Skip to content
2000
Volume 22, Issue 1
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828

Abstract

Alzheimer's disease (AD) and vascular dementia (VD) are the leading causes of dementia, presenting a significant challenge in differential diagnosis. While their clinical presentations can overlap, their underlying pathologies are distinct. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles, leading to progressive neurodegeneration. VD, on the other hand, arises from cerebrovascular insults that disrupt blood flow to the brain, causing neuronal injury and cognitive decline. Despite distinct etiologies, AD and VD share common risk factors such as hypertension, diabetes, and hyperlipidemia. Recent research suggests a potential role for oral microbiota in both diseases, warranting further investigation. The diagnostic dilemma lies in the significant overlap of symptoms including memory loss, executive dysfunction, and personality changes. The absence of definitive biomarkers and limitations of current neuroimaging techniques necessitate a multi-modal approach integrating clinical history, cognitive assessment, and neuroimaging findings. Promising avenues for improved diagnosis include the exploration of novel biomarkers like inflammatory markers, MMPs, and circulating microRNAs. Additionally, advanced neuroimaging techniques hold promise in differentiating AD and VD by revealing characteristic cerebrovascular disease patterns and brain atrophy specific to each condition. By elucidating the complexities underlying AD and VD, we can refine diagnostic accuracy and optimize treatment strategies for this ever-growing patient population. Future research efforts should focus on identifying disease-specific biomarkers and developing more effective neuroimaging methods to achieve a definitive diagnosis and guide the development of targeted therapies.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050319219240711103459
2024-07-29
2025-10-12

  • From This Site

    /content/journals/car/10.2174/0115672050319219240711103459
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. XuY. SunZ. Molecular basis of Klotho: from gene to function in aging.Endocr. Rev.201536217419310.1210/er.2013‑107925695404
     [Google Scholar]
  2. ShielsP.G. StenvinkelP. KoomanJ.P. McGuinnessD. Circulating markers of ageing and allostatic load: A slow train coming.Pract. Lab. Med.20177495410.1016/j.plabm.2016.04.00228856219
     [Google Scholar]
  3. SalvioliS. MontiD. LanzariniC. ConteM. PirazziniC. BacaliniM.G. GaragnaniP. GiulianiC. FontanesiE. OstanR. BucciL. SeviniF. YaniS.L. BarbieriA. LomartireL. BorelliV. VianelloD. BellavistaE. MartucciM. CeveniniE. PiniE. ScurtiM. BiondiF. SantoroA. CapriM. FranceschiC. Immune system, cell senescence, aging and longevity inflamm-aging reappraised.Curr. Pharm. Des.20131991675167923589904
     [Google Scholar]
  4. BaumgartM. SnyderH.M. CarrilloM.C. FazioS. KimH. JohnsH. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective.Alzheimers Dement.201511671872610.1016/j.jalz.2015.05.01626045020
     [Google Scholar]
  5. CampisiJ. Aging, cellular senescence, and cancer.Annu. Rev. Physiol.201375168570510.1146/annurev‑physiol‑030212‑18365323140366
     [Google Scholar]
  6. CampisiJ. d’Adda di FagagnaF. Cellular senescence: when bad things happen to good cells.Nat. Rev. Mol. Cell Biol.20078972974010.1038/nrm223317667954
     [Google Scholar]
  7. Alzheimer’s Association2016 Alzheimer’s disease facts and figures.Alzheimers Dement.201612445950910.1016/j.jalz.2016.03.00127570871
     [Google Scholar]
  8. PrinceM. BryceR. AlbaneseE. WimoA. RibeiroW. FerriC.P. The global prevalence of dementia: A systematic review and metaanalysis.Alzheimers Dement.2013916375.e210.1016/j.jalz.2012.11.00723305823
     [Google Scholar]
  9. SandersA.E. SchooC. KalishV.B. Vascular Dementia.StatPearls Publishing2024
     [Google Scholar]
  10. BekrisL.M. YuC.E. BirdT.D. TsuangD.W. Genetics of Alzheimer disease.J. Geriatr. Psychiatry Neurol.201023421322710.1177/089198871038357121045163
     [Google Scholar]
  11. BalasaM. GelpiE. AntonellA. ReyM.J. Sánchez-ValleR. MolinuevoJ.L. LladóA. Clinical features and APOE genotype of pathologically proven early-onset Alzheimer disease.Neurology201176201720172510.1212/WNL.0b013e31821a44dd21576687
     [Google Scholar]
  12. LyketsosC.G. CarrilloM.C. RyanJ.M. KhachaturianA.S. TrzepaczP. AmatniekJ. CedarbaumJ. BrashearR. MillerD.S. Neuropsychiatric symptoms in Alzheimer’s disease.Alzheimers Dement.20117553253910.1016/j.jalz.2011.05.241021889116
     [Google Scholar]
  13. BallardC. GauthierS. CorbettA. BrayneC. AarslandD. JonesE. Alzheimer’s disease.Lancet201137797701019103110.1016/S0140‑6736(10)61349‑921371747
     [Google Scholar]
  14. StelzmannR.A. Norman SchnitzleinH. Reed MurtaghF. MurtaghF.R. AlzheimerA. An english translation of Alzheimer’s 1907 paper, “über eine eigenartige erkankung der hirnrinde”.Clin. Anat.19958642943110.1002/ca.9800806128713166
     [Google Scholar]
  15. PolepalleT. MoogalaS. BoggarapuS. PesalaD.S. PalagiF.B. Acute phase proteins and their role in periodontitis: A review.J. Clin. Diagn. Res.2015911ZE01ZE0510.7860/JCDR/2015/15692.672826674303
     [Google Scholar]
  16. GuravA. N. Alzheimer's disease and periodontitis : An elusive link.Rev. Assoc. Med. Bras.2014602173180
     [Google Scholar]
  17. FennoJ.C. Treponema denticola interactions with host proteins.J. Oral Microbiol.201241992910.3402/jom.v4i0.992922368767
     [Google Scholar]
  18. StewartR. SabbahW. TsakosG. D’AiutoF. WattR.G. Oral health and cognitive function in the third national health and nutrition examination survey (NHANES III).Psychosom. Med.200870893694110.1097/PSY.0b013e3181870aec18842752
     [Google Scholar]
  19. OlsenI. SinghraoS.K. Can oral infection be a risk factor for Alzheimer’s disease?J. Oral Microbiol.2015712914310.3402/jom.v7.2914326385886
     [Google Scholar]
  20. KamerA.R. CraigR.G. PirragliaE. DasanayakeA.P. NormanR.G. BoylanR.J. NehorayoffA. GlodzikL. BrysM. de LeonM.J. TNF-α and antibodies to periodontal bacteria discriminate between Alzheimer’s disease patients and normal subjects.J. Neuroimmunol.20092161-2929710.1016/j.jneuroim.2009.08.01319767111
     [Google Scholar]
  21. WuZ. NakanishiH. Connection between periodontitis and Alzheimer’s disease: possible roles of microglia and leptomeningeal cells.J. Pharmacol. Sci.2014126181310.1254/jphs.14R11CP25168594
     [Google Scholar]
  22. DominyS.S. LynchC. ErminiF. BenedykM. MarczykA. KonradiA. NguyenM. HaditschU. RahaD. GriffinC. HolsingerL.J. Arastu-KapurS. KabaS. LeeA. RyderM.I. PotempaB. MydelP. HellvardA. AdamowiczK. HasturkH. WalkerG.D. ReynoldsE.C. FaullR.L.M. CurtisM.A. DragunowM. PotempaJ. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors.Sci. Adv.201951eaau333310.1126/sciadv.aau333330746447
     [Google Scholar]
  23. JiangT. YuJ.T. ZhuX.C. TanL. TREM2 in Alzheimer’s disease.Mol. Neurobiol.201348118018510.1007/s12035‑013‑8424‑823407992
     [Google Scholar]
  24. ZhongL. ChenX.F. The emerging roles and therapeutic potential of soluble TREM2 in Alzheimer’s disease.Front. Aging Neurosci.20191132810.3389/fnagi.2019.0032832038221
     [Google Scholar]
  25. ZhaoN. LiuC.C. QiaoW. BuG. ApolipoproteinE. Apolipoprotein E, receptors, and modulation of Alzheimer’s disease.Biol. Psychiatry201883434735710.1016/j.biopsych.2017.03.00328434655
     [Google Scholar]
  26. LiangS. DomonH. HosurK.B. WangM. HajishengallisG. Age-related alterations in innate immune receptor expression and ability of macrophages to respond to pathogen challenge in vitro.Mech. Ageing Dev.2009130853854610.1016/j.mad.2009.06.00619559723
     [Google Scholar]
  27. RahaA.A. HendersonJ.W. StottS.R.W. VuonoR. FoscarinS. FriedlandR.P. ZamanS.H. Raha-ChowdhuryR. Neuroprotective effect of TREM-2 in aging and Alzheimer’s disease model.J. Alzheimers Dis.201655119921710.3233/JAD‑16066327662313
     [Google Scholar]
  28. 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]
  29. KorczynA.D. Mixed dementia the most common cause of dementia.Ann. N. Y. Acad. Sci.2002977112913410.1111/j.1749‑6632.2002.tb04807.x12480742
     [Google Scholar]
  30. RizziL. RossetI. Roriz-CruzM. Global epidemiology of dementia: Alzheimer’s and vascular types.BioMed. Res. Int.201420141810.1155/2014/90891525089278
     [Google Scholar]
  31. SeymourG.J. FordP.J. CullinanM.P. LeishmanS. YamazakiK. Relationship between periodontal infections and systemic disease.Clin. Microbiol. Infect.200713431010.1111/j.1469‑0691.2007.01798.x17716290
     [Google Scholar]
  32. SnowD.E. EverettJ. MayerG. CoxS.B. MillerB. RumbaughK. WolcottR.A. WolcottR.D. The presence of biofilm structures in atherosclerotic plaques of arteries from legs amputated as a complication of diabetic foot ulcers.J. Wound Care201625Sup2S16S2210.12968/jowc.2016.25.Sup2.S1626878370
     [Google Scholar]
  33. LanterB.B. SauerK. DaviesD.G. Bacteria present in carotid arterial plaques are found as biofilm deposits which may contribute to enhanced risk of plaque rupture.MBio201453e01206-1410.1128/mBio.01206‑1424917599
     [Google Scholar]
  34. PlassmanB.L. LangaK.M. FisherG.G. HeeringaS.G. WeirD.R. OfstedalM.B. BurkeJ.R. HurdM.D. PotterG.G. RodgersW.L. SteffensD.C. WillisR.J. WallaceR.B. Prevalence of dementia in the United States: the aging, demographics, and memory study.Neuroepidemiology2007291-212513210.1159/00010999817975326
     [Google Scholar]
  35. VahiaV. Diagnostic and statistical manual of mental disorders 5: A quick glance.Indian J. Psychiatry201355322022310.4103/0019‑5545.11713124082241
     [Google Scholar]
  36. 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]
  37. WuY.T. BeiserA.S. BretelerM.M.B. FratiglioniL. HelmerC. HendrieH.C. HondaH. IkramM.A. LangaK.M. LoboA. MatthewsF.E. OharaT. PérèsK. QiuC. SeshadriS. SjölundB.M. SkoogI. BrayneC. The changing prevalence and incidence of dementia over time current evidence.Nat. Rev. Neurol.201713632733910.1038/nrneurol.2017.6328497805
     [Google Scholar]
  38. FranzenS. van den BergE. BossenbroekW. KranenburgJ. ScheffersE.A. van HoutM. van de WielL. GoudsmitM. van Bruchem-VisserR.L. van HemmenJ. JiskootL.C. PapmaJ.M. Neuropsychological assessment in the multicultural memory clinic: Development and feasibility of the TULIPA battery.Clin. Neuropsychol.2023371608010.1080/13854046.2022.204344735225154
     [Google Scholar]
  39. RobinsonR.G. JorgeR.E. Post-stroke depression: A review.Am. J. Psychiatry2016173322123110.1176/appi.ajp.2015.1503036326684921
     [Google Scholar]
  40. LiuF. TsangR.C.C. ZhouJ. ZhouM. ZhaF. LongJ. WangY. Relationship of barthel index and its short form with the modified rankin scale in acute stroke patients.J. Stroke Cerebrovasc. Dis.202029910503310.1016/j.jstrokecerebrovasdis.2020.10503332807445
     [Google Scholar]
  41. WetterlingT. KanitzR.D. BorgisK.J. Comparison of different diagnostic criteria for vascular dementia (ADDTC, DSM-IV, ICD-10, NINDS-AIREN).Stroke1996271303610.1161/01.STR.27.1.308553399
     [Google Scholar]
  42. ScheltensP. HijdraA.H. Diagnostic criteria for vascular dementia.Haemostasis1998283-415115710420062
     [Google Scholar]
  43. ErkinjunttiT. Clinical criteria for vascular dementia: the NINDS-AIREN criteria.Dementia199453-41891928087178
     [Google Scholar]
  44. WiederkehrS. SimardM. FortinC. van ReekumR. Validity of the clinical diagnostic criteria for vascular dementia: A critical review. Part II.J. Neuropsychiatry Clin. Neurosci.200820216217710.1176/jnp.2008.20.2.16218451187
     [Google Scholar]
  45. HachinskiV. IadecolaC. PetersenR.C. BretelerM.M. NyenhuisD.L. BlackS.E. PowersW.J. DeCarliC. MerinoJ.G. KalariaR.N. VintersH.V. HoltzmanD.M. RosenbergG.A. WallinA. DichgansM. MarlerJ.R. LeblancG.G. National institute of neurological disorders and stroke-canadian stroke network vascular cognitive impairment harmonization standards.Stroke20063792220224110.1161/01.STR.0000237236.88823.4716917086
     [Google Scholar]
  46. BonelliR.M. CummingsJ.L. Frontal-subcortical circuitry and behavior.Dialogues Clin. Neurosci.20079214115110.31887/DCNS.2007.9.2/rbonelli17726913
     [Google Scholar]
  47. PendleburyS.T. CuthbertsonF.C. WelchS.J.V. MehtaZ. RothwellP.M. Underestimation of cognitive impairment by mini- mental state examination versus the montreal cognitive Assessment in patients with transient ischemic attack and stroke: A population-based study.Stroke20104161290129310.1161/STROKEAHA.110.57988820378863
     [Google Scholar]
  48. SkrobotO.A. O’BrienJ. BlackS. ChenC. DeCarliC. ErkinjunttiT. FordG.A. KalariaR.N. PantoniL. PasquierF. RomanG.C. WallinA. SachdevP. SkoogI. Ben-ShlomoY. PassmoreA.P. LoveS. KehoeP.G. TaraganoF.E. KrilJ. CavalieriM. JellingerK.A. KovacsG.G. EngelborghsS. LafosseC. BertolucciP.H. BruckiS. CaramelliP. de Toledo Ferraz AlvesT.C. BoctiC. FulopT. HoganD.B. HsiungG.R. KirkA. LeachL. RobillardA. SahlasD.J. GuoQ. TianJ. HokkanenL. JokinenH. BenistyS. DeramecourtV. HauwJ. LenoirH. TsataliM. TsolakiM. SundarU. CoenR.F. KorczynA.D. AltieriM. BaldereschiM. CaltagironeC. CaravagliosG. Di CarloA. PieroD.I. The vascular impairment of cognition classification consensus study.Alzheimers Dement.201713662463310.1016/j.jalz.2016.10.00727960092
     [Google Scholar]
  49. SchneiderJ.A. ArvanitakisZ. BangW. BennettD.A. Mixed brain pathologies account for most dementia cases in community-dwelling older persons.Neurology200769242197220410.1212/01.wnl.0000271090.28148.2417568013
     [Google Scholar]
  50. KalariaR.N. Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease.Acta Neuropathol.2016131565968510.1007/s00401‑016‑1571‑z27062261
     [Google Scholar]
  51. Alzheimer’s Association WorkgroupRevised Criteria for Diagnosis and Staging of Alzheimer's Disease.2023Available from: https://aaic.alz.org/diagnostic-criteria.asp
  52. JackC.R.Jr BennettD.A. BlennowK. CarrilloM.C. DunnB. HaeberleinS.B. HoltzmanD.M. JagustW. JessenF. KarlawishJ. LiuE. MolinuevoJ.L. MontineT. PhelpsC. RankinK.P. RoweC.C. ScheltensP. SiemersE. SnyderH.M. SperlingR. ElliottC. MasliahE. RyanL. SilverbergN. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease.Alzheimers Dement.201814453556210.1016/j.jalz.2018.02.01829653606
     [Google Scholar]
  53. VillemagneV.L. LoprestiB.J. DoréV. TudorascuD. IkonomovicM.D. BurnhamS. MinhasD. PascoalT.A. MasonN.S. SnitzB. AizensteinH. MathisC.A. LopezO. RoweC.C. KlunkW.E. CohenA.D. What Is T+? a gordian knot of tracers, thresholds, and topographies.J. Nucl. Med.202162561461910.2967/jnumed.120.24542333384320
     [Google Scholar]
  54. BarthélemyN.R. LiY. Joseph-MathurinN. GordonB.A. HassenstabJ. BenzingerT.L.S. BucklesV. FaganA.M. PerrinR.J. GoateA.M. MorrisJ.C. KarchC.M. XiongC. AllegriR. MendezP.C. BermanS.B. IkeuchiT. MoriH. ShimadaH. ShojiM. SuzukiK. NobleJ. FarlowM. ChhatwalJ. Graff-RadfordN.R. SallowayS. SchofieldP.R. MastersC.L. MartinsR.N. O’ConnorA. FoxN.C. LevinJ. JuckerM. GabelleA. LehmannS. SatoC. BatemanR.J. McDadeE. AllegriR. BatemanR. BecharaJ. BenzingerT. BermanS. BodgeC. BrandonS. BrooksW.B. BuckJ. BucklesV. CheaS. ChhatwalJ. Chrem MendezP. ChuiH. CincoJ. CliffordJ. CruchagaC. DonahueT. DouglasJ. EdigoN. Erekin-TanerN. FaganA. FarlowM. FitzpatrickC. FlynnG. FoxN. FranklinE. FujiiH. GantC. GardenerS. GhettiB. GoateA. GoldmanJ. GordonB. Graff-RadfordN. GrayJ. GrovesA. HassenstabJ. Hoechst-SwisherL. HoltzmanD. HornbeckR. DiBariS.H. IkeuchiT. IkonomovicS. JeromeG. JuckerM. KarchC. KasugaK. KawarabayashiT. KlunkW.B. KoeppeR. Kuder-BulettaE. LaskeC. LeeJ.H. LevinJ. MartinsR. MasonN.S. MastersC. Maue-DreyfusD. McDadeE. MoriH. MorrisJ. NagamatsuA. NeimeyerK. NobleJ. NortonJ. PerrinR. RaichleM. RentonA. RingmanJ. RohJ.H. SallowayS. SchofieldP. ShimadaH. SigurdsonW. SohrabiH. SparksP. SuzukiK. TaddeiK. WangP. XiongC. XuX. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease.Nat. Med.202026339840710.1038/s41591‑020‑0781‑z32161412
     [Google Scholar]
  55. JanelidzeS. BerronD. SmithR. StrandbergO. ProctorN.K. DageJ.L. StomrudE. PalmqvistS. Mattsson-CarlgrenN. HanssonO. Associations of plasma phospho-Tau217 levels with tau positron emission tomography in early alzheimer disease.JAMA Neurol.202178214915610.1001/jamaneurol.2020.420133165506
     [Google Scholar]
  56. GrootC. SmithR. StomrudE. BinetteA.P. LeuzyA. WuestefeldA. WisseL.E.M. PalmqvistS. Mattsson-CarlgrenN. JanelidzeS. StrandbergO. OssenkoppeleR. HanssonO. Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals.Brain202314641580159110.1093/brain/awac32936084009
     [Google Scholar]
  57. OssenkoppeleR. ReimandJ. SmithR. LeuzyA. StrandbergO. PalmqvistS. StomrudE. ZetterbergH. ScheltensP. DageJ.L. BouwmanF. BlennowK. Mattsson-CarlgrenN. JanelidzeS. HanssonO. Tau PET correlates with different Alzheimer’s disease-related features compared to CSF and plasma p-tau biomarkers.EMBO Mol. Med.2021138e1439810.15252/emmm.20211439834254442
     [Google Scholar]
  58. LeuzyA. SmithR. CullenN.C. StrandbergO. VogelJ.W. BinetteA.P. BorroniE. JanelidzeS. OhlssonT. JögiJ. OssenkoppeleR. PalmqvistS. Mattsson-CarlgrenN. KleinG. StomrudE. HanssonO. Biomarker-based prediction of longitudinal tau positron emission tomography in alzheimer disease.JAMA Neurol.202279214915810.1001/jamaneurol.2021.465434928318
     [Google Scholar]
  59. Mattsson-CarlgrenN. AnderssonE. JanelidzeS. OssenkoppeleR. InselP. StrandbergO. ZetterbergH. RosenH.J. RabinoviciG. ChaiX. BlennowK. DageJ.L. StomrudE. SmithR. PalmqvistS. HanssonO. Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease.Sci. Adv.2020616eaaz238710.1126/sciadv.aaz238732426454
     [Google Scholar]
  60. TherriaultJ. PascoalT.A. LussierF.Z. TissotC. ChamounM. BezginG. ServaesS. BenedetA.L. AshtonN.J. KarikariT.K. Lantero-RodriguezJ. KunachP. WangY.T. Fernandez-AriasJ. MassarwehG. VitaliP. SoucyJ.P. Saha-ChaudhuriP. BlennowK. ZetterbergH. GauthierS. Rosa-NetoP. Biomarker modeling of Alzheimer’s disease using PET-based Braak staging.Nature Aging20222652653510.1038/s43587‑022‑00204‑037118445
     [Google Scholar]
  61. HorieK. BarthélemyN.R. SatoC. BatemanR.J. CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer’s disease.Brain2021144251552710.1093/brain/awaa37333283854
     [Google Scholar]
  62. BarthélemyN.R. SaefB. LiY. GordonB.A. HeY. HorieK. StomrudE. SalvadóG. JanelidzeS. SatoC. OvodV. HensonR.L. FaganA.M. BenzingerT.L.S. XiongC. MorrisJ.C. HanssonO. BatemanR.J. SchindlerS.E. CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer’s disease.Nature Aging20233439140110.1038/s43587‑023‑00380‑737117788
     [Google Scholar]
  63. Montoliu-GayaL. BenedetA.L. TissotC. VrillonA. AshtonN.J. BrumW.S. Lantero-RodriguezJ. StevensonJ. NilssonJ. SauerM. RahmouniN. BrinkmalmG. LussierF.Z. PascoalT.A. SkoogI. KernS. ZetterbergH. PaquetC. GobomJ. Rosa-NetoP. BlennowK. Mass spectrometric simultaneous quantification of tau species in plasma shows differential associations with amyloid and tau pathologies.Nature Aging20233666166910.1038/s43587‑023‑00405‑137198279
     [Google Scholar]
  64. SalvadóG. HorieK. BarthélemyN.R. VogelJ.W. BinetteA.P. ChenC.D. AschenbrennerA.J. GordonB.A. BenzingerT.L.S. HoltzmanD.M. MorrisJ.C. PalmqvistS. StomrudE. JanelidzeS. OssenkoppeleR. SchindlerS.E. BatemanR.J. HanssonO. Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer’s disease.medRxiv2023
     [Google Scholar]
  65. MintunM.A. LaRossaG.N. ShelineY.I. DenceC.S. LeeS.Y. MachR.H. KlunkW.E. MathisC.A. DeKoskyS.T. MorrisJ.C. [11C]PIB in a nondemented population.Neurology200667344645210.1212/01.wnl.0000228230.26044.a416894106
     [Google Scholar]
  66. AizensteinH.J. NebesR.D. SaxtonJ.A. PriceJ.C. MathisC.A. TsopelasN.D. ZiolkoS.K. JamesJ.A. SnitzB.E. HouckP.R. BiW. CohenA.D. LoprestiB.J. DeKoskyS.T. HalliganE.M. KlunkW.E. Frequent amyloid deposition without significant cognitive impairment among the elderly.Arch. Neurol.200865111509151710.1001/archneur.65.11.150919001171
     [Google Scholar]
  67. JackC.R.Jr LoweV.J. WeigandS.D. WisteH.J. SenjemM.L. KnopmanD.S. ShiungM.M. GunterJ.L. BoeveB.F. KempB.J. WeinerM. PetersenR.C. WeinerM. ThalL. WeinerM. ThalL. PetersenR. JackC.R. JagustW. TrojanowkiJ. TogaA.W. BeckettL. GreenR.C. GamstA. PotterW.Z. GreenR.C. MontineT. PetersenR. ThalL. JackC.R. AndersD. BernsteinM. FelmleeJ. FoxN. ThompsonP. SchuffN. AlexanderG. JagustW. BandyD. KoeppeR.A. FosterN. ReimanE.M. ChenK. TrojanowkiJ. ShawL. LeeV.M. KoreckaM. TogaA.W. CrawfordK. NeuS. BeckettL. HarveyD. GamstA. KornakJ. KachaturianZ. FrankR. SnyderP.J. MolchanS. KayeJ. VorobikR. QuinnJ. SchneiderL. PawluczykS. SpannB. FleisherA.S. VanderswagH. HeidebrinkJ.L. LordJ.L. PetersenR. JohnsonK. DoodyR.S. Villanueva-MeyerJ. ChowdhuryM. SternY. HonigL.S. BellK.L. MorrisJ.C. MintunM.A. SchneiderS. MarsonD. GriffithR. BadgerB. GrossmanH. TangC. SternJ. deToledo-MorrellL. ShahR.C. BachJ. DuaraR. IsaacsonR. StraumanS. AlbertM.S. PedrosoJ. ToroneyJ. RusinekH. de LeonM.J. De SantiS.M. DoraiswamyP.M. PetrellaJ.R. AielloM. ClarkC.M. PhamC. NunezJ. SmithC.D. GivenC.A. HardyP. DeKoskyS.T. OakleyM. SimpsonD.M. IsmailM.S. PorsteinssonA. McCallumC. CramerS.C. MulnardR.A. McAdams-OrtizC. Diaz-ArrastiaR. Martin-CookK. DeVousM. LeveyA.I. LahJ.J. CellarJ.S. BurnsJ.M. AndersonH.S. LaubingerM.M. BartzokisG. SilvermanD.H. LuP.H. FletcherR. ParfittF. JohnsonH. FarlowM. HerringS. HakeA.M. van DyckC.H. MacAvoyM.G. BifanoL.A. ChertkowH. BergmanH. HoseinC. BlackS. GrahamS. CaldwellC. FeldmanH. AssalyM. HsiungG.Y. KerteszA. RogersJ. TrostD. BernickC. GitelmanD. JohnsonN. MesulamM. SadowskyC. VillenaT. MesnerS. AisenP.S. JohnsonK.B. BehanK.E. SperlingR.A. RentzD.M. JohnsonK.A. RosenA. TinklenbergJ. AshfordW. SabbaghM. ConnorD. ObradovS. GreenR.C. KillianyR. NorbashA. ObisesanT.O. Jayam-TrouthA. WangP. AuchusA.P. HuangJ. FriedlandR.P. DeCarliC. FletcherE. CarmichaelO. KitturS. MirjeS. JohnsonS.C. BorrieM. LeeT.Y. AsthanaS. CarlssonC.M. PotkinS.G. HighumD. PredaA. NguyenD. TariotP.N. ReimanE.M. HendinB.A. ScharreD.W. KatakiM. BeversdorfD.Q. ZimmermanE.A. CelminsD. BrownA.D. GandyS. MarenbergM.E. RovnerB.W. PearlsonG. BlankK. AndersonK. SaykinA.J. SantulliR.B. PareN. WilliamsonJ.D. SinkK.M. PotterH. RajB.A. GiordanoA. OttB.R. WuC.K. CohenR. WilksK.L. SafirsteinB.E. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease.Brain200913251355136510.1093/brain/awp06219339253
     [Google Scholar]
  68. BatemanR.J. XiongC. BenzingerT.L.S. FaganA.M. GoateA. FoxN.C. MarcusD.S. CairnsN.J. XieX. BlazeyT.M. HoltzmanD.M. SantacruzA. BucklesV. OliverA. MoulderK. AisenP.S. GhettiB. KlunkW.E. McDadeE. MartinsR.N. MastersC.L. MayeuxR. RingmanJ.M. RossorM.N. SchofieldP.R. SperlingR.A. SallowayS. MorrisJ.C. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease.N. Engl. J. Med.2012367979580410.1056/NEJMoa120275322784036
     [Google Scholar]
  69. BenzingerT.L.S. BlazeyT. JackC.R.Jr KoeppeR.A. SuY. XiongC. RaichleM.E. SnyderA.Z. AncesB.M. BatemanR.J. CairnsN.J. FaganA.M. GoateA. MarcusD.S. AisenP.S. ChristensenJ.J. ErcoleL. HornbeckR.C. FarrarA.M. AldeaP. JasielecM.S. OwenC.J. XieX. MayeuxR. BrickmanA. McDadeE. KlunkW. MathisC.A. RingmanJ. ThompsonP.M. GhettiB. SaykinA.J. SperlingR.A. JohnsonK.A. SallowayS. CorreiaS. SchofieldP.R. MastersC.L. RoweC. VillemagneV.L. MartinsR. OurselinS. RossorM.N. FoxN.C. CashD.M. WeinerM.W. HoltzmanD.M. BucklesV.D. MoulderK. MorrisJ.C. Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease.Proc. Natl. Acad. Sci.201311047E4502E450910.1073/pnas.131791811024194552
     [Google Scholar]
  70. JackC.R.Jr WisteH.J. BothaH. WeigandS.D. TherneauT.M. KnopmanD.S. Graff-RadfordJ. JonesD.T. FermanT.J. BoeveB.F. KantarciK. LoweV.J. VemuriP. MielkeM.M. FieldsJ.A. MachuldaM.M. SchwarzC.G. SenjemM.L. GunterJ.L. PetersenR.C. The bivariate distribution of amyloid-β and tau: relationship with established neurocognitive clinical syndromes.Brain2019142103230324210.1093/brain/awz26831501889
     [Google Scholar]
  71. GuoT. KormanD. BakerS.L. LandauS.M. JagustW.J. Longitudinal cognitive and biomarker measurements support a unidirectional pathway in Alzheimer’s disease pathophysiology.Biol. Psychiatry202189878679410.1016/j.biopsych.2020.06.02932919611
     [Google Scholar]
  72. HerbertM.K. AertsM.B. KuiperijH.B. ClaassenJ.A.H.R. SpiesP.E. EsselinkR.A.J. BloemB.R. VerbeekM.M. Addition of MHPG to Alzheimer’s disease biomarkers improves differentiation of dementia with Lewy bodies from Alzheimer’s disease but not other dementias.Alzheimers Dement.2014104448455.e210.1016/j.jalz.2013.05.177524239248
     [Google Scholar]
  73. EwersM. MattssonN. MinthonL. MolinuevoJ.L. AntonellA. PoppJ. JessenF. HerukkaS.K. SoininenH. MaetzlerW. LeyheT. BürgerK. TaniguchiM. UrakamiK. ListaS. DuboisB. BlennowK. HampelH. CSF biomarkers for the differential diagnosis of Alzheimer’s disease: A large-scale international multicenter study.Alzheimers Dement.201511111306131510.1016/j.jalz.2014.12.00625804998
     [Google Scholar]
  74. RosenbergG.A. PrestopnikJ. AdairJ.C. HuisaB.N. KnoefelJ. CaprihanA. GasparovicC. ThompsonJ. ErhardtE.B. SchraderR. Validation of biomarkers in subcortical ischaemic vascular disease of the Binswanger type: Approach to targeted treatment trials.J. Neurol. Neurosurg. Psychiatry201586121324133010.1136/jnnp‑2014‑30942125618903
     [Google Scholar]
  75. SkillbäckT. FarahmandB.Y. RosénC. MattssonN. NäggaK. KilanderL. ReligaD. WimoA. WinbladB. SchottJ.M. BlennowK. EriksdotterM. ZetterbergH. Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia.Brain201513892716273110.1093/brain/awv18126133663
     [Google Scholar]
  76. StruyfsH. Van BroeckB. TimmersM. FransenE. SleegersK. Van BroeckhovenC. De DeynP.P. StrefferJ.R. MerckenM. EngelborghsS. Diagnostic accuracy of cerebrospinal fluid amyloid-β isoforms for early and differential dementia diagnosis.J. Alzheimers Dis.201545381382210.3233/JAD‑14198625633670
     [Google Scholar]
  77. VijayanM. KumarS. BhattiJ.S. ReddyP.H. Molecular links and biomarkers of stroke, vascular dementia, and alzheimer’s disease.Prog. Mol. Biol. Transl. Sci.20171469512610.1016/bs.pmbts.2016.12.01428253992
     [Google Scholar]
  78. SullivanG.W. SarembockI.J. LindenJ. The role of inflammation in vascular diseases.J. Leukoc. Biol.200067559160210.1002/jlb.67.5.59110810997
     [Google Scholar]
  79. BelkhelfaM. BederN. MouhoubD. AmriM. HayetR. TighiltN. BakhetiS. LaimoucheS. AzzouzD. BelhadjR. Touil-BoukoffaC. The involvement of neuroinflammation and necroptosis in the hippocampus during vascular dementia.J. Neuroimmunol.2018320485710.1016/j.jneuroim.2018.04.00429759140
     [Google Scholar]
  80. NagaiK. KozakiK. SonoharaK. AkishitaM. TobaK. Relationship between interleukin-6 and cerebral deep white matter and periventricular hyperintensity in elderly women.Geriatr. Gerontol. Int.201111332833210.1111/j.1447‑0594.2010.00686.x21265971
     [Google Scholar]
  81. HilalS. IkramM.A. VerbeekM.M. FrancoO.H. StoopsE. VandersticheleH. NiessenW.J. VernooijM.W. C-reactive protein, plasma amyloid-β levels, and their interaction with magnetic resonance imaging markers.Stroke201849112692269810.1161/STROKEAHA.118.02231730355213
     [Google Scholar]
  82. WeekmanE.M. WilcockD.M. Matrix metalloproteinase in blood-brain barrier breakdown in dementia.J. Alzheimers Dis.201649489390310.3233/JAD‑15075926599057
     [Google Scholar]
  83. RosenbergG.A. BjerkeM. WallinA. Multimodal markers of inflammation in the subcortical ischemic vascular disease type of vascular cognitive impairment.Stroke20144551531153810.1161/STROKEAHA.113.00453424692476
     [Google Scholar]
  84. DuitsF.H. Hernandez-GuillamonM. MontanerJ. GoosJ.D.C. MontañolaA. WattjesM.P. BarkhofF. ScheltensP. TeunissenC.E. van der FlierW.M. Matrix metalloproteinases in Alzheimer’s disease and concurrent cerebral microbleeds.J. Alzheimers Dis.201548371172010.3233/JAD‑14318626402072
     [Google Scholar]
  85. IharaM. PolvikoskiT.M. HallR. SladeJ.Y. PerryR.H. OakleyA.E. EnglundE. O’BrienJ.T. InceP.G. KalariaR.N. Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer’s disease, and dementia with Lewy bodies.Acta Neuropathol.2010119557958910.1007/s00401‑009‑0635‑820091409
     [Google Scholar]
  86. FitzpatrickA.L. IrizarryM.C. CushmanM. JennyN.S. ChiG.C. KoroC. Lipoprotein-associated phospholipase A2 and risk of dementia in the cardiovascular health study.Atherosclerosis2014235238439110.1016/j.atherosclerosis.2014.04.03224929287
     [Google Scholar]
  87. RagusaM. BoscoP. TamburelloL. BarbagalloC. CondorelliA.G. TornitoreM. SpadaR.S. BarbagalloD. ScaliaM. EliaM. Di PietroC. PurrelloM. miRNAs plasma profiles in vascular dementia: Biomolecular data and biomedical implications.Front. Cell. Neurosci.2016105110.3389/fncel.2016.0005126973465
     [Google Scholar]
  88. DongH. LiJ. HuangL. ChenX. LiD. WangT. HuC. XuJ. ZhangC. ZenK. XiaoS. YanQ. WangC. ZhangC.Y. Serum MicroRNA profiles serve as novel biomarkers for the diagnosis of Alzheimer’s disease.Dis. Markers2015201511110.1155/2015/62565926078483
     [Google Scholar]
  89. PrabhakarP. ChandraS.R. ChristopherR. Circulating microRNAs as potential biomarkers for the identification of vascular dementia due to cerebral small vessel disease.Age Ageing201746586186410.1093/ageing/afx09028633305
     [Google Scholar]
  90. IadecolaC. DueringM. HachinskiV. JoutelA. PendleburyS.T. SchneiderJ.A. DichgansM. Vascular cognitive impairment and dementia.J. Am. Coll. Cardiol.201973253326334410.1016/j.jacc.2019.04.03431248555
     [Google Scholar]
  91. BallardC.G. BurtonE.J. BarberR. StephensS. KennyR.A. KalariaR.N. O’BrienJ.T. NINDS AIREN neuroimaging criteria do not distinguish stroke patients with and without dementia.Neurology200463698398810.1212/01.WNL.0000138435.19761.9315452287
     [Google Scholar]
  92. De ReuckJ. AugerF. DurieuxN. CordonnierC. DeramecourtV. PasquierF. MaurageC.A. LeysD. BordetR. Topographic distribution of white matter changes and lacunar infarcts in neurodegenerative and vascular dementia syndromes: A post-mortem 7.0-tesla magnetic resonance imaging study.Eur. Stroke J.20161212212910.1177/239698731665078031008274
     [Google Scholar]
  93. PendleburyS.T. RothwellP.M. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: A systematic review and meta-analysis.Lancet Neurol.20098111006101810.1016/S1474‑4422(09)70236‑419782001
     [Google Scholar]
  94. PriceC.C. JeffersonA.L. MerinoJ.G. HeilmanK.M. LibonD.J. Subcortical vascular dementia.Neurology200565337638210.1212/01.WNL.0000168877.06011.1516087901
     [Google Scholar]
  95. RobertsR.O. KnopmanD.S. PrzybelskiS.A. MielkeM.M. KantarciK. PreboskeG.M. SenjemM.L. PankratzV.S. GedaY.E. BoeveB.F. IvnikR.J. RoccaW.A. PetersenR.C. JackC.R. Jr. Association of type 2 diabetes with brain atrophy and cognitive impairment.Neurology201482131132114110.1212/WNL.000000000000026924647028
     [Google Scholar]
  96. LlorensF. SchmitzM. KnipperT. SchmidtC. LangeP. FischerA. HermannP. ZerrI. Cerebrospinal fluid biomarkers of alzheimer’s disease show different but partially overlapping profile compared to vascular dementia.Front. Aging Neurosci.2017928910.3389/fnagi.2017.0028928955218
     [Google Scholar]
  97. RothwellP.M. HowardS.C. PowerD.A. GutnikovS.A. AlgraA. van GijnJ. ClarkT.G. MurphyM.F.G. WarlowC.P. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke.Stroke200435102300230510.1161/01.STR.0000141701.36371.d115345800
     [Google Scholar]
  98. Di NapoliM. PapaF. BocolaV. Prognostic influence of increased C-reactive protein and fibrinogen levels in ischemic stroke.Stroke200132113313810.1161/01.STR.32.1.13311136928
     [Google Scholar]
  99. ÖhmanF. HassenstabJ. BerronD. SchöllM. PappK.V. Current advances in digital cognitive assessment for preclinical Alzheimer’s disease.Alzheimers Dement.2021131e1221710.1002/dad2.1221734295959
     [Google Scholar]
  100. ChanJ.Y.C. YauS.T.Y. KwokT.C.Y. TsoiK.K.F. Diagnostic performance of digital cognitive tests for the identification of MCI and dementia: A systematic review.Ageing Res. Rev.20217210150610.1016/j.arr.2021.10150634744026
     [Google Scholar]
  101. Rhodius-MeesterH.F.M. PaajanenT. KoikkalainenJ. MahdianiS. BruunM. BaroniM. LemstraA.W. ScheltensP. HerukkaS.K. PikkarainenM. HallA. HänninenT. NganduT. KivipeltoM. GilsM. HasselbalchS.G. MecocciP. RemesA. SoininenH. der FlierW.M. LötjönenJ. cCOG: A web-based cognitive test tool for detecting neurodegenerative disorders.Alzheimers Dement.2020121e1208310.1002/dad2.1208332864411
     [Google Scholar]
  102. JuttenR.J. PeetersC.F.W. LeijdesdorffS.M.J. VisserP.J. MaierA.B. TerweeC.B. ScheltensP. SikkesS.A.M. Detecting functional decline from normal aging to dementia: Development and validation of a short version of the Amsterdam IADL Questionnaire.Alzheimers Dement.201781263510.1016/j.dadm.2017.03.00228462387
     [Google Scholar]
  103. PiauA. WildK. MattekN. KayeJ. Current state of digital biomarker technologies for real-life, home-based monitoring of cognitive function for mild cognitive impairment to mild Alzheimer disease and implications for clinical care: Systematic review.J. Med. Internet Res.2019218e1278510.2196/1278531471958
     [Google Scholar]
  104. TavabiN. StückD. SignoriniA. KarjadiC. Al HanaiT. SandovalM. LemkeC. GlassJ. HardyS. LavalleeM. WassermanB. AngT.F.A. NowakC.M. KainkaryamR. FoschiniL. AuR. Cognitive digital biomarkers from automated transcription of spoken language.J. Prev. Alzheimers Dis.20229479180036281684
     [Google Scholar]
  105. LamK.H. TwoseJ. McConchieH. LicitraG. MeijerK. de RuiterL. van LieropZ. MoraalB. BarkhofF. UitdehaagB. de GrootV. KillesteinJ. Smartphone-derived keystroke dynamics are sensitive to relevant changes in multiple sclerosis.Eur. J. Neurol.202229252253410.1111/ene.1516234719076
     [Google Scholar]
  106. WeinerM.W. VeitchD.P. MillerM.J. AisenP.S. AlbalaB. BeckettL.A. GreenR.C. HarveyD. JackC.R.Jr JagustW. LandauS.M. MorrisJ.C. NoshenyR. OkonkwoO.C. PerrinR.J. PetersenR.C. Rivera-MindtM. SaykinA.J. ShawL.M. TogaA.W. TosunD. TrojanowskiJ.Q. Increasing participant diversity in AD research: Plans for digital screening, blood testing, and a community-engaged approach in the Alzheimer’s Disease Neuroimaging Initiative 4.Alzheimers Dement.202319130731710.1002/alz.1279736209495
     [Google Scholar]
  107. StreitS. PoortvlietR.K.E. GusseklooJ. Lower blood pressure during antihypertensive treatment is associated with higher all- cause mortality and accelerated cognitive decline in the oldest-old. Data from the Leiden 85-plus Study.Age Ageing201847454555010.1093/ageing/afy07229741555
     [Google Scholar]
  108. LiW. JinC. VaidyaA. WuY. RexrodeK. ZhengX. GurolM.E. MaC. WuS. GaoX. Blood pressure trajectories and the risk of intracerebral hemorrhage and cerebral infarction.Hypertension201770350851410.1161/HYPERTENSIONAHA.117.0947928716992
     [Google Scholar]
  109. ZhuangS. LiJ. WangX. WangH. ZhangW. WangH. XingC. Renin–angiotensin system-targeting antihypertensive drugs and risk of vascular cognitive impairment: A meta-analysis.Neurosci. Lett.20166151810.1016/j.neulet.2016.01.01126797651
     [Google Scholar]
  110. PetersR. YasarS. AndersonC.S. AndrewsS. AntikainenR. ArimaH. BeckettN. BeerJ.C. BertensA.S. BoothA. van BoxtelM. BrayneC. BrodatyH. CarlsonM.C. ChalmersJ. CorradaM. DeKoskyS. DerbyC. DixonR.A. ForetteF. GanguliM. van GoolW.A. GuaitaA. HeverA.M. HoganD.B. JaggerC. KatzM. KawasC. KehoeP.G. Keinanen-KiukaanniemiS. KennyR.A. KöhlerS. KunutsorS.K. LaukkanenJ. MaxwellC. McFallG.P. van MiddelaarT. Moll van CharanteE.P. NgT.P. PetersJ. RawtaerI. RichardE. RockwoodK. RydénL. SachdevP.S. SkoogI. SkoogJ. StaessenJ.A. StephanB.C.M. SebertS. ThijsL. TrompetS. TullyP.J. TzourioC. VaccaroR. VaaramoE. WalshE. WarwickJ. AnsteyK.J. Investigation of antihypertensive class, dementia, and cognitive decline.Neurology2020943e267e28110.1212/WNL.000000000000873231827004
     [Google Scholar]
  111. SolomonA. KåreholtI. NganduT. WinbladB. NissinenA. TuomilehtoJ. SoininenH. KivipeltoM. Serum cholesterol changes after midlife and late-life cognition.Neurology2007681075175610.1212/01.wnl.0000256368.57375.b717339582
     [Google Scholar]
  112. SolomonA. KivipeltoM. WolozinB. ZhouJ. WhitmerR.A. Midlife serum cholesterol and increased risk of Alzheimer’s and vascular dementia three decades later.Dement. Geriatr. Cogn. Disord.2009281758010.1159/00023198019648749
     [Google Scholar]
  113. WeberM.A. SchiffrinE.L. WhiteW.B. MannS. LindholmL.H. KenersonJ.G. FlackJ.M. CarterB.L. MatersonB.J. RamC.V.S. CohenD.L. CadetJ.C. Jean-CharlesR.R. TalerS. KountzD. TownsendR.R. ChalmersJ. RamirezA.J. BakrisG.L. WangJ. SchutteA.E. BisognanoJ.D. TouyzR.M. SicaD. HarrapS.B. Clinical practice guidelines for the management of hypertension in the community: A statement by the American Society of Hypertension and the International Society of Hypertension.J. Clin. Hypertens.2014161142610.1111/jch.1223724341872
     [Google Scholar]
  114. AbbatecolaA.M. RizzoM.R. BarbieriM. GrellaR. ArcielloA. LaietaM.T. AcamporaR. PassarielloN. CacciapuotiF. PaolissoG. Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics.Neurology200667223524010.1212/01.wnl.0000224760.22802.e816864814
     [Google Scholar]
  115. WhitmerR.A. KarterA.J. YaffeK. QuesenberryC.P.Jr SelbyJ.V. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus.JAMA2009301151565157210.1001/jama.2009.46019366776
     [Google Scholar]
  116. PatelA. MacMahonS. ChalmersJ. NealB. BillotL. WoodwardM. MarreM. CooperM. GlasziouP. GrobbeeD. HametP. HarrapS. HellerS. LiuL. ManciaG. MogensenC.E. PanC. PoulterN. RodgersA. WilliamsB. BompointS. de GalanB.E. JoshiR. TravertF. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N. Engl. J. Med.2008358242560257210.1056/NEJMoa080298718539916
     [Google Scholar]
  117. LaunerL.J. MillerM.E. WilliamsonJ.D. LazarR.M. GersteinH.C. MurrayA.M. SullivanM. HorowitzK.R. DingJ. MarcovinaS. LovatoL.C. LovatoJ. MargolisK.L. O’ConnorP. LipkinE.W. HirschJ. CokerL. MaldjianJ. SunshineJ.L. TruwitC. DavatzikosC. BryanR.N. LaunerL.J. KramerR. WilliamsonJ.D. MillerM. CokerL. LovatoJ. LovatoL. HeplerJ. FeltonD. AndrewsL. MayerS. CarterC. WoolardN. BryanR.N. DesiderioL. DavatzikosC. BilelloM. MelhemE. KokaD. ParmpiE. BattapadyH. ErusG. GersteinH.C. YusufS. CapesS. PunthakeeZ. Cukierman-YaffeT. VallisM. HallS. MackieP. ReidingV. RussoR. TadesonB. ThompsonK. GersteinH.C. Cukierman-YaffeT. CapesS. PunthakeeZ. SmithA. VallaT. JoyceC. ParsonsM. RoweB. HramiakI. GehringM. TereschynS. LochnanH. MarangerJ. McLeanM. SigalR. WooV. BerardL. AnderlicT. BernardA. MawaniA. AbbottC. UrE. McCarthyG. YuilleM. MurdockH. PalmerT. PattersonA. GrimmR.H. KirpachB.R. BartkoskeM.M. BoyceC.M. DruckmanN. GillettA.M. LevinJ.A. LivingstonG.J. MurrayA.M. MargolisK.L. TruwitC. MurrayA.M. LivingstonG.J. MargolisK.L. TruwitC. KempainenS. MaddenM. HallK. WoodK. BergenstalR. CuddihyR. DavickB. ListS. WhippleD. AshantiC. KendallD. SeaquistE.R. MechM.V. BenedictL.E. DemmonD.J. KumarA.F. MartinsonS.M. MillerS.A. PeaseC. RaoJ.P. RedmonJ.B. SwansonJ.E. WimmerJ.K. OkorochaY. StilesM. KodlC. ChadhaC. PetersonK.A. SeaquistL.A. BoeseC. MendenhallT.J. PetersonA.M. RudeltA. SchrockT.M. Sperl-HillenJ.M. O’ConnorP.J. BuschM.E. ChungA. KleinB.K. KrugenN. Bunkers-LawsonT. EkstromH.L. GundersonH.S. JohnsonB.M. MacIndoeJ.H. PrewedoD.J. RawlJ.L. RoethkeC.M. QuinlanM. FoxC.R. BateB.M. CaoQ.T. OhnstadM.M. MeyersP.J. SivitzW.I. WaysonS.M. LowerT.A. OchsK.A. WellsD. BiggerJ.T. Lopez-JimenezC.R. BornholdtR. BusacaL. GinsbergH.N. GonzalesP. GoshD. LoveP. KosokA. RobinsonE. SteinmanR. WatsonC. ReyesG. LazarR.M. SlaneK. Lopez-JimenezC.R. HirschJ. BrownT. HirschJ. BrownT.R. DashnawS.M. Cruz-LoboJ. SchubartU.K. RussoJ. VincentyN. IbarrandoK. AldermanM.H. CarrollL. SanguilyM.J. MayerA.C. RamosL. BrillonD. CorderoJ. ChiongR. HyamsK. CharlesC. BastienA. GrudzinskiS. NiblackP. AbreuL. BrownK. CasaleM. DoughertyD. LinnemanD. SalvadorM.A. ZeeP. HymanD. AtabekD. MirandaJ. KumarI. BakerC. BrautigamD.F. FischerR. ScharfD.M. BrautigamE. NunnB. ChiarotJ.M. FlandersC. GolandR. KringasP. MontesJ. BelleJ. GetanehA. RamirezJ. KranwinkelG. VasquezE. DonovanD.S. FebresG. HernandezC. JonaitisM.A. Lopez-JimenezC. BanerjiM.A. NortonM. PatelP. HirschS. BanerjiM.A. NortonM. PatelP. HirschS. GenuthS. Ismail-BeigiF. ThibonnierM. VargoL. KellyC. BongornoT. DolishA. PavlikL. TiktinM. IsteitiehS. BartlettA. YeeK. KulowT. HorowitzK. PavlikL. DolishA. TiktinM. SunshineJ. ClampittM. Ismail-BeigiF. KrikorianA. MooreL. RichardsonL. Coles-HermanE. FrankinoJ. SoodA. HustakL. JuliusM. PavlikL. RossT. LongL. SullivanM.K. StraussL. BehmK. EskandariF. HallC. HayesD. HorowitzK. IsteitiehS. MadhunZ. SeeholzerE. ShinaJ. TaylorH. SchnallA. SadlerL.S. GriffithM. HornsbyA. KlynK. OspeltE. LongL. DeSmitM. McCannP. SchmidtN.P. KulowT. ZaletalJ. SchnallA.M. DragmenL. EllertR. SmithJ. LeksanJ. SussmanT. Ismail-BeigiF. HustakL. JuliusM. SchwingW. HallC. HorowitzK. IsteitiehS. JohnsonC. KernE. RichmondM.A. RichardsonL. RobertsK. ShinaJ. SuhanP. TaylorH. WattsS. MartinJ. StraussG.J. AkpunonuB. Franco-SaenzR. GilmoreJ. GilmoreM. RossP. BauerB. Pop-BusuiR. RomanJ. BlustZ. ThomasA. KahkonenD.M. CushmanT. RomanM. StysA.M. WhiteK. AustinM. ChattertonC. FrancisJ.K. JonesC. KrugerD. McLellanA. WhitehouseF. HigginsE. LevyS. SchoenherrA. GoffD.C. SummersonJ.H. CragoL. BlackwellC.S. BertoniA. BlaineR.L. KirkJ.K. SpachR.L. WilliamsonJ. CallesJ. KatulaJ. WishnietskyD.B. WoolardN. MayerS. GordineerL. WilliamsonJ. WoolardN. DingJ. MaldjianJ. KaminskyS. FullerD. FeinglosM.N. JonesJ. Gedon-LipscombG. AtkinsonH.H. StanfieldJ. Delvalle-FaganT. PedleyC.F. MauneyS. BuseJ.B. DuclosM.D. KirbyR.E. GoleyA. VukojicikK. MillerJ.L. BestermanW. NortonS.M. SurgenerM. DulinM. BarringerT. MorrisC. NortonS. PeaceR. StuartD.O. StricklandJ. CummingsL. StanfieldJ. PeaceR. StricklandJ. CummingsL. StanfieldJ. CrouseJ.R. EllisJ. FonsecaV. John-KalarickalJ. LegerS.M. MunshiK. BarzilayJ. BaderK. ElayM. ProbstfieldJ.L. SullivanM.D. KingryC. JohnsonJ.M. LineA.S. CorsonM.A. KnoppR. LipkinE. GriswoldC. LiebertK. BrownA. JulianoD. KurashigeE.M. MobergS. LeaderJ. SullivanM.D. JohnsonJ.M. ArianiM. GutierrezH. FailorR. EllsworthA. JacksonN. CapocciaK. ForceR. MacdonaldM. KoesterS. PettingillK. LinzP. PepperP. GriffinS. KozlowskiJ. EngleM. GutierrezP. RiddleM. McDanielP.A. Gammell-MatthewsS.C. MacNeilB. DesRochersS. SwiftR. WyshamC. WeeksD. KuntsmannL. DudlJ. WuP. LyonsL. HouseB. MurrayM. PalmaA. StevensonR. DaileyG. Philas-TsimikasA. GiannellaA. Bravo-MedinaA. JacobsonM. FarroE. CruzS. JuarezN. DadkhahC. ACCORD MIND investigators Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): A randomised open-label substudy.Lancet Neurol.2011101196997710.1016/S1474‑4422(11)70188‑021958949
     [Google Scholar]
  118. RománG.C. SallowayS. BlackS.E. RoyallD.R. DeCarliC. WeinerM.W. MolineM. KumarD. SchindlerR. PosnerH. Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size.Stroke20104161213122110.1161/STROKEAHA.109.57007720395618
     [Google Scholar]
  119. WilkinsonD. DoodyR. HelmeR. TaubmanK. MintzerJ. KerteszA. PrattR.D. Donepezil 308 Study Group Donepezil in vascular dementia.Neurology200361447948610.1212/01.WNL.0000078943.50032.FC12939421
     [Google Scholar]
  120. AuchusA.P. BrashearH.R. SallowayS. KorczynA.D. De DeynP.P. Gassmann-MayerC. GAL-INT-26 Study Group Galantamine treatment of vascular dementia.Neurology200769544845810.1212/01.wnl.0000266625.31615.f617664404
     [Google Scholar]
  121. GorelickP.B. ScuteriA. BlackS.E. DeCarliC. GreenbergS.M. IadecolaC. LaunerL.J. LaurentS. LopezO.L. NyenhuisD. PetersenR.C. SchneiderJ.A. TzourioC. ArnettD.K. BennettD.A. ChuiH.C. HigashidaR.T. LindquistR. NilssonP.M. RomanG.C. SellkeF.W. SeshadriS. Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the american heart association/american stroke association.Stroke20114292672271310.1161/STR.0b013e318229949621778438
     [Google Scholar]
  122. SwansonC.J. ZhangY. DhaddaS. WangJ. KaplowJ. LaiR.Y.K. LannfeltL. BradleyH. RabeM. KoyamaA. ReydermanL. BerryD.A. BerryS. GordonR. KramerL.D. CummingsJ.L. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody.Alzheimers Res. Ther.20211318010.1186/s13195‑021‑00813‑833865446
     [Google Scholar]
  123. van DyckC.H. SwansonC.J. AisenP. BatemanR.J. ChenC. GeeM. KanekiyoM. LiD. ReydermanL. CohenS. FroelichL. KatayamaS. SabbaghM. VellasB. WatsonD. DhaddaS. IrizarryM. KramerL.D. IwatsuboT. Lecanemab in early Alzheimer’s disease.N. Engl. J. Med.2023388192110.1056/NEJMoa221294836449413
     [Google Scholar]
  124. DhillonS. Aducanumab: First Approval.Drugs202181121437144310.1007/s40265‑021‑01569‑z34324167
     [Google Scholar]
  125. CummingsJ. AisenP. ApostolovaL.G. AtriA. SallowayS. WeinerM. Aducanumab: Appropriate use recommendations.J. Prev. Alzheimers Dis.20218439841034585212
     [Google Scholar]
  126. PatelS. BansoadA.V. SinghR. KhatikG.L. BACE1: A key regulator in Alzheimer’s disease progression and current development of its inhibitors.Curr. Neuropharmacol.20222061174119310.2174/1570159X1966621120109403134852746
     [Google Scholar]
  127. WillisB.A. ZhangW. Ayan-OshodiM. LoweS.L. AnnesW.F. SiroisP.J. FriedrichS. de la PeñaA. Semagacestat pharmacokinetics are not significantly affected by formulation, food, or time of dosing in healthy participants.J. Clin. Pharmacol.201252690491310.1177/009127001140719521724950
     [Google Scholar]
  128. DoggrellS.A. Lessons that can be learnt from the failure of verubecestat in Alzheimer’s disease.Expert Opin. Pharmacother.201920172095209910.1080/14656566.2019.165499831423903
     [Google Scholar]
  129. EganM.F. MukaiY. VossT. KostJ. StoneJ. FurtekC. MahoneyE. CummingsJ.L. TariotP.N. AisenP.S. VellasB. LinesC. MichelsonD. Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer’s disease.Alzheimers Res. Ther.20191116810.1186/s13195‑019‑0520‑131387606
     [Google Scholar]
  130. Moussa-PachaN.M. AbdinS.M. OmarH.A. AlnissH. Al-TelT.H. BACE1 inhibitors: Current status and future directions in treating Alzheimer’s disease.Med. Res. Rev.202040133938410.1002/med.2162231347728
     [Google Scholar]
  131. WesselsA.M. TariotP.N. ZimmerJ.A. SelzlerK.J. BraggS.M. AndersenS.W. LandryJ. KrullJ.H. DowningA.M. WillisB.A. ShcherbininS. MullenJ. BarkerP. SchumiJ. SheringC. MatthewsB.R. SternR.A. VellasB. CohenS. MacSweeneyE. BoadaM. SimsJ.R. Efficacy and safety of lanabecestat for treatment of early and mild Alzheimer disease.JAMA Neurol.202077219920910.1001/jamaneurol.2019.398831764959
     [Google Scholar]
  132. TimmersM. StrefferJ.R. RussuA. TominagaY. ShimizuH. ShiraishiA. TatikolaK. SmekensP. Börjesson-HansonA. AndreasenN. Matias-GuiuJ. BaqueroM. BoadaM. TesseurI. TritsmansL. Van NuetenL. EngelborghsS. Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer’s disease: randomized, double-blind, placebo-controlled study.Alzheimers Res. Ther.20181018510.1186/s13195‑018‑0415‑630134967
     [Google Scholar]
  133. SperlingR. HenleyD. AisenP.S. RamanR. DonohueM.C. ErnstromK. RafiiM.S. StrefferJ. ShiY. KarcherK. RaghavanN. TymofyeyevY. BogertJ. BrashearH.R. NovakG. ThipphawongJ. SaadZ.S. KolbH. RofaelH. SangaP. RomanoG. Findings of efficacy, safety, and biomarker outcomes of atabecestat in preclinical Alzheimer disease.JAMA Neurol.202178329330110.1001/jamaneurol.2020.485733464300
     [Google Scholar]
  134. BazzariF.H. BazzariA.H. BACE1 inhibitors for Alzheimer’s disease: the past, present and any future?Molecules20222724882310.3390/molecules2724882336557955
     [Google Scholar]
  135. HsiaoC.C. RomboutsF. GijsenH.J.M. New evolutions in the BACE1 inhibitor field from 2014 to 2018.Bioorg. Med. Chem. Lett.201929676177710.1016/j.bmcl.2018.12.04930709653
     [Google Scholar]
  136. MirandaA. MontielE. UlrichH. PazC. Selective secretase targeting for Alzheimer’s disease therapy.J. Alzheimers Dis.202181111710.3233/JAD‑20102733749645
     [Google Scholar]
  137. DoodyR.S. RamanR. FarlowM. IwatsuboT. VellasB. JoffeS. KieburtzK. HeF. SunX. ThomasR.G. AisenP.S. SiemersE. SethuramanG. MohsR. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease.N. Engl. J. Med.2013369434135010.1056/NEJMoa121095123883379
     [Google Scholar]
  138. HenleyD.B. SundellK.L. SethuramanG. DowsettS.A. MayP.C. Safety profile of semagacestat, a gamma-secretase inhibitor: IDENTITY trial findings.Curr. Med. Res. Opin.201430102021203210.1185/03007995.2014.93916724983746
     [Google Scholar]
  139. OstrowitzkiS. BittnerT. SinkK.M. MackeyH. RabeC. HonigL.S. CassettaE. WoodwardM. BoadaM. van DyckC.H. GrimmerT. SelkoeD.J. SchneiderA. BlondeauK. HuN. QuartinoA. ClaytonD. DoltonM. DangY. OstaszewskiB. Sanabria-BohórquezS.M. RabbiaM. TothB. EichenlaubU. SmithJ. HonigbergL.A. DoodyR.S. Evaluating the safety and efficacy of crenezumab vs. placebo in adults with early Alzheimer disease.JAMA Neurol.202279111113112110.1001/jamaneurol.2022.290936121669
     [Google Scholar]
  140. SallowayS. SperlingR. FoxN.C. BlennowK. KlunkW. RaskindM. SabbaghM. HonigL.S. PorsteinssonA.P. FerrisS. ReichertM. KetterN. NejadnikB. GuenzlerV. MiloslavskyM. WangD. LuY. LullJ. TudorI.C. LiuE. GrundmanM. YuenE. BlackR. BrashearH.R. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease.N. Engl. J. Med.2014370432233310.1056/NEJMoa130483924450891
     [Google Scholar]
  141. HonigL.S. VellasB. WoodwardM. BoadaM. BullockR. BorrieM. HagerK. AndreasenN. ScarpiniE. Liu-SeifertH. CaseM. DeanR.A. HakeA. SundellK. Poole HoffmannV. CarlsonC. KhannaR. MintunM. DeMattosR. SelzlerK.J. SiemersE. Trial of solanezumab for mild dementia due to Alzheimer’s disease.N. Engl. J. Med.2018378432133010.1056/NEJMoa170597129365294
     [Google Scholar]
  142. Liu-SeifertH. SiemersE. SundellK. MynderseM. CummingsJ. MohsR. AisenP. Analysis of the relationship of cognitive impairment and functional impairment in mild Alzheimer’s disease in expedition 3.J. Prev. Alzheimers Dis.20185318418729972211
     [Google Scholar]
  143. KleinG. DelmarP. VoyleN. RehalS. HofmannC. Abi-SaabD. AndjelkovicM. RisticS. WangG. BatemanR. KerchnerG.A. BaudlerM. FontouraP. DoodyR. Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: A PET substudy interim analysis.Alzheimers Res. Ther.201911110110.1186/s13195‑019‑0559‑z31831056
     [Google Scholar]
  144. BatemanR.J. CummingsJ. SchobelS. SallowayS. VellasB. BoadaM. BlackS.E. BlennowK. FontouraP. KleinG. AssunçãoS.S. SmithJ. DoodyR.S. Gantenerumab: An anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer’s disease.Alzheimers Res. Ther.202214117810.1186/s13195‑022‑01110‑836447240
     [Google Scholar]
  145. NicollJ.A.R. BucklandG.R. HarrisonC.H. PageA. HarrisS. LoveS. NealJ.W. HolmesC. BocheD. Persistent neuropathological effects 14 years following amyloid-β immunization in Alzheimer’s disease.Brain201914272113212610.1093/brain/awz14231157360
     [Google Scholar]
  146. OhtakeY. KongW. HussainR. HoriuchiM. TremblayM.L. GaneaD. LiS. Protein tyrosine phosphatase σ regulates autoimmune encephalomyelitis development.Brain Behav. Immun.20176511112410.1016/j.bbi.2017.05.01828559011
     [Google Scholar]
  147. PasquierF. SadowskyC. HolsteinA. LetermeG.L.P. PengY. JacksonN. FoxN.C. KetterN. LiuE. RyanJ.M. Two phase 2 multiple ascending–dose studies of vanutide cridificar (ACC-001) and QS-21 adjuvant in mild-to-moderate Alzheimer’s disease.J. Alzheimers Dis.20165141131114310.3233/JAD‑15037626967206
     [Google Scholar]
  148. HullM. SadowskyC. AraiH. Le Prince LetermeG. HolsteinA. BoothK. PengY. YoshiyamaT. SuzukiH. KetterN. LiuE. RyanJ.M. Long-term extensions of randomized vaccination trials of ACC-001 and QS-21 in mild to moderate alzheimer’s disease.Curr. Alzheimer Res.201714769670828124589
     [Google Scholar]
  149. LacostaA.M. Pascual-LucasM. PesiniP. CasabonaD. Pérez-GrijalbaV. Marcos-CamposI. SarasaL. CanudasJ. BadiH. MonleónI. San-JoséI. MunueraJ. Rodríguez-GómezO. AbdelnourC. LafuenteA. BuendíaM. BoadaM. TárragaL. RuizA. SarasaM. Safety, tolerability and immunogenicity of an active anti-Aβ40 vaccine (ABvac40) in patients with Alzheimer’s disease: A randomised, double-blind, placebo-controlled, phase I trial.Alzheimers Res. Ther.20181011210.1186/s13195‑018‑0340‑829378651
     [Google Scholar]
  150. WegmannS. BiernatJ. MandelkowE. A current view on Tau protein phosphorylation in Alzheimer’s disease.Curr. Opin. Neurobiol.20216913113810.1016/j.conb.2021.03.00333892381
     [Google Scholar]
  151. LovestoneS. BoadaM. DuboisB. HüllM. RinneJ.O. HuppertzH.J. CaleroM. AndrésM.V. Gómez-CarrilloB. LeónT. del SerT. FernándezM. Pérez de las HerasS. AlomJ. SolaD. Sánchez-ValleR. MolinuevoJ.L. A phase II trial of tideglusib in Alzheimer’s disease.J. Alzheimers Dis.2015451758810.3233/JAD‑14195925537011
     [Google Scholar]
  152. HaussmannR. NoppesF. BrandtM.D. BauerM. DonixM. Minireview: Lithium: A therapeutic option in Alzheimer’s disease and its prodromal stages?Neurosci. Lett.202176013604410.1016/j.neulet.2021.13604434119602
     [Google Scholar]
  153. HuW. ZhaoM. LianJ. LiD. WenJ. TanJ. Lithium cholesterol sulfate: A novel and potential drug for treating alzheimer’s disease and autism spectrum disorder.CNS Neurol. Disord. Drug Targets20232281250125836028968
     [Google Scholar]
  154. MuronagaM. TeraoT. KohnoK. HirakawaH. IzumiT. EtohM. Lithium in drinking water and Alzheimer’s dementia: Epidemiological findings from national data base of Japan.Bipolar Disord.202224878879410.1111/bdi.1325736073313
     [Google Scholar]
  155. LucaA. LucaM. Lithium in Alzheimer’s disease: from prevention to treatment.Psychogeriatrics202323120420510.1111/psyg.1291336385714
     [Google Scholar]
  156. TuckerD. LuY. ZhangQ. From mitochondrial function to neuroprotection—an emerging role for methylene blue.Mol. Neurobiol.20185565137515310.1007/s12035‑017‑0712‑228840449
     [Google Scholar]
  157. SeripaD. SolfrizziV. ImbimboB.P. DanieleA. SantamatoA. LozuponeM. ZulianiG. GrecoA. LogroscinoG. PanzaF. Tau-directed approaches for the treatment of Alzheimer’s disease: focus on leuco-methylthioninium.Expert Rev. Neurother.201616325927710.1586/14737175.2016.114003926822031
     [Google Scholar]
  158. HashwehN.N. BartochowskiZ. KhouryR. GrossbergG.T. An evaluation of hydromethylthionine as a treatment option for Alzheimer’s disease.Expert Opin. Pharmacother.202021661962710.1080/14656566.2020.171906632037892
     [Google Scholar]
  159. YeW. LiuT. ZhangW.M. ZhangW. LiS. The improvement of epothilone D yield by the disruption of epok gene in sorangium cellulosum using talen system.Mol. Biotechnol.202365228228910.1007/s12033‑022‑00602‑036401710
     [Google Scholar]
  160. BrundenK.R. ZhangB. CarrollJ. YaoY. PotuzakJ.S. HoganA.M.L. IbaM. JamesM.J. XieS.X. BallatoreC. SmithA.B.III LeeV.M.Y. TrojanowskiJ.Q. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy.J. Neurosci.20103041138611386610.1523/JNEUROSCI.3059‑10.201020943926
     [Google Scholar]
  161. GuoB. HuangY. GaoQ. ZhouQ. Stabilization of microtubules improves cognitive functions and axonal transport of mitochondria in Alzheimer’s disease model mice.Neurobiol. Aging20209622323210.1016/j.neurobiolaging.2020.09.01133039900
     [Google Scholar]
  162. QureshiI.A. TirucheraiG. AhlijanianM.K. KolaitisG. BechtoldC. GrundmanM. A randomized, single ascending dose study of intravenous BIIB092 in healthy participants.Alzheimers Dement.20184174675510.1016/j.trci.2018.10.00730581980
     [Google Scholar]
  163. BoxerA.L. QureshiI. AhlijanianM. GrundmanM. GolbeL.I. LitvanI. HonigL.S. TuiteP. McFarlandN.R. O’SuilleabhainP. XieT. TirucheraiG.S. BechtoldC. BordelonY. GeldmacherD.S. GrossmanM. IsaacsonS. ZesiewiczT. OlssonT. MuralidharanK.K. GrahamD.L. O’GormanJ. HaeberleinS.B. DamT. Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: A randomised, placebo-controlled, multiple ascending dose phase 1b trial.Lancet Neurol.201918654955810.1016/S1474‑4422(19)30139‑531122495
     [Google Scholar]
  164. TatebeH. KasaiT. OhmichiT. KishiY. KakeyaT. WaragaiM. KondoM. AllsopD. TokudaT. Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome.Mol. Neurodegener.20171216310.1186/s13024‑017‑0206‑828866979
     [Google Scholar]
  165. YangC.C. ChiuM.J. ChenT.F. ChangH.L. LiuB.H. YangS.Y. Assay of plasma phosphorylated tau protein (Threonine 181) and total tau protein in early-stage alzheimer’s disease.J. Alzheimers Dis.20186141323133210.3233/JAD‑17081029376870
     [Google Scholar]
  166. WestT. HuY. VergheseP.B. BatemanR.J. BraunsteinJ.B. FogelmanI. BudurK. FlorianH. MendoncaN. HoltzmanD.M. Preclinical and clinical development of ABBV-8E12, a humanized anti-tau antibody, for treatment of alzheimer’s disease and other tauopathies.J. Prev. Alzheimers Dis.20174423624129181488
     [Google Scholar]
  167. FlorianH. WangD. ArnoldS.E. BoadaM. GuoQ. JinZ. ZhengH. FissehaN. KalluriH.V. Rendenbach-MuellerB. BudurK. GoldM. Tilavonemab in early Alzheimer’s disease: results from a phase 2, randomized, double-blind study.Brain202314662275228410.1093/brain/awad02436730056
     [Google Scholar]
  168. NovakP. SchmidtR. KontsekovaE. ZilkaN. KovacechB. SkrabanaR. Vince-KazmerovaZ. KatinaS. FialovaL. PrcinaM. ParrakV. Dal-BiancoP. BrunnerM. StaffenW. RainerM. OndrusM. RopeleS. SmisekM. SivakR. WinbladB. NovakM. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: A randomised, double-blind, placebo-controlled, phase 1 trial.Lancet Neurol.201716212313410.1016/S1474‑4422(16)30331‑327955995
     [Google Scholar]
  169. NovakP. SchmidtR. KontsekovaE. KovacechB. SmolekT. KatinaS. FialovaL. PrcinaM. ParrakV. Dal-BiancoP. BrunnerM. StaffenW. RainerM. OndrusM. RopeleS. SmisekM. SivakR. ZilkaN. WinbladB. NovakM. FUNDAMANT: An interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer’s disease.Alzheimers Res. Ther.201810110810.1186/s13195‑018‑0436‑130355322
     [Google Scholar]
  170. NovakP. ZilkaN. ZilkovaM. KovacechB. SkrabanaR. OndrusM. FialovaL. KontsekovaE. OttoM. NovakM. AADvac1, an active immunotherapy for alzheimer’s disease and non alzheimer tauopathies: An overview of preclinical and clinical development.J. Prev. Alzheimers Dis.201961636930569088
     [Google Scholar]
  171. BachurinS.O. MakhaevaG.F. ShevtsovaE.F. BoltnevaN.P. KovalevaN.V. LushchekinaS.V. RudakovaE.V. DubovaL.G. VinogradovaD.V. SokolovV.B. AksinenkoA.Y. FisenkoV.P. RichardsonR.J. AlievG. Conjugates of methylene blue with γ-carboline derivatives as new multifunctional agents for the treatment of neurodegenerative diseases.Sci. Rep.201991487310.1038/s41598‑019‑41272‑430890752
     [Google Scholar]
  172. MakhaevaG.F. ShevtsovaE.F. BoltnevaN.P. LushchekinaS.V. KovalevaN.V. RudakovaE.V. BachurinS.O. RichardsonR.J. Overview of novel multifunctional agents based on conjugates of γ-carbolines, carbazoles, tetrahydrocarbazoles, phenothiazines, and aminoadamantanes for treatment of Alzheimer’s disease.Chem. Biol. Interact.201930822423410.1016/j.cbi.2019.05.02031100279
     [Google Scholar]
  173. ShevtsovaE.F. VinogradovaD.V. KireevaE.G. ReddyV.P. AlievG. BachurinS.O. Dimebon attenuates the Aβ-induced mitochondrial permeabilization.Curr. Alzheimer Res.201411542242910.2174/156720501166614050509480824801220
     [Google Scholar]
  174. SkvortsovaV.I. BachurinS.O. UstyugovA.A. KukharskyM.S. DeikinA.V. BuchmanV.L. NinkinaN.N. Gamma-carbolines derivatives as promising agents for the development of pathogenic therapy for proteinopathy.Acta Nat.2018104596210.32607/20758251‑2018‑10‑4‑59‑6230713762
     [Google Scholar]
  175. UstyugovA. ShevtsovaE. AshrafG.M. TarasovV.V. BachurinS.O. AlievG. New therapeutic property of dimebon as a neuroprotective agent.Curr. Med. Chem.201925395315532610.2174/092986732366616080412274627494393
     [Google Scholar]
  176. VoorheesJ.R. RemyM.T. Cintrón-PérezC.J. El RassiE. KhanM.Z. DutcaL.M. YinT.C. McDanielL.N. WilliamsN.S. BratD.J. PieperA.A. (−)-P7C3-S243 protects a rat model of alzheimer’s disease from neuropsychiatric deficits and neurodegeneration without altering amyloid deposition or reactive glia.Biol. Psychiatry201884748849810.1016/j.biopsych.2017.10.02329246437
     [Google Scholar]
  177. PieperA.A. XieS. CapotaE. EstillS.J. ZhongJ. LongJ.M. BeckerG.L. HuntingtonP. GoldmanS.E. ShenC.H. CapotaM. BrittJ.K. KottiT. UreK. BratD.J. WilliamsN.S. MacMillanK.S. NaidooJ. MelitoL. HsiehJ. De BrabanderJ. ReadyJ.M. McKnightS.L. Discovery of a proneurogenic, neuroprotective chemical.Cell20101421395110.1016/j.cell.2010.06.01820603013
     [Google Scholar]
  178. GuC. ZhangY. HuQ. WuJ. RenH. LiuC.F. WangG. P7C3 inhibits GSK3β activation to protect dopaminergic neurons against neurotoxin-induced cell death in vitro and in vivo.Cell Death Dis.201786e285810.1038/cddis.2017.25028569794
     [Google Scholar]
  179. De Jesús-CortésH. XuP. DrawbridgeJ. EstillS.J. HuntingtonP. TranS. BrittJ. TeslaR. MorlockL. NaidooJ. MelitoL.M. WangG. WilliamsN.S. ReadyJ.M. McKnightS.L. PieperA.A. Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of Parkinson disease.Proc. Natl. Acad. Sci.201210942170101701510.1073/pnas.121395610923027934
     [Google Scholar]
  180. De Jesús-CortésH. MillerA.D. BrittJ.K. DeMarcoA.J. De Jesús-CortésM. StuebingE. NaidooJ. Vázquez-RosaE. MorlockL. WilliamsN.S. ReadyJ.M. NarayananN.S. PieperA.A. Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson’s disease.NPJ Parkinsons Dis.2015111501010.1038/npjparkd.2015.1027158662
     [Google Scholar]
  181. NaidooJ. De Jesus-CortesH. HuntingtonP. EstillS. MorlockL.K. StarwaltR. ManganoT.J. WilliamsN.S. PieperA.A. ReadyJ.M. Discovery of a neuroprotective chemical, (S)-N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties.J. Med. Chem.20145793746375410.1021/jm401919s24697290
     [Google Scholar]
  182. DutcaL.M. StasheffS.F. Hedberg-BuenzA. RuddD.S. BatraN. BlodiF.R. YorekM.S. YinT. ShankarM. HerleinJ.A. NaidooJ. MorlockL. WilliamsN. KardonR.H. AndersonM.G. PieperA.A. HarperM.M. Early detection of subclinical visual damage after blast-mediated TBI enables prevention of chronic visual deficit by treatment with P7C3-S243.Invest. Ophthalmol. Vis. Sci.201455128330834110.1167/iovs.14‑1546825468886
     [Google Scholar]
  183. YinT.C. BrittJ.K. De Jesús-CortésH. LuY. GenovaR.M. KhanM.Z. VoorheesJ.R. ShaoJ. KatzmanA.C. HuntingtonP.J. WassinkC. McDanielL. NewellE.A. DutcaL.M. NaidooJ. CuiH. BassukA.G. HarperM.M. McKnightS.L. ReadyJ.M. PieperA.A. P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury.Cell Rep.2014861731174010.1016/j.celrep.2014.08.03025220467
     [Google Scholar]
  184. Vázquez-RosaE. ShinM.K. DharM. ChaubeyK. Cintrón-PérezC.J. TangX. LiaoX. MillerE. KohY. BarkerS. FrankeK. CrosbyD.R. SchroederR. EmeryJ. YinT.C. FujiokaH. ReynoldsJ.D. HarperM.M. JainM.K. PieperA.A. P7C3-A20 treatment one year after TBI in mice repairs the blood–brain barrier, arrests chronic neurodegeneration, and restores cognition.Proc. Natl. Acad. Sci. USA202011744276672767510.1073/pnas.201043011733087571
     [Google Scholar]
  185. CohenR.M. Rezai-ZadehK. WeitzT.M. RentsendorjA. GateD. SpivakI. BholatY. VasilevkoV. GlabeC.G. BreunigJ.J. RakicP. DavtyanH. AgadjanyanM.G. KepeV. BarrioJ.R. BannykhS. SzekelyC.A. PechnickR.N. TownT. A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric aβ, and frank neuronal loss.J. Neurosci.201333156245625610.1523/JNEUROSCI.3672‑12.201323575824
     [Google Scholar]
  186. VermerschP. Brieva-RuizL. FoxR.J. PaulF. Ramio-TorrentaL. SchwabM. MoussyA. MansfieldC. HermineO. MaciejowskiM. HechamN. DeriN.H. Djelilovic-VranicJ. MilanovI. ShotekovP. BlevinsG. GirardJ. LapierreY. CamuW. CastelnovoG. ClavelouP. HautecoeurP. MarziniakM. MayerC. OschmannP. ReifschneiderG. SchoellI. TackenbergB. BerghF.T. FakasN. GrigoriadisN. KalochristianakisD. MitsikostasD. OrologasA. TavernarakisA. ThomaidisT. KovacsK. MatyasK. PirosP. SatoriM. AnandK. ShifrinA. BanaszkiewiczK. BonekR. ChahwanM. Czernichowska - KotiuszkoM. Darda-LedzionL. Debrowska - WójcikJ. DzikiM. KrzystanekE. KulkaM. LisewskiP. RatajczakM. SzczudlikA. SzczygielJ. TomaszewskaM. WójcikJ. ZielonkaD. ChiruM. DemeS. ManescuS. NicaS. PopescuC. SzatmariS. FedyaninA. MalkovaN. PopovD. VolkovaL. VorobevaO. BrozmanM. CimprichovaA. CuchranP. GurcikL. KrastevG. LisáI. NyekyM. PoljakováJ. TurcaniP. FrostA. HeckmannJ. AgüeraE. CoretF. EscartinA. FernandezV. CallizoJ.R.A. MartinG. Martinez-RodriguezJ. GinesM.M. MunozD. OlascoagaJ. PrietoJ. Ramo-TelloC. BelalS. Ben AmmouS. Frih-AyedM. GouiderR. MhiriC. MrissaR. CherkezA. ChmyrH. ChudovskaL. DatskevychS. DziakL. GalushaA. KhavunkaM. KobysT. KozyolkinO. LekomtsevaY. LitovchenkoT. MorozO. MoskovkoG. PashkovskyV. SanotskyiY. ShkrobotS. BraleyT. ConwayJ. HughesB. KatzA. RizviS. SingerR. Efficacy and safety of masitinib in progressive forms of multiple sclerosis.Neurol. Neuroimmunol. Neuroinflamm.202293e114810.1212/NXI.000000000000114835190477
     [Google Scholar]
  187. DuboisB. López-ArrietaJ. LipschitzS. DoskasT. SpiruL. MorozS. VengerO. VermerschP. MoussyA. MansfieldC.D. HermineO. TsolakiM. Masitinib for mild-to-moderate Alzheimer’s disease: results from a randomized, placebo-controlled, phase 3, clinical trial.Alzheimers Res. Ther.20231513910.1186/s13195‑023‑01169‑x36849969
     [Google Scholar]
  188. 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. Psychiatry20222022jnnp-2021-32851935483916
     [Google Scholar]
  189. YamanakaT. UchidaY. SakuraiK. KatoD. MizunoM. SatoT. MadokoroY. KondoY. SuzukiA. UekiY. IshiiF. BorlonganC.V. MatsukawaN. Anatomical links between white matter hyperintensity and medial temporal atrophy reveal impairment of executive functions.Aging Dis.201910471171810.14336/AD.2018.092931440378
     [Google Scholar]
/content/journals/car/10.2174/0115672050319219240711103459
Loading
Alzheimer's Disease and Vascular Dementia, Connecting and Differentiating Features
Curr Alzheimer Res 22, 2 (2025); https://doi.org/10.2174/0115672050319219240711103459
/content/journals/car/10.2174/0115672050319219240711103459
/content/journals/car/10.2174/0115672050319219240711103459
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): aging; Alzheimer’s disease; clinical symptoms; Molecular factors; Parkinson’s disease; vascular neurocognitive disorder

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