Ri­vals line up in bat­tle on Alzheimer’s

The race is on to cure the grow­ing world­wide bur­den of the most com­mon form of de­men­tia. Kel­lie Bis­set re­ports

The Weekend Australian - Travel - - Health -

IT started with for­get­ting to close the front door. Then there was con­fu­sion over how to op­er­ate a wash­ing ma­chine, and sim­ple television drama plots sud­denly be­came hard to fol­low. Aged just 54, and wor­ried for her health, Marie Va­lenta took her­self off and had an MRI scan.

It re­turned an un­be­liev­able Alzheimer’s dis­ease.

There was no fam­ily his­tory, no clue at all in fact, that such a seem­ingly healthy per­son would be robbed of her me­mory so swiftly and so eas­ily. Just four years later, Va­lenta doesn’t know her hus­band and needs 24-hour care.

She can’t dress, eat, or go to the toi­let un­aided. She has de­vel­oped de­pres­sion and psy­chotic para­noia, and is dan­ger­ously un­der­weight. Doc­tors don’t think she’ll live for much more than a year.

She has not been my wife — or the per­son I knew as my wife — for the best part of two years now,’’ her hus­band, Tom, says. ‘‘ It has been a pretty long and tor­tur­ous night­mare.’’

Marie Va­lenta is one of more than 200,000 Aus­tralians en­dur­ing the tor­ment of Alzheimer’s dis­ease, a fig­ure ex­perts say will jump to 750,000 by the year 2050.

There is cur­rently no cure, al­though those in the field are up­beat about a wide range of re­search cur­rently un­der way.

Di­rec­tor of the Men­tal Health Re­search In­sti­tute at the Univer­sity of Melbourne and world ex­pert in the field, pro­fes­sor Colin Masters, says the race is on for an ef­fec­tive treat­ment, with each of the big pharma com­pa­nies run­ning their own re­search pro­grams — and this rep­re­sents an ex­cit­ing new era for pa­tients.

‘‘ The com­pe­ti­tion is very, very stiff at the mo­ment,’’ he says. ‘‘ Re­sults [from drug tri­als] are ex­pected in the next 12 to 24 months.’’

Pro­fes­sor Masters be­lieves the an­swer to the Alzheimer’s rid­dle will come in the next five years. But in the mean­time, re­searchers are in­ves­ti­gat­ing sev­eral av­enues, one of which is the link be­tween high choles­terol and brain func­tion.

New re­search just pub­lished in the jour­nal Neu­rol­ogy (2007; 69:878-885) sug­gests that widely pre­scribed choles­terol-low­er­ing drugs, known as statins, may cut the risk of de­vel­op­ing Alzheimer’s.

The re­searchers, from the Univer­sity of Wash­ing­ton, stud­ied 110 peo­ple who had do­nated their brains for re­search, and found

‘‘di­ag­no­sis: sig­nif­i­cant dif­fer­ences in the brains of those Alzheimer’s pa­tients who had taken a statin and those who had not.

Im­por­tant mark­ers of Alzheimer’s are clus­ters of pro­tein be­tween and around the brain cells called beta-amy­loid plaques, and groups of twisted fi­bres inside the cells called neu­rofib­ril­lary tan­gles.

Th­ese lead to a break­down in the cells’ abil­ity to com­mu­ni­cate with each other, caus­ing the cells to even­tu­ally die.

The Neu­rol­ogy study showed sig­nif­i­cantly fewer neu­rofib­ril­lary tan­gles in the brains of statin users. If statins are proved to have an ef­fect on Alzheimer’s, the im­pli­ca­tions would be huge.

Used to lower choles­terol and pre­vent heart at­tacks and strokes, they are among the most com­monly pre­scribed drugs in Aus­tralia.

Ator­vas­tatin and sim­vas­tatin alone are the big­gest drain on the Phar­ma­ceu­ti­cal Ben­e­fits Scheme — they cost the Gov­ern­ment nearly $800 mil­lion in the year to June 30 2006.

While there is in­creas­ing ev­i­dence of an as­so­ci­a­tion be­tween car­dio­vas­cu­lar risk fac­tors such as high blood pres­sure and high choles­terol and risk of Alzheimer’s, it’s still un­clear ex­actly what role choles­terol might play.

The au­thors of the Neu­rol­ogy study are cau­tious about ap­ply­ing their re­sults to a liv­ing pop­u­la­tion. And they ac­knowl­edge that while some re­search sug­gests a de­creased Alzheimer’s risk in statin users, there are other stud­ies that have found no over­all re­duc­tion in risk.

Ade­laide neu­rol­o­gist

Karyn

Boundy

is in­volved in one study that may shed some more light on the is­sue. The di­rec­tor of the me­mory unit at Queen El­iz­a­beth Hospi­tal says the re­sults of the trial, which is look­ing at whether statins slow the pro­gres­sion of Alzheimer’s, are not yet pub­lished.

But she’s con­fi­dent there is ‘‘ cer­tainly some­thing’’ in the choles­terol hy­poth­e­sis.

‘‘ We know choles­terol does in­ter­act with amy­loid,’’ she says. ‘‘ I think we are a fair way away from broad­en­ing the [PBS statin el­i­gi­bil­ity] for peo­ple at risk of Alzheimer’s dis­ease, but if peo­ple do qual­ify for lipid treat­ment un­der PBS cri­te­ria and they do have risk fac­tors for de­men­tia, then they should be dis­cussing with their doc­tor whether tak­ing a statin is ap­pro­pri­ate.’’

Boundy agrees that while statins may prove to be an ex­tra piece of ar­mour in the bat­tle against Alzheimer’s rather than a cure, if they have a role in de­lay­ing the on­set of symp­toms the con­se­quences would be sig­nif­i­cant.

‘‘ There have been epi­demi­o­log­i­cal stud­ies that have sug­gested if you can de­lay the on­set of symp­toms by a cou­ple of years, you might half the ac­tual preva­lence of the dis­ease.’’

Ac­cord­ing to Colin Masters though, the statin con­nec­tion re­mains elu­sive. ‘‘ What we are af­ter is a drug that ac­tu­ally al­ters the course of the ill­ness,’’ he says. ‘‘ The ques­tion is, do the statins do this or not? The tri­als to date have not been very con­vinc­ing.’’

An­other av­enue of in­quiry is a class of drugs called gamma-sec­re­tase in­hibitors, which could stop beta amy­loid plaques from form­ing.

Masters and his Men­tal Health Re­search In­sti­tute col­league pro­fes­sor Ash­ley Bush, are work­ing with com­pany Prana Biotech­nol­ogy on the the­ory that plaques are formed by an ab­nor­mal re­ac­tion with the brain’s own chem­istry.

By re­mov­ing cop­per and zinc ions, which bind amy­loid to­gether, the beta-amy­loid falls apart and the plaques can be cleared away.

Bush is fo­cus­ing on a drug called PBT2, which has shown ‘‘ spec­tac­u­lar re­sults’’ in mice and hu­man tri­als are about to be­gin.

‘‘ We are cau­tiously op­ti­mistic,’’ he says. ‘‘ It’s the most po­tent re­sult that has ever been seen at the mouse stage. But it is still an­other two to three years off — all things be­ing well.’’

An­other ex­cit­ing de­vel­op­ment in the pipe­line is positron emis­sion to­mog­ra­phy (PET), where the brain is scanned for beta-amy­loid pro­tein. A chem­i­cal tracer is in­jected into pa­tients and binds to the plaques in the brain, al­low­ing the PET scan to de­tect them.

Bush says this can pick up brain changes as­so­ci­ated with Alzheimer’s well be­fore symp­toms ap­pear.

And if new drugs be­come avail­able to break down plaques, the dis­ease could then be knocked on the head.

Mea­sur­ing mark­ers found in the cere­brospinal fluid (CSF) and the blood will also be­come more and more im­por­tant in de­tect­ing Alzheimer’s early, Masters says.

And hopes for a vac­cine are also on the hori­zon. Pa­tients in an early trial how­ever, suf­fered the se­ri­ous side ef­fect of brain in­flam­ma­tion and while that trial was halted, more re­search is con­tin­u­ing.

At the mo­ment, pa­tients treat­ment op­tions.

have

lim­ited

Cho­linesterase in­hibitors have been around for about 15 years, and a re­cent Cochrane Re­view found they caused only mod­est im­prove­ments in cog­ni­tive func­tion.

Newer drugs, called NMDA re­cep­tor an­tag­o­nists, pre­vent too much cal­cium mov­ing into the brain cells caus­ing dam­age, but Bush says while they of­fer a slight ben­e­fit, they don’t change the pathol­ogy of the dis­ease.

For those con­cerned about here and now pre­ven­tion rather than long-term cure, Alzheimer’s Aus­tralia says while it’s no guar­an­tee, adopt­ing a ‘‘ brain-healthy’’ lifestyle is as­so­ci­ated with a re­duced risk of de­men­tia.

Its ‘‘ mind your mind’’ pro­gram rec­om­mends sev­eral strate­gies, in­clud­ing keep­ing the brain ac­tive through mind games and hob­bies, phys­i­cal ex­er­cise, eat­ing a diet low in sat­u­rated fats and high in omega-3 fatty acids, an­tiox­i­dants and fo­late, and watch­ing your choles­terol, body weight, blood pres­sure and blood sugar lev­els.

For Marie Va­lenta though, who ‘‘ did ev­ery­thing right’’, none of this worked.

Hus­band Tom, who has re­cently pub­lished a book about his ex­pe­ri­ences, de­scribes his cyn­i­cism about po­ten­tial cures but he’s hope­ful enough to have do­nated all his roy­al­ties to re­search.

In the mean­time, he is cop­ing day-to-day with the grad­ual dis­ap­pear­ance of his ‘‘ ex­traor­di­nar­ily brave’’ wife. ‘‘ We had a good 12-18 months of good times when Marie was first di­ag­nosed,’’ he says. ‘‘ We squeezed ev­ery drop out of ev­ery day.’’

Pic­ture: Richard Cisar-Wright

Treat­ment: Marie Va­lenta pre­pares to un­dergo MRI

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