Neurotoxic chemicals in adipose tissue: A role in puzzling findings on obesity and dementia

Duk Hee Lee, Miquel Porta, Lars Lind, P. Monica Lind, David R. Jacobs

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Midlife obesity is associated with increased risk of dementia, whereas late-life obesity is commonly associated with a lower risk of dementia. Although methodologic issues are often discussed in this apparent risk reversal, chronic exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor for dementia in general populations, may contribute to a direct explanation for these differences. OCPs are strong lipophilic chemicals with very long half-lives (several years), primarily stored in adipose tissue and very slowly released and metabolized over years. As serum concentrations of neurotoxic OCPs strongly correlate with brain OCPs (r = 0.95), any condition enhancing the release of OCPs from the adipose tissue into circulation would increase the risk of dementia. Increased release of OCPs from adipose tissue typically occurs in (1) dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight loss. Weight gain may help sequester circulating OCPs in adipose tissue. As obesity is the most common reason that adipocytes become dysfunctional, midlife obesity can increase dementia risk through the chronic release of OCPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of OCPs while weight gain may actually decrease the release. These countervailing forces may underlie paradoxical associations with dementia of obesity in midlife vs late life which is influenced by weight change after midlife. This hypothesis should be tested in future experimental and human studies on obesity and dementia.

Original languageEnglish (US)
Pages (from-to)176-182
Number of pages7
Issue number4
StatePublished - 2018

Bibliographical note

Funding Information:
Supported by The Korean Health Technology R&D Project (HI13C0715), funded by the Ministry of Health and Welfare, and the Environmental Health Action Program (2016001370002), funded by the Korea Ministry of Environment of the Republic of Korea.

Publisher Copyright:
Copyright © 2018 American Academy of Neurology.


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