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2000
Volume 23, Issue 1
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

Background

Alzheimer's disease (AD) is characterized by neuropsychiatric symptoms (NPS), which cause great misery to those with dementia and those who care for them and may lead to early institutionalization.

Objective

The present systematic review aims to discuss the various aspects of Alzheimer’s, including treatment options.

Methods

The databases Embase, PubMed, and Web of Science were searched to collect data.

Results

Incipient cognitive deterioration is commonly accompanied by these early warning signals of neurocognitive diseases. The neurobiology of NPSs in Alzheimer's disease, as well as particular symptoms, including psychosis, agitation, apathy, sadness, and sleep disorders, will be examined in this review. For NPSs in Alzheimer's disease, clinical trial designs, as well as regulatory issues, were also addressed. A fresh wave of research, however, is helping to push the discipline ahead. For medication development and repurposing, we highlight the most recent results in genetics, neuroimaging, and neurobiology. Even though identifying and treating psychosis in adults with dementia is still a challenging endeavor, new options are coming up that give the field fresh focus and hope.

Conclusion

It can be concluded from the complete literature survey that Alzheimer's-related psychosis as well as other symptoms that are not psychotic, have made significant progress in the last decade. These milestones in the development of safer, more effective treatments have been achieved as a consequence of great focus on non-pharmacological interventions like DICE or WHELD; the investigation into ways to improve existing drugs like aripiprazole, risperidone, amisulpride, and Escitalopram for safer precision-based treatment; and the development of a clinical trial program for pimavanserin.

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References

  1. SteinbergM. ShaoH. ZandiP. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study.Int. J. Geriatr. Psychiatry200823217017710.1002/gps.185817607801
    [Google Scholar]
  2. LanctôtK.L. AmatniekJ. Ancoli-IsraelS. Neuropsychiatric signs and symptoms of Alzheimer’s disease: New treatment paradigms.Alzheimers Dement.20173344044910.1016/j.trci.2017.07.00129067350
    [Google Scholar]
  3. LyketsosC.G. CarrilloM.C. RyanJ.M. Neuropsychiatric symptoms in Alzheimer’s disease.Alzheimers Dement.20117553253910.1016/j.jalz.2011.05.241021889116
    [Google Scholar]
  4. CreeseB. Da SilvaM.V. JoharI. BallardC. The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer’s disease.Expert Rev. Neurother.201818646146710.1080/14737175.2018.147614029764230
    [Google Scholar]
  5. BallardC.G. GauthierS. CummingsJ.L. Management of agitation and aggression associated with Alzheimer disease.Nat. Rev. Neurol.20095524525510.1038/nrneurol.2009.3919488082
    [Google Scholar]
  6. WattJ.A. GoodarziZ. VeronikiA.A. Safety of pharmacologic interventions for neuropsychiatric symptoms in dementia: a systematic review and network meta-analysis.BMC Geriatr.202020121210.1186/s12877‑020‑01607‑732546202
    [Google Scholar]
  7. KauferD.I. CummingsJ.L. ChristineD. Assessing the impact of neuropsychiatric symptoms in Alzheimer’s Disease: The neuropsychiatric inventory caregiver distress scale.J. Am. Geriatr. Soc.199846221021510.1111/j.1532‑5415.1998.tb02542.x9475452
    [Google Scholar]
  8. WienerP.K. KiossesD.N. KlimstraS. MurphyC. AlexopoulosG.S. A short-term inpatient program for agitated demented nursing home residents.Int. J. Geriatr. Psychiatry200116986687210.1002/gps.43711571766
    [Google Scholar]
  9. FischerC.E. IsmailZ. SchweizerT.A. Delusions increase functional impairment in Alzheimer’s disease.Dement. Geriatr. Cogn. Disord.201233639339910.1159/00033995422814093
    [Google Scholar]
  10. WilsonR.S. TangY. AggarwalN.T. Hallucinations, cognitive decline, and death in Alzheimer’s disease.Neuroepidemiology2006262687510.1159/00009025116352909
    [Google Scholar]
  11. ScarmeasN. BrandtJ. AlbertM. Delusions and hallucinations are associated with worse outcome in Alzheimer disease.Arch. Neurol.200562101601160810.1001/archneur.62.10.160116216946
    [Google Scholar]
  12. ZahodneL.B. OrnsteinK. CosentinoS. DevanandD.P. SternY. Longitudinal relationships between Alzheimer disease progression and psychosis, depressed mood, and agitation/aggression.Am. J. Geriatr. Psychiatry201523213014010.1016/j.jagp.2013.03.01423871118
    [Google Scholar]
  13. RopackiS.A. JesteD.V. Epidemiology of and risk factors for psychosis of Alzheimer’s disease: a review of 55 studies published from 1990 to 2003.Am. J. Psychiatry2005162112022203010.1176/appi.ajp.162.11.202216263838
    [Google Scholar]
  14. BassionyM.M. SteinbergM.S. WarrenA. RosenblattA. BakerA.S. LyketsosC.G. Delusions and hallucinations in Alzheimer’s disease: prevalence and clinical correlates.Int. J. Geriatr. Psychiatry20001529910710.1002/(SICI)1099‑1166(200002)15:2<99:AID‑GPS82>3.0.CO;2‑510679840
    [Google Scholar]
  15. QianW. FischerC.E. SchweizerT.A. MunozD.G. Association between psychosis phenotype and APOE genotype on the clinical profiles of Alzheimer’s disease.Curr. Alzheimer Res.201815218719410.2174/156720501466617082911434628847281
    [Google Scholar]
  16. IsmailZ. NguyenM.Q. FischerC.E. SchweizerT.A. MulsantB.H. MamoD. Neurobiology of delusions in Alzheimer’s disease.Curr. Psychiatry Rep.201113321121810.1007/s11920‑011‑0195‑121404128
    [Google Scholar]
  17. CummingsJ. BallardC. TariotP. Pimavanserin: potential treatment for dementia-related psychosis.J. Prev. Alzheimers Dis.20185425325830298184
    [Google Scholar]
  18. Vik-MoA.O. GiilL.M. BallardC. AarslandD. Course of neuropsychiatric symptoms in dementia: 5-year longitudinal study.Int. J. Geriatr. Psychiatry201833101361136910.1002/gps.493329979473
    [Google Scholar]
  19. Vik-MoA.O. GiilL.M. BordaM.G. BallardC. AarslandD. The individual course of neuropsychiatric symptoms in people with Alzheimer’s and Lewy body dementia: 12-year longitudinal cohort study.Br. J. Psychiatry20202161434810.1192/bjp.2019.19531506117
    [Google Scholar]
  20. FischerC.E. QianW. SchweizerT.A. Determining the impact of psychosis on rates of false-positive and false-negative diagnosis in Alzheimer’s disease.Alzheimers Dement.20173338539210.1016/j.trci.2017.06.00129067344
    [Google Scholar]
  21. FischerC.E. QianW. SchweizerT.A. Lewy bodies, vascular risk factors, and subcortical arteriosclerotic leukoencephalopathy, but not Alzheimer pathology, are associated with development of psychosis in Alzheimer’s disease.J. Alzheimers Dis.201650128329510.3233/JAD‑15060626682680
    [Google Scholar]
  22. RubinE.H. DrevetsW.C. BurkeW.J. The nature of psychotic symptoms in senile dementia of the Alzheimer type.J. Geriatr. Psychiatry Neurol.198811162010.1177/0891988788001001043266997
    [Google Scholar]
  23. MurrayP.S. KumarS. DeMichele-SweetM.A.A. SweetR.A. Psychosis in Alzheimer’s disease.Biol. Psychiatry201475754255210.1016/j.biopsych.2013.08.02024103379
    [Google Scholar]
  24. NagahamaY. FukuiT. AkutagawaH. Prevalence and clinical implications of the mirror and TV signs in advanced Alzheimer’s disease and dementia with Lewy bodies.Dement. Geriatr. Cogn. Disord. Extra2020101566210.1159/00050651032308668
    [Google Scholar]
  25. RoaneD.M. FeinbergT.E. LibertaT.A. Delusional misidentification of the mirror image.Curr. Neurol. Neurosci. Rep.20191985510.1007/s11910‑019‑0972‑531250123
    [Google Scholar]
  26. FeinbergT.E. RoaneD. Self-representation in delusional misidentification and confabulated “others”.Cortex20178711812810.1016/j.cortex.2016.07.01427542857
    [Google Scholar]
  27. El HajM. RocheJ. JardriR. KapogiannisD. GalloujK. AntoineP. Clinical and neurocognitive aspects of hallucinations in Alzheimer’s disease.Neurosci. Biobehav. Rev.20178371372010.1016/j.neubiorev.2017.02.02128235545
    [Google Scholar]
  28. BallardC. OyebodeF. Psychotic symptoms in patients with dementia.Int. J. Geriatr. Psychiatry199510974375210.1002/gps.930100904
    [Google Scholar]
  29. JesteD.V. FinkelS.I. Psychosis of Alzheimer’s disease and related dementias. Diagnostic criteria for a distinct syndrome.Am. J. Geriatr. Psychiatry200081293410.1097/00019442‑200002000‑0000410648292
    [Google Scholar]
  30. Cohen-MansfieldJ. GolanderH. The measurement of psychosis in dementia: a comparison of assessment tools.Alzheimer Dis. Assoc. Disord.201125210110810.1097/WAD.0b013e3181f811f420921878
    [Google Scholar]
  31. IsmailZ. EmeremniC.A. HouckP.R. A comparison of the E-BEHAVE-AD, NBRS, and NPI in quantifying clinical improvement in the treatment of agitation and psychosis associated with dementia.Am. J. Geriatr. Psychiatry2013211788710.1016/j.jagp.2012.10.01323290205
    [Google Scholar]
  32. MonasteroR. MangialascheF. CamardaC. ErcolaniS. CamardaR. A systematic review of neuropsychiatric symptoms in mild cognitive impairment.J. Alzheimers Dis.2009181113010.3233/JAD‑2009‑112019542627
    [Google Scholar]
  33. CummingsJ. PintoL.C. CruzM. Criteria for psychosis in major and mild neurocognitive disorders: International Psychogeriatric Association (IPA) consensus clinical and research definition.Am. J. Geriatr. Psychiatry202028121256126910.1016/j.jagp.2020.09.00232958332
    [Google Scholar]
  34. SchneiderL.S. KatzI.R. ParkS. NapolitanoJ. MartinezR.A. AzenS.P. Psychosis of Alzheimer disease: validity of the construct and response to risperidone.Am. J. Geriatr. Psychiatry200311441442510.1097/00019442‑200307000‑0000412837670
    [Google Scholar]
  35. CummingsJ. MintzerJ. BrodatyH. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition.Int. Psychogeriatr.201527171710.1017/S104161021400196325311499
    [Google Scholar]
  36. De MauleonA. IsmailZ. RosenbergP. Agitation in Alzheimer’s disease: Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria.Alzheimers Dement.202117101687169710.1002/alz.1233534132461
    [Google Scholar]
  37. AaltenP. VerheyF.R.J. BozikiM. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I.Dement. Geriatr. Cogn. Disord.200724645746310.1159/00011073817986816
    [Google Scholar]
  38. SiafarikasN. SelbaekG. FladbyT. Šaltytė BenthJ AuningE AarslandD. Frequency and subgroups of neuropsychiatric symptoms in mild cognitive impairment and different stages of dementia in Alzheimer’s disease.Int. Psychogeriatr.201830110311310.1017/S104161021700187928927477
    [Google Scholar]
  39. LiewT.M. Symptom clusters of neuropsychiatric symptoms in mild cognitive impairment and their comparative risks of dementia: a cohort study of 8530 older persons.J. Am. Med. Dir. Assoc.20192081054105910.1016/j.jamda.2019.02.01230926409
    [Google Scholar]
  40. MartinE. VelayudhanL. Neuropsychiatric symptoms in mild cognitive impairment: a literature review.Dement. Geriatr. Cogn. Disord.202049214615510.1159/00050707832289790
    [Google Scholar]
  41. PetersM.E. RosenbergP.B. SteinbergM. Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: the Cache County Study.Am. J. Geriatr. Psychiatry201321111116112410.1016/j.jagp.2013.01.04923567370
    [Google Scholar]
  42. YokoiY. TakanoH. SakataM. MaruoK. NakagomeK. MatsudaH. Discrete effect of each mild behavioural impairment category on dementia conversion or cognitive decline in patients with mild cognitive impairment.Psychogeriatrics201919659160010.1111/psyg.1244730891900
    [Google Scholar]
  43. DietlinS. SotoM. KiyasovaV. Neuropsychiatric symptoms and risk of progression to Alzheimer’s disease among mild cognitive impairment subjects.J. Alzheimers Dis.2019701253410.3233/JAD‑19002531127783
    [Google Scholar]
  44. RosenbergP.B. MielkeM.M. ApplebyB.S. OhE.S. GedaY.E. LyketsosC.G. The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease.Am. J. Geriatr. Psychiatry201321768569510.1016/j.jagp.2013.01.00623567400
    [Google Scholar]
  45. PinkA. StokinG.B. BartleyM.M. Neuropsychiatric symptoms, APOE 4, and the risk of incident dementia: A population-based study.Neurology201584993594310.1212/WNL.000000000000130725653291
    [Google Scholar]
  46. FischerC.E. Agüera-OrtizL. Psychosis and dementia: risk factor, prodrome, or cause?Int. Psychogeriatr.201830220921910.1017/S104161021700087428560931
    [Google Scholar]
  47. LapidM.I. HoJ.B. Challenging our beliefs about delusional disorder in late life.Int. Psychogeriatr.202032442342510.1017/S104161021900135232295673
    [Google Scholar]
  48. NagendraJ. SnowdonJ. An Australian study of delusional disorder in late life.Int. Psychogeriatr.202032445346210.1017/S104161021900096631354123
    [Google Scholar]
  49. BrodatyH. SachdevP. KoscheraA. MonkD. CullenB. Long-term outcome of late-onset schizophrenia: 5-year follow-up study.Br. J. Psychiatry2003183321321910.1192/bjp.183.3.21312948993
    [Google Scholar]
  50. Köhler S, Allardyce J, Verhey FRJ, et al. Cognitive decline and dementia risk in older adults with psychotic symptoms: a prospective cohort study. Am J Geriatr Psychiatry20132121192810.1016/j.jagp.2012.10.01023343485
    [Google Scholar]
  51. SoaresW.B. dos SantosE.B. BottinoC.M.C. ElkisH. Psychotic symptoms in older people without dementia from a Brazilian community-based sample: A seven years’ follow-up.PLoS One2017126e017847110.1371/journal.pone.017847128622335
    [Google Scholar]
  52. LiewT.M. Neuropsychiatric symptoms in cognitively normal older persons, and the association with Alzheimer’s and non-Alzheimer’s dementia.Alzheimers Res. Ther.20201213510.1186/s13195‑020‑00604‑732234066
    [Google Scholar]
  53. Kørner A, Lopez AG, Lauritzen L, Andersen PK, Kessing LV. Late and very-late first-contact schizophrenia and the risk of dementia-a nationwide register based study.Int. J. Geriatr. Psychiatry2009241616710.1002/gps.207518561206
    [Google Scholar]
  54. Kørner A, Lopez AG, Lauritzen L, Andersen PK, Kessing LV. Acute and transient psychosis in old age and the subsequent risk of dementia: A nationwide register-based study.Geriatr. Gerontol. Int.200991626810.1111/j.1447‑0594.2009.00505.x19260981
    [Google Scholar]
  55. AlmeidaO.P. FordA.H. HankeyG.J. YeapB.B. GolledgeJ. FlickerL. Risk of dementia associated with psychotic disorders in later life: the health in men study (HIMS).Psychol. Med.201949223224210.1017/S003329171800065X29564993
    [Google Scholar]
  56. StaffordJ. DykxhoornJ. SommerladA. DalmanC. KirkbrideJ.B. HowardR. Association between risk of dementia and very late-onset schizophrenia-like psychosis: a Swedish population-based cohort study.Psychol. Med.20211910.1017/S003329172100209934030750
    [Google Scholar]
  57. NagaoS. YokotaO. IkedaC. Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders.Eur. Arch. Psychiatry Clin. Neurosci.2014264431733110.1007/s00406‑013‑0472‑624272318
    [Google Scholar]
  58. FischerC.E. IsmailZ. YouakimJ.M. Revisiting criteria for psychosis in Alzheimer’s disease and related dementias: toward better phenotypic classification and biomarker research.J. Alzheimers Dis.20207331143115610.3233/JAD‑19082831884469
    [Google Scholar]
  59. BacanuS.A. DevlinB. ChowdariK.V. DeKoskyS.T. NimgaonkarV.L. SweetR.A. Heritability of psychosis in Alzheimer disease.Am. J. Geriatr. Psychiatry200513762462710.1097/00019442‑200507000‑0001116009739
    [Google Scholar]
  60. DeMichele-SweetM.A.A. KleiL. CreeseB. Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease.Mol. Psychiatry202126105797581110.1038/s41380‑021‑01152‑834112972
    [Google Scholar]
  61. ShahC. DeMichele-SweetM.A.A. SweetR.A. Genetics of psychosis of Alzheimer disease.Am. J. Med. Genet. B. Neuropsychiatr. Genet.20171741273510.1002/ajmg.b.3241326756273
    [Google Scholar]
  62. KimJ. FischerC.E. SchweizerT.A. MunozD.G. Gender and pathology-specific effect of Apolipoprotein E genotype on psychosis in Alzheimer’s disease.Curr. Alzheimer Res.201714883484028219318
    [Google Scholar]
  63. DeMichele-SweetM A A. WeamerE.A. KleiL. Genetic risk for schizophrenia and psychosis in Alzheimer disease.Mol. Psychiatry201823496397210.1038/mp.2017.8128461698
    [Google Scholar]
  64. CreeseB. VassosE. BerghS. Examining the association between genetic liability for schizophrenia and psychotic symptoms in Alzheimer’s disease.Transl. Psychiatry20199127310.1038/s41398‑019‑0592‑531641104
    [Google Scholar]
  65. LeggeS.E. JonesH.J. KendallK.M. Association of genetic liability to psychotic experiences with neuropsychotic disorders and traits.JAMA Psychiatry201976121256126510.1001/jamapsychiatry.2019.250831553412
    [Google Scholar]
  66. EllisN. TeeA. McAllisterB. Genetic risk underlying psychiatric and cognitive symptoms in Huntington’s Disease.Biol. Psychiatry202087985786510.1016/j.biopsych.2019.12.01032087949
    [Google Scholar]
  67. PainO. DudbridgeF. CardnoA.G. Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders.Am. J. Med. Genet. B. Neuropsychiatr. Genet.2018177441642510.1002/ajmg.b.3263029603866
    [Google Scholar]
  68. BebbingtonP. FreemanD. Transdiagnostic extension of delusions: schizophrenia and beyond.Schizophr. Bull.201743227328210.1093/schbul/sbw19128399309
    [Google Scholar]
  69. GolanD. LanderE.S. RossetS. Measuring missing heritability: Inferring the contribution of common variants.Proc. Natl. Acad. Sci. USA201411149E5272E528110.1073/pnas.141906411125422463
    [Google Scholar]
  70. LunnonK. SmithR. HannonE. Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease.Nat. Neurosci.20141791164117010.1038/nn.378225129077
    [Google Scholar]
  71. SmithR.G. HannonE. De JagerP.L. Elevated DNA methylation across a 48‐kb region spanning the HOXA gene cluster is associated with Alzheimer’s disease neuropathology.Alzheimers Dement.201814121580158810.1016/j.jalz.2018.01.01729550519
    [Google Scholar]
  72. VianaJ. HannonE. DempsterE. Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions.Hum. Mol. Genet.201726121022528011714
    [Google Scholar]
  73. PishvaE. CreeseB. SmithA.R. Psychosis-associated DNA methylomic variation in Alzheimer’s disease cortex.Neurobiol. Aging202089838810.1016/j.neurobiolaging.2020.01.00132007278
    [Google Scholar]
  74. CreeseB. BellE. JoharI. FrancisP. BallardC. AarslandD. Glucocerebrosidase mutations and neuropsychiatric phenotypes in Parkinson’s disease and Lewy body dementias: Review and meta-analyses.Am. J. Med. Genet. B. Neuropsychiatr. Genet.2018177223224110.1002/ajmg.b.3254928548708
    [Google Scholar]
  75. ShinerT. MirelmanA. Gana WeiszM. High frequency of GBA gene mutations in dementia with Lewy bodies among Ashkenazi Jews.JAMA Neurol.201673121448145310.1001/jamaneurol.2016.159327723861
    [Google Scholar]
  76. IsmailZ. NguyenM.Q. FischerC.E. SchweizerT.A. MulsantB.H. Neuroimaging of delusions in Alzheimer’s disease.Psychiatry Res. Neuroimaging20122022899510.1016/j.pscychresns.2012.01.00822703622
    [Google Scholar]
  77. QianW. SchweizerT.A. ChurchillN.W. Gray matter changes associated with the development of delusions in Alzheimer disease.Am. J. Geriatr. Psychiatry201927549049810.1016/j.jagp.2018.09.01630503703
    [Google Scholar]
  78. LeeK. LeeY.M. ParkJ.M. Right hippocampus atrophy is independently associated with Alzheimer’s disease with psychosis.Psychogeriatrics201919210511010.1111/psyg.1236930430708
    [Google Scholar]
  79. McLachlanE. BousfieldJ. HowardR. ReevesS. Reduced parahippocampal volume and psychosis symptoms in Alzheimer’s disease.Int. J. Geriatr. Psychiatry201833238939510.1002/gps.475728741694
    [Google Scholar]
  80. Förstl H, Burns A, Levy R, Cairns N. Neuropathological correlates of psychotic phenomena in confirmed Alzheimer’s disease.Br. J. Psychiatry19941651535910.1192/bjp.165.1.537953058
    [Google Scholar]
  81. DonovanN.J. WadsworthL.P. LoriusN. Regional cortical thinning predicts worsening apathy and hallucinations across the Alzheimer disease spectrum.Am. J. Geriatr. Psychiatry201422111168117910.1016/j.jagp.2013.03.00623890751
    [Google Scholar]
  82. FischerC.E. TingW.K.C. MillikinC.P. IsmailZ. SchweizerT.A. Gray matter atrophy in patients with mild cognitive impairment/Alzheimer’s disease over the course of developing delusions.Int. J. Geriatr. Psychiatry2016311768210.1002/gps.429125821062
    [Google Scholar]
  83. BalthazarM.L.F. PereiraF.R.S. LopesT.M. Neuropsychiatric symptoms in Alzheimer’s disease are related to functional connectivity alterations in the salience network.Hum. Brain Mapp.20143541237124610.1002/hbm.2224823418130
    [Google Scholar]
  84. LeeJ.S. KimJ.H. LeeS.K. The relationship between neuropsychiatric symptoms and default-mode network connectivity in Alzheimer’s disease.Psychiatry Investig.202017766266610.30773/pi.2020.000932571002
    [Google Scholar]
  85. QianW. FischerC.E. ChurchillN.W. KumarS. RajjiT. SchweizerT.A. Delusions in Alzheimer disease are associated with decreased default mode network functional connectivity.Am. J. Geriatr. Psychiatry201927101060106810.1016/j.jagp.2019.03.02031130416
    [Google Scholar]
  86. TuM.C. HuangW.H. HsuY.H. LoC.P. DengJ.F. HuangC.F. Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer’s disease.BMC Neurol.201717114410.1186/s12883‑017‑0911‑528754095
    [Google Scholar]
  87. BlancF. NobletV. PhilippiN. Right anterior insula: core region of hallucinations in cognitive neurodegenerative diseases.PLoS One2014912e11477410.1371/journal.pone.011477425479196
    [Google Scholar]
  88. SultzerD.L. LeskinL.P. MelroseR.J. Neurobiology of delusions, memory, and insight in Alzheimer disease.Am. J. Geriatr. Psychiatry201422111346135510.1016/j.jagp.2013.06.00524021220
    [Google Scholar]
  89. NakatsukaM. MeguroK. TsuboiH. NakamuraK. AkanumaK. YamaguchiS. Content of delusional thoughts in Alzheimer’s disease and assessment of content-specific brain dysfunctions with BEHAVE-AD-FW and SPECT.Int. Psychogeriatr.201325693994810.1017/S104161021300009423433495
    [Google Scholar]
  90. SanthoshL. EstokK.M. VogelR.S. Regional distribution and behavioral correlates of 5-HT2A receptors in Alzheimer’s disease with [18F]deuteroaltanserin and PET.Psychiatry Res. Neuroimaging2009173321221710.1016/j.pscychresns.2009.03.00719682865
    [Google Scholar]
  91. ReevesS. BrownR. HowardR. GrasbyP. Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease.Neurology200972652853410.1212/01.wnl.0000341932.21961.f319204262
    [Google Scholar]
  92. KoppelJ. AckerC. DaviesP. Psychotic Alzheimer’s disease is associated with gender-specific tau phosphorylation abnormalities.Neurobiol. Aging20143592021202810.1016/j.neurobiolaging.2014.03.00324731519
    [Google Scholar]
  93. MurrayP.S. KirkwoodC.M. GrayM.C. Hyperphosphorylated tau is elevated in Alzheimer’s disease with psychosis.J. Alzheimers Dis.201439475977310.3233/JAD‑13116624270207
    [Google Scholar]
  94. EhrenbergA.J. SuemotoC.K. França ResendeE.P. Neuropathologic correlates of psychiatric symptoms in Alzheimer’s disease.J. Alzheimers Dis.201866111512610.3233/JAD‑18068830223398
    [Google Scholar]
  95. KrivinkoJ.M. EricksonS.L. DingY. Synaptic proteome compensation and resilience to psychosis in Alzheimer’s disease.Am. J. Psychiatry201817510999100910.1176/appi.ajp.2018.1708085830021459
    [Google Scholar]
  96. WhiteheadD. TunnardC. HurtC. Frontotemporal atrophy associated with paranoid delusions in women with Alzheimer’s disease.Int. Psychogeriatr.20122419910710.1017/S104161021100097421740613
    [Google Scholar]
  97. KoppelJ. SundayS. ButhornJ. GoldbergT. DaviesP. GreenwaldB. Elevated CSF Tau is associated with psychosis in Alzheimer’s disease.Am. J. Psychiatry2013170101212121310.1176/appi.ajp.2013.1304046624084821
    [Google Scholar]
  98. TakahataK. KimuraY. SaharaN. PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury.Brain2019142103265327910.1093/brain/awz23831504227
    [Google Scholar]
  99. MurrayPS KirkwoodCM GrayMC β-Amyloid 42/40 ratio and kalirin expression in Alzheimer disease with psychosis.Neurobiol. Aging201233122807281610.1016/j.neurobiolaging.2012.02.01522429885
    [Google Scholar]
  100. WhitfieldD.R. FrancisP.T. BallardC. WilliamsG. Associations between ZnT3, tau pathology, agitation, and delusions in dementia.Int. J. Geriatr. Psychiatry20183381146115210.1002/gps.490829856089
    [Google Scholar]
  101. WhitfieldD.R. VallortigaraJ. AlghamdiA. Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer’s disease: association with cognitive impairment.Neurobiol. Aging201435122836284410.1016/j.neurobiolaging.2014.06.01525104558
    [Google Scholar]
  102. TsuangD. SimpsonK. LarsonE.B. Predicting lewy body pathology in a community-based sample with clinical diagnosis of Alzheimer’s disease.J. Geriatr. Psychiatry Neurol.200619419520110.1177/089198870629275517085757
    [Google Scholar]
  103. TingS.K.S. HaoY. ChiaP.S. TanE.K. HameedS. Clinicopathological correlation of psychosis and brain vascular changes in Alzheimer’s disease.Sci. Rep.2016612085810.1038/srep2085826868671
    [Google Scholar]
  104. Vik-MoA.O. BenczeJ. BallardC. Hortobلgyi T, Aarsland D. Advanced cerebral amyloid angiopathy and small vessel disease are associated with psychosis in Alzheimer’s disease.J. Neurol. Neurosurg. Psychiatry201990672873010.1136/jnnp‑2018‑31844530054314
    [Google Scholar]
  105. KimJ. SchweizerT.A. FischerC.E. MunozD.G. The role of cerebrovascular disease on cognitive and functional status and psychosis in severe Alzheimer’s disease.J. Alzheimers Dis.201655138138910.3233/JAD‑16050627662301
    [Google Scholar]
  106. SteinbergM. HessK. CorcoranC. Vascular risk factors and neuropsychiatric symptoms in Alzheimer’s disease: the Cache County Study.Int. J. Geriatr. Psychiatry201429215315910.1002/gps.398023681754
    [Google Scholar]
  107. BidzanM. BidzanL. PachalskaM. Neuropsychiatric symptoms in patients with Alzheimer’s disease with a vascular component.Ann. Agric. Environ. Med.201421241241510.5604/1232‑1966.110861524959800
    [Google Scholar]
  108. HwangI. BaekK.H. HanJ.H. HaS.W. YangY. Hypertension and neuropsychiatric symptoms in patients with drug-naïve Alzheimer’s disease.Dement. Neurocognitive Disord.2017163788210.12779/dnd.2017.16.3.7830906375
    [Google Scholar]
  109. SweetR.A. HamiltonR.L. HealyM.T. Alterations of striatal dopamine receptor binding in Alzheimer disease are associated with Lewy body pathology and antemortem psychosis.Arch. Neurol.200158346647210.1001/archneur.58.3.46611255451
    [Google Scholar]
  110. ReevesS. McLachlanE. BertrandJ. Therapeutic window of dopamine D2/3 receptor occupancy to treat psychosis in Alzheimer’s disease.Brain201714041117112710.1093/brain/aww35928334978
    [Google Scholar]
  111. FanP. QiX. SweetR.A. WangL. Network systems pharmacology-based mechanism study on the beneficial effects of vitamin D against psychosis in Alzheimer’s disease.Sci. Rep.2020101613610.1038/s41598‑020‑63021‑832273551
    [Google Scholar]
  112. BallardC. BanisterC. KhanZ. Evaluation of the safety, tolerability, and efficacy of pimavanserin versus placebo in patients with Alzheimer’s disease psychosis: a phase 2, randomised, placebo-controlled, double-blind study.Lancet Neurol.201817321322210.1016/S1474‑4422(18)30039‑529452684
    [Google Scholar]
  113. SinclairL.I. KumarA. Darreh-ShoriT. LoveS. Visual hallucinations in Alzheimer’s disease do not seem to be associated with chronic hypoperfusion of to visual processing areas V2 and V3 but may be associated with reduced cholinergic input to these areas.Alzheimers Res. Ther.20191118010.1186/s13195‑019‑0519‑731511061
    [Google Scholar]
  114. WattJ.A. GoodarziZ. VeronikiA.A. Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis.Ann. Intern. Med.2019171963364210.7326/M19‑099331610547
    [Google Scholar]
  115. IsmailZ. GoodarziZ. Neuropsychiatric aspects of Alzheimer’s disease clinically significant neuropsychiatric symptoms need evidence-based treatment.Pract. Neurol.20197881[Available from: https://practicalneurology.com/articles/2019-june/neuropsychiatricaspects-of-alzheimersdisease
    [Google Scholar]
  116. KalesH.C. GitlinL.N. LyketsosC.G. Detroit Expert Panel on Assessment and Management of Neuropsychiatric Symptoms of Dementia. Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel.J. Am. Geriatr. Soc.201462476276910.1111/jgs.1273024635665
    [Google Scholar]
  117. WolinskyD. DrakeK. BostwickJ. Diagnosis and management of neuropsychiatric symptoms in Alzheimer’s disease.Curr. Psychiatry Rep.2018201211710.1007/s11920‑018‑0978‑830367272
    [Google Scholar]
  118. DaviesS.J.C. BurhanA.M. KimD. Sequential drug treatment algorithm for agitation and aggression in Alzheimer’s and mixed dementia.J. Psychopharmacol.201832550952310.1177/026988111774499629338602
    [Google Scholar]
  119. BallardC. OrrellM. Moniz-CookE. Improving mental health and reducing antipsychotic use in people with dementia in Care Homes: the WHELD research programme including two RCTs.Prog Grants App Res202086997
    [Google Scholar]
  120. ChenR.C. LiuC.L. LinM.H. Non-pharmacological treatment reducing not only behavioral symptoms, but also psychotic symptoms of older adults with dementia: A prospective cohort study in Taiwan.Geriatr. Gerontol. Int.201414244044610.1111/ggi.1212623910097
    [Google Scholar]
  121. GitlinL.N. KalesH.C. LyketsosC.G. Nonpharmacologic management of behavioral symptoms in dementia.JAMA2012308192020202910.1001/jama.2012.3691823168825
    [Google Scholar]
  122. AarslandD. Impact of dementia-related psychosis on patients and caregivers: the treatment imperative.J Clin Psychiatry2020816AD19038BR2C
    [Google Scholar]
  123. BallardC. Diagnosing dementia-related psychosis: Using tools and communicating with patients and caregivers.J Clin Psychiatry202082AD19038BR3C
    [Google Scholar]
  124. SchneiderL.S. DagermanK. InselP.S. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials.Am. J. Geriatr. Psychiatry200614319121010.1097/01.JGP.0000200589.01396.6d16505124
    [Google Scholar]
  125. TampiR.R. TampiD.J. BalachandranS. SrinivasanS. Antipsychotic use in dementia: a systematic review of benefits and risks from meta-analyses.Ther. Adv. Chronic Dis.20167522924510.1177/204062231665846327583123
    [Google Scholar]
  126. BallardC. CreeseB. CorbettA. AarslandD. Atypical antipsychotics for the treatment of behavioral and psychological symptoms in dementia, with a particular focus on longer term outcomes and mortality.Expert Opin. Drug Saf.2011101354310.1517/14740338.2010.50671120684745
    [Google Scholar]
  127. MaustD.T. KimH.M. SeyfriedL.S. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm.JAMA Psychiatry201572543844510.1001/jamapsychiatry.2014.301825786075
    [Google Scholar]
  128. MaherA.R. MaglioneM. BagleyS. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis.JAMA2011306121359136910.1001/jama.2011.136021954480
    [Google Scholar]
  129. BallardC. HowardR. Neuroleptic drugs in dementia: benefits and harm.Nat. Rev. Neurosci.20067649250010.1038/nrn192616715057
    [Google Scholar]
  130. YunusaI. AlsumaliA. GarbaA.E. RegesteinQ.R. EgualeT. Assessment of reported comparative effectiveness and safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms of dementia: a network meta-analysis.JAMA Netw. Open201923e19082810.1001/jamanetworkopen.2019.082830901041
    [Google Scholar]
  131. HowardR. CostafredaS.G. KarcherK. CoppolaD. BerlinJ.A. HoughD. Baseline characteristics and treatment-emergent risk factors associated with cerebrovascular event and death with risperidone in dementia patients.Br. J. Psychiatry2016209537838410.1192/bjp.bp.115.17768327388570
    [Google Scholar]
  132. ReevesS. BertrandJ. UchidaH. Towards safer risperidone prescribing in Alzheimer’s disease.Br. J. Psychiatry2021218526827510.1192/bjp.2020.22533176899
    [Google Scholar]
  133. HowardR. CortE. BradleyR. Antipsychotic treatment of very late-onset schizophrenia-like psychosis (ATLAS): a randomised, controlled, double-blind trial.Lancet Psychiatry20185755356310.1016/S2215‑0366(18)30141‑X29880238
    [Google Scholar]
  134. MalekizadehY. WilliamsG. KelsonM. Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects.Alzheimers Dement.202061e1207810.1002/trc2.1207832864416
    [Google Scholar]
  135. SchneiderL.S. DagermanK.S. InselP. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials.JAMA2005294151934194310.1001/jama.294.15.193416234500
    [Google Scholar]
  136. CummingsJ. IsaacsonS. MillsR. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial.Lancet2014383991653354010.1016/S0140‑6736(13)62106‑624183563
    [Google Scholar]
  137. HacksellU. BursteinE.S. McFarlandK. MillsR.G. WilliamsH. On the discovery and development of pimavanserin: a novel drug candidate for Parkinson’s psychosis.Neurochem. Res.201439102008201710.1007/s11064‑014‑1293‑324682754
    [Google Scholar]
  138. BallardC. YouakimJ.M. CoateB. StankovicS. Pimavanserin in Alzheimer’s disease psychosis: efficacy in patients with more pronounced psychotic symptoms.J. Prev. Alzheimers Dis.201961273330569083
    [Google Scholar]
  139. ACADIA Pharmaceuticals presents positive top-line results from pivotal phase 3 HARMONY trial of pimavanserin in patients with dementia-related psychosis at 12th Clinical Trials on Alzheimer’s Disease (CTAD) Meeting. Acadia. 2020. Available from: https://ir.acadia-pharm.com/news-releases/news-release-details/acadiapharmaceuticals-presents-positive-top-line-results
  140. BallardC.G. KreitzmanD.L. IsaacsonS. Long-term evaluation of open-label pimavanserin safety and tolerability in Parkinson’s disease psychosis.Parkinsonism Relat. Disord.20207710010610.1016/j.parkreldis.2020.06.02632712560
    [Google Scholar]
  141. FDA analysis finds no new or unexpected safety risks associated with Nuplazid (pimavanserin), a medication to treat the hallucinations and delusions of Parkinson’s disease psychosis. 2018. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-analysis-finds-no-newor-unexpected-safety-risks-associated-nuplazidpimavanserin-medication
  142. BallardC. IsaacsonS. MillsR. Impact of current antipsychotic medications on comparative mortality and adverse events in people with Parkinson disease psychosis.J. Am. Med. Dir. Assoc.20151610898.e1898.e710.1016/j.jamda.2015.06.02126239690
    [Google Scholar]
  143. PorsteinssonA.P. DryeL.T. PollockB.G. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial.JAMA2014311768269110.1001/jama.2014.9324549548
    [Google Scholar]
  144. EhrhardtS. PorsteinssonA.P. MunroC.A. Escitalopram for agitation in Alzheimer’s disease (S-CitAD): Methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial.Alzheimers Dement.201915111427143610.1016/j.jalz.2019.06.494631587995
    [Google Scholar]
  145. ShelineY.I. SniderB.J. BeerJ.C. Effect of escitalopram dose and treatment duration on CSF Aβ levels in healthy older adults.Neurology20209519e2658e266510.1212/WNL.000000000001072532913021
    [Google Scholar]
  146. DevanandD.P. CroccoE. Low dose lithium treatment of behavioral complications in Alzheimer’s disease: Lit-AD randomized clinical trial.Am. J. Geriatr. Psychiatry2021301324210.1016/j.jagp.2021.04.01434059401
    [Google Scholar]
  147. WonE. KimY.K. An oldie but goodie: lithium in the treatment of bipolar disorder through neuroprotective and neurotrophic mechanisms.Int. J. Mol. Sci.20171812267910.3390/ijms1812267929232923
    [Google Scholar]
  148. TanE.C.K. JohnellK. BellJ.S. Do acetylcholinesterase inhibitors prevent or delay psychotropic prescribing in people with dementia? Analyses of the Swedish Dementia Registry.Am. J. Geriatr. Psychiatry202028110811710.1016/j.jagp.2019.06.00831331724
    [Google Scholar]
  149. WangL. YingJ. FanP. Effects of vitamin D use on outcomes of psychotic symptoms in Alzheimer disease patients.Am. J. Geriatr. Psychiatry201927990891710.1016/j.jagp.2019.03.01631126722
    [Google Scholar]
  150. Orzelska-GórkaJ MikulskaJ WiszniewskaA BiałaG. New atypical antipsychotics in the treatment of schizophrenia and depression.Int. J. Mol. Sci.202223181062410.3390/ijms23181062436142523
    [Google Scholar]
  151. CalabreseF. TaraziF.I. RacagniG. RivaM.A. The role of dopamine D 3 receptors in the mechanism of action of cariprazine.CNS Spectr.202025334335110.1017/S109285291900083X31010452
    [Google Scholar]
  152. CeskovaE. Pharmacological strategies for the management of comorbid depression and schizophrenia.Expert Opin. Pharmacother.202021445946510.1080/14656566.2020.171746631983254
    [Google Scholar]
  153. GatchelJ.R. RabinJ.S. BuckleyR.F. Longitudinal association of depression symptoms with cognition and cortical amyloid among community-dwelling older adults.JAMA Netw. Open201928e19896410.1001/jamanetworkopen.2019.896431397865
    [Google Scholar]
  154. Krell-RoeschJ. VassilakiM. MielkeM.M. Cortical β-amyloid burden, neuropsychiatric symptoms, and cognitive status: the Mayo Clinic Study of Aging.Transl. Psychiatry20199112310.1038/s41398‑019‑0456‑z30923322
    [Google Scholar]
  155. RuthirakuhanM. IsmailZ. HerrmannN. GallagherD. LanctôtK.L. Mild behavioral impairment is associated with progression to Alzheimer’s disease: A clinicopathological study.Alzheimers Dement.202218112199220810.1002/alz.12519
    [Google Scholar]
  156. GoukasianN. HwangK.S. RomeroT. Association of brain amyloidosis with the incidence and frequency of neuropsychiatric symptoms in ADNI: a multisite observational cohort study.BMJ Open2019912e03194710.1136/bmjopen‑2019‑03194731857304
    [Google Scholar]
  157. LouhijaU.M. SaarelaT. JuvaK. AppelbergB. Brain atrophy is a frequent finding in elderly patients with first episode psychosis.Int. Psychogeriatr.201729111925192910.1017/S104161021700095328587701
    [Google Scholar]
  158. IsmailZ. SmithE.E. GedaY. Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment.Alzheimers Dement.201612219520210.1016/j.jalz.2015.05.01726096665
    [Google Scholar]
  159. TaraganoF.E. AllegriR.F. HeiseckeS.L. Risk of conversion to dementia in a mild behavioral impairment group compared to a psychiatric group and to a mild cognitive impairment group.J. Alzheimers Dis.201862122723810.3233/JAD‑17063229439333
    [Google Scholar]
  160. IsmailZ. Agüera-OrtizL. BrodatyH. The Mild Behavioral Impairment Checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations.J. Alzheimers Dis.201756392993810.3233/JAD‑16097928059789
    [Google Scholar]
  161. CreeseB. BrookerH. IsmailZ. Mild behavioral impairment as a marker of cognitive decline in cognitively normal older adults.Am. J. Geriatr. Psychiatry201927882383410.1016/j.jagp.2019.01.21530902566
    [Google Scholar]
  162. CreeseB. GriffithsA. BrookerH. Profile of mild behavioral impairment and factor structure of the Mild Behavioral Impairment Checklist in cognitively normal older adults.Int. Psychogeriatr.202032670571710.1017/S104161021900120031526407
    [Google Scholar]
  163. HuS. PattenS.B. FickG. SmithE.E. IsmailZ. Validation of the mild behavioral impairment checklist (MBI-C) in a clinic-based sample.Alzheimers Dement.201915P36510.1016/j.jalz.2019.06.872
    [Google Scholar]
  164. MalloS.C. IsmailZ. PereiroA.X. Assessing mild behavioral impairment with the mild behavioral impairment-checklist in people with mild cognitive impairment.J. Alzheimers Dis.2018661839510.3233/JAD‑18013130175974
    [Google Scholar]
  165. MalloS.C. IsmailZ. PereiroA.X. Assessing mild behavioral impairment with the mild behavioral impairment checklist in people with subjective cognitive decline.Int. Psychogeriatr.201931223123910.1017/S104161021800069830017017
    [Google Scholar]
  166. MatsuokaT. IsmailZ. NarumotoJ. Prevalence of mild behavioral impairment and risk of dementia in a psychiatric outpatient clinic.J. Alzheimers Dis.201970250551310.3233/JAD‑19027831177229
    [Google Scholar]
  167. KassamF. ChenH-Y. NoshenyR.L. Cognitive profile of mild behavioral impairment (MBI) in brain health registry participants.Alzheimers Dement.202016S6e04767310.1002/alz.047673
    [Google Scholar]
  168. IsmailZ. ElbayoumiH. FischerC.E. Prevalence of depression in patients with mild cognitive impairment: a systematic review and meta-analysis.JAMA Psychiatry2017741586710.1001/jamapsychiatry.2016.316227893026
    [Google Scholar]
  169. IsmailZ. McGirrA. GillS. HuS. ForkertN.D. SmithE.E. Mild behavioral impairment and subjective cognitive decline predict cognitive and functional decline.J. Alzheimers Dis.202180145946910.3233/JAD‑20118433554909
    [Google Scholar]
  170. NathanS. GillS. IsmailZ. Highlights From the Alzheimer's Association International Conference 2020. Alzheimer’s Association International Conference (AAIC), Chicago, July 30,2020
  171. LussierF.Z. PascoalT.A. ChamounM. Mild behavioral impairment is associated with β‐amyloid but not tau or neurodegeneration in cognitively intact elderly individuals.Alzheimers Dement.202016119219910.1002/alz.1200731914223
    [Google Scholar]
  172. MiaoR. Plasma β-amyloid in mild behavioural impairment-neuropsychiatric symptoms on the Alzheimer’s continuum.J. Geriatr. Psychiatry Neurol.202135343444110.1177/0891988721101606834036829
    [Google Scholar]
  173. LussierF. Mild behavioral impairment is associated with beta-amyloid and tau across the alzheimer’s disease spectrum.J. Cereb. Blood Flow Metab.201939158159
    [Google Scholar]
  174. JohanssonM. StomrudE. InselP.S. Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer’s disease.Transl. Psychiatry20211117610.1038/s41398‑021‑01206‑z33500386
    [Google Scholar]
  175. GillS Diffusion tensor imaging in pre-dementia risk states: white matter atrophy findings in mildbehavioral impairment (P5. 1-025).Neurology201992P5.1-025
    [Google Scholar]
  176. YoonE.J. IsmailZ. HanganuA. Mild behavioral impairment is linked to worse cognition and brain atrophy in Parkinson disease.Neurology2019938e766e77710.1212/WNL.000000000000796831320470
    [Google Scholar]
  177. NaudeJ.P. GillS. HuS. Plasma neurofilament Light: a marker of cognitive decline in mild behavioural impairment.J. Alzheimers Dis.20207631017102710.3233/JAD‑20001132597801
    [Google Scholar]
  178. AndrewsS.J. IsmailZ. AnsteyK.J. MortbyM. Association of Alzheimer’s genetic loci with mild behavioral impairment.Am. J. Med. Genet. B. Neuropsychiatr. Genet.2018177872773510.1002/ajmg.b.3268430378268
    [Google Scholar]
  179. CreeseB. ArathimosR. BrookerH. Genetic risk for Alzheimer’s disease, cognition, and mild behavioral impairment in healthy older adults.Alzheimers Dement.2021131e1216410.1002/dad2.1216433748395
    [Google Scholar]
  180. WolfovaK. CreeseB. AarslandD. Sex differences in the association of mild behavioral impairment with cognitive aging.medRxiv202110.1101/2021.05.20.21257514
    [Google Scholar]
  181. MortbyM.E. BlackS.E. GauthierS. Dementia clinical trial implications of mild behavioral impairment.Int. Psychogeriatr.201830217117510.1017/S104161021800004229448970
    [Google Scholar]
  182. IsmailZ. CreeseB. AarslandD. Psychosis in Alzheimer disease-mechanisms, genetics and therapeutic opportunities.Nat. Rev. Neurol.202218131144
    [Google Scholar]
  183. BlackmanJ. SwirskiM. ClynesJ. Pharmacological and non-pharmacological interventions to enhance sleep in mild cognitive impairment and mild Alzheimer’s disease: A systematic review.J. Sleep Res.2021309e1322933289311
    [Google Scholar]
  184. ZucchellaC SinforianiE tamburin S et al. The Multidisciplinary approach to Alzheimer’s Disease and Dementia. A narrative review of Non-Pharmacological Treatment.Front. Neurol.20189105830619031
    [Google Scholar]
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