Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Alzheimer Research
  4. Volume 21, Issue 7
  5. Article
Volume 21, Issue 7
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828
file format text download EPUB
file format pdf download PDF
side by side viewer icon HTML

Abstract

Background

Alzheimer's Disease (AD) is characterized by a progressive neurodegenerative process leading to cognitive decline and functional impairment. Endocrine factors, particularly sex hormones and their binding proteins, play a critical role in AD pathophysiology. Understanding the relationship between these factors and AD is essential for developing targeted interventions.

Objective

To investigate the potential links between sex hormone binding globulin (SHBG) levels, sex hormone profiles, inflammatory markers, and neurocognitive decline in patients with AD.

Methods

A retrospective case-control investigation was conducted with 110 AD patients who were admitted to our hospital from January 2021 to December 2023, and the patients were classified into either a mild neurocognitive impairment group (n=59) or a moderate to severe neurocognitive impairment group (n=51) according to their cognitive function. Correlation and regression analyses were conducted to examine relationships between variable factors.

Results

The study revealed a significant neurocognitive decline in AD patients with lower Mini-Mental State Examination (MMSE) and higher AD Assessment Scale-Cognitive Subscale (ADAS-Cog) scores in the moderate to severe neurocognitive impairment group compared to the mild neurocognitive impairment group. Additionally, the moderate to severe neurocognitive impairment group significantly increased for SHBG, estradiol, progesterone inflammatory markers [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β). It decreased for follicle-stimulating hormone (FSH) and luteinizing hormone (LH)]. Moreover, significant positive correlations were found between SHBG levels and ADAS-Cog scores, and significant negative correlations were found between SHBG levels and MMSE scores. FSH showed significant negative correlations with the MMSE score, while certain inflammatory markers demonstrated significant correlations with neurocognitive abilities. The correlation between sex hormones and inflammatory factors is weak. FSH, LH, SHBG, CRP, IL-6, TNF-α, and IL-1β are risk factors for neurocognitive impairment, while E2 and P are protective factors.

Conclusion

The study provides evidence of significant correlations between SHBG levels, sex hormone profiles, inflammatory markers, and neurocognitive decline in AD patients.

© 2024 Bentham Science Publishers
© 2024 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050341904241111082935
2024-11-25
2025-01-29

  • From This Site

    /content/journals/car/10.2174/0115672050341904241111082935
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/car/21/7/CAR-21-7-04.html?itemId=/content/journals/car/10.2174/0115672050341904241111082935&mimeType=html&fmt=ahah

References

  1. BondiM.W. EdmondsE.C. SalmonD.P. Alzheimer’s disease: Past, present, and future.J. Int. Neuropsychol. Soc.2017239-1081883110.1017/S135561771700100X29198280
     [Google Scholar]
  2. Graff-RadfordJ. YongK.X.X. ApostolovaL.G. BouwmanF.H. CarrilloM. DickersonB.C. RabinoviciG.D. SchottJ.M. JonesD.T. MurrayM.E. New insights into atypical Alzheimer’s disease in the era of biomarkers.Lancet Neurol.202120322223410.1016/S1474‑4422(20)30440‑333609479
     [Google Scholar]
  3. MantzavinosV. AlexiouA. Biomarkers for Alzheimer’s disease diagnosis.Curr. Alzheimer Res.201714111149115428164766
     [Google Scholar]
  4. RostagnoA.A. Pathogenesis of Alzheimer’s Disease.Int. J. Mol. Sci.202224110710.3390/ijms2401010736613544
     [Google Scholar]
  5. ScheltensP. De StrooperB. KivipeltoM. HolstegeH. ChételatG. TeunissenC.E. CummingsJ. van der FlierW.M. Alzheimer’s disease.Lancet2021397102841577159010.1016/S0140‑6736(20)32205‑433667416
     [Google Scholar]
  6. WellerJ. BudsonA. Current understanding of Alzheimer’s disease diagnosis and treatment.F1000 Res.20187116110.12688/f1000research.14506.130135715
     [Google Scholar]
  7. AshrafianH. ZadehE.H. KhanR.H. Review on Alzheimer’s disease: Inhibition of amyloid beta and tau tangle formation.Int. J. Biol. Macromol.202116738239410.1016/j.ijbiomac.2020.11.19233278431
     [Google Scholar]
  8. BuscheM.A. HymanB.T. Synergy between amyloid-β and tau in Alzheimer’s disease.Nat. Neurosci.202023101183119310.1038/s41593‑020‑0687‑632778792
     [Google Scholar]
  9. KnopmanD.S. AmievaH. PetersenR.C. ChételatG. HoltzmanD.M. HymanB.T. NixonR.A. JonesD.T. Alzheimer disease.Nat. Rev. Dis. Primers2021713310.1038/s41572‑021‑00269‑y33986301
     [Google Scholar]
  10. MarriottR.J. MurrayK. FlickerL. HankeyG.J. MatsumotoA.M. DwivediG. AntonioL. AlmeidaO.P. BhasinS. DobsA.S. HandelsmanD.J. HaringR. O’NeillT.W. OhlssonC. OrwollE.S. VanderschuerenD. WittertG.A. WuF.C.W. YeapB.B. Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study.Alzheimers Dement.202218101907191810.1002/alz.1252934978125
     [Google Scholar]
  11. YeungC.H.C. Au YeungS.L. KwokM.K. ZhaoJ.V. SchoolingC.M. The influence of growth and sex hormones on risk of alzheimer’s disease: a mendelian randomization study.Eur. J. Epidemiol.202338774575510.1007/s10654‑023‑01015‑237253999
     [Google Scholar]
  12. NarinxN. DavidK. WalravensJ. VermeerschP. ClaessensF. FiersT. LapauwB. AntonioL. VanderschuerenD. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology.Cell. Mol. Life Sci.2022791154310.1007/s00018‑022‑04562‑136205798
     [Google Scholar]
  13. SimonsP.I.H.G. ValkenburgO. StehouwerC.D.A. BrouwersM.C.G.J. Sex hormone–binding globulin: biomarker and hepatokine?Trends Endocrinol. Metab.202132854455310.1016/j.tem.2021.05.00234052096
     [Google Scholar]
  14. HuangJ. XuB. ChenX. YangL. LiuD. LinJ. LiuY. LeiX. HuangC. DouW. GuoD. WeiX. ZhangP. HuangY. GuX. ZhangH. Sex hormone-binding globulin and risk of incident dementia in middle-aged to older women: Results from the UK biobank Cohort study.Neuroendocrinology2024114217017810.1159/00053392937725912
     [Google Scholar]
  15. PanQ. GuoK. XueM. TuQ. Estradiol exerts a neuroprotective effect on SH-SY5Y cells through the miR-106b-5p/TXNIP axis.J. Biochem. Mol. Toxicol.2021359e2286110.1002/jbt.2286134318539
     [Google Scholar]
  16. XuW. SuB.J. ShenX.N. BiY.L. TanC.C. LiJ.Q. CaoX.P. DongQ. TanL. YuJ.T. Plasma sex hormone-binding globulin predicts neurodegeneration and clinical progression in prodromal Alzheimer’s disease.Aging (Albany NY)20201214145281454110.18632/aging.10349732699184
     [Google Scholar]
  17. LengF. EdisonP. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?Nat. Rev. Neurol.202117315717210.1038/s41582‑020‑00435‑y33318676
     [Google Scholar]
  18. ThakurS. DhapolaR. SarmaP. MedhiB. ReddyD.H. Neuroinflammation in Alzheimer’s Disease: Current progress in molecular signaling and therapeutics.Inflammation202346111710.1007/s10753‑022‑01721‑135986874
     [Google Scholar]
  19. WangC. ZongS. CuiX. WangX. WuS. WangL. LiuY. LuZ. The effects of microglia-associated neuroinflammation on Alzheimer’s disease.Front. Immunol.202314111717210.3389/fimmu.2023.111717236911732
     [Google Scholar]
  20. PrinsS. de KamM.L. TeunissenC.E. GroeneveldG.J. Inflammatory plasma biomarkers in subjects with preclinical Alzheimer’s disease.Alzheimers Res. Ther.202214110610.1186/s13195‑022‑01051‑235922871
     [Google Scholar]
  21. Al-GhraiybahN.F. WangJ. AlkhalifaA.E. RobertsA.B. RajR. YangE. KaddoumiA. Glial cell-mediated neuroinflammation in Alzheimer’s Disease.Int. J. Mol. Sci.202223181057210.3390/ijms23181057236142483
     [Google Scholar]
  22. MegurA. BaltriukienėD. BukelskienėV. BurokasA. The microbiota–gut–brain axis and Alzheimer’s Disease: Neuroinflammation is to blame?Nutrients20201313710.3390/nu1301003733374235
     [Google Scholar]
  23. Tahami MonfaredA.A. PhanN.T.N. PearsonI. MauskopfJ. ChoM. ZhangQ. HampelH. A systematic review of clinical practice guidelines for Alzheimer’s disease and strategies for future advancements.Neurol. Ther.20231241257128410.1007/s40120‑023‑00504‑637261607
     [Google Scholar]
  24. El-HayeckR. BaddouraR. WehbéA. BassilN. KoussaS. Abou KhaledK. RichaS. KhouryR. AlameddineA. SellalF. An arabic version of the mini-mental state examination for the lebanese population: Reliability, validity, and normative data.J. Alzheimers Dis.201971252554010.3233/JAD‑18123231424409
     [Google Scholar]
  25. JiangY. YangH. ZhaoJ. WuY. ZhouX. ChengZ. Reliability and concurrent validity of Alzheimer’s disease assessment scale - Cognitive subscale, Chinese version (ADAS-Cog-C) among Chinese community-dwelling older people population.Clin. Neuropsychol.202034sup1435310.1080/13854046.2020.175070432279575
     [Google Scholar]
  26. OliveiraJ. GamitoP. SoutoT. CondeR. FerreiraM. CorotneanT. FernandesA. SilvaH. NetoT. Virtual reality-based cognitive stimulation on people with mild to moderate dementia due to Alzheimer’s Disease: A pilot randomized controlled trial.Int. J. Environ. Res. Public Health20211810529010.3390/ijerph1810529034065698
     [Google Scholar]
  27. GustavssonA. NortonN. FastT. FrölichL. GeorgesJ. HolzapfelD. KirabaliT. Krolak-SalmonP. RossiniP.M. FerrettiM.T. LanmanL. ChadhaA.S. van der FlierW.M. Global estimates on the number of persons across the Alzheimer’s disease continuum.Alzheimers Dement.202319265867010.1002/alz.1269435652476
     [Google Scholar]
  28. NiksereshtS. BushA.I. AytonS. Treating Alzheimer’s disease by targeting iron.Br. J. Pharmacol.2019176183622363510.1111/bph.1456730632143
     [Google Scholar]
  29. SundermannE.E. PanizzonM.S. ChenX. AndrewsM. GalaskoD. BanksS.J. Sex differences in Alzheimer’s-related Tau biomarkers and a mediating effect of testosterone.Biol. Sex Differ.20201113310.1186/s13293‑020‑00310‑x32560743
     [Google Scholar]
  30. SyedA.A.S. HeL. ShiY. The potential effect of aberrant testosterone levels on common diseases: A mendelian randomization study.Genes (Basel)202011772110.3390/genes1107072132610558
     [Google Scholar]
  31. GiannosP. ProkopidisK. ChurchD.D. KirkB. MorganP.T. LochlainnM.N. MacphersonH. WoodsD.R. IspoglouT. Associations of bioavailable serum testosterone with cognitive function in older men: Results from the national health and nutrition examination survey.J. Gerontol. A Biol. Sci. Med. Sci.202378115115710.1093/gerona/glac16235927217
     [Google Scholar]
  32. XuJ. XiaL.L. SongN. ChenS.D. WangG. Testosterone, estradiol, and sex hormone-binding globulin in alzheimer’s disease: a meta-analysis.Curr. Alzheimer Res.201613321522210.2174/156720501366615121814575226679858
     [Google Scholar]
  33. KimH. JunS. KimB.S. KimI.J. Alzheimer’s Disease Neuroimaging Initiative Serum adiponectin in Alzheimer’s disease (AD): Association with AD biomarkers and cognitive outcome.J. Alzheimers Dis.20218431163117210.3233/JAD‑21072234633322
     [Google Scholar]
  34. DingH. LiY. AngT.F.A. LiuY. DevineS. AuR. DoraiswamyP.M. LiuC. Reproductive markers in Alzheimer’s disease progression: The framingham heart study.J. Prev. Alzheimers Dis.202310353053537357294
     [Google Scholar]
  35. SternbergZ. PodolskyR. NirA. YuJ. NirR. HalvorsenS.W. ChadhaK. QuinnJ.F. KayeJ. KolbC. Increased free prostate specific antigen serum levels in Alzheimer’s disease, correlation with Cognitive Decline.J. Neurol. Sci.201940018819310.1016/j.jns.2019.04.00630981123
     [Google Scholar]
  36. dos Anjos RosárioB. de Fátima SantanaNazaréM. de SouzaD.V. Le Sueur-MalufL. EstadellaD. RibeiroD.A. de Barros VianaM. The influence of sex and reproductive cycle on cocaine-induced behavioral and neurobiological alterations: a review.Exp. Brain Res.2022240123107314010.1007/s00221‑022‑06479‑436264315
     [Google Scholar]
  37. BassaniT.B. BartolomeoC.S. OliveiraR.B. UreshinoR.P. Progestogen-mediated neuroprotection in central nervous system disorders.Neuroendocrinology20231131143510.1159/00052567735760047
     [Google Scholar]
  38. SolfrizziV. CustoderoC. LozuponeM. ImbimboB.P. ValianiV. AgostiP. SchilardiA. D’IntronoA. La MontagnaM. CalvaniM. GuerraV. SardoneR. AbbresciaD.I. BellomoA. GrecoA. DanieleA. SeripaD. LogroscinoG. SabbáC. PanzaF. Relationships of dietary patterns, foods, and micro- and macronutrients with Alzheimer’s disease and late-life cognitive disorders: A systematic review.J. Alzheimers Dis.201759381584910.3233/JAD‑17024828697569
     [Google Scholar]
  39. NoroozianM. Alzheimer’s Disease.Neurol. Clin.20163416913110.1016/j.ncl.2015.08.00526613996
     [Google Scholar]
  40. IdeM. HarrisM. StevensA. SussamsR. HopkinsV. CullifordD. FullerJ. IbbettP. RaybouldR. ThomasR. PuenterU. TeelingJ. PerryV.H. HolmesC. Periodontitis and cognitive decline in Alzheimer’s disease.PLoS One2016113e015108110.1371/journal.pone.015108126963387
     [Google Scholar]
  41. CamposC. RochaN.B. VieiraR.T. RochaS.A. Telles-CorreiaD. PaesF. YuanT. NardiA.E. Arias-CarriónO. MachadoS. CaixetaL. Treatment of cognitive deficits in Alzheimer’s disease: A psychopharmacological review.Psychiatr. Danub.201628121226938815
     [Google Scholar]
  42. LiR. SinghM. Sex differences in cognitive impairment and Alzheimer’s disease.Front. Neuroendocrinol.201435338540310.1016/j.yfrne.2014.01.00224434111
     [Google Scholar]
  43. MillsZ.B. FaullR.L.M. KwakowskyA. Is hormone replacement therapy a risk factor or a therapeutic option for Alzheimer’s disease?Int. J. Mol. Sci.2023244320510.3390/ijms2404320536834617
     [Google Scholar]
  44. WangX. FengS. DengQ. WuC. DuanR. YangL. The role of estrogen in Alzheimer’s disease pathogenesis and therapeutic potential in women.Mol. Cell. Biochem.2024Epub ahead of print10.1007/s11010‑024‑05071‑439088186
     [Google Scholar]
  45. ZhouC. WuQ. WangZ. WangQ. LiangY. LiuS. The effect of hormone replacement therapy on cognitive function in female patients with Alzheimer’s disease: A meta-analysis.Am. J. Alzheimers Dis. Other Demen.202035153331752093858510.1177/153331752093858532677442
     [Google Scholar]
  46. BrodS.A. Anti-Inflammatory Agents: An Approach to Prevent Cognitive Decline in Alzheimer’s Disease.J. Alzheimers Dis.202285245747210.3233/JAD‑21512534842189
     [Google Scholar]
  47. HallerO.J. SemendricI. GeorgeR.P. Collins-PrainoL.E. WhittakerA.L. The effectiveness of anti-inflammatory agents in reducing chemotherapy-induced cognitive impairment in preclinical models – A systematic review.Neurosci. Biobehav. Rev.202314810512010.1016/j.neubiorev.2023.10512036906244
     [Google Scholar]
  48. UchidaY. KanH. SakuraiK. OishiK. MatsukawaN. Contributions of blood–brain barrier imaging to neurovascular unit pathophysiology of Alzheimer’s disease and related dementias.Front. Aging Neurosci.202315111144810.3389/fnagi.2023.111144836861122
     [Google Scholar]
  49. UchidaY. KanH. SakuraiK. HorimotoY. HayashiE. IidaA. OkamuraN. OishiK. MatsukawaN. APOE ɛ4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction.J. Neurol. Neurosurg. Psychiatry2022jnnp-2021-32851935483916
     [Google Scholar]
  50. UchidaY. KanH. SakuraiK. AraiN. InuiS. KobayashiS. KatoD. UekiY. MatsukawaN. Iron leakage owing to blood–brain barrier disruption in small vessel disease CADASIL.Neurology2020959e1188e119810.1212/WNL.000000000001014832586899
     [Google Scholar]
  51. Candelario-JalilE. DijkhuizenR.M. MagnusT. Neuroinflammation, stroke, blood-brain barrier dysfunction, and imaging modalities.Stroke20225351473148610.1161/STROKEAHA.122.03694635387495
     [Google Scholar]
  52. ChenS. LiL. PengC. BianC. OcakP.E. ZhangJ.H. YangY. ZhouD. ChenG. LuoY. Targeting oxidative stress and inflammatory response for blood–brain barrier protection in intracerebral hemorrhage.Antioxid. Redox Signal.2022371-311513410.1089/ars.2021.007235383484
     [Google Scholar]
  53. HuangX. HussainB. ChangJ. Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms.CNS Neurosci. Ther.2021271364710.1111/cns.1356933381913
     [Google Scholar]
  54. ZhaoY. GanL. RenL. LinY. MaC. LinX. Factors influencing the blood-brain barrier permeability.Brain Res.2022178814793710.1016/j.brainres.2022.14793735568085
     [Google Scholar]
/content/journals/car/10.2174/0115672050341904241111082935
Loading
Correlations between SHBG, Sex Hormones, Inflammation, and Neurocognitive Decline in Alzheimer's Disease: A Retrospective Study
Curr Alzheimer Res 21, 491 (2024); https://doi.org/10.2174/0115672050341904241111082935
/content/journals/car/10.2174/0115672050341904241111082935
/content/journals/car/10.2174/0115672050341904241111082935
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Alzheimer's disease; Correlation analysis; inflammation; neurocognitive abilities; retrospective; serum hormone binding globulin levels

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test