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From Anti-Alzheimer’s “Magic Bullets” to True Brain Health

If you fol­lowed lat­est head­lines sur­round­ing the release of the National Alzheimer’s Plan, you’d prob­a­bly con­clude that the likely solu­tion to main­tain life­long brain health is sim­ple: sim­ply wait until 2025 for a “magic bul­let” to be dis­cov­ered, to cure (or end or pre­vent) Alzheimer’s dis­ease and aging asso­ci­ated cog­ni­tive decline. These kinds of beliefs, often rein­forced by doc­tors and adver­tis­ing, may explain the bil­lions spent today by pharma com­pa­nies on dis­cov­er­ing new com­pounds, and by con­sumers on sup­ple­ments like ginkgo biloba. But the fail­ures to pro­duce bet­ter drugs and con­flicts of inter­est are mak­ing many peo­ple ask what is wrong with this picture.

We need a new cul­ture of life­long brain health to empower that 80% of the 38,000 adults over 50 sur­veyed in the 2010 AARP Mem­ber Opin­ion Sur­vey who indi­cated “Stay­ing Men­tally Sharp” as their top ranked inter­est and con­cern, not to men­tion youth, work­ers and elders fac­ing cog­ni­tive and emo­tional challenges.

The prob­lem? That the “magic bul­let” approach nei­ther does it reflect exist­ing clin­i­cal evi­dence or emerg­ing neu­ro­sci­en­tific think­ing, nor does it address the life­long needs and demands of our citizens.

That’s why we need to shake the Etch-A-Sketch and cre­ate a new image of the future.

Let’s first draw our true objec­tive: is it to pro­mote men­tal vital­ity and col­lec­tive wis­dom or to declare war on Alzheimer’s plaques and tan­gles? Those are two rad­i­cally dif­fer­ent objec­tives, lead­ing to very dif­fer­ent pri­or­i­ties. For exam­ple, let’s imag­ine the impli­ca­tions of being able to max­i­mize cog­ni­tive per­for­mance and to delay cog­ni­tive decline.

Sec­ond, let’s build on what we know today. We know that 30% or more of the pop­u­la­tion with plaques and tan­gles do not man­i­fest sig­nif­i­cant cog­ni­tive decline. This is a fact –often explained via the “Cog­ni­tive Reserve” the­ory. It is also a fact (ignored in the report’s pre­sen­ta­tion and related media cov­er­age) that the most exhaus­tive sys­tem­atic evi­dence review, per­formed in 2010 under the aus­pices of NIH, found that non­phar­ma­co­log­i­cal fac­tors (such as phys­i­cal exer­cise, cog­ni­tive engage­ment, cog­ni­tive train­ing, and Mediter­ranean diet) seemed to be pro­tec­tive against cog­ni­tive decline, whereas “magic pill” inter­ven­tions (drugs, sup­ple­ments such as vit­a­mins and gingko biloba) had no such effect.

Third, let’s select the right frame­work and toolkit. While bio­med­ical research is indeed part of the solu­tion, pub­lic health/ edu­ca­tion ini­tia­tives and tech­nol­ogy inno­va­tion are equally impor­tant. The 2011 Sharp­Brains Vir­tual Sum­mit, which brought together more than 260 research, tech­nol­ogy and indus­try inno­va­tors in 17 coun­tries, high­lighted the need to devote suf­fi­cient atten­tion and resources to pre­ven­tive brain health strate­gies across the whole lifes­pan, and the need to bring to mar­ket a new gen­er­a­tion of reli­able and inex­pen­sive assess­ment and mon­i­tor­ing strate­gies of cog­ni­tive and emo­tional health — in order to tar­get and deliver those pre­ven­tive strate­gies in effi­cient ways. Inno­v­a­tive pub­lic edu­ca­tion ini­tia­tives, such as Expe­ri­ence Corps and The Inter­gen­er­a­tional School, may lead to bet­ter cog­ni­tive and health out­comes over the long-haul.

It sim­ply makes no sense to put all our eggs in the bio­med­ical bas­ket. Each of this column’s co-authors is pro­duc­ing a dif­fer­ent con­fer­ence in June: Dr. White­house and col­leagues on “Healthy Envi­ron­ments Across Gen­er­a­tions” (June 7–8, NYC) and Mr. Fer­nan­dez on “Opti­miz­ing Health via Neu­ro­plas­tic­ity, Inno­va­tion and Data” (June 7-14th, fully online). There are a num­ber of excit­ing and com­ple­men­tary approaches to “Stay­ing Men­tally Sharp” such as phys­i­cal exer­cise, mind­ful­ness med­i­ta­tion, biofeed­back, cog­ni­tive ther­apy and train­ing, volunteering…How can con­sumers make informed and rel­e­vant deci­sions today? And how can they use these reen­er­gized healthy brains to solve chal­lenges like global cli­mate change and eco­nomic stagnation?

Sure, more research is bet­ter than less, and we hope that the new funded tri­als will result in use­ful drugs. But nei­ther policy-makers nor cit­i­zens should wait until then to fos­ter and make lifestyle deci­sions than can max­i­mize cog­ni­tive per­for­mance across the lifespan.

JFK chal­lenged us not only to go to the moon, but to take proac­tive care of our phys­i­cal fit­ness. Per­haps the time has come for a seri­ous open national con­ver­sa­tion on true brain health and how the newly announced Alzheimer’s strate­gic plan must include health­ier and brainer think­ing than a war on Alzheimer’s plaques and tan­gles.

Dr. Peter White­house is a Pro­fes­sor of Neu­rol­ogy at Case West­ern Reserve Uni­ver­sity and co-author of The Myth of Alzheimers: what you aren’t being told about today’s most dreaded diag­no­sis. Alvaro Fer­nan­dez, recently named a Young Global Leader by the World Eco­nomic Forum, is the co-author of The Sharp­Brains Guide to Best Fit­ness: 18 Inter­views with Sci­en­tists, Prac­ti­cal Advice, and Prod­uct Reviews, to Keep Your Brain Sharp, an AARP Best Book, and pro­ducer of the 2012 Sharp­Brains Vir­tual Sum­mit: Opti­miz­ing Health through Neu­ro­plas­tic­ity, Inno­va­tion and Data (June 7-14th, 2012).

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2 Responses

  1. Bruce Brotter, PhD says:

    We could not agree more with the con­cerns and argu­ment posed by Dr. White­house. Yes– the NIH report tells us that there is so much that can be help­ful to healthy older adults as well as indi­vid­u­als suf­fer­ing from MCI and early stage AD. And yet, the National Alzheimer’s Project Act (NAPA, new ver­sion just released 5/15) does not once men­tion cog­ni­tive ther­apy or train­ing as an effec­tive inter­ven­tion, or even men­tion as an inter­ven­tion to be funded for fur­ther study. Even in the face of the NIH report and count­less oth­ers (inter­est­ingly not listed in the NAPA bib­li­og­ra­phy) the pro­tec­tive and restora­tive effects of cog­ni­tive train­ing are not discussed.

    Is it pos­si­ble, as Dr. White­house sug­gests, that the fund­ing from phar­ma­ceu­ti­cal com­pa­nies and the search for the “magic bul­let” is result­ing in neglect of what we already know and have in the “arse­nal” to help our patients strug­gling with the early effects of Alzheimer’s dis­ease? We think it is, and that a true dis­ser­vice is being done to patients and fam­i­lies who are in des­per­ate need of help NOW.

    We could not agree more with Dr Whitehouse’s state­ment that: “It sim­ply makes no sense to put all our eggs in the bio­med­ical bas­ket.” While of course bio­med­ical research should con­tinue, it seems irre­spon­si­ble to not make every effort to keep the pub­lic well-informed regard­ing effec­tive non-pharmaceutical interventions.

    It is of course our hope that ongo­ing research will lead to new and improved ways of treat­ing patients with chronic neu­ro­logic dis­eases such as Alzheimer’s, includ­ing the pos­si­bil­ity of a “magic bul­let — cure”. But we also know that in clin­i­cal prac­tice, bio­med­ical and psy­cho­log­i­cal or reha­bil­i­ta­tive inter­ven­tions are not mutu­ally exclu­sive. In fact, study after study in var­i­ous sub­spe­cial­ties of clin­i­cal med­i­cine report the syn­er­gis­tic effects of the two. In the field of cog­ni­tive rehab, a March, 2012 review of the lit­er­a­ture by Cotelli, et al., makes the case for the ben­e­fits of com­bin­ing bio­med­ical and cog­ni­tive rehab inter­ven­tions in rela­tion to Alzheimer’s patients: ”The stud­ies described above have shown that non-pharmacological inter­ven­tion can enhance the effect of ChEI treat­ment.” (Cotelli, 2012)

    So we know from the NIH review and oth­ers that cog­ni­tive train­ing is an effec­tive treat­ment for cog­ni­tive decline and early stage AD. We also know from the NIH review that the ben­e­fits of phar­ma­ceu­ti­cal approaches showed no such effect. And we now know that adding cog­ni­tive train­ing to phar­ma­ceu­ti­cal inter­ven­tion “enhances” the effect of med­ica­tion alone. Still, NAPA does not speak of the prac­tice or fund­ing of cog­ni­tive intervention.

    And there is more bad news com­ing. Despite the NIH report, and despite rec­om­men­da­tions of advo­cates for the Alzheimer’s patient such as the Alzheimer’s Asso­ci­a­tion and the Alzheimer Foun­da­tion of Amer­ica to pro­vide early detec­tion and TREATMENT, one of Medicare’s largest Car­ri­ers — NGS — has removed cog­ni­tive reha­bil­i­ta­tion as an accept­able treat­ment for mem­ory loss. This rul­ing most directly impacts upon the early Alzheimer’s (pre-clinical) patient.

    It is impor­tant to note that in 2007, NGS reviewed the most cur­rent stud­ies of that time, and changed their pol­icy to allow Alzheimer’s patients to ben­e­fit from cog­ni­tive reha­bil­i­ta­tion espe­cially mem­ory train­ing. It is only in 2009/2010 when NGS was reor­ga­nized that the deci­sion was reversed. This occurred just at the time that NIH informed us that cog­ni­tive train­ing was the only fac­tor asso­ci­ated with a decreased risk of cog­ni­tive decline (with a strong degree of sci­en­tific strength behind the research). Is it pos­si­ble that NGS was unaware of the lat­est research in the field? Is it pos­si­ble that this piv­otal find­ing was known but ignored?

    The Mem­ory Train­ing Cen­ters of Amer­ica has requested of NGS that patients suf­fer­ing from Alzheimer’s dis­ease (as well as other chronic, neu­rode­gen­er­a­tive dis­eases) be, again, allowed to receive one of the only inter­ven­tions that at this point in our his­tory is known to be help­ful. This month, the NGS Med­ical Staff ‘s pre­lim­i­nary response was to reject this request. NGS will not allow cog­ni­tive rehab to be applied to neu­ro­log­i­cal dis­eases such as early Alzheimer’s dis­ease when they demon­strate mem­ory loss and other cog­ni­tive dys­func­tions. These patients will only be allowed inef­fec­tive med­ica­tion. We are appeal­ing that decision.

    One has to won­der what could pos­si­bly be the moti­va­tion of Medicare to stop a med­ically nec­es­sary treat­ment that can relieve or delay the major symp­toms of this dev­as­tat­ing dis­ease, in the face of the research, and in the absence of a “magic bul­let”. With NAPA’s goal of find­ing that bul­let by the year 2025. What are we to tell our patients TODAY, who we know we can help, but from whom Medicare is now with­hold­ing treatment?

    Bruce Brot­ter, PhD, Clin­i­cal Direc­tor, Mem­ory Train­ing Cen­ters of America

  2. Steve Zanon, Director Proactive Ageing says:

    The lat­est NIH per­spec­tive as sum­marised by 57 expert speak­ers and pan­el­lists at the recent NIH Alzheimer’s Dis­ease Research Sum­mit, May 2012 is now avail­able. These Research Rec­om­men­da­tions will go directly the Health and Human Ser­vices Sec­re­tary for her con­sid­er­a­tion toward meet­ing the research goals set forth in the National Plan to Address Alzheimer’s Dis­ease. Kath­leen Sebe­lius, her­self also pre­sented at this Sum­mit – adding her weight to the proceedings.

    Much of the Sum­mit was devoted to bio­mark­ers and drug inter­ven­tions, how­ever one ses­sion (out of a total of 6) cov­ered non-pharmacological inter­ven­tions. That’s good news in itself. It was also heart­en­ing to see that one rec­om­men­da­tion from this par­tic­u­lar ses­sion was to “Ini­ti­ate rig­or­ously designed clin­i­cal tri­als in asymp­to­matic and cog­ni­tively impaired older adults to estab­lish the effec­tive­ness of phys­i­cal exer­cise, cog­ni­tive train­ing, and the com­bi­na­tion of these inter­ven­tions for Alzheimer’s dis­ease treat­ment and prevention.”

    Unfor­tu­nately med­i­cines to pre­vent and/or treat Alzheimer’s are look­ing a long way off. Two com­ments from the Summit’s Research Rec­om­men­da­tions include .…. “In 2006 PhRMA, the phar­ma­ceu­ti­cal industry’s advo­cacy group, reported over 80 ther­a­pies in clin­i­cal devel­op­ment for AD. To date, none of these ther­a­pies has been suc­cess­ful in late-phase clin­i­cal tri­als, with at least 20 fail­ing in Phase III and many more fail­ing in Phase II”. .…. “Alzheimer’s is a highly het­ero­ge­neous, mul­ti­fac­to­r­ial dis­or­der with a very long pro­dro­mal period. There is grow­ing real­iza­tion that iden­ti­fy­ing suc­cess­ful inter­ven­tions for AD will require strat­i­fi­ca­tion of patients across mul­ti­ple criteria”.

    In the future, effec­tive treat­ment and pre­ven­tion inter­ven­tions will likely require a com­bi­na­tion of per­son­alised exercise/lifestyle plans and per­son­alised phar­ma­ceu­ti­cal strate­gies, with reg­u­lar re-assessments start­ing in our 40’s just like we have cho­les­terol tests and inter­ven­tion strate­gies. But for now sev­eral lifestyle fac­tors (includ­ing phys­i­cal & men­tal exer­cise) start­ing in mid life or ear­lier are our best bet for demen­tia pre­ven­tion. Doing noth­ing and hop­ing for an effec­tive generic Alzheimer’s phar­ma­ceu­ti­cal treat­ment in the near future is I believe a risky per­sonal strategy.

    We don’t yet have an assured solu­tion for Alzheimer’s or the other demen­tias and the evi­dence to date shows that researchers are strug­gling with prospec­tive phar­ma­ceu­ti­cal solu­tions. So we need to take some respon­si­bil­ity for man­ag­ing uncer­tainty – both indi­vid­u­ally and as a soci­ety. As I wrote back in 2010 “with any good risk man­age­ment strat­egy our best bet is to diver­sify risk across sev­eral of the most likely fac­tors. The [NIH] ‘Sys­tem­atic Evi­dence Review’ clearly iden­ti­fies the most likely risk fac­tors. We don’t have cer­tainty but we do have direc­tion and I think that is an encour­ag­ing mes­sage for the pub­lic”.…. and maybe for respon­si­ble gov­ern­ments too.

    Links .….
    – Alzheimer’s Dis­ease Research Sum­mit, May 2012 http://www.nia.nih.gov/newsroom/announcements/2012/05/alzheimers-research-summit-may-14–15-2012
    – Com­ments on 2010 NIH State-of-the-Science Review http://www.sharpbrains.com/blog/2010/05/14/cognitive-training-identified-as-protective-with-highest-evidence-in-recent-nih-alzheimers-cognitive-decline-prevention-report/

    Steve Zanon, Direc­tor Proac­tive Ageing

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