Insulin-Like Growth Factor, Inflammation, and MRI Markers of Alzheimer's Disease in Predominantly Middle-Aged Adults
Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults. To investigate the association of serum I...
Gespeichert in:
| Veröffentlicht in: | Journal of Alzheimer's disease Jg. 88; H. 1; S. 311 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
United States
01.01.2022
|
| Schlagworte: | |
| ISSN: | 1875-8908, 1875-8908 |
| Online-Zugang: | Weitere Angaben |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults.
To investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation.
We included participants from the Framingham Heart Study (n = 1,852, mean age 46±8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50±13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons.
Meta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [β] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes.
Our findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife. |
|---|---|
| AbstractList | Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults.BACKGROUNDInsulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults.To investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation.OBJECTIVETo investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation.We included participants from the Framingham Heart Study (n = 1,852, mean age 46±8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50±13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons.METHODSWe included participants from the Framingham Heart Study (n = 1,852, mean age 46±8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50±13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons.Meta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [β] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes.RESULTSMeta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [β] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes.Our findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife.CONCLUSIONOur findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife. Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults. To investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation. We included participants from the Framingham Heart Study (n = 1,852, mean age 46±8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50±13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons. Meta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [β] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes. Our findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife. |
| Author | Hosten, Norbert Aslam, Asra Vasan, Ramachandran S DeCarli, Charles Himali, Jayandra J Seshadri, Sudha Grabe, Hans J Conner, Sarah C Teumer, Alexander Habes, Mohamad Beiser, Alexa S Raman, Mekala R Satizabal, Claudia L Wittfeld, Katharina Nauck, Matthias |
| Author_xml | – sequence: 1 givenname: Katharina surname: Wittfeld fullname: Wittfeld, Katharina organization: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany – sequence: 2 givenname: Mekala R surname: Raman fullname: Raman, Mekala R organization: Framingham Heart Study, Framingham, MA, USA – sequence: 3 givenname: Sarah C surname: Conner fullname: Conner, Sarah C organization: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA – sequence: 4 givenname: Asra surname: Aslam fullname: Aslam, Asra organization: Long School of Medicine, UT Health San Antonio, San Antonio, TX, USA – sequence: 5 givenname: Alexander surname: Teumer fullname: Teumer, Alexander organization: Department of Population Medicine and Lifestyle Diseases Prevention, Medical University of Bialystok, Bialystok, Poland – sequence: 6 givenname: Matthias surname: Nauck fullname: Nauck, Matthias organization: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany – sequence: 7 givenname: Norbert surname: Hosten fullname: Hosten, Norbert organization: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany – sequence: 8 givenname: Mohamad surname: Habes fullname: Habes, Mohamad organization: Department of Neurology, Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA – sequence: 9 givenname: Charles surname: DeCarli fullname: DeCarli, Charles organization: Department of Neurology, University of California, Davis School of Medicine, Sacramento, CA, USA – sequence: 10 givenname: Ramachandran S surname: Vasan fullname: Vasan, Ramachandran S organization: Department of Epidemiology, Boston University School of Public Health, Boston MA, USA – sequence: 11 givenname: Alexa S surname: Beiser fullname: Beiser, Alexa S organization: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA – sequence: 12 givenname: Jayandra J surname: Himali fullname: Himali, Jayandra J organization: Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA – sequence: 13 givenname: Sudha surname: Seshadri fullname: Seshadri, Sudha organization: Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA – sequence: 14 givenname: Hans J surname: Grabe fullname: Grabe, Hans J organization: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany – sequence: 15 givenname: Claudia L surname: Satizabal fullname: Satizabal, Claudia L organization: Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35599493$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkL1OwzAYRS1UBC2w8ADIGwwE_BM79hgBhaBWIARz5NRfwNRxip0IwdODBEhM5w5HdzgzNAl9AIQOKTnjjPPz2_IyY4xwIbfQlKpCZEoTNfm3d9EspVdCCCe62EG7XAitc82naKhCGr0L2cKtAV_H_n14wXOzGvp4iqvQetN1ZnB9OMUmWLx8qPDSxDXEhPsWl_7zBVwH8TjhS5fAJMAu4PsItu9cMGHwH3jprPWQlc9gcWlHP6R9tN0an-Dgl3voaX71eHGTLe6uq4tyka0EyYesMAVvldASWkss2FwpRQ00lrSWg9ZGCiUkmJxK0za2EZrlgnJqFWlz2Ui2h05-fjexfxshDXXn0gq8NwH6MdVMSsUYpbT4Vo9-1bHpwNab6DoTP-q_UuwLNU5rqg |
| CitedBy_id | crossref_primary_10_1007_s10787_025_01641_0 crossref_primary_10_1007_s11357_025_01657_y crossref_primary_10_1016_j_psyneuen_2023_106946 crossref_primary_10_1161_HYPERTENSIONAHA_124_24341 crossref_primary_10_3390_ijms25084512 crossref_primary_10_1007_s11357_024_01426_3 crossref_primary_10_3389_fnagi_2024_1337397 crossref_primary_10_3389_fnins_2024_1301107 crossref_primary_10_1089_neu_2024_0114 crossref_primary_10_3390_ijms25052567 crossref_primary_10_1186_s13195_023_01288_5 crossref_primary_10_3233_JAD_231026 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.3233/JAD-220356 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| EISSN | 1875-8908 |
| ExternalDocumentID | 35599493 |
| Genre | Meta-Analysis Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: 75N92019D00031 – fundername: NIA NIH HHS grantid: U01 AG049505 – fundername: NINDS NIH HHS grantid: UH3 NS100605 – fundername: NINDS NIH HHS grantid: T32 NS007412 – fundername: NIA NIH HHS grantid: RF1 AG054409 – fundername: NIA NIH HHS grantid: R01 AG031287 – fundername: NINDS NIH HHS grantid: R01 NS017950 – fundername: NHLBI NIH HHS grantid: HHSN268201500001I – fundername: NHLBI NIH HHS grantid: T32 HL125232 – fundername: NINDS NIH HHS grantid: UF1 NS125513 |
| GroupedDBID | --- 0R~ 0VX 29J 36B 4.4 53G 5GY AAEJI AAFNC AAFWJ AAGLT AAPII AAQXI AAWTL ABDBF ABIVO ABJNI ABJZC ABUBZ ABUJY ACGFS ACPQW ACPRK ACUHS ADEBD ADZMO AEJQA AELRD AENEX AFRAH AFRHK AFYTF AGIAB AHDMH AIRSE AJGYC AJNRN ALIRC ALMA_UNASSIGNED_HOLDINGS APPIZ ARTOV CAG CGR COF CUY CVF DU5 EAD EAP EBS ECM EIF EJD EMB EMK EMOBN ESX F5P H13 HZ~ IL9 IOS J8X MET MIO MV1 NGNOM NPM O9- P2P Q1R SAUOL SCNPE SFC SV3 TUS VUG 7X8 |
| ID | FETCH-LOGICAL-c504t-7a73f8596efd0ded48881aebd0fd3e99a65856ea416afbdb59245131d80f46b62 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 13 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000828029000025&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1875-8908 |
| IngestDate | Sun Sep 28 04:26:58 EDT 2025 Mon Jul 21 06:03:42 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 1 |
| Keywords | epidemiology C-reactive protein cohort study hippocampus Alzheimer’s disease endophenotype insulin-like growth factor neuroimaging white matter hyperintensity |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c504t-7a73f8596efd0ded48881aebd0fd3e99a65856ea416afbdb59245131d80f46b62 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/9472289 |
| PMID | 35599493 |
| PQID | 2668221117 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2668221117 pubmed_primary_35599493 |
| PublicationCentury | 2000 |
| PublicationDate | 2022-01-01 |
| PublicationDateYYYYMMDD | 2022-01-01 |
| PublicationDate_xml | – month: 01 year: 2022 text: 2022-01-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Journal of Alzheimer's disease |
| PublicationTitleAlternate | J Alzheimers Dis |
| PublicationYear | 2022 |
| SSID | ssj0003097 |
| Score | 2.4135463 |
| SecondaryResourceType | review_article |
| Snippet | Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 311 |
| SubjectTerms | Adult Alzheimer Disease - diagnostic imaging Biomarkers C-Reactive Protein - metabolism Female Humans Inflammation - diagnostic imaging Insulin-Like Growth Factor Binding Protein 3 Insulin-Like Growth Factor I - analysis Magnetic Resonance Imaging Male Middle Aged |
| Title | Insulin-Like Growth Factor, Inflammation, and MRI Markers of Alzheimer's Disease in Predominantly Middle-Aged Adults |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/35599493 https://www.proquest.com/docview/2668221117 |
| Volume | 88 |
| WOSCitedRecordID | wos000828029000025&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3LS8MwGA_qPHjxga_5IoLgxbC2adLmJMU5nbgxRGG3kTaJG85urlPQv94vTYcnQfDSW0tIv8fve_0-hM5izXkKbosYn2sSAuglQqSMUEmFlOCARJSVyyaibjfu90WvSrgVVVvlwiaWhlpNMpsjb4AjAV8GmhldTt-I3Rplq6vVCo1lVKMAZaxUR_0ftnDqueUqgMlJLLzY0ZPSgNLGXdIkQeBRxn-HlqWLaW3893CbaL0Clzhx0rCFlnS-jeZt125O7kcvGt9A2D0f4la5ZucCt3MDIuHGFy-wzBXuPLSxHeABWIgnBifjr6EeverZeYGbrpiDRznuWZ5R10Uz_sSdMstBkmetcGIJPYod9NS6fry6JdWuBZIxL5yTSEbUxExwbZSntAK9jn2pU-UZRbUQEpAK41oCfpMmVSmDuI351FexZ0Ke8mAXreSTXO8jbKJQhRlVPpgu-AxPmW_C1AecxCDY4aqOTheXOABZtgUKmevJezH4ucY62nN_YjB1pBsDaqnRQkEP_vD2IVoL7JRCmSk5QjUDmqyP0Wr2MR8Vs5NSSODZ7XW-AYFyxh8 |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Insulin-Like+Growth+Factor%2C+Inflammation%2C+and+MRI+Markers+of+Alzheimer%27s+Disease+in+Predominantly+Middle-Aged+Adults&rft.jtitle=Journal+of+Alzheimer%27s+disease&rft.au=Wittfeld%2C+Katharina&rft.au=Raman%2C+Mekala+R&rft.au=Conner%2C+Sarah+C&rft.au=Aslam%2C+Asra&rft.date=2022-01-01&rft.eissn=1875-8908&rft.volume=88&rft.issue=1&rft.spage=311&rft_id=info:doi/10.3233%2FJAD-220356&rft_id=info%3Apmid%2F35599493&rft_id=info%3Apmid%2F35599493&rft.externalDocID=35599493 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1875-8908&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1875-8908&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1875-8908&client=summon |