Putting Alzheimer’s un­der the mi­cro­scope

Defin­ing the dis­ease based on bi­o­log­i­cal signs in­stead of symp­toms may lead to ear­lier di­ag­noses.

The Reporter (Lansdale, PA) - - FRONT PAGE - By Mar­i­lynn Mar­chione Mar­i­lynn Mar­chione can be fol­lowed on Twit­ter at http://twit­ter.com/MMar­chioneAP

Gov­ern­ment and other sci­en­tists are propos­ing a new way to de­fine Alzheimer’s dis­ease — bas­ing it on bi­o­log­i­cal signs, such as brain changes, rather than mem­ory loss and other symp­toms of de­men­tia that are used to­day.

The move is aimed at im­prov­ing re­search, by us­ing more ob­jec­tive cri­te­ria like brain scans to pick pa­tients for stud­ies and en­roll them sooner in the course of their ill­ness, when treat­ments may have more chance to help.

But it’s too soon to use these scans and other tests in rou­tine care, be­cause they haven’t been val­i­dated for that yet, ex­perts stress. For now, doc­tors will still rely on the tools they’ve long used to eval­u­ate think­ing skills to di­ag­nose most cases.

Re­gard­less of what tests are used to make the di­ag­no­sis, the new def­i­ni­tion will have a star­tling ef­fect: Many more people will be con­sid­ered to have Alzheimer’s, be­cause the bi­o­log­i­cal signs can show up 15 to 20 years be­fore symp­toms do.

“The num­bers will in­crease dra­mat­i­cally,” said Dr. Clif­ford R. Jack Jr., a Mayo Clinic brain imag­ing spe­cial­ist. “There are a lot more cog­ni­tively nor­mal people who have the pathol­ogy in the brain who will now be counted as hav­ing Alzheimer’s dis­ease.”

He led a panel of ex­perts, work­ing with the Alzheimer’s As­so­ci­a­tion and the Na­tional In­sti­tute on Ag­ing, that up­dated guide­lines on the dis­ease, pub­lished Tues­day in Alzheimer’s & De­men­tia: The Jour­nal of the Alzheimer’s As­so­ci­a­tion.


About 50 mil­lion people world­wide have de­men­tia, and Alzheimer’s is the most com­mon form. In the U.S., about 5.7 mil­lion have Alzheimer’s un­der its cur­rent def­i­ni­tion, which is based on mem­ory prob­lems and other symp­toms. About onethird of people over 70 who show no think­ing prob­lems ac­tu­ally have brain signs that sug­gest Alzheimer’s, Jack said.

There is no cure — cur­rent medicines Na­menda just such tem­po­rar­ily as Ari­cept ease and symp­toms. Dozens of hoped-for treat­ments have failed, and doc­tors think one rea­son may be that the stud­ies en­rolled pa­tients af­ter too much brain dam­age had al­ready oc­curred.

“By the time that you have the di­ag­no­sis of the dis­ease, it’s very late,” said Dr. Eliezer Masliah, neu­ro­science chief at the In­sti­tute on Ag­ing.

“What we’ve re­al­ized is that you have to go ear­lier and ear- lier and ear­lier,” just as doc­tors found with treat­ing cancer, he said.

Another prob­lem: as many as 30 per­cent of people en- rolled in Alzheimer’s stud­ies based on symp­toms didn’t ac- tu­ally have the dis­ease — they had other forms of de­men­tia or even other med­i­cal con­di­tions. That doesn’t give an ac­cu­rate pic­ture of whether a po­ten­tial treat­ment might help, and the new def­i­ni­tion aims to im­prove pa­tient se­lec­tion by us­ing brain scans and other tests.


Many other dis­eases, such as di­a­betes, al­ready are de­fined by mea­sur­ing a biomarker, an ob­jec­tive in­di­ca­tor such as blood sugar. That wasn’t pos­si­ble for Alzheimer’s dis­ease un­til a few years ago, when brain scans and spinal fluid tests were de­vel­oped to do this.

They mea­sure cer­tain forms of two pro­teins — amy­loid and tau — that form plaques and tan­gles in the brain — and signs of nerve in­jury, de­gen­er­a­tion and brain shrink­age.

The guide­lines spell out use of these biomark­ers over a spec­trum of men­tal de­cline, start­ing with early brain changes, through mild im­pair­ment and Alzheimer’s de­men­tia.


People may be wor­ried and want these tests for them­selves or a fam­ily mem­ber now, but Jack ad­vises: “Don’t bother. There’s no proven treat­ment yet.”

You might find a doc­tor will­ing to or­der them, but spinal fluid tests are some­what in­va­sive, and brain scans can cost up to $6,000. In­sur­ance usu­ally does not pay be­cause they’re con­sid­ered ex­per­i­men­tal out­side of re­search. A large study is un­der­way now to see whether Medi­care should cover them and when.

Any­one with symp­toms or fam­ily his­tory of de­men­tia, or even healthy people con­cerned about the risk can con­sider en­rolling in one of the many stud­ies un­der­way.

“We need more people in this pre-symp­to­matic stage” to see if treat­ments can help stave off de­cline, Masliah said.


In this file photo, R. Scott Turner, Pro­fes­sor of Neu­rol­ogy and Di­rec­tor of the Mem­ory Dis­or­der Cen­ter at Ge­orge­town Univer­sity Hospi­tal, points to PET scan re­sults that are part of a study on Alzheimer’s dis­ease at Ge­orge­town Univer­sity Hospi­tal in Wash­ing­ton.


This photo shows slices of hu­man brains re­searchers at North­west­ern Univer­sity are us­ing to study Alzheimer’s dis­ease in Chicago.


This photo shows slices of hu­man brains re­searchers at North­west­ern Univer­sity are us­ing to study Alzheimer’s dis­ease in Chicago.

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