And The Promise of Precision Medicine as an Intervention to the Spectrum of Symptoms

Written By: Stuart Zola, Ph.D.
Emeritus Interim Provost and Executive Vice President for Academic affairs,
Emeritus Professor, Department of Psychiatry and Behavioral Sciences
Emory University, Atlanta, Georgia 30322
Research Career Scientist (Retired), Atlanta VA Health Care System

Overview

Alzheimer’s disease traditionally has been viewed as a one-size-fits-all medical condition. Thinking of Alzheimer’s disease as a single disease state assumes that there is a single “magic bullet” that once found will effectively treat or cure all patients. However, as we know, there is no disease-modifying therapy for this disease yet, and despite several decades of research no cure and no effective treatments have been forthcoming. Interventions to stop, slow, or prevent the progression of Alzheimer’s are a world-wide healthcare imperative. In this regard, the present commentary proposes the following point for consideration:

Alzheimer’s disease should be reframed as a spectrum disorder (much like the reframing of autism), and as such individual Alzheimer’s patients will need to be profiled differently to maximize the efficacy of treatment and preventive measures.

Alzheimer’s Disease as a Spectrum Disorder

While earlier criteria for diagnosing Alzheimer’s disease were based on clinical criteria alone, new criteria for Alzheimer’s disease have been recently established that now includes the clinical characteristics of Alzheimer’s as well as the pathological features of the disease. The new criteria include the use of imaging and other biomarkers to aid in diagnosis and in understanding the underlying neurologic and genetic bases for behavioral changes associated with Alzheimer’s. Additionally, clinical features are now being supplemented with innovative behavioral assessment tools that currently are being validated and that can inform us further about the spectrum of Alzheimer’s disease.

A little medical history is helpful here. Some years ago, the condition known as autism was considered a “one-size-fits-all” condition. Research and clearer understanding of the condition did not advance until the condition became re-framed as autism-spectrum disorder. That is, although there was a core set of symptoms that helped define autism, it became clear that individuals could have different patterns and combinations of those symptoms. Importantly, the view developed that the evidence that one size did not fit all meant that treatments might more effectively be tailored to a particular individual’s pattern or profile of symptoms. Hence, the terminology of spectrum disorder.

In the field of Alzheimer’s disease, studies have begun to reveal varied patterns of behavioral changes and abnormalities. Many of these studies point to the fact that not all patients exhibit the same range and severity of behavioral abnormalities associated with Alzheimer’s and there are different profiles. Some behavioral changes do not seem directly correlated with impairments in cognition, for example. In a study of behavioral changes in Alzheimer’s disease where the frequency and severity of ten commonly reported behaviors were assessed, it was reported that the most common behavior was apathy, exhibited by 72% of the patients, followed by agitation (60%), anxiety (48%), dysphoria (38%), and disinhibition (36%). Agitation, dysphoria, and apathy were significantly correlated with cognitive impairment, but many other behavioral measures were not.

These findings, and others, point to the idea that despite having a diagnosis of AD, individual patients can have quite different clinical/behavioral profiles, and while some behavioral changes can be linked to cognitive changes, others are not.

Patterns of behavioral changes can be variable from patient to patient, even within a diagnostic category, e.g., mild, moderate or severe Alzheimer’s. When the cumulating research is taken together, it suggests that a perspective on Alzheimer’s disease could benefit from rethinking it and reframing it as a spectrum disorder. Moreover, considering Alzheimer’s as a spectrum disorder sets the stage for the application of one of the most promising and innovative approaches in modern medicine: personalized, precision medicine. I’ll discuss that development in my next post.

Dr. Stuart Zola is Co-Founder of MapHabit™. Learn more about MapHabit’s™ work to help people with memory impairment live better HERE.

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