The Dementias: Hope Through Research
Researchers are looking for new dementia treatments.
In 2012, the President announced the National Plan to Address Alzheimer’s Disease, a national effort to expand research in Alzheimer’s and related dementias prevention and treatment and to move the most promising drugs from discovery into clinical trials. The Plan aims to prevent and effectively treat Alzheimer’s and related dementias by 2025. Its foundation is the 2011 National Alzheimer’s Project Act (NAPA), which was developed to create and maintain a national strategy to overcome the disease. The National Plan calls for increased federal funding for AD research, support for those affected by AD and their families, increased public awareness about AD, and improved data collection and analysis to better understand the impact of AD on people with the disease, families, and the health and long-term care systems. These goals also apply to AD-related dementias, including dementia with Lewy bodies as well as frontotemporal, mixed (characteristics of more than one type of dementia occur simultaneously), and vascular dementias.
The National Institute of Neurological Disorders and Stroke (NINDS), a component of NIH, is the leading federal funder of research on nervous system disorders. Another NIH Institute, the National Institute on Aging (NIA), is the leading federal funder of research on AD. Together, these Institutes are world leaders in supporting research on the dementias, including Lewy body dementia, frontotemporal disorders, and vascular dementia.
Although scientists have some understanding of these dementias and the mechanisms involved, ongoing research may lead to new ways to diagnose, treat, or perhaps prevent or block disease development. Current areas of research include:
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, MD, 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. For a list of AD clinical trials and studies, see www.nia.nih.gov/alzheimers/clinical-trials. For a comprehensive list of all trials, go to www.clinicaltrials.gov.
Drugs. A number of agents that might slow the progression of AD and other dementias are in various stages of testing.
The NIA-supported Alzheimer’s Disease Cooperative Study (ADCS) is a consortium of academic medical centers and clinics set up by NIH in 1991 to collaborate on the development of promising Alzheimer’s treatments and diagnostic tools.
In the latest round of studies, the ADCS will test drug and exercise interventions in people in the early stages of the disease, examine a medication to reduce agitation in people with Alzheimer’s dementia, and test a cutting-edge approach to speed testing of drugs in clinical trials. Because Alzheimer’s-related brain changes begin years before symptoms appear, the A4 (Anti-amyloid Treatment in Asymptomatic Alzheimer’s Disease) trial is testing a promising therapy in the early stages of the disorder. This secondary prevention trial will test an amyloid-clearing drug in the symptom-free stage of the disease in 1,000 cognitively healthy older volunteers whose brain scans show abnormal levels of amyloid accumulation. Another of the newly funded ADCS drug trials is the Prazosin for Treating Agitation trial, which will test the use of the generic drug prazosin as a treatment for agitation that may also be well-tolerated in frail and elderly people.
Studies will show if physical fitness begets cognitive fitness.
Exercise. Researchers are assessing the effectiveness of a supervised aerobic exercise program to enhance general cognition in adults with age-related cognitive decline. They predict that greater cognitive gains will be made by individuals with more fitness gains. Another study will determine if exercise prevents memory loss from getting worse, and if it improves daily functioning and attitudes of those with probable AD. Researchers also hope to gain a better understanding of the effects of exercise and cognitive training on improving brain function in healthy older adults who may be at risk for developing AD.
Genetics. Several genes—most notably ApoE and the gene for tau (MAPT)—have been implicated in AD and other forms of dementia. Many dementia-related disorders share genetic and other characteristics of AD. Some families share a particular genetic mutation that causes dementia. Researchers are using samples of a person’s genetic material, or genome, to identify genes that may be responsible for the development of dementia and AD. For example, NIH-funded researchers recently examined ApoE’s role in the development of late-onset AD and found that one of the three forms of the ApoE gene triggers an inflammatory reaction and damages the blood vessels that feed the brain. Other researchers have identified a gene variant of TREM2 that is involved with a form of frontotemporal dementia that runs in families. Additional research may identify novel genes involved with FTD and other neurodegenerative diseases, perhaps leading to therapeutic approaches where delivery of normal genes would improve or restore normal brain function.
Researchers use brain scans to study dementia.
Imaging. Clinical imaging may help researchers better understand changes in the brains of people with dementia, as well as help diagnose these disorders. Magnetic resonance imaging may reveal structural and functional differences in the brains of individuals with Parkinson’s disease dementia and AD and identify small vessel disease. PET scanning uses ligands—radioactive molecules that bind to proteins to show chemical functions of tissues and organs in the body—to help produce images of brain activity. Scientists funded by NIA are testing new PET ligands that bind to beta-amyloid for early detection of Alzheimer’s-type pathology and cognitive decline. Studies of PET ligands that bind to aggregates of tau are ongoing in people with very early-stage AD.
Watch a video to learn more about Alzheimer’s disease biomarkers:
International efforts. The International Alzheimer’s Disease Research Portfolio (IADRP) helps individuals learn about AD research 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.
Proteins. One feature that several major dementias have in common is an excess in the brain of certain proteins or protein fragments that have taken abnormal forms thought to be toxic to brain cells. NIH-funded research projects are aimed at better understanding the toxic effects of protein buildup and how it is related to the development of AD and related dementias. Some of these protein abnormalities can be detected in cerebrospinal fluid.
For example, an abnormally high accumulation of beta-amyloid protein in the brain is a hallmark of AD. NINDS-funded researchers are determining which neural pathways are affected by beta-amyloid and contribute to the development of Alzheimer’s pathology and symptoms. NINDS funding also led to a genetically engineered rat model of AD that has the full array of brain changes associated with the human disease and may be used to better define causes and effects of AD related to beta-amyloid accumulation. Funding also was provided by NIA, the National Institute of Mental Health (also part of NIH), and other organizations.
In FTD, AD, and other neurodegenerative diseases, the protein tau collects in abnormal tangled masses of filaments that disrupt nerve signaling, cause cell death, and impair cognition. NINDS-funded researchers are determining whether specific forms of tau interfere with nerve cell signaling and decrease memory function. Others are studying how tau pathology spreads from cell to cell. Tau-related investigations are aimed at identifying common mechanisms of FTD, as well as biomarkers (signs that may indicate disease risk and progression, and improve diagnosis) that will speed the development of novel therapeutics for PDD and other forms of dementia.
Similarly, the abnormal accumulation of the protein alpha-synuclein is a hallmark of Parkinson’s disease and Lewy body dementia. Scientists hope to identify what causes alpha-synuclein to form abnormal aggregates and become toxic to nerve cells, and to understand why the aggregation is an age-related phenomenon in Parkinson’s disease and other synuclein-related disorders.
Sleep. The sleep and wakefulness cycle plays an integral, but not well understood, role in many dementias, including dementia with Lewy bodies, AD, prion dementias, and PDD. Sleep studies in individuals during periods of excessive daytime sleepiness and nocturnal sleep can help determine if fluctuations in mental status among people with DLB are related to excessive daytime sleepiness. Sleep studies also can assess whether declining cognition is predicted by sleep-related and neurobehavioral markers in parkinsonism.
Stem cells. Scientists are exploring various types of cells, including stem cells, to discover nerve cell mechanisms that lead to the initiation and progression of AD and other forms of dementia. Significant research efforts have focused on induced pluripotent stem cells (iPSC), which can be “reprogrammed” from skin cells into any cell type in the body, including nerve cells. NINDS funds three research consortia to develop well-characterized iPSC for amyotrophic lateral sclerosis (ALS), Huntington’s disease, and Parkinson’s disease. These cells can then be used by the research community to study the effects of mutant genes and misfolded proteins on nerve cell function and health, as well as to test potential drugs and therapies for AD and related dementias.
Scientists study how disease that underlies dementia starts and progresses.
Publication Date: September 2013
Page Last Updated: November 21, 2014