Can You Eat Your Way to De­men­tia?*

AN UN­HEALTHY DIET NOT ONLY IS BAD FOR YOUR WAIST—IT MAY ALSO TRIG­GER ALZHEIMER’S DISEASE

Reader's Digest (India) - - Contents - BI­JAL TRIVEDI

An un­healthy diet is bad for body and brain.

Suzanne de La Monte’s rats were disori­ented and con­fused. Nav­i­gat­ing their way around a cir­cu­lar wa­ter maze—a typ­i­cal mem­ory test—they for­got where they were and couldn’t re­mem­ber how to lo­cate the hid­den, sub­merged safety plat­form. A closer look at their

brains uncovered dev­as­tat­ing dam­age. Ar­eas as­so­ci­ated with mem­ory were stud­ded with bright pink plaques, like rocks in a climb­ing wall, while many neu­rons, full to burst­ing point with a toxic pro­tein, were col­laps­ing and crum­bling, tee­ter­ing on the brink of death.

Such changes are the hall­marks of Alzheimer’s disease, yet they arose in sur­pris­ing cir­cum­stances. De la Monte, a neu­ropathol­o­gist at Brown Univer­sity in Prov­i­dence, Rhode Is­land, USA, had treated the rats with a di­a­betes drug that in­ter­fered with how their brains re­sponded to in­sulin. The hor­mone is most fa­mous for con­trol­ling blood su­gar lev­els—poor sen­si­tiv­ity to in­sulin is typ­i­cally as­so­ci­ated with type 2 di­a­betes—but it also plays a key role in brain sig­nalling. And re­sults such as de la Monte’s have led some re­searchers to won­der whether Alzheimer’s may some­times be a ver­sion of di­a­betes that hits the brain. De la Monte even re­named it “type 3 di­a­betes,” and oth­ers con­cur.

If they are right, the im­pli­ca­tions are deeply trou­bling. Since sug­ary, caloric foods are known to im­pair our body’s re­sponse to in­sulin, we may be poi­son­ing our brains ev­ery time we chow down on burg­ers, fries, and soda.

This Is Your Brain on In­sulin

For more than a cen­tury, sci­en­tists blamed beta-amy­loid plaques that amass in the brains of peo­ple with Alzheimer’s as the cause of the disease. Beta-amy­loid is a frag­ment of a larger pro­tein that helps form brain cell mem­branes. It is also thought to carry out im­por­tant func­tions, such as fight­ing mi­crobes, trans­port­ing choles­terol, and reg­u­lat­ing cer­tain genes. What prompts the pro­tein to re­lease toxic frag­ments that clump into Alzheimer’s plaques is some­thing of a mys­tery, but if the new re­search is right, a di­a­betes-like ill­ness might be a trig­ger.

Un­til re­cently, in­sulin was type­cast as a reg­u­la­tor of blood su­gar, cue­ing mus­cle, liver, and fat cells to ex­tract su­gar from the blood and use it for en­ergy or store it as fat. We now know that the hor­mone is a mas­ter mul­ti­tasker: In the brain, it helps neu­rons take up glu­cose for en­ergy and reg­u­lates neu­ro­trans­mit­ters cru­cial for mem­ory and learn­ing. It also en­cour­ages plas­tic­ity—the process by which neu­rons make new con­nec­tions. And it is im­por­tant for the func­tion of blood ves­sels, which sup­ply the brain with oxy­gen and glu­cose.

As a re­sult, re­duc­ing the level of in­sulin in the brain can im­me­di­ately im­pair cog­ni­tion. Spatial mem­ory, in par­tic­u­lar, seems to suf­fer when you block in­sulin up­take in the hip­pocam­pus. Con­versely, a boost of in­sulin seems to im­prove its func­tion­ing.

How “Brain Di­a­betes” De­vel­ops

When peo­ple fre­quently gorge on fatty, sug­ary food, their in­sulin spikes re­peat­edly. Mus­cle, liver, and fat cells stop re­spond­ing to the hor­mone and don’t mop up glu­cose and fat in the

blood. As a re­sult, the pan­creas des­per­ately works over­time to make more in­sulin to con­trol the glu­cose, and lev­els of the two mol­e­cules sky­rocket. The the­ory: Th­ese con­stantly high in­sulin lev­els also over­whelm the brain, which then be­comes less re­spon­sive to in­sulin, im­pair­ing the abil­ity to think and form mem­o­ries, be­fore lead­ing to per­ma­nent neu­ral dam­age.

De la Monte’s study on the rats with de­men­tia was one of the first ex­per­i­ments to con­firm that a dis­rupted in­sulin sys­tem can lead to Alzheimer’s symp­toms. There are other US stud­ies: Wil­liam Klein at North­west­ern Univer­sity in Evanston, Illi­nois, has found that trig­ger­ing di­a­betes cre­ated Alzheimer’s-like brain changes in rab­bits. Ewan McNay of the Univer­sity at Al­bany in New York and Suzanne Craft at the Univer­sity of Wash­ing­ton in Seat­tle fed rats a high-fat diet for 12 months, which de­stroyed their abil­ity to reg­u­late in­sulin and led to di­a­betes. They also had trou­ble nav­i­gat­ing a maze and looked “much like an Alzheimer’s pa­tient,” says McNay.

An­i­mal stud­ies can re­veal only so much about hu­man disease, but an al­most Franken­steinian demon­stra- tion con­firms that the brains of peo­ple with Alzheimer’s are in­sulin- re­sis­tant. Us­ing ca­daver brains, Steven Arnold at the Univer­sity of Penn­syl­va­nia bathed var­i­ous sam­ples in in­sulin; tis­sue from peo­ple who had not had Alzheimer’s seemed to spring back to life, trig­ger­ing a cas­cade of re­ac­tions sug­ges­tive of synap­tic ac­tiv­ity. In con­trast, the neu­rons of those who had had Alzheimer’s barely re­acted at all. “The in­sulin sig­nalling is par­a­lyzed,” says Arnold.

Another line of re­search sug­gests how: In­sulin and beta-amy­loid are both bro­ken down by the same en­zyme. Un­der nor­mal cir­cum­stances, that en­zyme can deal with both, but if too much in­sulin is wash­ing around, the en­zyme gets over­whelmed. The beta-amy­loid gets ne­glected and be­gins to ac­cu­mu­late, per­haps into the toxic plaques that kill brain cells.

By study­ing rat neu­rons, Klein has found that toxic clus­ters of be­taamy­loid at­tack and de­stroy brain tis­sue cov­ered in in­sulin re­cep­tors, which would re­sult in im­me­di­ate cog­ni­tive im­pair­ment. Worse still, this

“The epi­demic of type 2 di­a­betes is likely to be fol­lowed by an epi­demic of de­men­tia.”

Ewan McNay of the Univer­sity at Al­bany in New York

in­sulin re­sis­tance en­cour­ages cells to make even more beta-amy­loid, which then goes on to harm more brain cells, trig­ger­ing a vi­cious cy­cle.

In­sulin In­no­va­tions: Treat­ing and Pre­vent­ing De­men­tia

Re­searchers are keen to point out that this re­search is still in its early days. Klein, for ex­am­ple, thinks that lack of in­sulin in the brain may be just one of many trig­gers for beta-amy­loid tox­ins, so he’s search­ing for other cul­prits. Af­ter all, most peo­ple with Alzheimer’s don’t have full-blown type 2 di­a­betes, though many do have some in­sulin re­sis­tance.

Even so, the re­search should ring warn­ing bells for the fu­ture. In In­dia alone, some 60 mil­lion peo­ple are di­a­betic, a fig­ure that could reach 100 mil­lion by 2030. Many mil­lions are also pre­di­a­betic, show­ing some of the early signs of in­sulin re­sis­tance. If Alzheimer’s and type 2 di­a­betes share a sim­i­lar mech­a­nism, lev­els of de­men­tia may fol­low a sim­i­lar tra­jec­tory.

But even if some­one doesn’t de­velop di­a­betes, a bad diet might set the wheels in mo­tion for brain de­gen­er­a­tion, ac­cord­ing to an on­go­ing study led by Craft. For one month, vol­un­teers—none of whom had di­a­betes—ate foods high in sat­u­rated fat and su­gar, while a con­trol group ate a diet low in su­gar and sat­u­rated fat. In just four weeks, the for­mer had higher lev­els of in­sulin in their blood and sig­nif­i­cantly higher beta-amy­loid lev­els in their spinal fluid. The con­trol group showed de­creases in both.

On the plus side, a new un­der­stand­ing of the disease might lead to new treat­ments. Craft, for in­stance, is in­ves­ti­gat­ing whether a boost

of in­sulin might im­prove symp­toms in Alzheimer’s pa­tients. She has tested a de­vice that de­liv­ers in­sulin deep into the nose, where it then trav­els to the brain. The study lasted just four months and in­volved only 104 peo­ple, but those who re­ceived the treat­ment could re­call more de­tails of sto­ries, had longer at­ten­tion spans, re­gained more in­ter­est in their hob­bies, and were bet­ter able to care for them­selves. The glu­cose me­tab­o­lism in their brains also im­proved.

Clin­i­cal tri­als are in­ves­ti­gat­ing whether cer­tain di­a­betes drugs can im­prove Alzheimer’s symp­toms by reg­u­lat­ing in­sulin. Other groups plan to use ad­vanced brain imag- ing to see if di­a­betes med­i­ca­tions can shrink beta-amy­loid plaques, which might re­verse some brain dam­age.

In the mean­time, this re­search in­di­cates that main­tain­ing a healthy weight and life­style may help stave off cog­ni­tive de­cline. Since in­sulin re­sis­tance emerges from a bad diet, lay­ing off harm­ful fats and sweet foods might help re­duce the risk of Alzheimer’s. Con­versely, di­ets rich in omega-3 fatty acids might help the brain man­age in­sulin ef­fi­ciently. Ex­er­cise, too, can en­cour­age the body to con­quer in­sulin re­sis­tance, which may ex­plain why reg­u­lar phys­i­cal ac­tiv­ity re­duces your risk of Alzheimer’s by 40 per­cent.

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