New Study Shows Mortality from Alzheimer’s May Be 5-6 Times Higher Than Officially Estimated

BrightFocus grantee, Kristine Yaffe, MD, of the University of California, San Francisco is one of the coauthors of this published study. Well-known for her investigations into predictors of cognitive decline and dementia with aging, Dr. Yaffe has received funding from BrightFocus Foundation for research linking several important blood markers of diabetes and glucose regulation with cognition and brain MRI changes.

Experts have long recognized that the number of deaths from Alzheimer’s disease (AD) tends to be underreported. Now a new study published in Neurology attempts to quantify that under-reporting and projects the AD mortality rate to be five to six times higher than official estimates, suggesting that AD may be responsible for more than 500,000 annual deaths in the United States. This figure is in stark contrast to the 83,494 deaths from AD in 2010 that were reported by the U.S. Centers for Disease Control. If applied to the general population, these findings would make AD the third leading (rather than sixth) cause of death in the United States, behind heart disease and cancer.

There are some limitations to the data. However BrightFocus Foundation and others who are calling for increased AD funding and research have welcomed the study as one that paints a truer picture of the growing Alzheimer’s epidemic and the burden it places on society and individual Americans.

Overview of Study

“Contribution of Alzheimer’s Disease to Mortality in the United States” was published online March 6, 2014, in Neurology, one of the leading journals in the field. Authors included Bryan D. James, PhD, of Chicago’s Rush University, and fellow investigators.

The group analyzed data collected in two previous studies involving a total of 2,566 persons aged 65 years and older who did not have AD at baseline. In those original studies, patients underwent yearly clinical evaluations that included medical history, neurologic exams, and cognitive testing, and then were tracked for multiple years. During that time their health status and causes of death were recorded and, in the case of AD, confirmed by postmortem pathologic examination. All enrolled patients agreed to brain donation.

The Results

Over follow-up averaging 8 years, about one-fifth (22%) of the study population was diagnosed with AD and 398 patients died (72% of all deaths in the entire study population). This translated into a death rate 3 to 4 times higher among AD than non-AD persons. Among the AD group, the median survival averaged 3.8 years following diagnosis. Importantly, deaths and median survival were only calculated among persons aged 75 and older because of too few deaths among younger age brackets.

Researchers then applied their findings to similar age brackets in the U.S. population and estimated there may be as many as 503,400 deaths attributable to AD each year.

The Strengths

CDC’s AD mortality figures (83,494 deaths in 2010) are based strictly on information derived from death certificates attributing AD as the cause of death. All too often, AD goes undiagnosed and untreated, or is not recognized on death certificates as the underlying cause of death for more immediate reasons, such as pneumonia. This leads to underreporting. In contrast, this is one of the first large studies of its kind to control for variables such as annual clinical evaluations, standardized diagnostic criteria, and high rates of follow-up among the AD vs. non-AD population, and that lends scientific validity to the findings.

The Limitations

Patient data used in the study may not be reflective of the general U.S. population. For example, these individuals may not be dying earlier from other diseases, possibly skewing the numbers attributed to AD mortality. Similarly, the fact that mortality rates could only be calculated among persons over 75 years of age may reflect a “survival bias,” i.e., the percentage of persons succumbing to AD versus another chronic disease may be higher in this study than in the general population.

Why Are These Findings Important – and Where Will They Lead?

The authors acknowledge their projection of a half-million deaths per year from AD is a “crude” estimate; however, they also point out that even if their estimate is off by a factor of 2, it would still result in 200,000 deaths per year directly attributable to AD—more than double CDC’s figure. This suggests that AD should be regarded alongside chronic lower respiratory diseases, stroke, and accidents (the 3rd through 5th leading causes of death, according to CDC) in terms of research and funding priorities.

Another key point raised by these authors is that AD, in addition to being a primary cause of death, is a major contributor to death from mixed causes. Dementia makes people vulnerable to poor overall health and nutrition, and contributes to the risk of accidents, falls, and other mortality risks. Attempting to identify a single cause of death may not capture the reality of the process of dying for most elderly people because multiple factors might come into play. As the authors note, the concept of “mixed mortality” might more accurately reflect the contribution of AD to death in rapidly aging populations. Thus, this study may thus contribute to an important debate over the need to “fine-tune” mortality reporting to include comorbidities (i.e., other contributing illnesses) and possibly more than one cause of death. BrightFocus Foundation agrees that comorbidities should be included on death certificates as a more accurate measure of mortality for elderly people, and a way of demonstrating the involvement of AD in deaths from multiple causes.