aducanumab

Could I be wrong? Exploring cognitive bias, curiosity, intellectual humility, and lifelong learning

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Wel­come to a new edi­tion of Sharp­Brains’ e‑newsletter, fea­tur­ing eight time­ly sci­en­tif­ic and indus­try news plus a few fun teasers to appre­ci­ate our unique human brains.

#1. Could I be wrong? Explor­ing research on cog­ni­tive bias, curios­i­ty, intel­lec­tu­al humil­i­ty, and life­long learning

“None of us thinks that our beliefs and atti­tudes are incor­rect; if we did, we obvi­ous­ly wouldn’t hold those beliefs and atti­tudes. Yet, despite our sense that we are usu­al­ly cor­rect, we must accept that our views may some­times turn out to be wrong. This kind of humil­i­ty isn’t sim­ply virtuous—the research sug­gests that it results in bet­ter deci­sions, rela­tion­ships, and out­comes. So, the next time you feel cer­tain about some­thing, you might stop and ask your­self: Could I be wrong?”

#2. Great inter­view on bilin­gual­ism, sports, edu­ca­tion and neu­ro­plas­tic­i­ty — en español

#3. Should old­er politi­cians, and oth­er lead­ers, under­go cog­ni­tive test­ing? The debate con­tin­ues … here are some good com­ments from the online debate we had last summer:

  • PRO: “Def­i­nite­ly. We rou­tine­ly screen appli­cants for a wide range of jobs. Apply for the police, you will be test­ed. Join the mil­i­tary, you will be eval­u­at­ed. Should we not know if a can­di­date for the high­est posi­tion in the coun­try has a seri­ous emo­tion­al, intel­lec­tu­al or psy­cho­log­i­cal impairment?”
  • CON: “I dis­agree because these tests are very bad at pre­dict­ing how good some­one would be in lead­ing a coun­try. It doesn’t require the abil­i­ty to store a lot of infor­ma­tion in your work­ing mem­o­ry. Being a good leader requires only one essen­tial thing: hav­ing the right priorities.”
  • IT DEPENDS: “Who makes the test? What cog­ni­tive met­rics do we use? The bias­es in that design could lead to sig­nif­i­cant unex­pect­ed or even inten­tion­al­ly skewed results.”

#4. Click Ther­a­peu­tics rais­es fur­ther $52M to build up dig­i­tal ther­a­peu­tics pipeline for depres­sion, insom­nia, smok­ing ces­sa­tion and more

What a year for Click and for dig­i­tal therapeutics!

#5. The Amer­i­can Med­ical Association’s (AMA) to ease access to remote Cog­ni­tive Behav­ioral Ther­a­py Monitoring

The road to heav­en is paved with good decisions…

#6. FDA-approved, Cybin-spon­sored clin­i­cial tri­al to mea­sure ketamine’s impact on the brain via Ker­nel Flow neu­roimag­ing helmet

“The word psy­che­del­ic means ‘mind-man­i­fest­ing,’ but what has been miss­ing is use­ful ‘mind-imaging’—the abil­i­ty to dynam­i­cal­ly trace the neur­al cor­re­lates of human con­scious expe­ri­ence. Con­ven­tion­al neu­roimag­ing just isn’t dynam­ic enough to study the psy­che­del­ic expe­ri­ence in the brain as it hap­pens. This study of ketamine’s psy­che­del­ic effects while wear­ing head­gear equipped with sen­sors to record brain activ­i­ty could open up new fron­tiers of under­stand­ing” — Dr. Alex Belser, Cybin’s Chief Clin­i­cal Officer

#7. Bea­con Biosig­nals rais­es $27M to scale EEG, AI-based neu­ro­bio­mark­er dis­cov­ery platform

“ana­lyz­ing EEGs is labor inten­sive and inter­pre­ta­tion of these tests can vary from one clin­i­cian to another..…Beacon Biosig­nals has assem­bled what it claims is one of the world’s largest clin­i­cal EEG data­bas­es. By apply­ing its pro­pri­etary machine-learn­ing algo­rithms to the data­base, the com­pa­ny says it has iden­ti­fied neurobiomarkers—biological indi­ca­tors that are asso­ci­at­ed with cer­tain groups of patients, drug activ­i­ty, and ther­a­peu­tic efficacy.”

#8. Amy­loid-relat­ed imag­ing abnor­mal­i­ties (ARIA) found in approx­i­mate­ly 40% of patients tak­ing “Alzheimer’s drug” Aduhelm

Not good, yet com­plete­ly pre­dictable, and let’s remem­ber this is for a “treat­ment” cost­ing as much as $100,000/ year with exact­ly ZERO proven clin­i­cal ben­e­fit: “…The researchers found 425 cas­es in the com­bined adu­canum­ab group expe­ri­enced ARIA (41.3%), and ARIA-ede­ma was iden­ti­fied in 362 patients or 35.2%. Of them, 94 (26%) had symp­toms, such as headache, con­fu­sion, dizzi­ness and nau­sea. They found ARIA-micro­he­m­or­rhage and ARIA-super­fi­cial sidero­sis in 197 patients (19.1%) and 151 patients (14.7%), respectively.”

Final­ly, Let’s Thank our unique Human Brains and Minds with a few fam­i­ly-friend­ly riddles

Q: What does, “you must come and vis­it us some­time!” actu­al­ly mean?

 

Wish­ing you and yours a Hap­py & Healthy Hanukkah, Decem­ber and Christmas,

The Sharp­Brains Team

 

Amyloid-related imaging abnormalities (ARIA) found in approximately 40% of patients taking “Alzheimer’s drug” Aduhelm

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Study: Biogen’s Aduhelm Caused Brain Swelling in Over One-Third of Study Par­tic­i­pants (Bio­Space):

Atten­tion is being focused on a side effect of Biogen’s Alzheimer’s drug, Aduhelm (adu­canum­ab). Even before its con­tro­ver­sial approval on June 7, there were cas­es of amy­loid-relat­ed imag­ing abnor­mal­i­ties (ARIA‑E), or cere­bral ede­ma, observed in the tri­als. [Read more…] about Amy­loid-relat­ed imag­ing abnor­mal­i­ties (ARIA) found in approx­i­mate­ly 40% of patients tak­ing “Alzheimer’s drug” Aduhelm

Study: Fewer than 1% of geriatric patients with cognitive complaints met Aduhelm research trial criteria. What can we expect about its real-world safety?

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Bio­gen’s Aduhelm label far exceeds clin­i­cal tri­al pop­u­la­tion, study says. That could bring real-world sur­pris­es (Fierce Pharma):

While the chat­ter sur­round­ing Biogen’s con­tro­ver­sial Alzheimer’s med Aduhelm has large­ly been cen­tered on a piv­otal Medicare reim­burse­ment deci­sion as of late, ana­lysts are point­ing to one new study that sug­gests there may be “room for sur­pris­es” when it comes to the treatment’s safe­ty. [Read more…] about Study: Few­er than 1% of geri­atric patients with cog­ni­tive com­plaints met Aduhelm research tri­al cri­te­ria. What can we expect about its real-world safety?

Veterans Affairs won’t cover Biogen’s new “Alzheimer’s drug” given concerns over safety and lack of evidence

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VA Health Sys­tem Won’t Cov­er Biogen’s Alzheimer’s Drug (The Wall Street Journal):

The Depart­ment of Vet­er­ans Affairs won’t cov­er Bio­gen Inc.’s new Alzheimer’s drug, the lat­est rebuke of the con­tro­ver­sial treat­ment since it was approved ear­li­er this summer.

The VA decid­ed not add the drug, called Aduhelm, to its for­mu­la­ry list of avail­able med­i­cines because of the drug’s risk of caus­ing seri­ous side effects and a lack of evi­dence that it improves cog­ni­tive func­tion, an agency spokes­woman said. [Read more…] about Vet­er­ans Affairs won’t cov­er Biogen’s new “Alzheimer’s drug” giv­en con­cerns over safe­ty and lack of evidence

Update on the aducanumab (Aduhelm) saga, retirement, financial advice, cognitive health, excessive worrying, neurotech, and more

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Wel­come to a new edi­tion of Sharp­Brains’ e‑newsletter, pro­vid­ing this time a sum­ma­ry of the saga around the FDA approval of adu­canum­ab (Aduhelm) as a sup­posed treat­ment for Alzheimer’s Dis­ease, plus a range of time­ly research find­ings and resources for life­long brain health.

First, below are some key reads to nav­i­gate “prob­a­bly the worst drug approval deci­sion in recent U.S. his­to­ry” — Dr. Aaron Kessel­heim, the Pro­fes­sor of Med­i­cine at Har­vard Med­ical School who resigned rom the FDA Advi­so­ry Com­mit­tee in protest.

#1. Grow­ing back­lash against the FDA approval of unproven Alzheimer’s treat­ment Aduhelm, by Bio­gen:

“The Insti­tute for Clin­i­cal and Eco­nom­ic Review (ICER) believes that the FDA, in approv­ing adu­canum­ab (Aduhelm by Bio­gen) for the treat­ment of Alzheimer’s dis­ease, has failed in its respon­si­bil­i­ty to pro­tect patients and fam­i­lies from unproven treat­ments with known harms.”

#2. First, do no harm? Six rea­sons to approach anti-amy­loid drug Aduhelm cau­tious­ly, if at all:

“The FDA’s approval of Aduhelm rais­es more ques­tions and cre­ates more prob­lems than a new drug approval should. It’s time for gov­ern­men­tal, pro­fes­sion­al, and advo­ca­cy enti­ties to step in where Bio­gen and the FDA have failed and explain to patients, care­givers, and clin­i­cians how this drug is not the “new day” in the fight against Alzheimer’s dis­ease and needs to be approached cau­tious­ly, if at all.” — Dr. Sam Gandy, Pro­fes­sor of Neu­rol­o­gy and Psy­chi­a­try at the Icahn School of Med­i­cine at Mount Sinai, where he holds the Mount Sinai Chair in Alzheimer’s Research

#3. Can the con­tro­ver­sial FDA approval of Aduhelm back­fire and delay the dis­cov­ery of actu­al Alzheimer’s treat­ments? (Yes, it can):

“In short, while the amy­loid hypoth­e­sis has fal­tered, the approval of adu­canum­ab, which is based pri­mar­i­ly on this the­o­ry, sug­gests that the the­o­ry may once again dom­i­nate research, and could reduce the chances of find­ing more promis­ing treat­ments. For exam­ple, tau pro­tein, which also accu­mu­lates in the brains of Alzheimer’s patients — long before the amy­loid pro­tein does — has been shown to be close­ly asso­ci­at­ed with the cog­ni­tive impair­ment result­ing from the dis­ease … we must not inter­rupt research on bio­mark­ers and new ther­a­peu­tic approaches.”

#4. US Sen­a­tor Joe Manchin calls for a new FDA Com­mis­sion­er to replace cur­rent (act­ing) one who “has repeat­ed­ly ignored pub­lic health con­cerns and shown a dere­lic­tion of duty” over opi­oids and adu­canum­ab:

“I write today con­cern­ing the lack of per­ma­nent lead­er­ship at the Food and Drug Admin­is­tra­tion (FDA), and the con­tin­ued tenure of Dr. Janet Wood­cock as inter­im com­mis­sion­er. Just last week, the FDA grant­ed approval for Aduhelm (adu­canum­ab), a treat­ment for Alzheimer’s, despite its advi­so­ry pan­el vot­ing near­ly unan­i­mous­ly against its approval, with no pan­el mem­ber vot­ing in favor of approval”

(Let’s hope some­thing use­ful emerges from this very unhealthy FDA deci­sion. Quite dis­turb­ing, though, to notice the links between the opi­oid epi­dem­ic and the recent Aduhelm approval.)

#5. Health payers–including Medicare and Point32Health–to ques­tion Aduhelm pric­ing and its “rea­son­able and nec­es­sary” use:

“Under the broad label that FDA approved, the drug is avail­able to all Alzheimer’s patients, and the agency did not place lim­its on treat­ment dura­tion sug­gest­ing that patients could remain on the drug indef­i­nite­ly. We are trou­bled by reports that those fac­tors could lead the drug to com­mand “some­where between” the $37 bil­lion we cur­rent­ly spend on Medicare Part B and the $90 bil­lion we cur­rent­ly spend on Medicare Part D. This lev­el of poten­tial new spend­ing, par­tic­u­lar­ly for just one prod­uct with lim­it­ed evi­dence of clin­i­cal effi­ca­cy thus far, tests the program’s resiliency.”

The stakes could­n’t be higher.

Now let’s review oth­er impor­tant devel­op­ments in June.

#6. Debate: What is the role of finan­cial advi­sors and plat­forms in detect­ing and address­ing cog­ni­tive decline among old­er clients?:

” … big do-it-your­self invest­ing and trad­ing venues like Van­guard Group, Fideli­ty Invest­ments and Charles Schwab Corp. are strength­en­ing some of the ways they detect pos­si­ble signs of decline. Among oth­er things, all three firms check for clients’ dif­fi­cul­ty nav­i­gat­ing secu­ri­ty pro­to­cols or need for fre­quent pass­word resets. In such cas­es, a des­ig­nat­ed fam­i­ly mem­ber might be informed.

Van­guard also checks client-call record­ings for keywords—such as “con­fused” and “dementia”—that might sig­nal trouble.”

#7. Study in Chi­na finds that retire­ment may accel­er­ate cog­ni­tive decline, even for those with sta­ble income:

“While retire­ment schemes like the 401(k) and sim­i­lar pro­grams in oth­er coun­tries are typ­i­cal­ly intro­duced to ensure the wel­fare of aging adults, our research sug­gests they need to be designed care­ful­ly to avoid unin­tend­ed and sig­nif­i­cant adverse con­se­quences. When peo­ple con­sid­er retire­ment, they should weigh the ben­e­fits with the sig­nif­i­cant down­sides of a sud­den lack of men­tal activ­i­ty. A good way to ame­lio­rate these effects is to stay engaged in social activ­i­ties and con­tin­ue to use your brains in the same way you did when you were working.

In short, we show that if you rest, you rust.”

#8. The explo­sion of men­tal health apps rais­es sub­stan­tial opportunities–and tough ques­tions:

“Dig­i­tal men­tal health can be viewed as a way to extend the men­tal resources that we have,” said David Mohr, who directs the Cen­ter for Behav­ioral Inter­ven­tion Tech­nolo­gies at the North­west­ern Uni­ver­si­ty Fein­berg School of Med­i­cine. A step-care mod­el, for exam­ple, would allow patients with milder symp­toms to be treat­ed via tech­nol­o­gy while reserv­ing in-per­son care for patients who need some­thing more.

#9. Pre­scrip­tion soft­ware firm Pear Ther­a­peu­tics to go pub­lic via $1.6 bil­lion SPAC deal, har­ness­ing 3 FDA-autho­rized prod­ucts and 14 can­di­dates:

“Pear is one of nine com­pa­nies invit­ed to par­tic­i­pate in the U.S. Food and Drug Administration’s (FDA) Pre­cer­ti­fi­ca­tion Pilot Pro­gram. Pear has devel­oped and com­mer­cial­ized the first three FDA-autho­rized PDTs, has 14 prod­uct can­di­dates, and is scal­ing its plat­form for third-par­ty prod­uct dis­tri­b­u­tion oppor­tu­ni­ties. The Company’s three FDA-autho­rized prod­ucts, reSET®, reSET‑O® and Som­ryst®, address large mar­ket oppor­tu­ni­ties with more than 20 mil­lion patients suf­fer­ing from sub­stance and opi­oid use dis­or­ders and more than 30 mil­lion from chron­ic insom­nia, in the U.S. alone, respectively.”

#10. Don’t wor­ry, be hap­py: How exces­sive wor­ry­ing may influ­ence the rate of neu­rode­gen­er­a­tion:

“(Research find­ings) sug­gest that cog­ni­tive func­tion may need to be mon­i­tored close­ly in indi­vid­u­als with affec­tive dis­or­ders, as these indi­vid­u­als may be at par­tic­u­lar risk of greater cog­ni­tive decline.”

#11. Smarter cars are com­ing soon … : Eye-track­ing pio­neer Smart Eye acquires MIT spin-off Affec­ti­va to aug­ment dri­ver mon­i­tor­ing sys­tems and more

#12. And, much more: DARPA-fund­ed non­sur­gi­cal neu­rotech­nolo­gies push the fron­tier of brain-machine interfaces

Final­ly, a quick cog­ni­tive exer­cise. Giv­en the uni­ver­sal beau­ty of math, you don’t need to speak Span­ish to try this quick teas­er: Brain teasers en español: ¿cuál es el número que fal­ta en el cuar­to triángulo?

Wish­ing you a hap­py and healthy summer,

The Sharp­Brains Team

Can the controversial FDA approval of Aduhelm backfire and delay the discovery of actual Alzheimer’s treatments? (Yes, it can)

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The U.S. Food and Drug Admin­is­tra­tion (FDA) recent­ly approved adu­canum­ab, the first treat­ment that aims to slow the pro­gres­sion of Alzheimer’s dis­ease. But approval of the drug has pro­voked mixed reac­tions from the sci­en­tif­ic community.

Alzheimer’s dis­ease is char­ac­ter­ized by pro­gres­sive mem­o­ry loss, spa­tial dis­ori­en­ta­tion and many oth­er cog­ni­tive and behav­iour­al dis­or­ders that ulti­mate­ly lead to a state of total depen­dence. [Read more…] about Can the con­tro­ver­sial FDA approval of Aduhelm back­fire and delay the dis­cov­ery of actu­al Alzheimer’s treat­ments? (Yes, it can)