Research Article On Alzheimer's Disease
In the history of medicine, one means to progress is when we make the decision that our assumptions and definitions of disease are no longer consistent with the scientific evidence, and no longer serve our health care needs. The arc of scientific progress is now requiring a change in how we diagnose Alzheimer's disease. Both the National Institute on Aging—Alzheimer's Association (NIA-AA) 2011 workgroup and the International Work Group (IWG) have proposed guidelines that use detectable measures of biological changes in the brain, commonly known as biological markers, or biomarkers, as part of the diagnosis. This Special Report examines how the development and validation of Alzheimer's disease biomarkers—including those detectable in the blood or cerebral spinal fluid, or through neuroimaging—is a top research priority. This has the potential to markedly change how we diagnose Alzheimer's disease and, as a result, how we count the number of people with this disease. As research advances a biomarker-based method for diagnosis and treatment at the earliest stages of Alzheimer's disease, we envision a future in which Alzheimer's disease is placed in the same category as other chronic diseases, such as cardiovascular disease or diabetes, which can be readily identified with biomarkers and treated before irrevocable disability occurs. A biomarker, or biological marker, is a measurable indicator of some biological state or condition in the human body.
Clinicians use biomarkers to diagnose the presence or absence of disease, assess the risk of developing a disease, or understand how a patient has responded to a treatment. For example, a high blood glucose level (blood sugar) may indicate the presence of diabetes, and lowering that level can indicate the success of a prescribed diet or medication.Researchers are investigating several promising biomarkers for Alzheimer's disease.
These include, but are not limited to, the amount of accumulation of the proteins beta-amyloid and tau in the brain. These proteins can be measured using brain imaging or the levels in cerebrospinal fluid.
Another kind of biomarker is changes in brain size and activity.Identifying and then validating biomarkers for Alzheimer's is critical. They will facilitate early diagnosis and treatment.
Many researchers believe that early intervention—either at the mild cognitive impairment (MCI) stage or even before symptoms appear—offers the best chance of slowing or stopping the progression of Alzheimer's disease and therefore the best chance of preserving brain function.Biomarkers also have an important role in the discovery of treatments. They enable researchers to identify which individuals to enroll in clinical trials to test new therapies. Biomarkers allow researchers to enroll those individuals with the brain changes that treatments target. (It's important to note that the most effective biomarker test or combination of tests may differ depending on the stage of the disease and other factors.) Biomarkers also allow researchers to monitor the effects of these treatments. The more a change in a biomarker maps onto the health of the patient, the better that biomarker is in assessment of whether a treatment is effective.Research on new strategies for earlier diagnosis, including ongoing efforts to identify and validate biomarkers for Alzheimer's disease, is among the most active areas in Alzheimer's science. Has, since 2011, charted a national plan to address Alzheimer's disease. The first of the plan's five goals is to effectively treat and prevent the disease by 2025 x 22 U.S.
Department of Health and Human Services. National Plan to Address Alzheimer's Disease 2012. Available at:. Accessed January 18, 2017. 22. Researchers and those who translate research into clinical practice have reached a consensus. A core strategy to achieve this goal relies on studies testing drugs in persons who have biomarker confirmation of the presence of Alzheimer's disease x 23 Kozauer, N.
Research Article On Alzheimer's Disease Pictures
Regulatory innovation and drug development for early-stage Alzheimer's disease. N Engl J Med.
2013;368: 1169–1171 23. Studies such as the A4 Study discussed above, as well as trials in persons with Alzheimer's disease dementia, are enrolling persons who have these biomarkers x 24 Honig LS, Aisen PS, Carrillo MC, Vellas B, Seimers ER. Expedition 3: A Phase 3 Trial of Solanezumab in Mild Dementia Due to Alzheimer's Disease. Available at:. Accessed December 22, 2016., x 25 Sevigny, J., Suhy, J., Chiao, P., Chen, T., Klein, G., Purcell, D. Amyloid PET screening for enrichment of early-stage Alzheimer disease clinical trials: experience in a phase 1b clinical trial. Alzheimer Dis Assoc Disord.
2016;30: 1–7.This strategy aligns with approaches taken with other common diseases of aging, such as cardiovascular disease. Clinicians use measures of biological change, such as elevated levels of blood pressure or cholesterol, to diagnose and treat individuals. Their goal is to prevent the person from suffering another heart attack or worsening heart failure, or to prevent these problems from happening in the first place. Someday, clinicians may have a similar strategy to diagnose and treat Alzheimer's disease. They may use biological measures (biomarker-based) to diagnose and then prescribe treatments to these persons, treatments that trials have shown to slow cognitive and functional decline or even prevent the onset of symptoms of dementia.Alzheimer's-related brain changes—amyloid plaques and tau tangles among others—contribute to the cognitive impairment observed in dementia due to Alzheimer's x 26 Schneider, J.A., Arvanitakis, Z., Bang, W., and Bennett, D.A.
Mixed brain pathologies account for most dementia cases in community-dwelling older persons. 2007;69: 2197–2204, x 27 Schneider, J.A., Arvanitakis, Z., Leurgans, S.E., and Bennett, D.A.
The neuropathology of probable Alzheimer disease and mild cognitive impairment. 2009;66: 200–208, x 28 Mormino, E.C., Betensky, R.A., Hedden, T., Schultz, A.P., Amariglio, R.E., Rentz, D.M. Synergistic effect of beta-amyloid and neurodegeneration on cognitive decline in clinically normal individuals.
2014;71: 1379–1385, x 29 Sperling, R.A., Johnson, K.A., Doraiswamy, P.M., Reiman, E.M., Fleisher, A.S., Sabbagh, M.N. Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiol Aging. 2013;34: 822–831. A clinically effective intervention that targets these brain changes will help to validate the disease as a continuum that begins before cognitive decline. This confirmation will change how we identify (and therefore estimate) individuals with Alzheimer's disease. It will alter the estimated prevalence and incidence of the disease, just as the treatment of vascular disease has altered the estimated prevalence of dementia among individuals with primarily vascular lesions x 30 Langa, K.M., Larson, E.B., Crimmins, E.M., Faul, J.D., Levine, D.A., Kabeto, M.U.
A comparison of the prevalence of dementia in the United States in 2000 and 2012. JAMA Intern Med.
2017;177: 51–58, x 31 Sposato, L.A., Kapral, M.K., Fang, J., Gill, S.S., Hackam, D.G., Cipriano, L.E. Declining Incidence of Stroke and Dementia: Coincidence or Prevention Opportunity? 2015;72: 1529–1531. As these events unfold, they compel us to plan for a future when Alzheimer's disease is defined using biomarkers alone, not symptoms.
(See sidebar: “Determining the incidence and prevalence of Alzheimer's disease.”). Today, we understand that Alzheimer's disease exists as a continuum beginning with a phase that may only be detectable through biomarkers and ending with the dementia stage.
In the future, a biomarker-based diagnosis of Alzheimer's disease will impact the estimates of incidence and prevalence of Alzheimer's. It will add a population of individuals that currently is not included in estimates (people with Alzheimer's biomarkers but no dementia) and remove a population that currently is included (people with dementia but no Alzheimer's biomarkers).The Alzheimer's Association 2017 Alzheimer's Disease Facts and Figures (DOI: ) reports the prevalence and incidence of Alzheimer's in the U.S.
Among individuals age 65 and older, the prevalence in 2017 is estimated to be 5.3 million (one in 10 people age 65 and older, or 10 percent, have Alzheimer's dementia), and 480,000 people age 65 or older will develop Alzheimer's dementia in the U.S. In 2017.Epidemiologists, demographers, and biostatisticians will use these prevalence and incidence estimates to calculate other statistics, such as the numbers of people providing care and support for someone with the disease, the costs of care, and mortality. Even with scientific progress, a common question from the public has been, “What's the difference between Alzheimer's disease and dementia?” The NINCDS-ADRDA diagnostic criteria of 1984 aimed to help answer that question x 3 McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., and Stadlan, E.M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. 1984;34: 939–944 3. Alzheimer's disease is the most frequent cause of the dementia syndrome.As dementia science has progressed, biomarker-based data have advanced our understanding of who has Alzheimer's disease as well as contributed to a more accurate clinical diagnosis of who has dementia due to Alzheimer's. Biomarker-based clinical criteria and future clinical trial data will continue to change our understanding of who has Alzheimer's disease, as improved diagnostic techniques will provide earlier identification of cognitive impairment, and of the brain changes that lead to it.As with cardiovascular disease, we must care not just about those who have had a disease-manifesting event, such as a heart attack, but everyone who has cardiovascular disease-related biological changes that precede the heart attack.
All of these individuals represent the societal burden of cardiovascular disease. Similarly, although we have known for years about the occurrence of dementia due to Alzheimer's, as a result of the recent use of biomarkers in studies, we have learned that a proportion of people previously thought to have cognitive impairment caused by Alzheimer's disease lack those biomarkers. The diagnosis of Alzheimer's disease will come to include the full spectrum of persons with Alzheimer's biomarkers, those who are symptomatic—with either dementia or MCI—and those who are still asymptomatic but have preclinical Alzheimer's disease. All individuals with biomarkers of Alzheimer's disease, including those with and without dementia symptoms, will represent the full disease burden.Additional research and development of guidelines for the future use of biomarkers is urgently needed to optimize therapeutic strategies for this potentially much larger population of people with Alzheimer's disease. Successful validation of biomarkers will bring our definition of Alzheimer's disease in line with the remarkable advances we have seen in Alzheimer's research over the past decade. This latest research is now allowing us to envision a future in which Alzheimer's is no longer a disease leading to irrevocable cognitive and functional decline and death, but rather a chronic condition like cardiovascular disease, AIDS, or some cancers that can often be managed with early intervention.