Public Health

Area of Science:

• Environmental Health
• Neuroscience
• Toxicology

Background:

• Environmental exposures are increasingly recognized as risk factors for Alzheimer's and Related Dementias (ADRD).
• Previous research linked higher serum DDE (a persistent DDT metabolite) to increased Alzheimer's risk and cognitive decline.
• Animal studies show DDT/DDE reduce cognitive function and increase amyloid pathology, indicated by lower plasma Aβ 42/40 ratio.

Purpose of the Study:

• To investigate the effects of prenatal DDE exposure on plasma amyloid-beta (Aβ) levels and cognitive function in humans.
• To assess the association between prenatal DDE exposure and midlife cognitive performance and Aβ 42/40 ratio.

Main Methods:

• Utilized data from the Child Health and Development Studies (CHDS) pregnancy cohort (1959-1963).
• Assessed midlife cognitive function using the Digit Symbol Test (DSST) and measured plasma Aβ 42/40 ratio in 179 participants.
• Measured prenatal p,p'-DDE levels in archived maternal serum and analyzed associations using generalized linear regression models.

Main Results:

• Prenatal p,p'-DDE levels were significantly associated with lower midlife plasma Aβ 42/40 ratio (β = -0.37, p = 0.03).
• Higher prenatal p,p'-DDE levels correlated with worse performance on the DSST in midlife (β = -0.020, p = 0.02).
• These associations remained robust after adjusting for covariates.

Conclusions:

• Prenatal exposure to p,p'-DDE is associated with altered Aβ 42/40 levels and impaired cognitive function in midlife.
• Identifying populations with higher DDT/DDE exposure may help pinpoint individuals at increased risk for ADRD.
• Early intervention and prevention strategies can be developed for those at risk of ADRD progression.