A statistical approach used to support amyloid-targeting treatment for Alzheimer's disease may lead to overstated claims about amyloid-cognition relationships, an analysis suggested. @sfackley.bsky.social https://www.medpagetoday.com/neurology/alzheimersdisease/121382

Study Questions Methods Used in Alzheimer's Drug Analysis

Quantile aggregation may lead to overstated claims about amyloid-cognition relationships

medpagetoday.com

Check out our new research letter!

JAMA Neurology@jamaneurology.com · 3mo ago

Quantile aggregation may artificially inflate amyloid-cognition associations in #AlzheimerDisease trials, highlighting need for causally interpretable methods when assessing surrogate endpoints. ja.ma/3RkFrBW

🧪 #alzheimer #amyloid Amazing new paper from @sfackley.bsky.social that exposes the statistical alchemy Lilly applied to their donanemab data: jamanetwork.com/journals/jam... There is little to no correlation between amyoid removal and clinical outcomes with donanemab (or lecanemab).

Methodological Considerations for Quantile Aggregation in Alzheimer Disease Trials

This study evaluates the quantile-aggregation method using both simulated data and publicly available Alzheimer disease randomized trial data.

jamanetwork.com

Beware the reanalysis -

Sarah Ackley @sfackley.bsky.social · 3mo ago

Eli Lilly’s reanalysis of TRAILBLAZER-ALZ 2 proposes a new method for evaluating amyloid as a surrogate endpoint and argues the resulting high R-squared values are “unlikely to be artificially inflated.” Our response now out in JAMA Neurology: they are. jamanetwork.com/journals/jam...

Appreciation to @mikegreicius.bsky.social for sharing this and to @sfackley.bsky.social for this important paper. It carefully examines whether amyloid removal in donanemab aligns with meaningful clinical benefit. Follow @academaxjournals.bsky.social for relevant research. #Science #Neuroscience

Mike Greicius@mikegreicius.bsky.social · 3mo ago

🧪 #alzheimer #amyloid Amazing new paper from @sfackley.bsky.social that exposes the statistical alchemy Lilly applied to their donanemab data: jamanetwork.com/journals/jam... There is little to no correlation between amyoid removal and clinical outcomes with donanemab (or lecanemab).

Professor @sfackley.bsky.social finds prior methods of studying cognition and amyloid, which builds up in the brains of Alzheimer’s patients "made a failed trial look like it had successfully removed amyloid." Learn more 🧠 https://sph.brown.edu/news/2026-05-18/alzheimers-analysis-donanemab

Lilly used "quantile-aggregation" to transform individual level data with 100s of data points and a correlation of 0.08 (see figure) into 10 data points with a correlation of 0.87! Dr. Ackley clearly debunks this approach with simulations and real-world data. Check it out. Spread the word.

Eli Lilly’s reanalysis of TRAILBLAZER-ALZ 2 proposes a new method for evaluating amyloid as a surrogate endpoint and argues the resulting high R-squared values are “unlikely to be artificially inflated.” Our response now out in JAMA Neurology: they are. jamanetwork.com/journals/jam...

Methodological Considerations for Quantile Aggregation in Alzheimer Disease Trials

This study evaluates the quantile-aggregation method using both simulated data and publicly available Alzheimer disease randomized trial data.

jamanetwork.com

"I am a clinical epidemiologist whose research focuses on assessing interventions for the treatment and prevention of dementia," @sfackley.bsky.social writes. "I believe it is premature to promote coffee for the prevention of dementia." https://wapo.st/4s5WRiD

For those of you attending #GSA2025 in Boston, consider this panel of #NIH awardees, Drs. Alden Gross, @mariaglymour.bsky.social , @sfackley.bsky.social , and @bryandjames.bsky.social. Please remember to tag #geronsky and @geronsociety.bsky.social in your posts.

🔔 #TRCI Special Issue 🔔 Marking the 10th anniversary of AD Drug Development Pipeline articles led by Dr. Jeffrey Cummings! Submit your research highlighting advances in ADRD clinical trials and drug development! ⏰Oct. 31, 2026 alz-journals.onlinelibrary.wiley.com/hub/journal/...

Alzheimer's & Dementia: Translational Research & Clinical Interventions

<em>Alzheimer's & Dementia: Translational Research & Clinical Interventions</em> journal bridges drug discovery research and clinical studies for dementia & Alzheimer's.

alz-journals.onlinelibrary.wiley.com

Such a cool paper. #EpiSky @amjepi.bsky.social #DataScience #Reproducibility Led by @sfackley.bsky.social at @brown-epi.bsky.social Research on reproducible research funded by NIH/NIA - thank you!

Triangulation of Innovative Methods to End Alzheimer’s Disease@timead.bsky.social · 11mo ago

🔎 Meta-analysis and triangulation depend on credible science. 📈 TIME-AD’s latest paper, led by Dr. Sarah Ackley, examines 20,000+ abstracts using an LLM to determine whether P value trends reflect changes in p-hacking, publication bias, or statistical power. Read it: tinyurl.com/3f3nuxma

Check out our recently published paper at AJE! academic.oup.com/aje/advance-... We analyzed 21,332 abstracts (2000-2024) from four major epidemiology journals, extracting 25,288 P values using ChatGPT’s 4o model with few-shot in-context prompting. #episky #reproducibility #metasci #metascience

#TIME-AD is heading to #AAIC25! 📊 We’ll be sharing results from our latest preprint examining whether reductions in brain amyloid—a key Alzheimer’s biomarker—can meaningfully predict changes in cognition and functioning. 🔗 Read the preprint: tinyurl.com/5n8psura

Looking forward to presenting this renanalysis of the A4 study, as well as a simulation study evaluating SILA's ability to detect ceilings in amyloid accumulation at #AAIC25. #ENDALZ www.medrxiv.org/content/10.1...

Evaluation of Amyloid Removal as a Surrogate for Cognitive Decline: Pilot Analysis in Individual-Level Data from the A4 Study of Solanezumab

Background Amyloid removal has been used as a surrogate outcome in Alzheimer’s disease trials, allowing accelerated approval of aducanumab and lecanemab. The A4 (Alzheimer’s Clinical Trial Consortium ...

medrxiv.org

🧠 TIME-AD is now on Bluesky! #TIME-AD brings together results from different study designs and populations to find what really works to prevent and delay dementia. Follow along as we share what we’re learning and check out our website to learn more: www.time-ad.org #EndALZ #EpiSky #NeuroSky

New preprint up! Evaluation of Amyloid Removal as a Surrogate for Cognitive Decline: Pilot Analysis in Individual-Level Data from the A4 Study of Solanezumab www.medrxiv.org/content/10.1...

Excellent talk at #MELODEM2025 by @sfackley.bsky.social evaluating amyloid as a surrogate marker with individual level A4 trial data One big take away — 5 years was not enough time to see cognitive decline in the placebo group == a major challenge

Now at #MELODEM2025 Is reducing/removing amyloid from the brain a reasonable surrogate for slowing/stopping cognitive decline in dementia? @sfackley.bsky.social uses data from the A4 RCT (of solanezumab) to answer this q, ... @melodem.bsky.social

I was invited to comment for AlzForum on GLP-1s and dementia. GLP-1s show promise, but RCTs like GRADE have not demonstrated clear cognitive benefits. Observational studies may be confounded by socioeconomic factors and prescribing patterns. Read the full comment: www.alzforum.org/papers/gluco...

In addition to today's NIH-grant-related anxiety, a cat vomited a fur ball in my shoe.

www.nytimes.com/2025/04/14/u...

Harvard Will Not Comply With a List of Trump Administration Demands (Gift Article)

Federal officials said Harvard must enact “merit-based reform” in hiring and admissions and report international students who broke rules, among other steps. Harvard called the demands unlawful.

nytimes.com

I wrote 1/3 of a page of my grant!

So many more people than I realized!

Conor McDonough@conormcdonough.com · last yr.

This is what democracy looks like in Providence, RI #handsoff @indivisibleri.bsky.social @indivisible.org @alexagagosz.bsky.social @fitzprov.bsky.social @tednesi.bsky.social @globeri.bsky.social @steveahlquist.bsky.social @nancyklavin.bsky.social

Note on my previous calculation--arguably 1/1000 is too high.

Seth Edmunds@phealthy.bsky.social · last yr.

That figure is pretty old by this point and suffers from MAUP, these areas are more akin to LMICs than the typical US counties. www.thelancet.com/journals/lan...

1/ The number of deaths (3) in this measles outbreak seems high given its size (480 TX + 50 OK + 10 NM = 544). Typically, ~1/1000 die from measles based on past data (pre- and post-elimination). Is it possible cases are underreported? #episky

Some math/physics history I happened across yesterday— David Hilbert lived to see the Nazis purge many prominent faculty members at the University of Göttingen in 1933, including Hermann Weyl, Emmy Noether, and Edmund Landau. (Wikipedia)

Breaking News: The Trump administration intends to block $510 million in federal contracts and grants for Brown University.

Trump Administration Set to Pause $510 Million for Brown University

The administration has now targeted five schools’ federal funding as part of a pledge to combat what it considers to be antisemitism on university campuses.

nytimes.com

Of all the important questions and issues raised here, the least pressing (but still curious) is... why is the thumbnail a photo of MIT? www.msn.com/en-us/news/p...

Hmmm… This must be why my work backpack is always covered in cat fur