PMID- 38001936
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240325
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 11
IP  - 11
DP  - 2023 Oct 30
TI  - The Association between Metformin Use and Risk of Developing Severe Dementia 
      among AD Patients with Type 2 Diabetes.
LID - 10.3390/biomedicines11112935 [doi]
LID - 2935
AB  - This study explores the potential impact of metformin on the development of 
      severe dementia in individuals with Alzheimer's disease (AD) and type 2 diabetes 
      mellitus (T2DM). With an emerging interest in the role of the APOE genotype in 
      mediating metformin's effects on cognitive decline in AD patients, we sought to 
      investigate whether metformin usage is associated with a reduced risk of severe 
      dementia. Using data from the National Alzheimer's Coordinating Center (NACC) 
      database (2005-2021), we identified 1306 participants with both AD and T2DM on 
      diabetes medications. These individuals were categorized based on metformin 
      usage, and a propensity score-matched cohort of 1042 participants was analyzed. 
      Over an average follow-up of 3.6 years, 93 cases of severe dementia were 
      observed. A Kaplan-Meier analysis revealed that metformin users and non-users had 
      similar probabilities of remaining severe dementia-free (log-rank p = 0.56). Cox 
      proportional hazards models adjusted for covariates showed no significant 
      association between metformin usage and a lower risk of severe dementia (HR, 
      0.96; 95% CI, 0.63-1.46; p = 0.85). A subgroup analysis based on APOE epsilon4 carrier 
      status demonstrated consistent results, with metformin use not correlating with a 
      reduced severe dementia risk. In conclusion, our findings from a substantial 
      cohort of AD and T2DM patients suggest that metformin usage is not significantly 
      associated with a decreased risk of severe dementia. This observation persists 
      across APOE epsilon4 carriers and non-carriers, indicating a lack of genotype-mediated 
      effect.
FAU - Xue, Ying
AU  - Xue Y
AUID- ORCID: 0000-0002-2348-0356
AD  - Department of Pharmacy and Therapeutics, School of Pharmacy, University of 
      Pittsburgh, Pittsburgh, PA 15261, USA.
AD  - Department of Pharmaceutical Sciences and Computational Chemical Genomics 
      Screening Center, Pharmacometrics & System Pharmacology (PSP) PharmacoAnalytics, 
      School of Pharmacy, Pittsburgh, PA 15261, USA.
AD  - National Center of Excellence for Computational Drug Abuse Research, University 
      of Pittsburgh, Pittsburgh, PA 15261, USA.
FAU - Xie, Xiangqun
AU  - Xie X
AD  - Department of Pharmaceutical Sciences and Computational Chemical Genomics 
      Screening Center, Pharmacometrics & System Pharmacology (PSP) PharmacoAnalytics, 
      School of Pharmacy, Pittsburgh, PA 15261, USA.
AD  - National Center of Excellence for Computational Drug Abuse Research, University 
      of Pittsburgh, Pittsburgh, PA 15261, USA.
LA  - eng
GR  - R56 AG074951/AG/NIA NIH HHS/United States
GR  - P30 AG066515/AG/NIA NIH HHS/United States
GR  - P30 AG062421/AG/NIA NIH HHS/United States
GR  - P30 AG066508/AG/NIA NIH HHS/United States
GR  - P30 AG066519/AG/NIA NIH HHS/United States
GR  - P30 AG072973/AG/NIA NIH HHS/United States
GR  - P30 AG066462/AG/NIA NIH HHS/United States
GR  - P30 AG066530/AG/NIA NIH HHS/United States
GR  - P30 AG066546/AG/NIA NIH HHS/United States
GR  - P30 AG072972/AG/NIA NIH HHS/United States
GR  - P30 AG066514/AG/NIA NIH HHS/United States
GR  - P30 AG072979/AG/NIA NIH HHS/United States
GR  - P30 AG072975/AG/NIA NIH HHS/United States
GR  - P30 AG066444/AG/NIA NIH HHS/United States
GR  - P30 AG066507/AG/NIA NIH HHS/United States
GR  - P30 AG072946/AG/NIA NIH HHS/United States
GR  - P30 AG066518/AG/NIA NIH HHS/United States
GR  - P30 AG066511/AG/NIA NIH HHS/United States
GR  - U24 AG072122/AG/NIA NIH HHS/United States
GR  - P30 AG066512/AG/NIA NIH HHS/United States
GR  - P30 AG072978/AG/NIA NIH HHS/United States
GR  - P30 AG062429/AG/NIA NIH HHS/United States
GR  - P30 AG062422/AG/NIA NIH HHS/United States
GR  - R01 AG079280/AG/NIA NIH HHS/United States
GR  - P50 AG005133/AG/NIA NIH HHS/United States
GR  - P30 AG066509/AG/NIA NIH HHS/United States
GR  - P30 AG072977/AG/NIA NIH HHS/United States
GR  - P30 AG062677/AG/NIA NIH HHS/United States
GR  - P30 AG062715/AG/NIA NIH HHS/United States
GR  - P30 AG066506/AG/NIA NIH HHS/United States
GR  - P30 AG066468/AG/NIA NIH HHS/United States
GR  - P30 AG072976/AG/NIA NIH HHS/United States
GR  - P30 AG072947/AG/NIA NIH HHS/United States
GR  - P30 AG072931/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20231030
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC10669124
OTO - NOTNLM
OT  - APOE
OT  - Alzheimer's disease
OT  - MMSE
OT  - diabetes
OT  - metformin
OT  - severe dementia
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/25 12:43
MHDA- 2023/11/25 12:44
PMCR- 2023/10/30
CRDT- 2023/11/25 01:07
PHST- 2023/08/16 00:00 [received]
PHST- 2023/10/12 00:00 [revised]
PHST- 2023/10/13 00:00 [accepted]
PHST- 2023/11/25 12:44 [medline]
PHST- 2023/11/25 12:43 [pubmed]
PHST- 2023/11/25 01:07 [entrez]
PHST- 2023/10/30 00:00 [pmc-release]
AID - biomedicines11112935 [pii]
AID - biomedicines-11-02935 [pii]
AID - 10.3390/biomedicines11112935 [doi]
PST - epublish
SO  - Biomedicines. 2023 Oct 30;11(11):2935. doi: 10.3390/biomedicines11112935.