMH)
National Institutes of Health, DHHS
6001 Executive Blvd. Rm. 8184, MSC 9663
Bethesda, MD 20892-9663
Tel: 301-443-4513; 866-415-8051; 301-443-8431 (TTY)
alpha-synuclein—the major protein present in abnormal clumps called Lewy bodies, which are seen in the brains of people with Parkinson’s disease and some dementias. Disorders in which alpha-synuclein accumulates inside nerve cells are called synucleinopathies.
Alzheimer’s disease—the most common cause of dementia. Nearly all brain functions, including memory, movement, language, judgment, and behavior, are eventually affected. Alzheimer’s disease is defined by observing high levels of amyloid-containing plaques and tau protein-containing neurofibrillary tangles in the brain.
amyloid—a protein with beta-pleated sheets, which aggregate to form the characteristic clumps (called plaques) that appear in the brains of people with Alzheimer’s disease. Other proteins that form aggregates are tau proteins also seen in Alzheimer’s disease, and alpha-synuclein present in dementia with Lewy Body and in Parkinson’s Disease.
biomarkers—measurable biological signs in the living body that may indicate risk or progression of a disease and improve diagnosis
corticobasal degeneration—a progressive disorder characterized by abnormal buildup of the protein tau, nerve cell loss, and atrophy in multiple areas of the brain
dementia—a term for a condition that significantly interferes with daily life because of impaired thinking and memory
Dementia with Lewy bodies—a type of Lewy body dementia that is a form of progressive dementia
frontotemporal disorders—a group of dementias characterized by degeneration of nerve cells, especially those in the frontal and temporal lobes of the brain
Lewy body dementia—a progressive dementia characterized by the presence of abnormal structures called Lewy bodies in the brain
mild cognitive impairment—a stage between normal cognitive changes that may occur with age and the more serious symptoms that indicate dementia
mixed dementia—dementia in which one form of dementia and another condition or dementia cause damage to the brain; for example, Alzheimer’s disease and small vessel disease or vascular dementia
multi-infarct dementia—a type of vascular cognitive impairment and dementia caused by numerous small strokes in the brain
neurodegeneration—the progressive loss of nerve cell structure or function
neurofibrillary tangles—bundles of twisted filaments largely made up of a protein called tau found in nerve cells in the brains of people with Alzheimer’s disease and other types of dementia such as FTD.
Parkinson’s disease dementia—a secondary dementia that sometimes occurs in people with advanced Parkinson’s disease. Many people with Parkinson’s have the amyloid plaques and neurofibrillary tangles found in Alzheimer’s disease, but it is not clear if the diseases are linked.
plaques—abnormal clumps of amyloid protein that are found in large numbers in the brains of persons with Alzheimer’s disease
tau—a protein that helps the functioning of microtubules, which are part of the cell’s structural support and help deliver substances throughout the cell. In several dementia disorders, tau twists into filaments that become tangles. Disorders associated with an accumulation of tau, such as frontotemporal dementia, are called tauopathies.
vascular dementia—a type of dementia caused by brain damage from cerebrovascular or cardiovascular problems, usually strokes
"Dementia: Hope Through Research", NINDS, Publication date December 2017.
NIH Publication No. 17-NS-2252
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The Dementias: Hope Through Research was jointly produced by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging, both part of the National Institutes of Health.
NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.