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.

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

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

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.

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.

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

@melodem.bsky.social

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.)

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

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