PMID- 32096335
OWN - NLM
STAT- MEDLINE
DCOM- 20210121
LR  - 20210121
IS  - 1552-5279 (Electronic)
IS  - 1552-5260 (Linking)
VI  - 16
IP  - 4
DP  - 2020 Apr
TI  - Intensive weight loss and cognition: The dynamics of persistent organic 
      pollutants in adipose tissue can explain the unexpected results from the Action 
      for Health in Diabetes (Look AHEAD) study.
PG  - 696-703
LID - 10.1002/alz.12065 [doi]
AB  - OBJECTIVE: The aim of this paper is to propose a new hypothesis for the role of 
      lipophilic chemical mixtures stored in adipose tissue in the development of 
      dementia. Specifically, we present how the dynamics of these chemicals can 
      explain the unexpected findings from the Action for Health in Diabetes (Look 
      AHEAD) study, which failed to show long-term benefits of intentional weight loss 
      on cognition, despite substantial improvements in many known risk factors for 
      dementia. Moreover, we discuss how the role of obesity in the risk of dementia 
      can change depending on the dynamics of these chemicals in adipose tissue. NEW 
      HYPOTHESIS: Human adipose tissue is widely contaminated with various neurotoxic 
      chemicals. Typical examples are persistent organic pollutants (POPs), strong 
      lipophilic chemicals with long half-lives. Both unintentional and intentional 
      weight loss increases the release of POPs from adipocytes into the circulation. 
      As POPs in the blood can easily reach the brain, the intentional weight-loss 
      group of the Look AHEAD study may have experienced an unappreciated and long-term 
      disadvantage on their cognition. Additionally, POPs may be involved in the link 
      between obesity and dementia, as dysfunctional hypertrophic adipocytes enhance 
      the release of POPs from adipocytes to the circulation through uncontrolled 
      lipolysis. In contrast, metabolically healthy obese people may have a low risk of 
      dementia because the safe storage of POPs in adipose tissue would decrease the 
      amount of POPs reaching the brain. MAJOR CHALLENGES FOR THE HYPOTHESIS: In human 
      studies, there are practical difficulties involved with measuring POPs in the 
      blood, including high costs and complex assays. As the serum concentrations of 
      POPs are continuously affected by weight loss and gain, prospective studies may 
      require serial measurements of POPs. In in-vitro and in-vivo experimental 
      studies, how to simulate the exposure dose, duration, and mixture patterns in 
      humans would be critical. LINKAGE TO OTHER MAJOR THEORIES: Even though POPs are 
      direct neurotoxins at a high dosage, low-dose POPs are mitochondrial toxins. 
      Therefore, chronic exposure to low-dose POPs is linked to known key interrelated 
      mechanisms in the pathogenesis of dementia, such as mitochondrial dysfunction and 
      neuroinflammation.
CI  - (c) 2020 the Alzheimer's Association.
FAU - Lee, Yu-Mi
AU  - Lee YM
AD  - Department of Preventive Medicine, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
FAU - Park, Sun-Hee
AU  - Park SH
AD  - Department of Internal Medicine, School of Medicine, Kyungpook National 
      University, Kyungpook National University Hospital, Daegu, Republic of Korea.
FAU - Lee, Duk-Hee
AU  - Lee DH
AD  - Department of Preventive Medicine, School of Medicine, Kyungpook National 
      University, Daegu, Republic of Korea.
LA  - eng
GR  - National Research Foundation of Korea/International
GR  - 2019R1A2C1008958/Korean government (Ministry of Science and ICT)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200224
PL  - United States
TA  - Alzheimers Dement
JT  - Alzheimer's & dementia : the journal of the Alzheimer's Association
JID - 101231978
RN  - 0 (Environmental Pollutants)
SB  - IM
MH  - Adipose Tissue/*physiopathology
MH  - Cognition/*physiology
MH  - Environmental Pollutants/adverse effects
MH  - Humans
MH  - Obesity
MH  - Persistent Organic Pollutants/*adverse effects
MH  - Prospective Studies
MH  - Risk Factors
MH  - Weight Loss/*physiology
OTO - NOTNLM
OT  - dementia
OT  - diabetes
OT  - neurotoxic chemicals
OT  - obesity
OT  - persistent organic pollutants
OT  - weight loss
EDAT- 2020/02/26 06:00
MHDA- 2021/01/22 06:00
CRDT- 2020/02/26 06:00
PHST- 2019/08/06 00:00 [received]
PHST- 2019/10/03 00:00 [revised]
PHST- 2019/12/05 00:00 [accepted]
PHST- 2020/02/26 06:00 [pubmed]
PHST- 2021/01/22 06:00 [medline]
PHST- 2020/02/26 06:00 [entrez]
AID - 10.1002/alz.12065 [doi]
PST - ppublish
SO  - Alzheimers Dement. 2020 Apr;16(4):696-703. doi: 10.1002/alz.12065. Epub 2020 Feb 
      24.