Jennifer Weuve

Additional gratitude to The @tejenson.bsky.social for orchestrating the session, which included the best marketing prose on an epi/EH methods seminar invite in recent memory.

What was esp helpful about Amanda's talk was getting a firmer sense of seeing how ITB plays out with exposures distributed on a continuum (an expansion on the examples many of us have seen that involve dichotomous exposures).

In the true-story example she chronicled, effects estimated using a design that induced ITB were impressively large (one might call a HR of 51 gargantuan). Upon correction, they all shrank. & though some remained large (that HR of 51 became a HR of 5.5), some previously adverse findings became null.

A big holler-y grateful shout-out to **Amanda Gassett**, Research Scientist at University of Washington, for presenting clearly and constructively on dodging immortal time bias in studies of air pollution's health effects. #EnviroBrain #CONFAB @busph.bsky.social

Patterns of earnings trajectories (age 25 thru 60) differed by sex and a bit by birth cohort.

Cognitive decline was faster among ppl w earnings trajectories that cycled and that were consistently low. Those w consistently high earnings had the slowest mean decline.

@melodem.bsky.social

@ccolvin94.bsky.social presents meticulously thought-thru & generated results on life course earnings trajectories & cognitive decline, by birth cohort. The #MELODEM2025 equivalent of a walk-off HR will launch us into deep thoughts, conversations, and collaborations over the coming weeks and months.

Proposed setting/Discovery cohort: WHICAP Offspring Study (many wmn had not entered menopause as of baseline)

More enlightening lightning (talks) at #MELODEM2025: Justina Avila-Rieger dares to wade thru the thicket that is reproductive status (and aging) in relation to dementia risk. Idea: exploit DNA methylation, which can reflect changes in the endocrine system and hormonal status.

@melodem.bsky.social

Exposure to fluoride was assoc'd w higher achievement in education (e.g., math). Not at all assoc'd w cogn at age 60.

So ... how about cogn later on in life?

Setting: High School & Beyond

Exposure: Based on location of pt's secondary school (>1000 high schools are represented here) and the fluoridation status of water there. Sufficient for none, part, or all of childhood.

Fluoride. Great for oral health and stunning teeth. Does it exposure to it in childhood related to cogn later in life? @ #MELODEM2025, Rob Warren (U MN) points out the extraordinarily high exposures in studies of kids' IQs: not relevant to what's in our public water supply.

@melodem.bsky.social

Trend 1: cardiometabolic RF prevalence has been increasing
Trend 2: dementia incidence and prevalence have been decreasing

But, in the absence of trend 1, trend 2 (the decreases in dementia inc and prev) would have been steeper.

Now up @ #MELODEM2025, @astokespop.bsky.social teases out the contribution of secular trends in midlife cardiometabolic health in relation to trends in dementia incidence and prevalence in the US.

@melodem.bsky.social

Cool innovation here: this is about the cog effects of incident trauma, not the effects of prevalent (historical) trauma.

Our next lightning bolt @ #MELODEM2025 is from Katrina Kezios, presenting research on incident traumatic experiences in relation to cog change in older adults. Upshot: these exp were assoc'd w cog decline, esp among those w worse financial well-being.

@melodem.bsky.social

@melodem.bsky.social

Iris Strangmann issues the first bolt of a lightning talk in today's #MELODEM2025. Does being multilingual offer cognitive benefits in older age? She is using data from LASI-DAD to answer this q, evaluating assns within strata of urbanicity and SES.

Younger age, male (v fem), being White (not Latinx, Black), higher mid-life income, lower cog scores, more disability, and more comorbidities. (Others coming to a journal near you.)

Carrying the #MELODEM2025 baton now is Melinda Power (GW). Among ppl who have #dementia, a large % have not been diagnosed. What predicts who gets diagnosed in a timely fashion?

@melodem.bsky.social

A shout-out to yesterday afternoon's and todays moderators--Suzanne Judd, @ermayeda.bsky.social, @relajoie.bsky.social, & @miguelarce.bsky.social--for shrewdly ensuring that talks run on time and discussions are inclusive.

@melodem.bsky.social

A key ingredient to the appeal and success of #MELODEM2025 (as with other #MELODEM mtgs) comes from the generous blocks of time dedicated to discussion. And a key ingredient of that discussion is excellent moderating.

Broader context: A4 was viewed as innovative bc it started earlier in the course of disease. It was 5 years long. Is longer treatment duration needed? Or maybe a different agent operating via a different mechanism?

little evidence of cognitive benefit in spite of amyloid reduction. So not much in way of mediation.

... and adopted an IV approach that is a complement to mediation analysis.

1. % of treatment effect mediated by the surrogate (amyloid)
2. Assess treatment effect (on cogn) per change in surrogate

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

In Sim 2, the expected regression bias occurred, but ESPECIALLY wrt p-tau (blood).

Are these errors responsible for weaker findings wrt blood biomarkers? Is it better to recruit a smaller # of ppl and do imaging, vs use blood biomarkers and recruit far more ppl (needed to detect an effect).

Sim 1: age-->amyloid (imaging) and age-->ptau-181 (blood)
Sim 2: amyloid (imaging)-->MMSE and ptau-181 (blood)-->MMSE

(Wild: in simulating measured centiloids of amyloid, there was not much published data to reference on noise in measuring this entity.)

Why care about error in the measure of AD-related blood biomarkers? @ #MELODEM2025, Eleanor Hayes-Larson examines situations when a biomarker is the "exposure" and when it is the "outcome," using ADNI-informed simulations.

@melodem.bsky.social

Less dramatic diffs between AoU and NHANES in associations of a range of factors w mortality, except wrt clinical factors.