Background: 

Adverse social exposome: cumulative harmful exposure to social and environmental factors throughout the life-course

Lewy body dementia (LBD):

No studies have examined the interrelationship between the adverse social exposome and Lewy body neuropathology.

Methods: 

Study Sample: Brain donors from two sites (n=1,182; donations: 1985-2018).

Adverse Social Exposome Determination:

Outcome: Presence of Lewy body neuropathology

Covariates: Age, sex, and highest level of education

Statistical analyses: multiple imputation chain equations; pooled multivariate logistic regression models

Results:

Cumulative exposure to the adverse social exposome increased odds of Lewy body neuropathology throughout the life-course. Every 5 additional years living in high ADI adverse social exposomes in mid and late life was linked to 17-18% increased odds of Lewy body neuropathology.

Living in a higher ADI adverse social exposome in early and midlife increased the odds of Lewy body neuropathology by over 20% compared to donors living is lower ADI exposomes. At last known residence, higher ADI was linked to more than a two-fold increase in odds of Lewy body neuropathology.

Discussion: 

High ADI adverse social exposomes linked to greater odds of Lewy body neuropathology, with associations persisting throughout the life-course

Limitations: Predominantly White/non-Hispanic, highly educated sample living in lower ADI areas compared to the United States population

Impact: Leveraging the modifiable adverse social exposome with future blood-based biomarker discoveries to revolutionize risk reduction and prevention in LBD.

Next Steps: Replicate study in a larger and more diverse brain bank and further characterize staging and clinical correlates of LBD neuropathology.

Conclusions:

The adverse social exposome via high ADI is linked to Lewy body neuropathology providing tremendous opportunity to reduce or mitigate risk for Lewy body neuropathology earlier in the life-course.

Acknowledgements:

This research was supported by the National Institute on Aging of the National Institutes of Health (NIH) under grant numbers K00AG083275 (principal investigator [PI], Dr Lee; co-PI, Dr Kind), R01AG070883 (PI, Dr Kind; MPI, Dr Bendlin), P30AG062715 (PI, Sanjay Asthana, MD; Core H Leader, Dr Kind), and P30AG062429 (PI, James B. Brewer, MD, PhD).