Prevention Requires A Global Solution
Alzheimer disease (AD) is the most common dementia in the elderly and is a growing epidemic across the globe. Although the risks associated with developing AD are numerous, the greatest risk factor by far is aging. The age-specific risk of AD dramatically increases as individuals get older; findings from the Framingham study in the early 1990s showed that the incidence doubles every five years up to the ages of 89 years. Age-dependent increases have been seen in other studies. Unsurprisingly therefore, with global reductions in fertility and extended life expectancy, the number of patients with AD is expected to increase as populations age. In the United States, it is estimated that approximately 5.3 million people had AD in 2015; 5.1 million people being 65 years and older and approximately 200,000 people under the age of 65 years with early onset AD (EOAD). It is estimated that the number of new cases of AD and other forms of dementia will at least double by 2050 and substantially increase the socioeconomic burden worldwide.
In 2017, 16.1 million family caregivers in the United States provided an estimated 18.4 billion hours of unpaid care in for people with Alzheimer’s disease and other dementia. A new report from shows that the U.S. has vastly underestimated the public costs and consequences of the Alzheimer’s epidemic, and major social trends have direct and adverse implications for our capacity to cope with the Alzheimer’s epidemic in the years ahead.
Alzheimer’s disease is the fastest-growing cause of death in the world;
Alzheimer’s disease is the most feared disease in the U.S.; and
Alzheimer’s disproportionately impacts women and communities of color.
In 2010, it was estimated that dementia afflicted 35.6 million people worldwide, many of which will have AD, with the projection that this figure will double every twenty years. The incidence of AD is generally lower in many less economically developed countries than in North America and Europe, however, sharp rises in prevalence have been predicted and seen in China, India and Latin America.
The effect of this increasing dementia has obvious socioeconomic consequences for each country affected, through costs of hospital care and also of caregivers. In the USA, the total payments were estimated at $226 billion of which Medicare and Medicaid provided 68%, while out-of-pocket expenses for patients and their families were expected to be $44 billion.
The actual number of individuals with active disease are gross underestimates because they are based on approximations of diagnosed symptomatic patients and largely ignores the vast number of individuals who are preclinical, in whom the disease process is active but asymptomatic. This long pre-clinical phase of AD is characterized by progressive neuronal loss, the formation of neurofibrillary tangles (NFT) and the deposition of amyloid plaques within the brain. Although the exact pathogenesis of AD is debated, the prevailing hypothesis is that the neurodegeneration is the result of the amyloid cascade, in which aberrant digestion and processing of the amyloid precursor protein (APP) results in the accumulation of neurotoxic Aβ oligomeric proteins. These proteins aggregate to form the insoluble amyloid plaques that are seen at microscopic examination of autopsy brains of AD patients.
A large body of evidence suggests that cardiovascular disease increases the risk of dementia.
Studies that have investigated patients with clinical and subclinical cardiovascular disease have poorer cognitive function than those without. Cortical ischemic changes can increase the risk of dementia. However, studying the role of cardiovascular disease and AD is complicated by several issues, notably that extensive cardiovascular disease and dementia may preclude from a clinical diagnosis of AD and may instead favor a diagnosis of multi-infarct dementia.
Studies have shown mixed results with regard to the influence of hypertension and this is in part due to differences in study design. Observational studies however have generally shown that increased hypertension are associated with cognitive decline and an increased likelihood of developing AD, possibly through blood vessel injury, protein extravasation, neuronal injury and subsequent Aβ accumulation.
One of the most concerning developments over the past few years has been the accumulation of evidence that suggests infectivity of amyloid in a prion-like fashion. In a recent case series of iatrogenic CJD, a proportion of patients who received homogenized human pituitaries for growth hormone replacement were found to have significant cerebral amyloid angiopathy at autopsy, to an extent that was inconsistent with age. Given that pituitaries may have amyloid deposits, there is the possibility that amyloid could seed through peripheral injection with proteopathic spread over subsequent decades. The proteopathic spread of amyloid in the brain has been demonstrated in numerous animal models and in human AD pathological staging.
The main fear that stem from these findings is that iatrogenic infection may occur from re-used surgical instruments, since amyloid is difficult to remove from metal devices. Further research is needed in this area in order to gauge the significance of these findings on amyloid infectivity.
The research community believes it will be possible to prevent or control Alzheimer’s within the next 10 years with adequate research funding and other reforms to accelerate the drug pipeline. Federal research funding is a fraction of that of other major diseases.
More than $250 billion is spent annually in out-of-pocket healthcare for Alzheimer’s, which is more than 179 times the amount spent on finding a cure. For every dollar the federal government spends today on the costs of Alzheimer’s care, it invests less than a penny in research to find a cure.
Official mortality figures may have substantially underreported deaths due to Alzheimer’s disease in 2010 show two recent studies supported in part by NIA. Underreporting of Alzheimer’s as a cause of death on death certificates is a well-known phenomenon. Some people with the disease never receive a diagnosis. Many others have dementia-related conditions, such as aspiration pneumonia, listed as the primary cause of death while the underlying cause, Alzheimer’s, is never reported.
When a person dies, the cause or causes of death are listed on death certificates, typically by a physician, and filed with the state’s Bureau of Vital Statistics. This information is then forwarded to the National Center for Health Statistics of the Centers for Disease Control and Prevention (CDC), which compiles and reports the totals each year as the official U.S. mortality figures and leading causes of death. The CDC’s tally of 83,494 Alzheimer’s deaths in 2010, based on death certificates, ranks the disease as the sixth leading cause of death.
Two groups of investigators at Rush University, Chicago, wanted to examine this phenomenon to gain a clearer picture of the full burden of Alzheimer’s disease now and in the decades to come. While their estimates of deaths due to Alzheimer’s in 2010 vary slightly, both groups determined that Alzheimer’s-related mortality rates were several times higher than the official figure.
In one study, the researchers combined data from the Chicago Health and Aging Project (CHAP) with U.S. census data to estimate the number of deaths of older Americans with Alzheimer’s (Weuve et al., 2014). In a random sample of 1,913 CHAP participants age 65 and older, 990 people died over the course of 6 years. Data from this sample were used to calculate national Alzheimer’s mortality rates.
These findings, reported in the March 2014 issue of Alzheimer’s and Dementia, showed that an estimated 600,000 people age 65 and older with Alzheimer’s died in 2010. The researchers estimate that this number will rise to 900,000 in 2030 and to 1.6 million by 2050. This is an increase from 32 percent of deaths in people age 65 and older attributed to Alzheimer’s in 2010 to an estimated 43 percent in this population in 2050.
The second study, published online on March 5, 2014, in Neurology, found that the number of deaths due to Alzheimer’s disease in people 75 and older could be six times higher than the official count (James et al., 2014). Researchers’ estimate of 503,400 deaths due to Alzheimer’s in 2010 among people in that age group would have made the disease the third leading cause of death in 2010, behind heart disease and cancer.
Researchers followed 2,566 participants in the ongoing Religious Orders Study and the Rush Memory and Aging Study for 8 years. All participants, age 65 and older, were cognitively normal when they entered the studies. Over the course of the research, 22 percent of the volunteers developed Alzheimer’s dementia. About 72 percent of the people with Alzheimer’s disease died during that time frame, compared with 34 percent of those who remained symptom-free. Based on autopsy findings, the researchers concluded that death certificates do not reflect the large number of Alzheimer’s-related deaths.
The first person cured of Alzheimer’s will be in a clinical trial. We must speed up clinical trials and ensure that participants reflect the diversity of those with Alzheimer’s disease.
Important clinical trials that focus on potential prevention and treatment for Alzheimer’s are under way. See our clinical trial page for more information.
Alzheimer’s is a global crisis that requires a global solution. It is a grave threat to the world’s health and finances if not stopped. Worldwide about 50 million people have some form of dementia, and someone in the world develops dementia every three seconds.
When the world has faced catastrophic challenges before, nations have marshaled significant resources behind clear goals and objectives to achieve great things. For example, the world committed to ambitious, aggressive, and well-funded efforts to prevent and treat HIV/AIDS, tuberculosis, and malaria. Those efforts have paid significant dividends in lives saved and economic development fostered.