PMID- 35128745
OWN - NLM
STAT- MEDLINE
DCOM- 20221115
LR  - 20230411
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 56
IP  - 9
DP  - 2022 Nov
TI  - Diabetes: Risk factor and translational therapeutic implications for Alzheimer's 
      disease.
PG  - 5727-5757
LID - 10.1111/ejn.15619 [doi]
AB  - Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) commonly co-occur. 
      T2DM increases the risk for AD by approximately twofold. Animal models provide 
      one means of interrogating the relationship of T2DM to AD and investigating brain 
      insulin resistance in the pathophysiology of AD. Animal models show that 
      persistent hyperglycaemia results in chronic low-grade inflammation that may 
      contribute to the development of neuroinflammation and accelerate the 
      pathobiology of AD. Epidemiological studies suggest that patients with T2DM who 
      received treatment with specific anti-diabetic agents have a decreased risk for 
      the occurrence of AD and all-cause dementia. Agents such as metformin ameliorate 
      T2DM and may have other important systemic effects that lower the risk of AD. 
      Glucagon-like peptide 1 (GLP-1) agonists have been associated with a decreased 
      risk for AD in patients with T2DM. Both insulin and non-insulin anti-diabetic 
      treatments have been evaluated for the treatment of AD in clinical trials. In 
      most cases, patients included in the trials have clinical features of AD but do 
      not have T2DM. Many of the trials were conducted prior to the use of diagnostic 
      biomarkers for AD. Trials have had a wide range of durations and population 
      sizes. Many of the agents used to treat T2DM do not cross the blood brain 
      barrier, and the effects are posited to occur via lowering of peripheral 
      hyperglycaemia and reduction of peripheral and central inflammation. Clinical 
      trials of anti-diabetic agents to treat AD are ongoing and will provide insight 
      into the therapeutic utility of these agents.
CI  - (c) 2022 The Authors. European Journal of Neuroscience published by Federation of 
      European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Cummings, Jeffrey
AU  - Cummings J
AUID- ORCID: 0000-0001-8944-4158
AD  - Chambers-Grundy Center for Transformative Neuroscience, Department of Brain 
      Health, School of Integrated Health Sciences, University of Nevada Las Vegas 
      (UNLV), Las Vegas, Nevada, USA.
FAU - Ortiz, Andrew
AU  - Ortiz A
AUID- ORCID: 0000-0002-5432-046X
AD  - Department of Brain Health, School of Integrated Health Sciences, University of 
      Nevada Las Vegas (UNLV), Las Vegas, Nevada, USA.
FAU - Castellino, Janelle
AU  - Castellino J
AD  - School of Medicine, University of Nevada Las Vegas, Las Vegas, Nevada, USA.
FAU - Kinney, Jefferson
AU  - Kinney J
AD  - Chambers-Grundy Center for Transformative Neuroscience, Department of Brain 
      Health, School of Integrated Health Sciences, University of Nevada Las Vegas 
      (UNLV), Las Vegas, Nevada, USA.
AD  - Department of Brain Health, School of Integrated Health Sciences, University of 
      Nevada Las Vegas (UNLV), Las Vegas, Nevada, USA.
LA  - eng
GR  - P20 AG068053/AG/NIA NIH HHS/United States
GR  - R35 AG071476/AG/NIA NIH HHS/United States
GR  - U01 NS093334/NS/NINDS NIH HHS/United States
GR  - P30 AG072980/AG/NIA NIH HHS/United States
GR  - P20 GM109025/GM/NIGMS NIH HHS/United States
GR  - R01 AG053798/AG/NIA NIH HHS/United States
GR  - R56 AG062762/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220223
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Hypoglycemic Agents)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - *Alzheimer Disease/drug therapy
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Risk Factors
MH  - *Hyperglycemia/chemically induced/complications/drug therapy
MH  - Inflammation/complications
PMC - PMC9393901
MID - NIHMS1778165
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - GLP-1 agonist
OT  - dapagliflozin
OT  - diabetes
OT  - empagliflozin
OT  - insulin
OT  - liraglutide
OT  - metformin
OT  - mouse model
OT  - pioglitazone
OT  - rosiglitazone
OT  - semaglutide
COIS- JC has provided consultation to AB Science, Acadia, Alkahest, AlphaCognition, 
      ALZPath, Annovis, AriBio, Artery, Avanir, Biogen, Cassava, Cerevel, Clinilabs, 
      Cortexyme, Diadem, EIP Pharma, Eisai, GatehouseBio, GemVax, Genentech, Green 
      Valley, Grifols, Janssen, Karuna, Lexeo, Lilly, Lundbeck, LSP, Merck, NervGen, 
      Novo Nordisk, Oligomerix, Otsuka, PharmacotrophiX, PRODEO, Prothena, ReMYND, 
      Renew, Resverlogix, Roche, Signant Health, Suven, Unlearn AI, Vaxxinity, 
      VigilNeuro, Zai Laboratories pharmaceutical, assessment and investment companies. 
      AO, JC and JK have no conflicts of interest.
EDAT- 2022/02/08 06:00
MHDA- 2022/11/16 06:00
PMCR- 2022/12/25
CRDT- 2022/02/07 05:40
PHST- 2022/01/25 00:00 [revised]
PHST- 2021/10/25 00:00 [received]
PHST- 2022/01/27 00:00 [accepted]
PHST- 2022/02/08 06:00 [pubmed]
PHST- 2022/11/16 06:00 [medline]
PHST- 2022/02/07 05:40 [entrez]
PHST- 2022/12/25 00:00 [pmc-release]
AID - EJN15619 [pii]
AID - 10.1111/ejn.15619 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2022 Nov;56(9):5727-5757. doi: 10.1111/ejn.15619. Epub 2022 Feb 
      23.