Diseases: on a continuum rather than discrete entitiesBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d3363 (Published 31 May 2011) Cite this as: BMJ 2011;342:d3363
All rapid responses
We completely agree on the point that most diseases are certain
stages of a continuum rather than "all-or-none" type entities. Indeed,
many factors leading to "diseases" are physiologically adaptive responses
in nature. Take Alzheimer's disease for example. Amyloids, neurofibrillary
tangles and apoE alleles, three key biomarkers of the disorder, are all
active components of normal neuroplastic processes. There is growing
evidence that Alzheimer's disease is not a simple entity of abnormal
molecular profiles, but represents compensatory processes that result in
unsustainable levels of plasticity-related cellular activity and finally
neurodegeneration over years. In other words, AD is not a "disease", but a
physiological yet detrimental response to increased neuroplasticity load.
No doubt that these understandings make it hard to have appropriate
"disease" definitions. One solution for this problem is to define health,
before diseases. This is taken by the US Alzheimer's Association and the
National Institute of Aging, who have recently proposed a new three-staged
continuum of Alzheimer's disease. This proposal emphasizes the early
preclinical phase of the disorder when no signs of cognitive impairment
are present except some abnormal biomarkers. At this stage, the patients
are clinically healthy and do not require interventions, but will be
monitored for potential progression to the second (mild cognitive
impairment) and third (Alzheimer's dementia) stages of the disease.
Define health first, then diseases - such a strategy will overcome
the problem that most diseases appear in a dormant manner originating from
a physiological continuum. It not only provides a consensual framework for
researchers, but also benefits early diagnosis and intervention for
1. Sleath JD. Diseases: on a continuum rather than discrete entities.
BMJ. 2011; 342:d3363. (1 June.)
2. Mesulam MM. Neuroplasticity failure in Alzheimer's disease:
bridging the gap between plaques and tangles. Neuron. 1999; 24: 521-9.
Competing interests: No competing interests