A recent article published in the New England Journal of Medicine reports that Alzheimer’s disease (AD) can be identified decades before clinical symptoms are recognized—through changes in clinical and biological markers.
The NEJM study is significant because it sheds light on how certain gene mutations lead to AD over a period of 20 years or longer. Knowledge of the lengthy preclinical period of time might lead more people to confront their risk for the disease sooner rather than later.
However, because the NEJM study was limited to individuals at high risk (50 percent), one should be cautious about its implications. The study looked at gene mutations known as autosomal-dominant which account for only about 1 percent of all AD cases.
Still, much can be learned from the study’s findings. The study highlights the importance of identifying Alzheimer’s disease at its earliest stage. It examines the relative order and severity of the marker changes that indicate brain degeneration. It provides a major step toward understanding the pathway that underlies autosomal AD. It might also aid in the development of therapies to prevent or delay the most severe aspects of AD.
Yet the vast majority of those afflicted with Alzheimer’s disease do not carry one of the specific autosomal-dominant genetic mutations that were the focus of the study. In light of this, when screening elderly populations, it is likely not yet feasible to rely on the specific markers that were examined in the NEJM study.
One important reason is that existing studies on elderly patients diagnosed with AD show that many have what is known as the “mixed” form of dementia. Mixed dementia may include Alzheimer’s disease combined with other causes of dementia such as vascular disease. Mild cognitive impairment, or impaired memory, often comes before dementia and is associated with high risk factors, including progression to AD and death.
As a result, there is a real need to use screening measures that are cost-effective and sensitive and that can be administered to large segments of the population. A two-stage screening process that first identifies those at high risk and then uses measures such as those proposed by the researchers in the NEJM study might be more effective. The AD markers might be expanded to include measures of cardiovascular disease to help us better understand the link between the two disease processes, something this study could not explore due to the relative youth of its participants, only 15 percent of whom had vascular risk factors.
Even in the absence of a cure or of effective long-term therapies, patients and families who are well-informed can better plan financially and arrange for future caretaking of loved ones at risk of AD. Doctors and other healthcare providers may emphasize preventive strategies to maintain an individual’s well-being as well as suggest clinical trials geared toward therapy or prevention.
Preparing for such a paradigm shift in thinking (and acting) will require much education and support for patients, families and medical professionals. Counseling patients appropriately will take time, knowledge, commitment and resources.