If you can’t de­fine the con­di­tion, how can you find a treat­ment?

The Buffalo News - - WASHINGTON NEWS -

DE­MEN­TIA •fromA1

though al­most all of these pa­tients are given a di­ag­no­sis of Alzheimer’s dis­ease, nearly every one of them has a mix­ture of brain ab­nor­mal­i­ties.

For re­searchers try­ing to find treat­ments, these so-called mixed patholo­gies have be­come a huge sci­en­tific prob­lem. Re­searchers can’t tell which of these con­di­tions is the cul­prit in me­mory loss in a par­tic­u­lar pa­tient, or whether all of them to­gether are to blame.

An­other real pos­si­bil­ity, noted Rod­er­ick Cor­riveau, who di­rects de­men­tia re­search pro­grams at the Na­tional In­sti­tute of Neu­ro­log­i­cal Dis­or­ders and Stroke, is that these ab­nor­mal­i­ties are them­selves the ef­fects of a yet-to-be-dis­cov­ered cause of de­men­tia.

These ques­tions strike at the very def­i­ni­tion of Alzheimer’s dis­ease. And if you can’t de­fine the con­di­tion, how can you find a treat­ment?

In ad­di­tion to plaques and tan­gles, other po­ten­tial vil­lains found in the brains of peo­ple with a di­ag­no­sis of Alzheimer’s in­clude silent strokes and other blood ves­sel dis­eases, as well as a poorly un­der­stood con­di­tion called hip­pocam­pal scle­ro­sis.

Po­ten­tial cul­prits also in­clude an ac­cu­mu­la­tion of Al­pha-synu­clein, the ab­nor­mal pro­tein that makes up Lewy bodies. And some pa­tients have yet an­other ab­nor­mal pro­tein in their brains, TDP-43.

No one knows how to be­gin ap­proach­ing the mul­ti­tude of other po­ten­tial prob­lems found in the brains of Alzheimer’s pa­tients. So, un­til re­cently, they were mostly ig­nored.

“I wouldn’t say it’s a dirty lit­tle se­cret,” said John Hardy, an Alzheimer’s re­searcher at Univer­sity Col­lege Lon­don. “Every­body knows about it. But we don’t know what to do about it.”

Some ex­perts said they had been re­luc­tant to talk much about mixed patholo­gies for fear of sound­ing too neg­a­tive. But “at a cer­tain point we have to be some­what more re­al­is­tic and re­think what we are do­ing,” said Dr. Al­bert Hof­man, chair­man of the epi­demi­ol­ogy depart­ment at Har­vard’s T.H. Chan School of Pub­lic Health.

The prob­lem be­gan with the very dis­cov­ery of Alzheimer’s dis­ease. In 1906, Dr. Alois Alzheimer, a Ger­man psy­chi­a­trist and neu­roanatomist, de­scribed a 50-year-old woman with de­men­tia. On au­topsy, he found pe­cu­liar plaques and twisted, spaghetti-like pro­teins known as tan­gles in her brain. Ever since, they have been con­sid­ered the defin­ing fea­tures of Alzheimer’s dis­ease.

But sci­en­tists now be­lieve this woman must have had a very rare ge­netic mu­ta­tion that guar­an­tees a per­son will get a pure form of Alzheimer’s by mid­dle age.

Pa­tients with the mu­ta­tion ap­peared to de­velop only plaques and tan­gles, and no other patholo­gies, so for decades, plaques and tan­gles were the fo­cus of re­search.

The rare ge­netic mu­ta­tions led to an over­pro­duc­tion of amy­loid, it turned out, the ab­nor­mal pro­tein in those plaques. To many sci­en­tists, that sug­gested that amy­loid was the fun­da­men­tal cause of Alzheimer’s.

More plaques usu­ally meant more se­vere de­men­tia, in both older and younger pa­tients. So re­searchers tested drugs that could at­tack amy­loid or stop its pro­duc­tion in ge­net­i­cally en­gi­neered mice. The drugs worked beau­ti­fully.

Sci­en­tists rec­og­nized that mice were an im­per­fect model – they never de­velop de­men­tia – but the stud­ies were en­cour­ag­ing. So it was a huge dis­ap­point­ment when, over and over, those drugs failed in clin­i­cal trials in pa­tients.

Tests of anti-plaque drugs con­tinue, de­spite the in­creas­ing recog­ni­tion that many fac­tors may com­bine to cause de­men­tia – or that, per­haps, the true cause has yet to be found.

What to do now? Sci­en­tists are strug­gling to re­frame the prob­lem. Some think re­search should be more fo­cused on age.

“We can’t avoid the fact the num­ber one risk fac­tor for Alzheimer’s dis­ease is age and many of these other patholo­gies are age-as­so­ci­ated,” said Dr. John Mor­ris, a pro­fes­sor of neu­rol­ogy at Wash­ing­ton Univer­sity in St. Louis. “We don’t see them in younger peo­ple.”

Carol Brayne, an epi­demi­ol­o­gist at Cam­bridge Univer­sity, has been say­ing as much for decades. There is some­thing sig­nif­i­cant, she has found, about the ob­vi­ous fact that the older a per­son gets, the more likely he or she is to de­velop de­men­tia. By their 90s, 1 out of 2 peo­ple has de­men­tia.

A more op­ti­mistic view is that there may be some­thing in the brain that sets off a cas­cade of mul­ti­ple patholo­gies. If true, block­ing that fac­tor could stop the process and prevent de­men­tia. Hof­man is con­vinced the pre­cip­i­tat­ing fac­tor is di­min­ished blood flow to the brain.

Sup­port­ing this view, he added, are data from nine stud­ies in the U.S. and West­ern Europe con­sis­tently find­ing a 15 per­cent de­cline in the in­ci­dence of new Alzheimer’s cases over the past 25 years.

Or per­haps it re­ally is amy­loid that be­gins the avalanche of other prob­lems.

Some re­searchers still hold out hope that if anti-amy­loid drugs are started early enough, they might prevent de­men­tia. Clin­i­cal trials are test­ing the idea now in peo­ple ge­net­i­cally dis­posed to get Alzheimer’s dis­ease.

Newspapers in English

Newspapers from USA

© PressReader. All rights reserved.