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2000
Volume 21, Issue 4
  • ISSN: 2666-0822
  • E-ISSN: 2666-0830

Abstract

With an ageing global population, understanding the potential links between mental health and neurodegenerative disorders has become increasingly crucial for comprehensive patient care. A comprehensive search of electronic databases yielded a selection of studies encompassing clinical trials, longitudinal cohorts, and cross-sectional analyses, published between 2000 and 2023. Key inclusion criteria focused on investigations involving both Alzheimer's disease and depression, encompassing a range of methodologies, including neuroimaging, epidemiological surveys, and clinical assessments. The analysis reveals compelling evidence of a bidirectional relationship, where depression serves as a potential precursor to Alzheimer's disease, and . Neurobiological mechanisms, including neuroinflammation, neurotransmitter imbalances, and genetic predispositions, emerge as significant contributors to this complex association. Furthermore, psychosocial factors, such as chronic stress and social isolation, are identified as potential accelerators of cognitive decline in individuals with co-occurring depression and Alzheimer's. Additionally, therapeutic interventions targeting both conditions concurrently exhibit promising outcomes in mitigating cognitive decline and ameliorating depressive symptoms. Approaches encompassing cognitive behavioural therapy, pharmacological interventions, and lifestyle modifications demonstrate potential avenues for integrated treatment strategies. This review underscores the imperative for a multidisciplinary approach to patient care, emphasizing the importance of early detection and intervention for individuals presenting with symptoms of depression and cognitive impairment. Future research avenues should prioritize longitudinal studies with larger cohorts to delineate the causal pathways and further elucidate effective treatment modalities for this intricate comorbidity. By unravelling the complexities of the Alzheimer's-depression nexus, we pave the way for more targeted and comprehensive interventions to improve the lives of those affected by these debilitating conditions.

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2025-11-14

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References

  1. SmithE.E. IsmailZ. GedaY. SultzerD. BrodatyH. SmithG. Agüera-OrtizL. SweetR. MillerD.S. LyketsosC.G. Neuropsychiatric symptoms as early manifestations of emergent dementia: Provisional diagnostic criteria for mild behavioral impairment.JAMA Neurol.2018752136142
     [Google Scholar]
  2. 2020 Alzheimer's disease facts and figures.Alzheimers Dement.202010.1002/alz.12068.32157811
     [Google Scholar]
  3. Depression.Available from: https://www.who.int/health-topics/depression#tab=tab_1
  4. KesslerR.C. Aguilar-GaxiolaS. AlonsoJ. ChatterjiS. LeeS. OrmelJ. ÜstünT.B. WangP.S. The global burden of mental disorders: An update from the WHO World Mental Health (WMH) Surveys.Epidemiol. Psichiatr. Soc.2009181233310.1017/S1121189X0000142119378696
     [Google Scholar]
  5. OwnbyR.L. CroccoE. AcevedoA. JohnV. LoewensteinD. Depression and risk for Alzheimer disease: Systematic review, meta-analysis, and metaregression analysis.Arch. Gen. Psychiatry200663553053810.1001/archpsyc.63.5.53016651510
     [Google Scholar]
  6. ByersA.L. YaffeK. Depression and risk of developing dementia.Nat. Rev. Neurol.20117632333110.1038/nrneurol.2011.6021537355
     [Google Scholar]
  7. OwnbyR.L. AcevedoA. ArataniS. Waldrop-ValverdeD. JacobsR. Depression and risk for Alzheimer disease: A systematic review, meta-analysis, and metaregression analysis.Arch. Gen. Psychiatry201673323724216651510
     [Google Scholar]
  8. IsmailZ. SmithE.E. GedaY. SultzerD. BrodatyH. SmithG. Agüera-OrtizL. SweetR. MillerD. LyketsosC.G. 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]
  9. DinizB.S. ButtersM.A. AlbertS.M. DewM.A. ReynoldsC.F.III Late-life depression and risk of vascular dementia and Alzheimer’s disease: Systematic review and meta-analysis of community-based cohort studies.Br. J. Psychiatry2013202532933510.1192/bjp.bp.112.11830723637108
     [Google Scholar]
  10. HolmesS.E. HinzR. ConenS. GregoryC.J. MatthewsJ.C. Anton-RodriguezJ.M. GerhardA. TalbotP.S. BannisterC. Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: A positron emission tomography study.Biol. Psychiatry2018831616910.1016/j.biopsych.2017.08.00528939116
     [Google Scholar]
  11. RosenbergP.B. NowrangiM.A. LyketsosC.G. HolmesS.E. Chronic pain and neuropsychiatric illness in older adults: The role of depression and sleep disturbance.Am. J. Geriatr. Psychiatry201624212612810.1016/j.jagp.2015.10.00726238228
     [Google Scholar]
  12. 2021 Alzheimer's disease facts and figures.Alzheimers Dement.202117332740610.1002/alz.12328.33756057
     [Google Scholar]
  13. HardyJ.A. HigginsG.A. Alzheimer’s disease: The amyloid cascade hypothesis.Science1992256505418418510.1126/science.15660671566067
     [Google Scholar]
  14. HenekaM.T. CarsonM.J. KhouryJ.E. LandrethG.E. BrosseronF. FeinsteinD.L. JacobsA.H. Wyss-CorayT. VitoricaJ. RansohoffR.M. HerrupK. FrautschyS.A. FinsenB. BrownG.C. VerkhratskyA. YamanakaK. KoistinahoJ. LatzE. HalleA. PetzoldG.C. TownT. MorganD. ShinoharaM.L. PerryV.H. HolmesC. BazanN.G. BrooksD.J. HunotS. JosephB. DeigendeschN. GaraschukO. BoddekeE. DinarelloC.A. BreitnerJ.C. ColeG.M. GolenbockD.T. KummerM.P. Neuroinflammation in Alzheimer’s disease.Lancet Neurol.201514438840510.1016/S1474‑4422(15)70016‑525792098
     [Google Scholar]
  15. American Psychiatric AssociationDiagnostic and statistical manual of mental disorders.201310.1176/appi.books.9780890425596
     [Google Scholar]
  16. CampbellS. MacqueenG. The role of the hippocampus in the pathophysiology of major depression.J. Psychiatry Neurosci.200429641742615644983
     [Google Scholar]
  17. BelmakerR.H. AgamG. Major depressive disorder.N. Engl. J. Med.20083581556810.1056/NEJMra07309618172175
     [Google Scholar]
  18. NestlerE.J. BarrotM. DiLeoneR.J. EischA.J. GoldS.J. MonteggiaL.M. Neurobiology of depression.Neuron2002341132510.1016/S0896‑6273(02)00653‑011931738
     [Google Scholar]
  19. DrevetsW.C. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders.Curr. Opin. Neurobiol.200111224024910.1016/S0959‑4388(00)00203‑811301246
     [Google Scholar]
  20. FrodlT. MeisenzahlEM. ZetzscheT. BornC. JägerM. GrollC. BottlenderR. LeinsingerG. MöllerHJ. Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects.Biol. Psychiatry200863432433112586453
     [Google Scholar]
  21. MacQueenG. FrodlT. The hippocampus in major depression: Evidence for the convergence of the bench and bedside in psychiatric research?Mol. Psychiatry201116325226410.1038/mp.2010.8020661246
     [Google Scholar]
  22. CastrénE. HenR. Neuronal plasticity and antidepressant actions.Trends Neurosci.201336525926710.1016/j.tins.2012.12.01023380665
     [Google Scholar]
  23. PittengerC. DumanR.S. Stress, depression, and neuroplasticity: A convergence of mechanisms.Neuropsychopharmacology20083318810910.1038/sj.npp.130157417851537
     [Google Scholar]
  24. HolsboerF. Stress, hypercortisolism and corticosteroid receptors in depression: Implicatons for therapy.J. Affect. Disord.2001621-2779110.1016/S0165‑0327(00)00352‑911172875
     [Google Scholar]
  25. AnackerC. ZunszainP.A. CattaneoA. CarvalhoL.A. GarabedianM.J. ThuretS. PriceJ. ParianteC.M. Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor.Mol. Psychiatry201116773875010.1038/mp.2011.2621483429
     [Google Scholar]
  26. McEwenB.S. Protection and damage from acute and chronic stress: allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders.Ann. N. Y. Acad. Sci.2004103211710.1196/annals.1314.00115677391
     [Google Scholar]
  27. MolendijkM.L. SpinhovenP. PolakM. BusB A A. PenninxB.W.J.H. ElzingaB.M. Serum BDNF concentrations as peripheral manifestations of depression: Evidence from a systematic review and meta-analyses on 179 associations (N=9484).Mol. Psychiatry201419779180010.1038/mp.2013.10523958957
     [Google Scholar]
  28. RaisonC.L. MillerA.H. Is depression an inflammatory disorder?Curr. Psychiatry Rep.201113646747510.1007/s11920‑011‑0232‑021927805
     [Google Scholar]
  29. NunomuraA. PerryG. AlievG. HiraiK. TakedaA. BalrajE.K. JonesP.K. GhanbariH. WatayaT. ShimohamaS. ChibaS. AtwoodC.S. PetersenR.B. SmithM.A. Oxidative damage is the earliest event in Alzheimer disease.J. Neuropathol. Exp. Neurol.200160875976710.1093/jnen/60.8.75911487050
     [Google Scholar]
  30. MaesM. GaleckiP. ChangY.S. BerkM. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness.Prog. Neuropsychopharmacol. Biol. Psychiatry201135367669210.1016/j.pnpbp.2010.05.00420471444
     [Google Scholar]
  31. HolsingerR.M.D. SchnarrJ. HenryP. CasteloV.T. FahnestockM. Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer’s disease.Brain Res. Mol. Brain Res.200076234735410.1016/S0169‑328X(00)00023‑110762711
     [Google Scholar]
  32. PolyakovaM. StukeK. SchuembergK. MuellerK. SchoenknechtP. SchroeterM.L. BDNF as a biomarker for successful treatment of mood disorders: A systematic & quantitative meta-analysis.J. Affect. Disord.201517443244010.1016/j.jad.2014.11.04425553404
     [Google Scholar]
  33. SapolskyR.M. KreyL.C. McewenB.S. The neuroendocrinology of stress and aging: The glucocorticoid cascade hypothesis.Endocr. Rev.19867328430110.1210/edrv‑7‑3‑2843527687
     [Google Scholar]
  34. GreenK.N. BillingsL.M. RoozendaalB. McGaughJ.L. LaFerlaF.M. Glucocorticoids increase amyloid-β and tau pathology in a mouse model of Alzheimer’s disease.J. Neurosci.200626359047905610.1523/JNEUROSCI.2797‑06.200616943563
     [Google Scholar]
  35. FrancisP.T. PalmerA.M. SnapeM. WilcockG.K. The cholinergic hypothesis of Alzheimer’s disease: A review of progress.J. Neurol. Neurosurg. Psychiatry199966213714710.1136/jnnp.66.2.13710071091
     [Google Scholar]
  36. BelujonP. GraceA.A. Dopamine system dysregulation in major depressive disorders.Int. J. Neuropsychopharmacol.201720121036104610.1093/ijnp/pyx05629106542
     [Google Scholar]
  37. HaroldD. AbrahamR. HollingworthP. SimsR. GerrishA. HamshereM.L. PahwaJ.S. MoskvinaV. DowzellK. WilliamsA. JonesN. ThomasC. StrettonA. MorganA.R. LovestoneS. PowellJ. ProitsiP. LuptonM.K. BrayneC. RubinszteinD.C. GillM. LawlorB. LynchA. MorganK. BrownK.S. PassmoreP.A. CraigD. McGuinnessB. ToddS. HolmesC. MannD. SmithA.D. LoveS. KehoeP.G. HardyJ. MeadS. FoxN. RossorM. CollingeJ. MaierW. JessenF. SchürmannB. HeunR. van den BusscheH. HeuserI. KornhuberJ. WiltfangJ. DichgansM. FrölichL. HampelH. HüllM. RujescuD. GoateA.M. KauweJ.S.K. CruchagaC. NowotnyP. MorrisJ.C. MayoK. SleegersK. BettensK. EngelborghsS. De DeynP.P. Van BroeckhovenC. LivingstonG. BassN.J. GurlingH. McQuillinA. GwilliamR. DeloukasP. Al-ChalabiA. ShawC.E. TsolakiM. SingletonA.B. GuerreiroR. MühleisenT.W. NöthenM.M. MoebusS. JöckelK.H. KloppN. WichmannH.E. CarrasquilloM.M. PankratzV.S. YounkinS.G. HolmansP.A. O’DonovanM. OwenM.J. WilliamsJ. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease.Nat. Genet.200941101088109310.1038/ng.44019734902
     [Google Scholar]
  38. KendlerK.S. GardnerC.O. PrescottC.A. Toward a comprehensive developmental model for major depression in women.Am. J. Psychiatry200215971133114510.1176/appi.ajp.159.7.113312091191
     [Google Scholar]
  39. SelkoeD.J. HardyJ. The amyloid hypothesis of Alzheimer’s disease at 25 years.EMBO Mol. Med.20168659560810.15252/emmm.20160621027025652
     [Google Scholar]
  40. BauerM. LondonE.D. SilvermanD.H. RasgonN. KirchheinerJ. WhybrowP.C. Thyroid, brain and mood modulation in affective disorder: Insights from molecular research and functional brain imaging.Pharmacopsychiatry2005381505614677082
     [Google Scholar]
  41. IadecolaC. The pathobiology of vascular dementia.Neuron201380484486610.1016/j.neuron.2013.10.00824267647
     [Google Scholar]
  42. MattsonM.P. Glutamate and neurotrophic factors in neuronal plasticity and disease.Ann. N. Y. Acad. Sci.2008114419711210.1196/annals.1418.00519076369
     [Google Scholar]
  43. HogervorstE. CombrinckM. SmithA.D. HodgesJ.R. The effects of gonadal hormone replacement therapy on cognitive function in healthy postmenopausal women.Psychoneuroendocrinology2003287883893
     [Google Scholar]
  44. UddinM. KoenenK.C. AielloA.E. WildmanD.E. de los SantosR. GaleaS. Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample.Psychol. Med.2011415997100710.1017/S003329171000167420836906
     [Google Scholar]
  45. CryanJ.F. DinanT.G. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour.Nat. Rev. Neurosci.2012131070171210.1038/nrn334622968153
     [Google Scholar]
  46. KaltschmidtB. KaltschmidtC. NF-kappaB in the nervous system.Cold Spring Harb. Perspect. Biol.200913a00127110.1101/cshperspect.a00127120066105
     [Google Scholar]
  47. SweeneyM.D. SagareA.P. ZlokovicB.V. Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders.Nat. Rev. Neurol.201814313315010.1038/nrneurol.2017.18829377008
     [Google Scholar]
  48. CraftS. The role of metabolic disorders in Alzheimer disease and vascular dementia: Two roads converged.Arch. Neurol.200966330030510.1001/archneurol.2009.2719273747
     [Google Scholar]
  49. Mukaetova-LadinskaE.B. Abdel-AllZ. DoddsS. AndradeJ. Alves da SilvaJ. KalariaR.N. O’BrienJ.T. Platelet tau hyperphosphorylation in Alzheimer’s disease: A marker of early-stage pathology?Neuropsychiatry (London)201223209215
     [Google Scholar]
  50. IadecolaC. The neurovascular unit coming of age: A journey through neurovascular coupling in health and disease.Neuron2017961174210.1016/j.neuron.2017.07.03028957666
     [Google Scholar]
  51. Candelario-JalilE. Injury and repair mechanisms in ischemic stroke: Considerations for the development of novel neurotherapeutics.Curr. Opin. Investig. Drugs200910764465419579170
     [Google Scholar]
  52. OlloquequiJ. Cornejo-CórdovaE. VerdaguerE. SorianoF.X. BinvignatO. AuladellC. CaminsA. Excitotoxicity in the pathogenesis of neurological and psychiatric disorders: Therapeutic implications.J. Psychopharmacol.201832326527510.1177/026988111875468029444621
     [Google Scholar]
  53. RappM.A. Schnaider-BeeriM. GrossmanH.T. SanoM. PerlD.P. PurohitD.P. GormanJ.M. HaroutunianV. Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression.Arch. Gen. Psychiatry200663216116710.1001/archpsyc.63.2.16116461859
     [Google Scholar]
  54. SextonC. E. MackayC. E. EbmeierK. P. A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain.Neuroimage2013828610126477656
     [Google Scholar]
  55. 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]
  56. LuppinoF.S. de WitL.M. BouvyP.F. StijnenT. CuijpersP. PenninxB.W.J.H. ZitmanF.G. Overweight, obesity, and depression: A systematic review and meta-analysis of longitudinal studies.Arch. Gen. Psychiatry201067322022910.1001/archgenpsychiatry.2010.220194822
     [Google Scholar]
  57. BerkM. WilliamsL.J. JackaF.N. O’NeilA. PascoJ.A. MoylanS. AllenN.B. StuartA.L. HayleyA.C. ByrneM.L. MaesM. So depression is an inflammatory disease, but where does the inflammation come from?BMC Med.201311120010.1186/1741‑7015‑11‑20024228900
     [Google Scholar]
  58. SallowayS. MalloyP. KohnR. GillardE. DuffyJ. RoggJ. TungG. RichardsonE. ThomasC. WestlakeR. MRI and neuropsychological differences in early- and late-life-onset geriatric depression.Neurology19964661567157410.1212/WNL.46.6.15678649550
     [Google Scholar]
  59. WernerP. Stein‐ShvachmanI. Quality of life and Alzheimer’s disease: The influence of participation in a cluster‐randomized controlled trial.Int. J. Geriatr. Psychiatry201328329129622555993
     [Google Scholar]
  60. SaczynskiJ.S. BeiserA. SeshadriS. AuerbachS. WolfP.A. AuR. Depressive symptoms and risk of dementia.Neurology2010751354110.1212/WNL.0b013e3181e6213820603483
     [Google Scholar]
  61. YaffeK. YaffeK. ByersA.L. McCormickM. SchaeferC. WhitmerR.A. Midlife vs late-life depressive symptoms and risk of dementia: Differential effects for Alzheimer disease and vascular dementia.Arch. Gen. Psychiatry201269549349810.1001/archgenpsychiatry.2011.148122566581
     [Google Scholar]
  62. ChenR. HuZ. WeiL. QinX. McCrackenC. CopelandJ.R. Severity of depression and risk for subsequent dementia: cohort studies in China and the UK.Br. J. Psychiatry2008193537337710.1192/bjp.bp.107.04497418978315
     [Google Scholar]
  63. GreenR.C. CupplesL.A. KurzA. AuerbachS. GoR. SadovnickD. DuaraR. KukullW.A. ChuiH. EdekiT. GriffithP.A. FriedlandR.P. BachmanD. FarrerL. Depression as a risk factor for Alzheimer disease: The MIRAGE Study.Arch. Neurol.200360575375910.1001/archneur.60.5.75312756140
     [Google Scholar]
  64. DotsonV.M. BeydounM.A. ZondermanA.B. Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment.Neurology2010751273410.1212/WNL.0b013e3181e6212420603482
     [Google Scholar]
  65. WilsonR.S. BarnesL.L. Mendes de LeonC.F. AggarwalN.T. SchneiderJ.S. BachJ. PilatJ. BeckettL.A. ArnoldS.E. EvansD.A. BennettD.A. Depressive symptoms, cognitive decline, and risk of AD in older persons.Neurology200259336437010.1212/WNL.59.3.36412177369
     [Google Scholar]
  66. WuJ.J. WangH.X. YaoW. YanZ. PeiJ.J. Late-life depression and the risk of dementia in 14 countries: A 10-year follow-up study from the survey of health, ageing and retirement in europe.J. Affect. Disord.202027467167710.1016/j.jad.2020.05.05932664001
     [Google Scholar]
  67. JormA.F. The informant questionnaire on cognitive decline in the elderly (IQCODE): A review.Int. Psychogeriatr.200416327529310.1017/S104161020400039015559753
     [Google Scholar]
  68. ZhuY. LiC. WuT. WangY. HuaR. MaY. XieW. Associations of cumulative depressive symptoms with subsequent cognitive decline and adverse health events: Two prospective cohort studies.J. Affect. Disord.2023320919710.1016/j.jad.2022.09.12836183825
     [Google Scholar]
  69. BeckerJ.T. ChangY.F. LopezO.L. DewM.A. SweetR.A. BarnesD. YaffeK. YoungJ. KullerL. ReynoldsC.F.III Depressed mood is not a risk factor for incident dementia in a community-based cohort.Am. J. Geriatr. Psychiatry200917865366310.1097/JGP.0b013e3181aad1fe19634208
     [Google Scholar]
  70. HebertL.E. WeuveJ. ScherrP.A. EvansD.A. Alzheimer disease in the United States (2010–2050) estimated using the 2010 census.Neurology201380191778178310.1212/WNL.0b013e31828726f523390181
     [Google Scholar]
  71. ZalsmanG. AizenbergD. SiglerM. NahshonyE. KarpL. WeizmanA. Increased risk for dementia in elderly psychiatric inpatients with late-onset major depression.J. Nerv. Ment. Dis.2000188424224310.1097/00005053‑200004000‑0001010790004
     [Google Scholar]
  72. GeerlingsM.I. SchmandB. BraamA.W. JonkerC. BouterL.M. van TilburgW. Depressive symptoms and risk of Alzheimer’s disease in more highly educated older people.J. Am. Geriatr. Soc.20004891092109710.1111/j.1532‑5415.2000.tb04785.x10983909
     [Google Scholar]
  73. LindsayJ. LaurinD. VerreaultR. HébertR. HelliwellB. HillG.B. McDowellI. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian study of health and aging.Am. J. Epidemiol.2002156544545310.1093/aje/kwf07412196314
     [Google Scholar]
  74. FuhrerR. DufouilC. DartiguesJ.F. Exploring sex differences in the relationship between depressive symptoms and dementia incidence: Prospective results from the PAQUID Study.J. Am. Geriatr. Soc.20035181055106310.1046/j.1532‑5415.2003.51352.x12890066
     [Google Scholar]
  75. AndersenK. LolkA. Kragh-SørensenP. PetersenN.E. GreenA. Depression and the risk of Alzheimer disease.Epidemiology200516223323810.1097/01.ede.0000152116.32580.2415703539
     [Google Scholar]
  76. GatzJ.L. TyasS.L. St JohnP. MontgomeryP. Do depressive symptoms predict Alzheimer’s disease and dementia?J. Gerontol. A Biol. Sci. Med. Sci.200560674474710.1093/gerona/60.6.74415983177
     [Google Scholar]
  77. CankurtaranM. YavuzB.B. CankurtaranE.S. HalilM. UlgerZ. AriogulS. Risk factors and type of dementia: Vascular or Alzheimer?Arch. Gerontol. Geriatr.2008471253410.1016/j.archger.2007.06.00517692938
     [Google Scholar]
  78. IrieF. MasakiK.H. PetrovitchH. AbbottR.D. RossG.W. TaaffeD.R. LaunerL.J. WhiteL.R. Apolipoprotein E epsilon4 allele genotype and the effect of depressive symptoms on the risk of dementia in men: The Honolulu-Asia aging study.Arch. Gen. Psychiatry200865890691210.1001/archpsyc.65.8.90618678795
     [Google Scholar]
  79. Dal FornoG. PalermoM.T. DonohueJ.E. KaragiozisH. ZondermanA.B. KawasC.H. Depressive symptoms, sex, and risk for Alzheimer’s disease.Ann. Neurol.200557338138710.1002/ana.2040515732103
     [Google Scholar]
  80. GeerlingsM.I. den HeijerT. KoudstaalP.J. HofmanA. BretelerM.M.B. History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease.Neurology200870151258126410.1212/01.wnl.0000308937.30473.d118391157
     [Google Scholar]
  81. BarnesDE. YaffeK. ByersAL. McCormickM. SchaeferC. WhitmerRA. 2010Mid-life versus late-life depressive symptoms and risk of dementia: Differential effects for Alzheimer’s disease and vascular dementia.Arch Gen Psychiatry.2012695493810.1001/archgenpsychiatry.2011.1481.
     [Google Scholar]
  82. Sáiz-VázquezO. Gracia-GarcíaP. Ubillos-LandaS. Puente-MartínezA. Casado-YustaS. OlayaB. SantabárbaraJ. Depression as a risk factor for Alzheimer’s disease: A systematic review of longitudinal meta-analyses.J. Clin. Med.2021109180910.3390/jcm1009180933919227
     [Google Scholar]
  83. HuseboB.S. BallardC. SandvikR. NilsenO.B. AarslandD. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: Cluster randomised clinical trial.BMJ2011343d406510.1136/bmj.d406521765198
     [Google Scholar]
  84. PanzaF. FrisardiV. CapursoC. D’IntronoA. ColaciccoA.M. ImbimboB.P. SantamatoA. VendemialeG. SeripaD. PilottoA. CapursoA. SolfrizziV. Late-life depression, mild cognitive impairment, and dementia: Possible continuum?Am. J. Geriatr. Psychiatry20101829811610.1097/JGP.0b013e3181b0fa1320104067
     [Google Scholar]
  85. SteffensD.C. R McQuoidD. PotterG.G. Amnestic mild cognitive impairment and incident dementia and Alzheimer’s disease in geriatric depression.Int. Psychogeriatr.201426122029203610.1017/S104161021400144625032667
     [Google Scholar]
  86. DonovanN.J. HsuD.C. DagleyA.S. SchultzA.P. AmariglioR.E. MorminoE.C. OkerekeO.I. RentzD.M. JohnsonK.A. SperlingR.A. MarshallG.A. Depressive symptoms and biomarkers of Alzheimer’s disease in cognitively normal older adults.J. Alzheimers Dis.2015461637310.3233/JAD‑14294025697700
     [Google Scholar]
  87. ButtersM.A. KlunkW.E. MathisC.A. PriceJ.C. ZiolkoS.K. HogeJ.A. TsopelasN.D. LoprestiB.J. ReynoldsC.F.III DeKoskyS.T. MeltzerC.C. Imaging Alzheimer pathology in late-life depression with PET and Pittsburgh Compound-B.Alzheimer Dis. Assoc. Disord.200822326126810.1097/WAD.0b013e31816c92bf18580591
     [Google Scholar]
  88. González-SalvadorT. LyketsosC.G. BakerA. HovanecL. RoquesC. BrandtJ. SteeleC. Quality of life in dementia patients in long-term care.Int. J. Geriatr. Psychiatry200015218118910.1002/(SICI)1099‑1166(200002)15:2<181::AID‑GPS96>3.0.CO;2‑I10679850
     [Google Scholar]
  89. ModregoP.J. FerrándezJ. Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: A prospective cohort study.Arch. Neurol.20046181290129310.1001/archneur.61.8.129015313849
     [Google Scholar]
  90. RosenbergP.B. MartinB.K. FrangakisC. MintzerJ.E. WeintraubD. PorsteinssonA.P. SchneiderL.S. RabinsP.V. MunroC.A. MeinertC.L. LyketsosC.G. DryeL.T. Sertraline for the treatment of depression in Alzheimer disease.Am. J. Geriatr. Psychiatry201018213614510.1097/JGP.0b013e3181c796eb20087081
     [Google Scholar]
  91. JormA.F. History of depression as a risk factor for dementia: An updated review.Aust. N. Z. J. Psychiatry200135677678110.1046/j.1440‑1614.2001.00967.x11990888
     [Google Scholar]
  92. McCleeryJ. CohenD.A. SharpleyA.L. Pharmacotherapies for sleep disturbances in Alzheimer’s disease.Cochrane Database Syst. Rev.201433CD00917824659320
     [Google Scholar]
  93. QiuW.Q. ZhuH. DeanM. LiuZ. VuL. FanG. LiH. MwamburiM. SteffensD.C. AuR. Amyloid‐associated depression and ApoE4 allele: Longitudinal follow‐up for the development of Alzheimer’s disease.Int. J. Geriatr. Psychiatry201631331632210.1002/gps.433926250797
     [Google Scholar]
  94. McEwenB.S. NascaC. GrayJ.D. Stress effects on neuronal structure: Hippocampus, amygdala, and prefrontal cortex.Neuropsychopharmacology201641132310.1038/npp.2015.17126076834
     [Google Scholar]
  95. SapolskyR.M. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders.Arch. Gen. Psychiatry2000571092593510.1001/archpsyc.57.10.92511015810
     [Google Scholar]
  96. SotiropoulosI. CataniaC. RiedemannT. FryJ.P. BreenK.C. MichaelidisT.M. AlmeidaO.F.X. Glucocorticoids trigger Alzheimer disease‐like pathobiochemistry in rat neuronal cells expressing human tau.J. Neurochem.2008107238539710.1111/j.1471‑4159.2008.05613.x18691381
     [Google Scholar]
  97. FratiglioniL. WangH.X. EricssonK. MaytanM. WinbladB. Influence of social network on occurrence of dementia: A community-based longitudinal study.Lancet200035592121315131910.1016/S0140‑6736(00)02113‑910776744
     [Google Scholar]
  98. CacioppoJ.T. HawkleyL.C. ErnstJ.M. BurlesonM. BerntsonG.G. NourianiB. SpiegelD. Loneliness within a nomological net: An evolutionary perspective.J. Res. Pers.20064061054108510.1016/j.jrp.2005.11.007
     [Google Scholar]
  99. EricksonK.I. VossM.W. PrakashR.S. BasakC. SzaboA. ChaddockL. KimJ.S. HeoS. AlvesH. WhiteS.M. WojcickiT.R. MaileyE. VieiraV.J. MartinS.A. PenceB.D. WoodsJ.A. McAuleyE. KramerA.F. Exercise training increases size of hippocampus and improves memory.Proc. Natl. Acad. Sci. USA201110873017302210.1073/pnas.101595010821282661
     [Google Scholar]
  100. MorrisM.C. EvansD.A. TangneyC.C. BieniasJ.L. WilsonR.S. Associations of vegetable and fruit consumption with age-related cognitive change.Neurology20066781370137610.1212/01.wnl.0000240224.38978.d817060562
     [Google Scholar]
  101. McEwenB.S. SapolskyR.M. Stress and cognitive function.Curr. Opin. Neurobiol.19955220521610.1016/0959‑4388(95)80028‑X7620309
     [Google Scholar]
  102. StarksteinS.E. MizrahiR. CapizzanoA.A. AcionL. Apathy following cerebrovascular lesions.Stroke20053610202820328236333
     [Google Scholar]
  103. NortonS. MatthewsF.E. BarnesD.E. YaffeK. BrayneC. Potential for primary prevention of Alzheimer’s disease: An analysis of population-based data.Lancet Neurol.201413878879410.1016/S1474‑4422(14)70136‑X25030513
     [Google Scholar]
  104. HerrmannN. LanctôtK.L. KhanL.R. The role of norepinephrine in the behavioral and psychological symptoms of dementia.J. Neuropsychiatry Clin. Neurosci.200416326127610.1176/jnp.16.3.26115377733
     [Google Scholar]
  105. WeintraubD. RosenbergP.B. MartinB.K. FrangakisC. MintzerJ.E. PorsteinssonA.P. SchneiderL.S. MunroC.A. MeinertC.L. LyketsosC.G. DryeL.T. RabinsP.V. Sertraline for the treatment of depression in Alzheimer disease: Week-24 outcomes.Am. J. Geriatr. Psychiatry201018433234010.1097/JGP.0b013e3181cc033320220589
     [Google Scholar]
  106. SinyorM. SchafferA. LevittA. DoesM. The sequenced treatment alternatives to relieve depression (STAR*D) trial: A review.Can. J. Psychiatry201055312613510.1177/07067437100550030320370962
     [Google Scholar]
  107. PinquartM. SörensenS. Associations of stressors and uplifts of caregiving with caregiver burden and depressive mood: A meta-analysis.J Gerontol B Psychol Sci Soc Sci2003582P112P12810.1093/geronb/58.2.P11212646594
     [Google Scholar]
  108. FeldmanH.H. FerrisS. WinbladB. SfikasN. MancioneL. HeY. TekinS. BurnsA. CummingsJ. del SerT. InzitariD. OrgogozoJ.M. SauerH. ScheltensP. ScarpiniE. HerrmannN. FarlowM. PotkinS. CharlesH.C. FoxN.C. LaneR. Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: The InDDEx study.Lancet Neurol.20076650151210.1016/S1474‑4422(07)70109‑617509485
     [Google Scholar]
  109. VickreyB.G. MittmanB.S. ConnorK.I. PearsonM.L. Della PennaR.D. GaniatsT.G. DeMonteR.W.Jr ChodoshJ. CuiX. VassarS. DuanN. LeeM. The effect of a disease management intervention on quality and outcomes of dementia care: A randomized, controlled trial.Ann. Intern. Med.20061451071372610.7326/0003‑4819‑145‑10‑200611210‑0000417116916
     [Google Scholar]
  110. BrodatyH. GreenA. KoscheraA. Meta-analysis of psychosocial interventions for caregivers of people with dementia.J. Am. Geriatr. Soc.200351565766410.1034/j.1600‑0579.2003.00210.x12752841
     [Google Scholar]
  111. SchneiderL.S. KennedyR.E. CutterG.R. Requiring an amyloid‐β 1‐42 biomarker for prodromal Alzheimer’s disease or mild cognitive impairment does not lead to more efficient clinical trials.Alzheimers Dement.20106536737710.1016/j.jalz.2010.07.00420813339
     [Google Scholar]
  112. BirksJ.S. HarveyR.J. Donepezil for dementia due to Alzheimer’s disease.Cochrane Libr.201820186CD00119010.1002/14651858.CD001190.pub329923184
     [Google Scholar]
  113. McShaneR. WestbyM.J. RobertsE. MinakaranN. SchneiderL. FarrimondL.E. MaayanN. WareJ. DebarrosJ. Memantine for dementia.Cochrane Database Syst. Rev.201933CD00315430891742
     [Google Scholar]
  114. WoodsB. AguirreE. SpectorA.E. OrrellM. Cognitive stimulation to improve cognitive functioning in people with dementia.Cochrane Libr.201222CD00556210.1002/14651858.CD005562.pub222336813
     [Google Scholar]
  115. ForbesD. ThiessenE.J. BlakeC.M. ForbesS.C. ForbesS. Exercise programs for people with dementia.Cochrane Database Syst. Rev.20131212CD00648924302466
     [Google Scholar]
  116. GitlinL.N. MarxK. StanleyI.H. HodgsonN. Translating evidence-based dementia caregiving interventions into practice: State-of-the-science and next steps.Gerontologist201555221022610.1093/geront/gnu12326035597
     [Google Scholar]
  117. CiprianiA. FurukawaT.A. SalantiG. ChaimaniA. AtkinsonL.Z. OgawaY. LeuchtS. RuheH.G. TurnerE.H. HigginsJ.P.T. EggerM. TakeshimaN. HayasakaY. ImaiH. ShinoharaK. TajikaA. IoannidisJ.P.A. GeddesJ.R. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis.Lancet2018391101281357136610.1016/S0140‑6736(17)32802‑729477251
     [Google Scholar]
  118. CuijpersP. KaryotakiE. WeitzE. AnderssonG. HollonS.D. van StratenA. The effects of psychotherapies for major depression in adults on remission, recovery and improvement: A meta-analysis.J. Affect. Disord.201415911812610.1016/j.jad.2014.02.02624679399
     [Google Scholar]
  119. MuraG. MoroM.F. PattenS.B. CartaM.G. TarriconeI. Exercise as an add-on strategy for the treatment of major depressive disorder: A systematic review.CNS Spectr.201419649650810.1017/S109285291300095324589012
     [Google Scholar]
  120. BlackD.S. SlavichG.M. Mindfulness meditation and the immune system: A systematic review of randomized controlled trials.Ann. N. Y. Acad. Sci.201613731132410.1111/nyas.1299826799456
     [Google Scholar]
  121. ReisbergB. FerrisS.H. de LeonM.J. CrookT. The global deterioration scale for assessment of primary degenerative dementia.Am. J. Psychiatry198213991136113910.1176/ajp.139.9.11367114305
     [Google Scholar]
  122. LyketsosC.G. OlinJ. AmatniekJ. Modified mini-mental state (3MS) examination.J. Geriatr. Psychiatry Neurol.2006194184191
     [Google Scholar]
  123. CuijpersP. van StratenA. WarmerdamL. Behavioral activation treatments of depression: A meta-analysis.Clin. Psychol. Rev.200727331832610.1016/j.cpr.2006.11.00117184887
     [Google Scholar]
  124. ButlerA. ChapmanJ. FormanE. BeckA. The empirical status of cognitive-behavioral therapy: A review of meta-analyses.Clin. Psychol. Rev.2006261173110.1016/j.cpr.2005.07.00316199119
     [Google Scholar]
  125. BassukS.S. GlassT.A. BerkmanL.F. Social disengagement and incident cognitive decline in community-dwelling elderly persons.Ann. Intern. Med.1999131316517310.7326/0003‑4819‑131‑3‑199908030‑0000210428732
     [Google Scholar]
  126. HofmannS.G. SawyerA.T. WittA.A. OhD. The effect of mindfulness-based therapy on anxiety and depression: A meta-analytic review.J. Consult. Clin. Psychol.201078216918310.1037/a001855520350028
     [Google Scholar]
  127. MorrisM.C. TangneyC.C. WangY. SacksF.M. BarnesL.L. BennettD.A. AggarwalN.T. MIND diet slows cognitive decline with aging.Alzheimers Dement.20151191015102210.1016/j.jalz.2015.04.01126086182
     [Google Scholar]
  128. MaustD.T. KalesH.C. McCammonR.J. BlowF.C. LeggettA. LangaK.M. Distress associated with dementia-related psychosis and agitation in relation to healthcare utilization and costs.Am. J. Geriatr. Psychiatry2016241210731082
     [Google Scholar]
  129. AlgaseD.L. BeckC. KolanowskiA. WhallA. BerentS. RichardsK. Need-driven dementia-compromised behavior: An alternative view of disruptive behavior.Am. J. Alzheimers Dis. Other Demen.19961161019
     [Google Scholar]
  130. DonovanN.J. LocascioJ.J. MarshallG.A. GatchelJ. HanseeuwB.J. RentzD.M. JohnsonK.A. SperlingR.A. Longitudinal association of amyloid beta and anxious-depressive symptoms in cognitively normal older adults.Am. J. Psychiatry2018175653053710.1176/appi.ajp.2017.1704044229325447
     [Google Scholar]
  131. KarchC.M. GoateA.M. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis.Biol. Psychiatry2015771435110.1016/j.biopsych.2014.05.00624951455
     [Google Scholar]
  132. BrownB.M. PeifferJ.J. TaddeiK. LuiJ.K. LawsS.M. GuptaV.B. TaddeiT. WardV.K. RodriguesM.A. BurnhamS. Rainey-SmithS.R. VillemagneV.L. BushA. EllisK.A. MastersC.L. AmesD. MacaulayS.L. SzoekeC. RoweC.C. MartinsR.N. Physical activity and amyloid-β plasma and brain levels: Results from the Australian imaging, biomarkers and lifestyle study of ageing.Mol. Psychiatry201318887588110.1038/mp.2012.10722889922
     [Google Scholar]
  133. JanelidzeS. ZetterbergH. MattssonN. PalmqvistS. VandersticheleH. LindbergO. van WestenD. StomrudE. MinthonL. BlennowK. HanssonO. CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: Better diagnostic markers of Alzheimer disease.Ann. Clin. Transl. Neurol.20163315416510.1002/acn3.27427042676
     [Google Scholar]
  134. MorimotoS.S. WexlerB.E. AlexopoulosG.S. Neuroplasticity‐based computerized cognitive remediation for geriatric depression.Int. J. Geriatr. Psychiatry201227121239124710.1002/gps.377622451346
     [Google Scholar]
  135. JackC.R.Jr HoltzmanD.M. Biomarker modeling of Alzheimer’s disease.Neuron20138061347135810.1016/j.neuron.2013.12.00324360540
     [Google Scholar]
  136. TanziR.E. The genetics of Alzheimer disease.Cold Spring Harb. Perspect. Med.2012210a00629610.1101/cshperspect.a00629623028126
     [Google Scholar]
  137. SweattJ.D. Neural plasticity and behavior – Sixty years of conceptual advances.J. Neurochem.2016139S217919910.1111/jnc.1358026875778
     [Google Scholar]
  138. SaykinA.J. ShenL. YaoX. KimS. NhoK. RisacherS.L. RamananV.K. ForoudT.M. FaberK.M. SarwarN. MunsieL.M. HuX. SoaresH.D. PotkinS.G. ThompsonP.M. KauweJ.S.K. Kaddurah-DaoukR. GreenR.C. TogaA.W. WeinerM.W. Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans.Alzheimers Dement.201511779281410.1016/j.jalz.2015.05.00926194313
     [Google Scholar]
  139. CotelliM. CalabriaM. ZanettiO. ZanettiM. Cognitive rehabilitation in Alzheimer’s disease.Aging Clin. Exp. Res.200618214114310.1007/BF0332742916702783
     [Google Scholar]
  140. WilsonR.S. BoyleP.A. YuL. BarnesL.L. SchneiderJ.A. BennettD.A. Life-span cognitive activity, neuropathologic burden, and cognitive aging.Neurology201381431432110.1212/WNL.0b013e31829c5e8a23825173
     [Google Scholar]
  141. GaoY. LiH. LuoY. AnK. ZhengY. A survey of big data architectures and machine learning algorithms in healthcare.Int. J. Biomed. Eng. Technol.20172518210.1504/IJBET.2017.087722.
     [Google Scholar]
  142. DorseyE.R. TopolE.J. State of telehealth.N. Engl. J. Med.2016375215416110.1056/NEJMra160170527410924
     [Google Scholar]
  143. CummingsJ.L. MorstorfT. ZhongK. Alzheimer’s disease drug-development pipeline: Few candidates, frequent failures.Alzheimers Res. Ther.2014643710.1186/alzrt26925024750
     [Google Scholar]
  144. KivipeltoM. SolomonA. AhtiluotoS. NganduT. LehtisaloJ. AntikainenR. BäckmanL. HänninenT. JulaA. LaatikainenT. LindströmJ. MangialascheF. NissinenA. PaajanenT. PajalaS. PeltonenM. RauramaaR. Stigsdotter-NeelyA. StrandbergT. TuomilehtoJ. SoininenH. The Finnish geriatric intervention study to prevent cognitive impairment and disability (FINGER): Study design and progress.Alzheimers Dement.20139665766510.1016/j.jalz.2012.09.01223332672
     [Google Scholar]
  145. KnopmanD.S. DeKoskyS.T. CummingsJ.L. ChuiH. Corey-BloomJ. RelkinN. SmallG.W. MillerB. StevensJ.C. Practice parameter: Diagnosis of dementia (an evidence-based review).Neurology20015691143115310.1212/WNL.56.9.114311342678
     [Google Scholar]
  146. AlexopoulosG.S. Depression in the elderly.Lancet200536594751961197010.1016/S0140‑6736(05)66665‑215936426
     [Google Scholar]
  147. BanerjeeS. HellierJ. DeweyM. RomeoR. BallardC. BaldwinR. BenthamP. FoxC. HolmesC. KatonaC. KnappM. LawtonC. LindesayJ. LivingstonG. McCraeN. Moniz-CookE. MurrayJ. NurockS. OrrellM. O’BrienJ. PoppeM. ThomasA. WalwynR. WilsonK. BurnsA. Sertraline or mirtazapine for depression in dementia (HTA-SADD): A randomised, multicentre, double-blind, placebo-controlled trial.Lancet2011378978940341110.1016/S0140‑6736(11)60830‑121764118
     [Google Scholar]
  148. Alzheimer’s AssociationCaregiver support.Alzheimers Dement.2015117804807
     [Google Scholar]
  149. HeinC. HeinK. The importance of comprehensive geriatric assessment in managing older adults with cancer.Cancer J.201824524424730247260
     [Google Scholar]
  150. Depression in adults: Recognition and management.2009Available from: https://www.nice.org.uk/guidance/cg90
  151. Practice guideline for the treatment of patients with major depressive disorder (revision).Am. J. Psychiatry200015714510767867
     [Google Scholar]
  152. LogsdonR.G. McCurryS.M. TeriL. A home health care approach to the treatment of Alzheimer’s disease.Clin. Gerontol.20073112136
     [Google Scholar]
  153. EttersL. GoodallD. HarrisonB.E. Caregiver burden among dementia patient caregivers: A review of the literature.J. Am. Acad. Nurse Pract.200820842342810.1111/j.1745‑7599.2008.00342.x18786017
     [Google Scholar]
/content/journals/cprr/10.2174/0126660822303361240903075653
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Understanding the Bidirectional Relationship between Alzheimer's and Depression
Curr Psyc Res Rev 21, 448 (2025); https://doi.org/10.2174/0126660822303361240903075653
/content/journals/cprr/10.2174/0126660822303361240903075653
/content/journals/cprr/10.2174/0126660822303361240903075653
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  • Article Type:     Review Article
Keyword(s): Alzheimer’s disease; bidirectional relationship; cognitive behavioural therapy; Depression; neurobiological mechanism; psychological factors

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