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Innovations inCLINICAL NEUROSCIENCE [ V O L U M E 9 , N U M B E R 1 1 – 1 2 , N O V E M B E R – D E C E M B E R 2 0 1 2 ] 10ABSTRACTRecent studies have identified anassociation between memorydeficits and defects of theintegrated neuronal cortical areasknown collectively as the defaultmode network. It is conceivablethat the amyloid deposition orother molecular abnormalities seenin patients with Alzheimer’s diseasemay interfere with this network anddisrupt neuronal circuits beyondthe localized brain areas.Therefore, Alzheimer’s disease maybe both a degenerative disease anda broader system-level disorderaffecting integrated neuronalpathways involved in memory. Inthis paper, we describe therationale and provide someevidence to support the study ofdeep brain stimulation of thehippocampal fornix as a noveltreatment to improve neuronalcircuitry within these integratednetworks and thereby sustainmemory function in earlyAlzheimer’s disease.KEY WORDSAlzheimer’s disease, deep brainstimulation, hippocampus; fornix,neuronal circuitryINTRODUCTIONAlzheimer’s disease (AD)continues to be a growing publichealth concern. It is estimated thatthere will be over 115 million newworldwide cases of AD within thenext 40 years, resulting in anoverwhelming health and economicburden on society. 1 Given the majorpublic health priority of AD, theAlzheimer’s Association releasedthe National Alzheimer’s Plan, FromAct to Action, in May 2012outlining a national strategy toaddress AD research, care, andservices with the specific goal offinding effective ways to preventand treat the disease by 2025. ADis characterized by progressivecognitive dysfunction oftenbeginning with an early disturbanceof episodic memory and ultimatelyleading to absolute functionalimpairment. The apparentpathological processes causing ADinclude misprocessing of fibrillaramyloid leading to oligomerization,the deposition of amyloid plaquecausing a disruption of neuralnetwork activity, a loss of synapticfunction, and eventual neuronaldeath. 2,3The United States Food andDrug Administration (FDA) hasapproved three cholinesteraseinhibitors and the N-Methyl-D-aspartic acid (NMDA) antagonistmemantine for the treatment ofAD. In practice, these therapieshave had only modest, short-termbenefits for clinical symptoms butthey continue to be widely usedbecause of a lack of alternativeDeep Brain Stimulation:A Novel Strategy for Treating Alzheimer’s Diseaseby Constantine G. Lyketsos, MD, MHS; Steven D. Targum, MD; Jo Cara Pendergrass, PhD; and Andres M. Lozano, MD, PhD, FRCSC, FRSCInnov Clin Neurosci. 2012;9(11–12):10–17Research to Practice