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pharmacological risk factors?’ But this time the paper was not even accepted by a medical journal. The Alzheimer's Connection pharmacological risk factors?"’ But this time the paper From the 1880s, phenacetin, an aniline derivative, | was not even accepted by a medical journal. was widely used as an analgesic. The consumption o phenacetin and other analgesics increased steeply after Timelines of AD and Paracetamol World War II. In 1971, the first paper was published The term Alzheimer's disease was coined in 1910 for hat linked high use of phenacetin with the an unusual form of early-onset dementia. It had been development of Alzheimer's disease. Autopsies were independently recognised in 1901 by Oskar Fischer in performed on a series of individuals who had died o Prague and then by Alois Alzheimer in Frankfurt. idney disease caused by high intake of analgesics Fischer's first patient died in 1903; Alzheimer's in 1906. (analgesic nephropathy). Senile plaques were foundin The cortex of each patient showed rare plaque-like six individuals aged from 52 to 67 years who had lesions. Both published their findings in 1907. Despite ifetime high intakes of phenacetin, while no plaques intensive search, only 12 instances of plaques in were seen in two subjects aged 68 and 72 years who dementia patients had been found before 1907. Over ad consumed similar amounts of aspirin but no _ the next five years, 115 new cases were discovered; phenacetin over their lifetimes. These findings do no Fischer described 56 of these. only apply to phenacetin itself, but also to its active Compare the timing of these events leading to the metabolite paracetamol which eventually replaced recognition and definition of AD to the introduction phenacetin because of its lower kidney toxicity. and use of phenacetin. Both phenacetin and The Abstract of this 1971 paracetamol were first tried on paper reads: “Psychometric patients in 1887. At that time, and psychiatric studies on . . phenacetin became the eight patients who had abused ...the introduction and preferred drug, and its sales compound analgesics widespread use of established Bayer as a leading containing phenacetin showed . pharmaceutical company. hat four had definite evidence phenacetin preceded the Originally, very high doses were and two possible evidence of sudden appearance and recommended by some doctors. organic dementia. Neuro- . Use of phenacetin spread pathological studies on nine explosive spread of AD by internationally on a large scale other analgesic abusers one or two decades. as a result of the 1889-90 Asiatic influenza pandemic. At incidence of the histological he same time also, its kidney eatures of Alzheimer's disease. oxicity became apparent. By t is suggested that gross abuse of phenacetin may comparing the two timelines, we see that the disclosed a surprisingly hig overwhelm the antioxidant protection of the body, introduction and widespread use of phenacetin eading to premature deposition of lipofuscin, and preceded the sudden appearance and explosive spread accelerated neuronal ageing." of AD by one or two decades. Also, these early AD This study was not followed up by other researchers victims typically displayed the kidney damage or health agencies. But some time later, a "strange" characteristic of phenacetin overuse. Another incident happened to Robert Jones, PhD, that made _ indication of a possible causal connection is the him dig more deeply into the possible link between _ statistical fact that presently paracetamol use and AD paracetamol and AD. Dr Jones worked mainly as a__ incidence are almost twice as high in women than in British cancer researcher who fell out with the men. establishment when he published his protocol for the Originally, phenacetin and later paracetamol were treatment of cancer with promethazine, an mainly used and produced in industrialised countries antihistamine also known as Phenergan®.* Twenty years and that is where AD initially flourished. But in more ago, he took paracetamol for about 10 days to alleviate recent years (2008) production has stopped in Europe pain while painting his house. Two weeks later, he and is now mainly based in China and India which noticed short- and long-term memory problems. _ presently also have the highest projected growth rates Gradually these improved again, but 10 years later the of AD. The estimated annual world production of same sequence repeated itself. That pricked his paracetamol is about 145,000 tonnes. That is an awful curiosity and he started looking into a possible amount of tablets to swallow, and, at the maximum connection between paracetamol and AD. The result of | dose of four grams per day, sufficient to control the his research was an article in Medical Hypotheses in 2001.2 chronic pain of about 100 million people. It also shows This did not make much of an impact, and so he _ us where the incidence rates of AD may be heading; in recently wrote another article, "Does placing the 2010, about 35 million cases of AD exist worldwide. histories of certain analgesics and Fischer-Alzheimer's So far, indications are that a high intake of disease (F-AD) in relative alignment reveal connected paracetamol for extended periods is required to lead to widespread use of phenacetin preceded the men. Originally, phenacetin and later paracetamol were mainly used and produced in industrialised countries and that is where AD initially flourished. But in more recent years (2008) production has stopped in Europe and is now mainly based in China and India which presently also have the highest projected growth rates of AD. The estimated annual world production of paracetamol is about 145,000 tonnes. That is an awful amount of tablets to swallow, and, at the maximum dose of four grams per day, sufficient to control the chronic pain of about 100 million people. It also shows us where the incidence rates of AD may be heading; in 2010, about 35 million cases of AD exist worldwide. So far, indications are that a high intake of paracetamol for extended periods is required to lead to an 42 * NEXUS ...the introduction and sudden appearance and explosive spread of AD by one or two decades. FEBRUARY - MARCH 2011 www.nexusmagazine.com