A Speculative and Probably Incorrect Paper on Alzheimer's Disease as a Consequence of Modern Painkillers

Once you know enough of the basics in a field to get by as a layperson, you'll find that scientific literature is far removed from being dry and uncontroversial. There are always heretics and novel positions being advanced - most of them wrong, but all new fields and new directions start with a few heretics, and the mainstream is consistently overturned with time, to be replaced with the new consensus. Distinguishing a good speculative hypothesis from a work of overreaching fancy can be a challenge wherever you stand in the hierarchy of knowledge, and the good-looking fallacies far outnumber the seeds of tomorrow's scientific mainstream. This is why few researchers bother to spend any time on reviewing this sort of thing when there are so very many other demands on their time.

One of the SENS Research Foundation folk turned up the open access paper linked below in the course of ongoing reviews of scientific literature relevant to aging, and thought it heretical enough to share as an item of interest - as a curio well outside the current consensus, not as anything to be acted on. It makes for a good read, and is well-researched, but I think that ultimately the points being made here can be explained away by the coincidence of development of medical technology, increasing longevity, and increasing wealth. When it comes down to the biochemistry, the dots aren't really joined well enough to be very compelling.

So I offer this as an example of the fact that if you go digging around, you'll find very interesting papers that are well-researched, highly speculative, and probably wrong. The author of this paper has been advancing his theory for more than a decade, evidently without gathering much support. That is all part and parcel of the scientific process:

The Alzheimer Pandemic: Is Paracetamol to Blame?

Historical Background:

The clinical recognition of a form of dementia closely resembling Alzheimer's disease dates from around 1800. The role of analgesics derived from coal-tar in the spread of the pandemic is traced in terms of the introduction of phenacetin (PN) in 1887; its nephrotoxicity; the observation of lesions characteristic of the disease by Fischer and Alzheimer; the discovery of paracetamol (PA) as the major metabolite of PN; the linking of kidney injury and dementia with high PN usage; and the failure of PN replacement by PA to halt and reverse the exponential, inexorable rise in the incidence of Alzheimer-type dementia. Fischer observed his first case before Alzheimer; it is proposed to rename the syndrome Fischer-Alzheimer disease (F-AD).

Disease development:

PA-metabolising enzymes are localised in the synaptic areas of the frontal cortex and hippocampus, where F-AD lesions arise. The initiating chemical lesions in liver poisoning comprise covalent binding of a highly reactive product of PA metabolism to proteins; similar events are believed to occur in brain, where alterations in the antigenic profiles of cerebral proteins activate the microglia. β-Amyloid forms, and, like PA itself, induces nitric oxide synthase.


F-AD is primarily a man-made condition with PA as its principal risk factor.

The ending line there is something of a bold conclusion, and as I noted above I don't think it stands too well against Occam's razor. It is simpler to point to rising wealth driving the sedentary, high-calorie lifestyle that greatly raises the risk of suffering age-related diseases such as Alzheimer's, and note that this coincides with advances in medical technology that allow for more reliable identification of the condition, progress in other technologies that improve record-keeping and reliability in medicine, and the concurrent trend in rising life spans such that more people survive to ages in which neurodegenerative conditions become a significant risk.

I still suggest you read the paper, as you'll find that a great deal of interesting historical data is referenced therein. You'll probably learn some things that you didn't know about the history of painkillers, for example.


I find your invocation of Occam's razor inappropriate and irrelevant. The question is whether paracetamol is the principal risk factor for Alzheimer's disease as the author proposes or, rather, whether it has any bearing at all - i share your scepticism. Paracetamol might be an aggravating factor in neurodegeneration so it is certainly worth researching but dementia has been recorded since the times of Pythagoras. Is the author proposing that the Ancient Greeks took this analgesic?

For you to claim that "rising wealth driving the sedentary, high-calorie lifestyle that greatly raises the risk of suffering age-related diseases such as Alzheimer's" is groundless if not offensive. Perhaps you are thinking of the rising incidence of diabetes?

Posted by: Richard Wilson at April 26th, 2014 6:47 AM

Oh dear. I am sorry these ideas have come in for some stick. No serious opposition has been advanced. It took the best part of four years to get this work into print, attracting high levels of opposition and harassment from various quarters. I am sorry the writer joined the club.

The essential facts are these. 1887; phenacetin introduced. 1901; Alzheimer-type dementia (ATD) detected. 1949; paracetamol discovered to be the chief metabolite for phenacetin and responsible for analgesia. 1971; ATD linked with high lifetime phenacetin intakes. 1953-81; phenacetin replaced by paracetamol. 2001; suggestion made that its metabolite also causes ATD.

Yes; the paper mentions the discovery of ATD by Pinel around 1800, and yes, it can arise spontaneously. Bu there is much much more ATD around now than ever there was in 1800 or, for that matter, 1900. Data are needed for earlier times.

More information can be found in the paper. The replacement of phenacetin by paracetamol has NOT stemmed the exponential rise in ATD incidence. If the writer cares to tell me what other cause ATD might have, I would be delighted to hear from him.

Robert Jones.....

Posted by: Robert Jones at May 23rd, 2014 8:38 AM

It is always good to hear of new theories and evidence relating to diseases.
I don't believe in shooting the messenger! We need to keep an open mind and explore all avenues.
Drugs affect different people in different ways. Prolonged use of most drugs will have some affects.
Paracetamol is also in other medicines, such as cough medicine.
I see now the NSAID group is being hailed as helping with AD.

Posted by: Jim Dean at August 21st, 2015 5:58 PM
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