Response to: Chen M et al. (2011) J Alzheimers Dis 24, 3-10

1 August 2011

I read with interest a recent article by Chen et al. [1] in the Journal of Alzheimer’s Disease (JAD) where the authors review various concepts relating to the possible cause of Alzheimer’s disease (AD). In that paper, Dr. Chen states: “Thus, put together we propose that advanced aging plus risk factors best explain most SD (senile dementia) cases (4)”. That reference “(4)” cites Dr. Chen’s previous paper from Frontiers in Bioscience published in 2001. In that Frontiers article, Dr. Chen writes: “Accordingly, we have further deduced that advanced aging intensified by risk factorsmost likely underlie late-onset sporadic AD (16, 17)” [2]. The references 16 and 17 provided by Dr. Chen in the Frontiers article refer to two papers previously published in JAD, June 2000, where he briefly affirms: “Accordingly, we proposed a third model, that is, risk factors under the condition of advanced aging can play a primary role in late onset sporadic AD” [3]. In the same paper, Dr. Chen asserts how he arrived at the aging-risk factor concept: “Indeed, it was a surprise to ourselves as well when it first came as an inevitable outcome of our analytic reasoning” [3].

While I am pleased that Dr. Chen finds the concept of aging + risk factors a viable hypothesis to explain the primary cause of sporadic AD, I would like to point out to him that we constructed this concept and published in previous papers to his and in many conference lectures beginning in 1997, when we showed how aging + AD risk factors were associated with the development of AD [4]. This concept was based on extensive experimental and clinical observations from my laboratory as an extension of our vascular hypothesis of AD [5]. The most thorough of those publications discussing AD causality appeared in Acta Neuropathologica in July 1999 [6], (fully a year prior to Dr. Chen’s article in JAD in June 2000), where I reviewed in a lengthy paper the reasoning and the neurodegenerative pathways related to our proposal that advanced aging + AD risk factors are the likely primary trigger leading to cerebral hypoperfusion, neurodegenerative changes and eventual onset of AD [6]. The Acta paper in 1999 was followed by a number of additional papers published in 2000 (also prior to the article by Dr. Chen in JAD in June 2000), extending our thinking and observational evidence on the pathogenesis of AD (see ref [7]). I have not seen any citations to any of our papers on the topic that Dr. Chen claims as his ‘concept’ although I welcome him to the club that considers that AD can be prevented or slowed down by detecting and controlling its major risk factors [8].

J.C. de la Torre, MD, PhD
Professor of Psychology (Adjunct)
University of Texas, Austin

[1] Chen M, Maleski JJ, Sawmiller DR (2011) Scientific truth or false hope? Understanding Alzheimer's disease from an aging perspective. J Alzheimers Dis 24, 3-10.
[2] Chen M, Fernandez HL (2001) Alzheimer’s disease revisited 25 years later: Is it a “disease” or senile condition? Front Biosci 6, e30-e40.
[3] Chen M, Fernandez HL (2000) How Important are risk factors in Alzheimer's disease? J Alzheimers Dis 2, 119-121.
[4] de la Torre JC (1997) Hemodynamic consequences of deformed microvessels in the brain in Alzheimer's disease. Ann N Y Acad Sci 826, 75-91.
[5] de la Torre JC (2010) The vascular hypothesis of Alzheimer's disease: bench to bedside and beyond. Neurodegener Dis 7, 116-121.
[6] de la Torre JC (1999) Critical threshold cerebral hypoperfusion causes Alzheimer's disease? Acta Neuropathol 98, 1-8.
[7] de la Torre JC (2000) Critically attained threshold of cerebral hypoperfusion: the CATCH hypothesis of Alzheimer's pathogenesis. Neurobiol Aging 21, 331-342.
[8] de la Torre JC (2010) Vascular risk factor detection and control may prevent Alzheimer's disease. Ageing Res Rev 9, 218-225.


Response to Letter to the Editor from de la Torre

I checked Dr. de la Torre’s papers [1, 2] and found that we do share "advanced aging" in our hypotheses, the well-known greatest risk factor for senile dementia (SD; aka, Alzheimer’s disease). But we also differ significantly in the meaning of "risk factors". While he suggests the importance of morphological and structural changes (deformed microvessels), we emphasize the roles of social, environmental, and lifestyle factors (IQ at young age, social isolation, storytelling, etc.).

In fact, "advanced aging plus risk factors" is street knowledge in the public. It is also shared by many in the medical and clinical community. A search of the keywords "Alzheimer and lifestyle" in PubMed will result in many such papers.

Healthy lifestyle is known as the "key for successful aging" and many people consider SD a "lifestyle disease". Similar views are also found in health books, newspapers, and mass media. So, the model of "advanced aging plus risk factors" is not new, but one going back to common sense, as we emphasized. These issues are further discussed in our recent paper [3].

But the model of advanced aging plus risk factors contrasts sharply with the current dominant hypotheses in the "AD" basic research field, which all assume a single "causal" factor leading to AD. So we together face much more challenging questions:

1.   Is it correct to define SD as a "disease" without emphasizing its senile nature?
2.   Is there a factor that can contribute to SD more than aging and risk factors in life?
3.   What we should logically look for in SD beyond "causal" factors?
4.   How to keep the objectivity of science in politically-contentious subjects such as SD?
5.    Is SD such a subject?

Ming Chen, Ph.D.

[1] de la Torre JC (1997) Hemodynamic consequences of deformed microvessels in the brain in Alzheimer's disease. Ann N Y Acad Sci 826, 75-91.
[2] de la Torre JC (1999) Critical threshold cerebral hypoperfusion causes Alzheimer's disease? Acta Neuropathol 98, 1-8.
[3]Chen M, Nguyen, HT, Sawmiller DR (2011) What to look for beyond "pathogenic" factor in senile dementia? Functional deficiency of Ca2+ signaling. J Alzheimers Dis 27, 679-689.