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Journal of Neural Transmission

, Volume 123, Issue 7, pp 775–783 | Cite as

The rationale for deep brain stimulation in Alzheimer’s disease

Neurology and Preclinical Neurological Studies - Review Article

Abstract

Alzheimer’s disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer’s disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer’s disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer’s disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials.

Keywords

Deep brain stimulation Alzheimer’s disease Dementia Fornix Nucleus basalis of Meynert Cognition 

Abbreviations

AD

Alzheimer’s disease

ADAS-Cog

Alzheimer’s disease assessment scale-cognitive subscale

DBS

Deep brain stimulation

FDG

Fluorodeoxyglucose

MMSE

Mini-mental state examination

NBM

Nucleus basalis of Meynert

PET

Positron emission tomography

QALY

Quality-adjusted life year

sLORETA

Standardized low-resolution electromagnetic tomography

STN

Subthalamic nucleus

Notes

Compliance with ethical standards

Conflict of interest

AML is a consultant to Medtronic, St. Jude, and Boston Scientific. AML serves on the scientific advisory board of Ceregene, Codman, Neurophage, Aleva and Alcyone Life Sciences. AML is cofounder of Functional Neuromodulation Inc. and hold intellectual property in the field of Deep Brain Stimulation. All other authors declare no relevant conflicts.

References

  1. Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, Gage FH (2014) Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94(4):991–1026. doi: 10.1152/physrev.00004.2014 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Blennow K (2004) Cerebrospinal fluid protein biomarkers for Alzheimer’s disease. NeuroRx J Am Soc Exp NeuroTher 1(2):213–225. doi: 10.1602/neurorx.1.2.213 Google Scholar
  3. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc 3(3):186–191. doi: 10.1016/j.jalz.2007.04.381 CrossRefGoogle Scholar
  4. Browning PG, Gaffan D, Croxson PL, Baxter MG (2010) Severe scene learning impairment, but intact recognition memory, after cholinergic depletion of inferotemporal cortex followed by fornix transection. Cereb Cortex 20(2):282–293. doi: 10.1093/cercor/bhp097 CrossRefPubMedGoogle Scholar
  5. Bruel-Jungerman E, Davis S, Rampon C, Laroche S (2006) Long-term potentiation enhances neurogenesis in the adult dentate gyrus. J Neurosci 26(22):5888–5893. doi: 10.1523/JNEUROSCI.0782-06.2006 CrossRefPubMedGoogle Scholar
  6. Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, Sheline YI, Klunk WE, Mathis CA, Morris JC, Mintun MA (2005) Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci 25(34):7709–7717. doi: 10.1523/JNEUROSCI.2177-05.2005 CrossRefPubMedGoogle Scholar
  7. Buzsaki G, Bickford RG, Ponomareff G, Thal LJ, Mandel R, Gage FH (1988) Nucleus basalis and thalamic control of neocortical activity in the freely moving rat. J Neurosci 8(11):4007–4026PubMedGoogle Scholar
  8. Chun SK, Sun W, Park JJ, Jung MW (2006) Enhanced proliferation of progenitor cells following long-term potentiation induction in the rat dentate gyrus. Neurobiol Learn Mem 86(3):322–329. doi: 10.1016/j.nlm.2006.05.005 CrossRefPubMedGoogle Scholar
  9. Davies P, Maloney AJ (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2(8000):1403CrossRefPubMedGoogle Scholar
  10. Derrick BE, York AD, Martinez JL Jr (2000) Increased granule cell neurogenesis in the adult dentate gyrus following mossy fiber stimulation sufficient to induce long-term potentiation. Brain Res 857(1–2):300–307CrossRefPubMedGoogle Scholar
  11. Encinas JM, Hamani C, Lozano AM, Enikolopov G (2011) Neurogenic hippocampal targets of deep brain stimulation. J Comp Neurol 519(1):6–20. doi: 10.1002/cne.22503 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4(11):1313–1317. doi: 10.1038/3305 CrossRefPubMedGoogle Scholar
  13. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198CrossRefPubMedGoogle Scholar
  14. Fontaine D, Deudon A, Lemaire JJ, Razzouk M, Viau P, Darcourt J, Robert P (2013) Symptomatic treatment of memory decline in Alzheimer’s disease by deep brain stimulation: a feasibility study. J Alzheimers Dis JAD 34(1):315–323. doi: 10.3233/JAD-121579 PubMedGoogle Scholar
  15. Freund HJ, Kuhn J, Lenartz D, Mai JK, Schnell T, Klosterkoetter J, Sturm V (2009) Cognitive functions in a patient with Parkinson-dementia syndrome undergoing deep brain stimulation. Arch Neurol 66(6):781–785. doi: 10.1001/archneurol.2009.102 CrossRefPubMedGoogle Scholar
  16. Grothe M, Heinsen H, Teipel SJ (2012) Atrophy of the cholinergic Basal forebrain over the adult age range and in early stages of Alzheimer’s disease. Biol Psychiatry 71(9):805–813. doi: 10.1016/j.biopsych.2011.06.019 CrossRefPubMedGoogle Scholar
  17. Hamani C, McAndrews MP, Cohn M, Oh M, Zumsteg D, Shapiro CM, Wennberg RA, Lozano AM (2008) Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Ann Neurol 63(1):119–123. doi: 10.1002/ana.21295 CrossRefPubMedGoogle Scholar
  18. Hamani C, Stone SS, Garten A, Lozano AM, Winocur G (2011) Memory rescue and enhanced neurogenesis following electrical stimulation of the anterior thalamus in rats treated with corticosterone. Exp Neurol 232(1):100–104. doi: 10.1016/j.expneurol.2011.08.023 CrossRefPubMedGoogle Scholar
  19. Higgins GA, Mufson EJ (1989) NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer’s disease. Exp Neurol 106(3):222–236CrossRefPubMedGoogle Scholar
  20. Ihl R, Bunevicius R, Frolich L, Winblad B, Schneider LS, Dubois B, Burns A, Thibaut F, Kasper S, Moller HJ, WFSBP Task Force on Mental Disorders in Primary Care, WFSBP Task Force on Dementia (2015) World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of dementias in primary care. Int J Psychiatry Clin Pract 19(1):2–7. doi: 10.3109/13651501.2014.961931 CrossRefPubMedGoogle Scholar
  21. Ito K, Ahadieh S, Corrigan B, French J, Fullerton T, Tensfeldt T, Alzheimer’s Disease Working Group (2010) Disease progression meta-analysis model in Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc 6(1):39–53. doi: 10.1016/j.jalz.2009.05.665 CrossRefGoogle Scholar
  22. Jessberger S, Gage FH (2014) Adult neurogenesis: bridging the gap between mice and humans. Trends Cell Biol 24(10):558–563. doi: 10.1016/j.tcb.2014.07.003 CrossRefPubMedGoogle Scholar
  23. Kilgard MP, Merzenich MM (1998) Cortical map reorganization enabled by nucleus basalis activity. Science 279(5357):1714–1718CrossRefPubMedGoogle Scholar
  24. Kitamura T, Saitoh Y, Murayama A, Sugiyama H, Inokuchi K (2010) LTP induction within a narrow critical period of immature stages enhances the survival of newly generated neurons in the adult rat dentate gyrus. Mol Brain 3:13. doi: 10.1186/1756-6606-3-13 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Koubeissi MZ, Kahriman E, Syed TU, Miller J, Durand DM (2013) Low-frequency electrical stimulation of a fiber tract in temporal lobe epilepsy. Ann Neurol 74(2):223–231. doi: 10.1002/ana.23915 PubMedGoogle Scholar
  26. Kuhn J, Hardenacke K, Lenartz D, Gruendler T, Ullsperger M, Bartsch C, Mai JK, Zilles K, Bauer A, Matusch A, Schulz RJ, Noreik M, Buhrle CP, Maintz D, Woopen C, Haussermann P, Hellmich M, Klosterkotter J, Wiltfang J, Maarouf M, Freund HJ, Sturm V (2015) Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer’s dementia. Mol Psychiatry 20(3):353–360. doi: 10.1038/mp.2014.32 CrossRefPubMedGoogle Scholar
  27. Laxton AW, Lozano AM (2013) Deep brain stimulation for the treatment of Alzheimer disease and dementias. World Neurosurg 80(3–4):S28.(e21–28). doi: 10.1016/j.wneu.2012.06.028 Google Scholar
  28. Laxton AW, Tang-Wai DF, McAndrews MP, Zumsteg D, Wennberg R, Keren R, Wherrett J, Naglie G, Hamani C, Smith GS, Lozano AM (2010) A phase I trial of deep brain stimulation of memory circuits in Alzheimer’s disease. Ann Neurol 68(4):521–534. doi: 10.1002/ana.22089 CrossRefPubMedGoogle Scholar
  29. Laxton AW, Stone S, Lozano AM (2014) The neurosurgical treatment of Alzheimer’s disease: a review. Stereotact Funct Neurosurg 92(5):269–281. doi: 10.1159/000364914 CrossRefPubMedGoogle Scholar
  30. Lo RY, Hubbard AE, Shaw LM, Trojanowski JQ, Petersen RC, Aisen PS, Weiner MW, Jagust WJ, Alzheimer’s Disease Neuroimaging I (2011) Longitudinal change of biomarkers in cognitive decline. Arch Neurol 68(10):1257–1266. doi: 10.1001/archneurol.2011.123 CrossRefPubMedGoogle Scholar
  31. Mayeux R, Sano M (1999) Treatment of Alzheimer’s disease. N Engl J Med 341(22):1670–1679. doi: 10.1056/NEJM199911253412207 CrossRefPubMedGoogle Scholar
  32. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc 7(3):263–269. doi: 10.1016/j.jalz.2011.03.005 CrossRefGoogle Scholar
  33. Mielke MM, Okonkwo OC, Oishi K, Mori S, Tighe S, Miller MI, Ceritoglu C, Brown T, Albert M, Lyketsos CG (2012) Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer’s disease. Alzheimers Dement J Alzheimers Assoc 8(2):105–113. doi: 10.1016/j.jalz.2011.05.2416 CrossRefGoogle Scholar
  34. Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE (1997) Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol 42(1):85–94. doi: 10.1002/ana.410420114 CrossRefPubMedGoogle Scholar
  35. Mirsaeedi-Farahani K, Halpern CH, Baltuch GH, Wolk DA, Stein SC (2015) Deep brain stimulation for Alzheimer disease: a decision and cost-effectiveness analysis. J Neurol 262(5):1191–1197. doi: 10.1007/s00415-015-7688-5 CrossRefPubMedGoogle Scholar
  36. Palop JJ, Mucke L (2010) Synaptic depression and aberrant excitatory network activity in Alzheimer’s disease: two faces of the same coin? NeuroMol Med 12(1):48–55. doi: 10.1007/s12017-009-8097-7 CrossRefGoogle Scholar
  37. Pascual-Marqui RD (2002) Standardized low-resolution brain electromagnetic tomography (sLORETA): technical details. Methods Find Exp Clin Pharmacol 24 (Suppl D):5–12Google Scholar
  38. Pearson RC, Sofroniew MV, Cuello AC, Powell TP, Eckenstein F, Esiri MM, Wilcock GK (1983) Persistence of cholinergic neurons in the basal nucleus in a brain with senile dementia of the Alzheimer’s type demonstrated by immunohistochemical staining for choline acetyltransferase. Brain Res 289(1–2):375–379CrossRefPubMedGoogle Scholar
  39. Petersen RC, Jack CR Jr (2009) Imaging and biomarkers in early Alzheimer’s disease and mild cognitive impairment. Clin Pharmacol Ther 86(4):438–441. doi: 10.1038/clpt.2009.166 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Qaseem A, Snow V, Cross JT Jr, Forciea MA, Hopkins R Jr, Shekelle P, Adelman A, Mehr D, Schellhase K, Campos-Outcalt D, Santaguida P, Owens DK, American College of Physicians/American Academy of Family Physicians Panel on D (2008) Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 148(5):370–378CrossRefPubMedGoogle Scholar
  41. Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362(4):329–344. doi: 10.1056/NEJMra0909142 CrossRefPubMedGoogle Scholar
  42. Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D (1996) Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 334(12):752–758. doi: 10.1056/NEJM199603213341202 CrossRefPubMedGoogle Scholar
  43. Rosen WG, Mohs RC, Davis KL (1984) A new rating scale for Alzheimer’s disease. Am J Psychiatry 141(11):1356–1364CrossRefPubMedGoogle Scholar
  44. Sankar T, Chakravarty MM, Bescos A, Lara M, Obuchi T, Laxton AW, McAndrews MP, Tang-Wai DF, Workman CI, Smith GS, Lozano AM (2015) Deep brain stimulation influences brain structure in Alzheimer’s disease. Brain Stimul 8(3):645–654. doi: 10.1016/j.brs.2014.11.020 CrossRefPubMedGoogle Scholar
  45. Schaltenbrand G, Wahren W (1977) Atlas for stereotaxy of the human brain. Georg Thieme Verlag, StuttgartGoogle Scholar
  46. Schliebs R, Arendt T (2011) The cholinergic system in aging and neuronal degeneration. Behav Brain Res 221(2):555–563. doi: 10.1016/j.bbr.2010.11.058 CrossRefPubMedGoogle Scholar
  47. Sharma M, Deogaonkar M, Rezai A (2015) Assessment of potential targets for deep brain stimulation in patients with Alzheimer’s disease. J Clin Med Res 7(7):501–505. doi: 10.14740/jocmr2127w CrossRefPubMedPubMedCentralGoogle Scholar
  48. Smith GS, de Leon MJ, George AE, Kluger A, Volkow ND, McRae T, Golomb J, Ferris SH, Reisberg B, Ciaravino J et al (1992) Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer’s disease. Pathophysiologic implications. Arch Neurol 49(11):1142–1150CrossRefPubMedGoogle Scholar
  49. Sperling RA, Dickerson BC, Pihlajamaki M, Vannini P, LaViolette PS, Vitolo OV, Hedden T, Becker JA, Rentz DM, Selkoe DJ, Johnson KA (2010) Functional alterations in memory networks in early Alzheimer’s disease. NeuroMol Med 12(1):27–43. doi: 10.1007/s12017-009-8109-7 CrossRefGoogle Scholar
  50. Stone SS, Teixeira CM, Devito LM, Zaslavsky K, Josselyn SA, Lozano AM, Frankland PW (2011) Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. J Neurosci 31(38):13469–13484. doi: 10.1523/JNEUROSCI.3100-11.2011 CrossRefPubMedGoogle Scholar
  51. Toda H, Hamani C, Fawcett AP, Hutchison WD, Lozano AM (2008) The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation. J Neurosurg 108(1):132–138. doi: 10.3171/JNS/2008/108/01/0132 CrossRefPubMedGoogle Scholar
  52. Tsivilis D, Vann SD, Denby C, Roberts N, Mayes AR, Montaldi D, Aggleton JP (2008) A disproportionate role for the fornix and mammillary bodies in recall versus recognition memory. Nat Neurosci 11(7):834–842. doi: 10.1038/nn.2149 CrossRefPubMedGoogle Scholar
  53. Turnbull IM, McGeer PL, Beattie L, Calne D, Pate B (1985) Stimulation of the basal nucleus of Meynert in senile dementia of Alzheimer’s type. A preliminary report. Appl Neurophysiol 48(1–6):216–221PubMedGoogle Scholar
  54. Watt AD, Villemagne VL, Barnham KJ (2013) Metals, membranes, and amyloid-beta oligomers: key pieces in the Alzheimer’s disease puzzle? J Alzheimers Dis JAD 33(Suppl 1):S283–S293. doi: 10.3233/JAD-2012-129017 PubMedGoogle Scholar
  55. Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR (1982) Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215(4537):1237–1239CrossRefPubMedGoogle Scholar
  56. Wilson CR, Baxter MG, Easton A, Gaffan D (2008) Addition of fornix transection to frontal-temporal disconnection increases the impairment in object-in-place memory in macaque monkeys. Eur J Neurosci 27(7):1814–1822. doi: 10.1111/j.1460-9568.2008.06140.x CrossRefPubMedPubMedCentralGoogle Scholar
  57. Zibly Z, Shaw A, Harnof S, Sharma M, Graves C, Deogaonkar M, Rezai A (2014) Modulation of mind: therapeutic neuromodulation for cognitive disability. J Clin Neurosci 21(9):1473–1477. doi: 10.1016/j.jocn.2013.11.040 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  1. 1.Division of Neurosurgery, Barrow Neurological InstituteSt. Joseph’s Hospital and Medical CenterPhoenixUSA
  2. 2.Division of NeurosurgeryUniversity of TorontoTorontoCanada

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