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American Journal of Alzheimer's Disease and Other Dementias logoLink to American Journal of Alzheimer's Disease and Other Dementias
. 2009 Apr-May;24(2):95–121. doi: 10.1177/1533317508328602

Reviews: Current Concepts in Alzheimer's Disease: A Multidisciplinary Review

Ludovico Minati 1, Trudi Edginton 2, Maria Grazia Bruzzone 3, Giorgio Giaccone 4
PMCID: PMC10846154  PMID: 19116299

Abstract

This comprehensive, pedagogically-oriented review is aimed at a heterogeneous audience representative of the allied disciplines involved in research and patient care. After a foreword on epidemiology, genetics, and risk factors, the amyloid cascade model is introduced and the main neuropathological hallmarks are discussed. The progression of memory, language, visual processing, executive, attentional, and praxis deficits, and of behavioral symptoms is presented. After a summary on neuropsychological assessment, emerging biomarkers from cerebrospinal fluid assays, magnetic resonance imaging, nuclear medicine, and electrophysiology are discussed. Existing treatments are briefly reviewed, followed by an introduction to emerging disease-modifying therapies such as secretase modulators, inhibitors of Abeta aggregation, immunotherapy, inhibitors of tau protein phosphorylation, and delivery of nerve growth factor.

Keywords: Alzheimer's disease, neuropathology, neuropsychological testing, neuroimaging, pharmacotherapy

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Contributor Information

Ludovico Minati, Science Direction, unit, Fondazione IRCCS Istituto Nazionale Neurologico "Carlo Besta", Milano, Italy, Neuroradiology, unit, Fondazione IRCCS Istituto Nazionale Neurologico "Carlo Besta", Milano, Italy, lminati@istituto-besta.it .

Trudi Edginton, Cognitive Science Research Unit University of Westminster, London, United Kingdom.

Maria Grazia Bruzzone, Neuroradiology, unit, Fondazione IRCCS Istituto Nazionale Neurologico "Carlo Besta", Milano, Italy.

Giorgio Giaccone, Neuropathology, unit, Fondazione IRCCS Istituto Nazionale Neurologico "Carlo Besta", Milano, Italy.

References

  1. Alzheimer A. Uber eine eigenartige Erkrankung der Hirnrinde . Allg Z Psychiat Psych-Gerichtl Med. 1907. ;64: 146-148. [Google Scholar]
  2. Katzman R. The prevalence and malignancy of Alzheimer's disease: a major killer . Arch Neurol. 1976;33: 217-218. [DOI] [PubMed] [Google Scholar]
  3. World Health Organization. World Health Report 2003: Shaping the Future. Geneva: WHO; 2003. [Google Scholar]
  4. Ferri CP, Prince M., Brayne C. et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366: 2112-2117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Comas-Herrera A., Wittenberg R., Pickard L., Knapp M. Cognitive impairment in older people: future demand for long-term care services and the associated costs. Int J Geriatr Psychiatry. 2007;22:1037-1045. [DOI] [PubMed] [Google Scholar]
  6. Langa KM, Chernew ME, Kabeto MU, et al. National estimates of the quantity and cost of informal caregiving for the elderly with dementia. J Gen Intern Med. 2001;16:770-778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Serretti A., Olgiati P., De Ronchi D. Genetics of Alzheimer's disease. A rapidly evolving field. J Alzheimers Dis. 2007;12:73-92. [DOI] [PubMed] [Google Scholar]
  8. Goate A., Chartier-Harlin MC, Mullan M., et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991;349:704-706. [DOI] [PubMed] [Google Scholar]
  9. Papassotiropoulos A., Fountoulakis M., Dunckley T., et al. Genetics, transcriptomics and proteomics of Alzheimer's disease. J Clin Psychiatry. 2006;67:652-670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Irizarry MC , Deng A., Lleo A., et al. Apolipoprotein E modulates gamma-secretase cleavage of the amyloid precursor protein. J Neurochem. 2004;90:1132-1143. [DOI] [PubMed] [Google Scholar]
  11. Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261:921-923. [DOI] [PubMed] [Google Scholar]
  12. Corder EH, Saunders AM, Risch NJ, et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet. 1994;7:180-184. [DOI] [PubMed] [Google Scholar]
  13. Blomqvist ME , Chalmers K., Andreasen N., et al. Sequence variants of IDE are associated with the extent of beta-amyloid deposition in the Alzheimer's disease brain . Neurobiol Aging. 2005;26:795-802. [DOI] [PubMed] [Google Scholar]
  14. Hiltunen M. , Lu A., Thomas AV, et al. Ubiquilin 1 modulates amyloid precursor protein trafficking and amyloid-b secretion. J Biol Chem. 2006;281:32240-32253. [DOI] [PubMed] [Google Scholar]
  15. Rogaeva E., Meng Y., Lee JH, et al. The neuronal sortilinrelated receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007;39:168-177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dreses-Werringloer U., Lambert JC, Vingtdeux V., et al. A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk. Cell. 2008;133:1149-1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Farkas E., Luiten PG Cerebral microvascular pathology in aging and Alzheimer's disease . Prog Neurobiol. 2001;64:575-611. [DOI] [PubMed] [Google Scholar]
  18. Longstreth WT Jr, Dulberg C., Manolio TA, et al. Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke. 2002;33:2376-2382. [DOI] [PubMed] [Google Scholar]
  19. Vermeer SE, Prins ND, den Heijer T., et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348:1215-1222. [DOI] [PubMed] [Google Scholar]
  20. Van Den Heuvel C., Thornton E., Vink R. Traumatic brain injury and Alzheimer's disease: a review. Prog Brain Res. 2007;161:303-316. [DOI] [PubMed] [Google Scholar]
  21. Ownby RL, Crocco E., Acevedo A., et al. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry . 2006;63:530-538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Geerlings MI , den Heijer T., Koudstaal PJ, et al. History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease . Neurology. 2008;70:1258-1264. [DOI] [PubMed] [Google Scholar]
  23. Koepsell TD , Kurland BF, Harel O., et al. Education, cognitive function, and severity of neuropathology in Alzheimer disease. Neurology . 2008;70:1732-1739. [DOI] [PubMed] [Google Scholar]
  24. Hardy J., Selkoe DJ The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002. ;297:353-356. [DOI] [PubMed] [Google Scholar]
  25. Nathalie P. , Jean-Noël O. Processing of amyloid precursor protein and amyloid peptide neurotoxicity. Curr Alzheimer Res. 2008;5:92-99. [DOI] [PubMed] [Google Scholar]
  26. Matsui T., Ingelsson M., Fukumoto H., et al. Expression of APP pathway mRNAs and proteins in Alzheimer's disease. Brain Res. 2007;1161:116-123. [DOI] [PubMed] [Google Scholar]
  27. Asai M., Hattori C., Szabo B., et al. Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase . Biochem Biophys Res Commun. 2003;301: 231-235. [DOI] [PubMed] [Google Scholar]
  28. Cole SL, Vassar R. BACE1 structure and function in health and Alzheimer's disease. Curr Alzheimer Res. 2008;5:100-120. [DOI] [PubMed] [Google Scholar]
  29. Stockley JH , O'Neill C. The proteins BACE1 and BACE2 and beta-secretase activity in normal and Alzheimer's disease brain. Biochem Soc Trans. 2007;35:574-576. [DOI] [PubMed] [Google Scholar]
  30. Postina R. A closer look at alpha-secretase. Curr Alzheimer Res . 2008;5:179-186. [DOI] [PubMed] [Google Scholar]
  31. Kaether C., Haass C., Steiner H. Assembly, trafficking and function of gamma-secretase. Neurodegener Dis. 2006;3:275-283. [DOI] [PubMed] [Google Scholar]
  32. El-Agnaf OM , Mahil DS, Patel BP, Austen BM Oligomerization and toxicity of beta-amyloid-42 implicated in Alzheimer's disease. Biochem Biophys Res Commun . 2000;273:1003-1007. [DOI] [PubMed] [Google Scholar]
  33. Zhang L., Song L., Terracina G., et al. Biochemical characterization of the gamma-secretase activity that produces beta-amyloid peptides. Biochemistry. 2001;40:5049-5055. [DOI] [PubMed] [Google Scholar]
  34. Yin YI, Bassit B., Zhu L., et al. {gamma}-Secretase Substrate Concentration Modulates the Abeta42/Abeta40 Ratio: Implications For Alzheimer Disease. J Biol Chem. 2007;282:23639-23644. [DOI] [PubMed] [Google Scholar]
  35. Carson JA, Turner AJ Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases ? J Neurochem. 2002;81:1-8. [DOI] [PubMed] [Google Scholar]
  36. Meyer-Luehmann M., Spires-Jones TL, Prada C., et al. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature. 2008;451:720-724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Haass C., Selkoe DJ Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol. 2007;8: 101-112. [DOI] [PubMed] [Google Scholar]
  38. Brion JP The role of neurofibrillary tangles in Alzheimer disease. Acta Neurol Belg. 1998;98:165-174. [PubMed] [Google Scholar]
  39. Sorrentino G. , Bonavita V. Neurodegeneration and Alzheimer's disease: the lesson from tauopathies. Neurol Sci. 2007. ;28:63-71. [DOI] [PubMed] [Google Scholar]
  40. Braak H., Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol (Berl). 1991;82:239-259. [DOI] [PubMed] [Google Scholar]
  41. Berg L., McKeel DW, Miller JP, et al. Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol. 1998. ;55:326-335. [DOI] [PubMed] [Google Scholar]
  42. Eriksen JL, Janus CG Plaques, tangles, and memory loss in mouse models of neurodegeneration . Behav Genet. 2007;37:79-100. [DOI] [PubMed] [Google Scholar]
  43. Mott RT, Hulette CM Neuropathology of Alzheimer's disease. Neuroimaging Clin N Am. 2005;15:755-765. [DOI] [PubMed] [Google Scholar]
  44. Duyckaerts C. , Dickson DW Neuropathology of Alzheimer's disease . In: Dickson D, ed. Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders. Basel: ISN Neuropath Press; 2003. . [Google Scholar]
  45. Tagliavini F., Giaccone G., Frangione B., Bugiani O. Pre-amyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals. Neurosci Lett. 1988;93:191-196. [DOI] [PubMed] [Google Scholar]
  46. Braak H., Braak E., Grundke-Iqbal I., Iqbal K. Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett. 1986;65:351-355. [DOI] [PubMed] [Google Scholar]
  47. Delaère P., He Y., Fayet G., Duyckaerts C., Hauw JJ Beta A4 deposits are constant in the brain of the oldest old: an immunocytochemical study of 20 French centenarians. Neurobiol Aging. 1993;14:191-194. [DOI] [PubMed] [Google Scholar]
  48. Hof PR, Glannakopoulos P., Bouras C. The neuropathological changes associated with normal brain aging. Histol Histopathol. 1996;11:1075-1088. [PubMed] [Google Scholar]
  49. Blessed G., Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry . 1968;114:797-811. [DOI] [PubMed] [Google Scholar]
  50. Braak H., Braak E. Frequency of stages of Alzheimer-related lesions in different age categories . Neurobiol Aging. 1997;18:351-357. [DOI] [PubMed] [Google Scholar]
  51. Goedert M. Tau protein and neurodegeneration. Semin Cell Dev Biol. 2004;15:45-49. [DOI] [PubMed] [Google Scholar]
  52. Näslund J., Haroutunian V., Mohs R., et al. Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. JAMA. 2000;283: 1571-1577. [DOI] [PubMed] [Google Scholar]
  53. Perry EK, Tomlinson BE, Blessed G., et al. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 1978;2:1457-1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Whitehouse PJ, Price DL, Clark AW, et al. Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis . Ann Neurol . 1981;10: 122-126. [DOI] [PubMed] [Google Scholar]
  55. Wu D., Hersh LB Choline acetyltransferase: celebrating its fiftieth year. J Neurochem. 1994;62:1653-1663. [DOI] [PubMed] [Google Scholar]
  56. Storey E., Kinsella GJ, Slavin MJ The neuropsychological diagnosis of Alzheimer's disease. J Alzheimers Dis. 2001;3:261-285. [DOI] [PubMed] [Google Scholar]
  57. Small BJ, Mobly JL, Laukka EJ, et al. Cognitive deficits in preclinical Alzheimer's disease. Acta Neurol Scand Suppl. 2003;179:29-33. [DOI] [PubMed] [Google Scholar]
  58. Petersen RC , Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch. Neurol . 1999;56:303-308. [DOI] [PubMed] [Google Scholar]
  59. Gauthier S. , Reisberg B., Zaudig M., et al. Mild cognitive impairment. Lancet. 2006;367:1262-1270. [DOI] [PubMed] [Google Scholar]
  60. Beatty WW, Salmon DP, Butters N., et al. Retrograde amnesia in patients with Alzheimer's disease or Huntington's disease. Neurobiol Aging. 1988;9:181-186. [DOI] [PubMed] [Google Scholar]
  61. Jones S., Livner A., Bäckman L. Patterns of prospective and retrospective memory impairment in preclinical Alzheimer's disease. Neuropsychology. 2006. ;20:144-152. [DOI] [PubMed] [Google Scholar]
  62. Damasio AR Time-locked multiregional retroactivation: a systems level proposal for the neural substrates of recall and recognition. Cognition . 1989;33:25-62. [DOI] [PubMed] [Google Scholar]
  63. Squire LR, Alvarez P. Retrograde amnesia and memory consolidation: a neurobiological perspective . Curr Opin Neurobiol. 1995;5:169-77. [DOI] [PubMed] [Google Scholar]
  64. Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol. 2007;6: 1004-1014. [DOI] [PubMed] [Google Scholar]
  65. Moulin CJ, James N., Freeman JE, et al. Deficient acquisition and consolidation: intertrial free recall performance in Alzheimer's disease and mild cognitive impairment. J Clin Exp Neuropsychol. 2004;26:1-10. [DOI] [PubMed] [Google Scholar]
  66. Pepin EP, Eslinger PJ Verbal memory decline in Alzheimer's disease: a multiple-processes deficit . Neurology. 1989;39:1477-1482. [DOI] [PubMed] [Google Scholar]
  67. Bayley PJ, Salmon DP, Bondi MW, et al. Comparison of the serial position effect in very mild Alzheimer's disease, mild Alzheimer's disease, and amnesia associated with electroconvulsive therapy. J Int Neuropsychol Soc. 2000;6:290-298. [DOI] [PubMed] [Google Scholar]
  68. Kensinger EA , Brierley B., Medford N., et al. Effects of normal aging and Alzheimer's disease on emotional memory. Emotion . 2002. ;2:118-134. [DOI] [PubMed] [Google Scholar]
  69. Vitali P., Minati L., Chiarenza G., et al. The Von Restorff effect in ageing and Alzheimer's disease. Neurol Sci. 2006;27:166-172. [DOI] [PubMed] [Google Scholar]
  70. Helkala EL, Laulumaa V., Soininen H., Riekkinen PJ Recall and recognition memory in patients with Alzheimer's and Parkinson's diseases. Ann Neurol. 1988;24: 214-217. [DOI] [PubMed] [Google Scholar]
  71. Becker JT, Overman AA The semantic memory deficit in Alzheimer's disease. Rev Neurol . 2002;35:777-783. [PubMed] [Google Scholar]
  72. Monsch AU, Bondi MW, Butters N., et al. A comparison of category and letter fluency in Alzheimer's disease and Huntington's disease. Neuropsychologia. 1994;8:25-30. [Google Scholar]
  73. Salmon DP, Heindel WC, Lange KL Differential decline in word generation from phonemic and semantic categories during the course of Alzheimer's disease: implications for the integrity of semantic memory. J Int Neuropsychol Soc. 1999. ;5:692-703. [DOI] [PubMed] [Google Scholar]
  74. Hodges J., Patterson KE, Graham N., Dawson K. Naming and knowing in dementia of the Alzheimer's type. Brain Lang. 1996;54:302-325. [DOI] [PubMed] [Google Scholar]
  75. Dick MB, Nielson K., Beth RE, et al. Acquisition and long-term retention of a fine motor skill in Alzheimer s disease. Brain Cogn. 1995;29:294-306. [DOI] [PubMed] [Google Scholar]
  76. Camus JF, Wenisch NE, Blanchard MF, et al. Implicit memory for words presented in short texts is preserved in Alzheimer s disease? Psychol Med. 2003;33:169-174. [DOI] [PubMed] [Google Scholar]
  77. Park SM, Gabrieli JD, Reminger SL, et al. Preserved priming across study-test picture transformations in patients with Alzheimer s disease. Neuropsychology. 1998;12:340-352. [DOI] [PubMed] [Google Scholar]
  78. Kempler D., Curtiss S., Jackson C. Syntactic preservation in Alzheimer's disease. J Speech Hear Res. 1987;30:343-350. [DOI] [PubMed] [Google Scholar]
  79. Murdoch BE, Chenery HJ, Wilks V., Boyle RS Language disorders in dementia of the Alzheimer type. Brain Lang. 1987;31:122-137. [DOI] [PubMed] [Google Scholar]
  80. Chan AS, Salmon DP Semantic memory deficits associated with Alzheimer's disease. Neuropsychology. 1994;8: 385-394. [Google Scholar]
  81. Emery VO Language impairment in dementia of the Alzheimer type: a hierarchical decline ? Int J Psychiatry Med. 2000;30:145-164. [DOI] [PubMed] [Google Scholar]
  82. Groves-Wright K., Neils-Strunjas J., Burnett R., et al. A comparison of verbal and written language in Alzheimer's disease. J Commun Disord. 2004;37:109-130. [DOI] [PubMed] [Google Scholar]
  83. Glosser G., Kohn SE, Sands L., et al. Impaired spelling in Alzheimer's disease: a linguistic deficit ? Neuropsychologia. 1999;37:807-815. [DOI] [PubMed] [Google Scholar]
  84. Forbes KE, Shanks MF, Venneri A. The evolution of dysgraphia in Alzheimer's disease. Brain Res Bull. 2004;63: 19-24. [DOI] [PubMed] [Google Scholar]
  85. Kaskie B., Storandt M. Visuospatial deficit in dementia of the Alzheimer type. Arch Neurol. 1995;52:422-425. [DOI] [PubMed] [Google Scholar]
  86. Fujimori M. , Imamura T., Yamashita H., et al. The disturbances of object vision and spatial vision in Alzheimer's disease. Dementia Geriat Cog Disord. 1997;8:228-231. [DOI] [PubMed] [Google Scholar]
  87. Binetti G., Cappa SF, Magni E., et al. Visual and spatial perception in the early phase of Alzheimer's disease. Neuropsychology. 1998;12:29-33. [DOI] [PubMed] [Google Scholar]
  88. Laatu S., Revonsuo A., Jäykkä H., et al. Visual object recognition in early Alzheimer's disease: deficits in semantic processing. Acta Neurol Scand. 2003;108:82-89. [DOI] [PubMed] [Google Scholar]
  89. Kurylo DD, Corkin S., Growdon JH Perceptual organization in Alzheimer's disease. Psychol Aging . 1994;9:562-567. [DOI] [PubMed] [Google Scholar]
  90. Mendez MF, Ghajarania M., Perryman KM Posterior cortical atrophy: clinical characteristics and differences compared to Alzheimer's disease. Dement Geriatr Cogn Disord . 2002;14:33-40. [DOI] [PubMed] [Google Scholar]
  91. Lafleche G. , Albert MS Executive function deficits in mild Alzheimer's disease. Neuropsychology. 1995;9:313-320. [Google Scholar]
  92. Perry RJ, Hodges JR Attention and executive deficits in Alzheimer's disease. A critical review . Brain. 1999;122: 383-404. [DOI] [PubMed] [Google Scholar]
  93. Collette F. , Van der Linden M., Salmon E. Executive dysfunction in Alzheimer's disease . Cortex. 1999;35: 57-72. [DOI] [PubMed] [Google Scholar]
  94. Baudic S., Barba GD, Thibaudet MC, et al. Executive function deficits in early Alzheimer's disease and their relations with episodic memory. Arch Clin Neuropsychol . 2006;21:15-21. [DOI] [PubMed] [Google Scholar]
  95. Patterson MB , Mack JL, Geldmacher DS, Whitehouse PJ Executive functions and Alzheimer's disease: problems and prospects. Eur J Neurol . 1996. ;3: 5-15. [Google Scholar]
  96. Baddeley AD , Baddeley HA, Bucks RS, et al. Attentional control in Alzheimer's disease. Brain. 2001. ;124: 1492-508. [DOI] [PubMed] [Google Scholar]
  97. Parasuraman R., Greenwood PM, Haxby JV, et al. Visuospatial attention in dementia of the Alzheimer type. Brain. 1992;115:711-733. [DOI] [PubMed] [Google Scholar]
  98. Perry RJ, Watson P., Hodges JR The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer's disease: relationship to episodic and semantic memory impairment . Neuropsychologia. 2000;38:252-271. [DOI] [PubMed] [Google Scholar]
  99. Capitani E. , Della Sala S., Lucchelli F., et al. Perceptual attention in aging and dementia measured by Gottschaldt's Hidden Figure Test. J Gerontol . 1988;43: 157-163. [DOI] [PubMed] [Google Scholar]
  100. Filoteo JV , Delis DC, Massman PJ, et al. Directed and divided attention in Alzheimer s disease: impairment in shifting of attention to global and local stimuli. J Clin Exp Neuropsychol. 1992;14:871-883. [DOI] [PubMed] [Google Scholar]
  101. Parasuraman R., Greenwood PM, Alexander GE Alzheimer disease constricts the dynamic range of spatial attention in visual search. Neuropsychologia. 2000;38: 1126-1135. [DOI] [PubMed] [Google Scholar]
  102. Mendez M., Cherrier M., Cymerman J. Hemispatial neglect on visual search tasks in Alzheimer's disease . Neuropsychiatry Neuropsychol Behav Neurol. 1997;10: 203-208. [PubMed] [Google Scholar]
  103. Berardi AM , Parasuraman R., Haxby JV Sustained attention in mild Alzheimer's disease . Dev Neuropsychol. 2005;28:507-537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Edwards DF , Deuela RK, Bauma CM, Morrisa JC A Quantitative Analysis of Apraxia in Senile Dementia of the Alzheimer Type: Stage-Related Differences in Prevalence and Type. Dement Geriatr Cogn Disord . 1991;2:142-149. [Google Scholar]
  105. Della Sala S., Lucchelli F., Spinnler H. Ideomotor apraxia in patients with dementia of Alzheimer type. J Neurol. 1987;234:91-93. [DOI] [PubMed] [Google Scholar]
  106. Dumont C., Ska B., Joanette Y. Conceptual apraxia and semantic memory deficit in Alzheimer's disease: two sides of the same coin? J Int Neuropsychol Soc. 2000;6:693-703. [DOI] [PubMed] [Google Scholar]
  107. Lucchelli F. , Lopez OL, Faglioni P., Boller F. Ideomotor and ideational apraxia in alzheimer's disease. Int J Ger Psych. 2004;8:413-417. [Google Scholar]
  108. Jacobs DH, Adair JC, Williamson DJ, et al. Apraxia and motor-skill acquisition in Alzheimer's disease are dissociable. Neuropsychologia. 1999;37:875-880. [DOI] [PubMed] [Google Scholar]
  109. Capone JG, Della Sala S., Spinnler H., et al. Upper and lower face and ideomotor apraxia in patients with Alzheimer's disease. Behav Neurol. 2003;14:1-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Smith MZ, Esiri MM, Barnetson L., et al. Constructional apraxia in Alzheimer's disease: association with occipital lobe pathology and accelerated cognitive decline. Dement Geriatr Cogn Disord. 2001;12: 281-288. [DOI] [PubMed] [Google Scholar]
  111. Guérin F., Belleville S., Ska B. Characterization of visuoconstructional disabilities in patients with probable dementia of Alzheimer's type. J Clin Exp Neuropsychol . 2002;24:1-17. [DOI] [PubMed] [Google Scholar]
  112. Kwak YT "Closing-in" phenomenon in Alzheimer's disease and subcortical vascular dementia. BMC Neurol. 2004;4:3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Jost BC, Grossberg GT The evolution of psychiatric symptoms in Alzheimer's disease: a natural history study. J Am Geriatr Soc. 1996;44:1078-1081. [DOI] [PubMed] [Google Scholar]
  114. Mega MS, Cummings JL, Fiorello T., Gornbein J. The spectrum of behavioral changes in Alzheimer's disease. Neurology. 1996;46:130-135. [DOI] [PubMed] [Google Scholar]
  115. Ballard C. , Ayre G., Gray A. Psychotic symptoms and behavioral disturbances in dementia: A review. Rev Neurol. 1999;155:44-52. [PubMed] [Google Scholar]
  116. Starkstein SE, Jorge R., Mizrahi R., Robinson RG The construct of minor and major depression in Alzheimer's disease. Am J Psychiatry. 2005. ;162:2086-2093. [DOI] [PubMed] [Google Scholar]
  117. Gilley DW, Bienias JL, Wilson RS, et al. Influence of behavioral symptoms on rates of institutionalization for persons with Alzheimer's disease. Psychol Med. 2004;34:1129-1135. [DOI] [PubMed] [Google Scholar]
  118. Shimabukuro J., Awata S., Matsuoka H. Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients. Psychiatry Clin Neurosci. 2005;59:274-279. [DOI] [PubMed] [Google Scholar]
  119. Cole CS, Richards KC Sleep and cognition in people with Alzheimer's disease. Issues Ment Health Nurs. 2005;26:687-698. [DOI] [PubMed] [Google Scholar]
  120. Starkstein SE, Migliorelli R., Tesón A., et al. Prevalence and clinical correlates of pathological affective display in Alzheimer's disease . J Neurol Neurosurg Psychiatry. 1995;59:55-60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Derouesné C., Piquard A., Thibault S., et al. Noncognitive symptoms in Alzheimer's disease. A study of 150 community-dwelling patients using a questionnaire completed by the caregiver. Rev Neurol (Paris). 2001;157:162-177. [PubMed] [Google Scholar]
  122. Raskind MA , Peskind ER Neurobiologic bases of non-cognitive behavioral problems in Alzheimer disease. Alzheimer Dis Assoc Disord . 1994;8:54-60. [PubMed] [Google Scholar]
  123. Shinosaki K., Nishikawa T., Takeda M. Neurobiological basis of behavioral and psychological symptoms in dementia of the Alzheimer type . Psychiatry Clin Neurosci. 2000;54:611-620. [DOI] [PubMed] [Google Scholar]
  124. Pomara N., Greenberg WM, Branford MD, Doraiswamy PM Therapeutic implications of HPA axis abnormalities in Alzheimer's disease: review and update. Psychopharmacol Bull. 2003. ;37:120-134. [PubMed] [Google Scholar]
  125. Garcia-Alloza M., Hirst WD, Chen CP, et al. Differential involvement of 5-HT(1B/1D) and 5-HT6 receptors in cognitive and non-cognitive symptoms in Alzheimer's disease. Neuropsychopharmacology. 2004;29:410-416. [DOI] [PubMed] [Google Scholar]
  126. Lai MK , Tsang SW, Alder JT, et al. Loss of serotonin 5-HT2A receptors in the postmortem temporal cortex correlates with rate of cognitive decline in Alzheimer's disease. Psychopharmacology (Berl). 2005;179: 73-677. [DOI] [PubMed] [Google Scholar]
  127. Lee DY , Choo IH, Jhoo JH, et al. Frontal dysfunction underlies depressive syndrome in Alzheimer disease: a FDG-PET study. Am J Geriatr Psychiatry. 2006;14: 625-628. [DOI] [PubMed] [Google Scholar]
  128. Levy-Cooperman N., Burhan AM, Rafi-Tari S., et al. Frontal lobe hypoperfusion and depressive symptoms in Alzheimer disease. J Psychiatry Neurosci. 2008;33: 218-226. [PMC free article] [PubMed] [Google Scholar]
  129. Sun X. , Steffens DC, Au R., et al. Amyloid-associated depression: a prodromal depression of Alzheimer disease? Arch Gen Psychiatry. 2008;65:542-550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  130. Wilson RS, Arnold SE, Beck TL, et al. Change in depressive symptoms during the prodromal phase of Alzheimer disease. Arch Gen Psychiatry. 2008. ;65:439-445. [DOI] [PubMed] [Google Scholar]
  131. Kalbe E., Salmon E., Perani D., et al. Anosognosia in very mild Alzheimer's disease but not in mild cognitive impairment. Dement Geriatr Cogn Disord. 2005;19: 349-356. [DOI] [PubMed] [Google Scholar]
  132. Harwood DG , Sultzer DL, Wheatley MV Impaired insight in Alzheimer disease: association with cognitive deficits, psychiatric symptoms, and behavioral disturbances . Neuropsychiatry Neuropsychol Behav Neurol. 2000;13:83-88. [PubMed] [Google Scholar]
  133. Gil R. , Arroyo-Anllo EM, Ingrand P., et al. Self-consciousness and Alzheimer's disease. Acta Neurol Scand. 2001;104:296-300. [DOI] [PubMed] [Google Scholar]
  134. Sato J., Nakaaki S., Murata Y., et al. Two dimensions of anosognosia in patients with Alzheimer's disease: reliability and validity of the Japanese version of the Anosognosia Questionnaire for Dementia (AQ-D). Psychiatry Clin Neurosci. 2007;61:672-677. [DOI] [PubMed] [Google Scholar]
  135. McKhann G. , Drachman D., Folstein M., et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease . Neurology. 1984;34:939-944. [DOI] [PubMed] [Google Scholar]
  136. World Health Organization. The ICD-10 Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines . Geneva, Switzerland: World Health Organization; 1992. [Google Scholar]
  137. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994. [Google Scholar]
  138. Folstein MF, Folstein SE, McHugh PR "Mini-Mental State" A Practical Method for Grading the Cognitive State of patients for the Clinician. J Psychiat Res. 1975;12:189-198. [DOI] [PubMed] [Google Scholar]
  139. Rosen WG, Mohs RC, Davis KL A new rating scale for Alzheimer's disease. Am J Psychiatr . 1984;141: 1356-1364. [DOI] [PubMed] [Google Scholar]
  140. Morris JC, Heyman A., Mohs RC, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology. 1989;39:1159-1165. [DOI] [PubMed] [Google Scholar]
  141. Saykin AJ, Janssen RS, Sprehn GC, et al. Longitudinal evaluation of neuropsychological function in homosexual men with HIV infection: 18-month follow-up. J Neuropsychiatry Clin Neurosci. 1991;3:2860-298. [DOI] [PubMed] [Google Scholar]
  142. Cummings JL , Mega M., Gray K., et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44: 2308-2314. [DOI] [PubMed] [Google Scholar]
  143. Olin JT, Katz IR, Meyers BS, et al. Provisional diagnostic criteria for depression of Alzheimer disease: rationale and background. Am J Geriatr Psychiatry . 2002;10:129-141. [PubMed] [Google Scholar]
  144. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA Cornell Scale for Depression in Dementia. Biol Psychiatry. 1988;23:271-284. [DOI] [PubMed] [Google Scholar]
  145. Mayer LS, Bay RC, Politis A., et al. Comparison of three rating scales as outcome measures for treatment trials of depression in Alzheimer disease: findings from DIADS. Int J Geriatr Psychiatry. 2006;21:930-936. [DOI] [PubMed] [Google Scholar]
  146. Teng E., Ringman JM, Ross LK, et al. Diagnosing depression in Alzheimer disease with the national institute of mental health provisional criteria. Am J Geriatr Psychiatry. 2008;16:469-477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  147. Reisberg B. , Ferris SH, Leon MJ, et al. The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry . 1982;139:1136-1139. [DOI] [PubMed] [Google Scholar]
  148. Berg L. Clinical Dementia Rating (CDR). Psychopharmacol Bull . 1988;24:637-639. [PubMed] [Google Scholar]
  149. Maddrey AM , Cullum CM, Weiner MF, Filley CM Premorbid intelligence estimation and level of dementia in Alzheimer's disease. J Int Neuropsychol Soc . 1996;2:551-555. [DOI] [PubMed] [Google Scholar]
  150. Fox LS , Olin JT, Erblich J., et al. Severity of cognitive impairment in Alzheimer's disease affects list learning using the California Verbal Learning Test (CVLT). Int J Geriatr Psychiatry. 1998. ;13:544-549. [DOI] [PubMed] [Google Scholar]
  151. Hogervorst E., Combrinck M., Lapuerta P., et al. The Hopkins Verbal Learning Test and screening for dementia. Dement Geriatr Cogn Disord. 2002;13: 13-20. [DOI] [PubMed] [Google Scholar]
  152. Barzotti T. , Gargiulo A., Marotta MG, et al. Correlation between cognitive impairment and the Rey auditory-verbal learning test in a population with Alzheimer disease . Arch Gerontol Geriatr Suppl. 2004;9:57-62. [DOI] [PubMed] [Google Scholar]
  153. Lowndes G. , Savage G. Early detection of memory impairment in Alzheimer's disease: a neurocognitive perspective on assessment. Neuropsychol Rev. 2007;17: 193-202. [DOI] [PubMed] [Google Scholar]
  154. Bigler ED, Rosa L., Schultz F., et al. Rey-Auditory Verbal Learning and Rey-Osterrieth Complex Figure Design performance in Alzheimer's disease and closed head injury. J Clin Psychol. 1989;45:277-280. [DOI] [PubMed] [Google Scholar]
  155. Cahn DA, Salmon DP, Monsch AU, et al. Screening for dementia of the alzheimer type in the community: the utility of the Clock Drawing Test. Arch Clin Neuropsychol . 1996;11:529-539. [PubMed] [Google Scholar]
  156. Carlesimo GA, Fadda L., Lorusso S., Caltagirone C. Verbal and spatial memory spans in Alzheimer's and multi-infarct dementia. Acta Neurol Scand. 1994;89: 132-138. [DOI] [PubMed] [Google Scholar]
  157. Wilson B., Cockburn J., Baddeley A., Hiorns R. The development and validation of a test battery for detecting and monitoring everyday memory problems. J Clin Exp Neuropsychol . 1989;11:855-870. [DOI] [PubMed] [Google Scholar]
  158. Kazui H., Matsuda A., Hirono N., et al. Everyday memory impairment of patients with mild cognitive impairment . Dement Geriatr Cogn Disord. 2005;19:331-337. [DOI] [PubMed] [Google Scholar]
  159. Binetti G. , Magni E., Padovani A., et al. Executive dysfunction in early Alzheimer's disease. J Neurol Neurosurg Psychiatry . 1996. ;60:91-93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  160. Nagahama Y. , Okina T., Suzuki N., et al. Factor structure of a modified version of the Wisconsin card sorting test: an analysis of executive deficit in Alzheimer's disease and mild cognitive impairment. Dement Geriatr Cogn Disord. 2003;16:103-112. [DOI] [PubMed] [Google Scholar]
  161. Amieva H., Lafont S., Rouch-Leroyer I., et al. Evidencing inhibitory deficits in Alzheimer's disease through interference effects and shifting disabilities in the Stroop test. Arch Clin Neuropsychol. 2004;19:791-803. [DOI] [PubMed] [Google Scholar]
  162. Stokholm J. , Vogel A., Gade A., Waldemar G. Heterogeneity in executive impairment in patients with very mild Alzheimer's disease. Dement Geriatr Cogn Disord . 2006;22:54-59. [DOI] [PubMed] [Google Scholar]
  163. Houston WS , Delis DC, Lansing A., et al. Executive function asymmetry in older adults genetically at-risk for Alzheimer's disease: verbal versus design fluency . J Int Neuropsychol Soc. 2005;11:863-870. [DOI] [PubMed] [Google Scholar]
  164. Hodges JR, Salmon DP, Butters N. The nature of the naming deficit in Alzheimer's and Huntington's disease . Brain. 1991;114:1547-1558. [DOI] [PubMed] [Google Scholar]
  165. Travniczek-Marterer A., Danielczyk W., Simanyi M., Fischer P. Ideomotor apraxia in Alzheimer's disease. Acta Neurol Scand. 1993;88:1-4. [DOI] [PubMed] [Google Scholar]
  166. Hodges JR, Patterson K. Is semantic memory consistently impaired early in the course of Alzheimer's disease? Neuroanatomical and diagnostic implications. Neuropsychologia . 1995;33:441-459. [DOI] [PubMed] [Google Scholar]
  167. Plassman BL, Khachaturian AS, Townsend JJ, et al. Comparison of clinical and neuropathologic diagnoses of Alzheimer's disease in 3 epidemiologic samples. Alzheimers Dement. 2006;2:2-11. [DOI] [PubMed] [Google Scholar]
  168. Dubois B., Feldman HH, Jacova C., et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6: 734-746. [DOI] [PubMed] [Google Scholar]
  169. Mayeux R., Saunders AM, Shea S., et al. Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease. N Engl J Med. 1998. ;338:506-511. [DOI] [PubMed] [Google Scholar]
  170. McConnell LM , Sanders GD, Owens DK Evaluation of genetic tests: APOE genotyping for the diagnosis of Alzheimer disease. Genet Test. 1999;3:47-53. [DOI] [PubMed] [Google Scholar]
  171. Sunderland T., Hampel H., Takeda M., et al. Biomarkers in the diagnosis of Alzheimer's disease: are we ready? J Geriatr Psychiatry Neurol. 2006;19:172-179. [DOI] [PubMed] [Google Scholar]
  172. Galasko D. , Chang L., Motter R., et al. High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. Arch Neurol . 1998;55:937-945. [DOI] [PubMed] [Google Scholar]
  173. Steinerman JR, Honig LS Laboratory biomarkers in Alzheimer's disease . Curr Neurol Neurosci Rep. 2007;7:381-387. [DOI] [PubMed] [Google Scholar]
  174. Sjogren M. , Minthon L., Davidsson P., et al. CSF Levels of tau,b-amyloid-42 and GAP-43 in Frontotemporal dementia, other types of dementia and normal aging . J Neural Transm. 2000;107:563-576. [DOI] [PubMed] [Google Scholar]
  175. Vandermeeren M., Merken Vanmechelen J., Six A., et al. Detection of TAU proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem . 1993;61:1828-1834. [DOI] [PubMed] [Google Scholar]
  176. Blennow K. , Wallin A., Agren H., et al. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer's disease. Mol Chem Neuropathology. 1995;26:231-245. [DOI] [PubMed] [Google Scholar]
  177. Itoh N., Arai H., Urakami K., et al. Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease . Ann Neurol. 2001;50:150-156. [DOI] [PubMed] [Google Scholar]
  178. Minati L., Grisoli M., Bruzzone MG MR spectroscopy, functional MRI, and diffusion-tensor imaging in the aging brain: a conceptual review. J Geriatr Psychiatry Neurol . 2007;20:3-21. [DOI] [PubMed] [Google Scholar]
  179. Lehéricy S. , Marjanska M., Mesrob L., et al. Magnetic resonance imaging of Alzheimer's disease. Eur Radiol. 2007;17:347-362. [DOI] [PubMed] [Google Scholar]
  180. Petersen RC , Knopman D., Boeve BF, et al. Role of hippocampal volumes in predicting progression to mild cognitive impairment. Neurology. 2005;64:126-127. [Google Scholar]
  181. Schuff N., Amend D., Ezekiel F., et al. Changes of hippocampal N-acetyl aspartate and volume in Alzheimer's disease. A proton MR spectroscopic imaging and MRI study. Neurology. 1997;49:1513-1521. [DOI] [PubMed] [Google Scholar]
  182. Catani M., Cherubini A., Howard R., et al. (1)H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging. Neuroreport. 2001. ;12:2315-2317. [DOI] [PubMed] [Google Scholar]
  183. Hanyu H., Sakurai H., Iwamoto T., et al. Diffusion-weighted MR imaging of the hippocampus and temporal white matter in Alzheimer's disease. J Neurol Sci. 1998;156:195-200. [DOI] [PubMed] [Google Scholar]
  184. Kantarci K. , Jack CR, Xu YC, et al. Mild cognitive impairment and Alzheimer disease: regional diffusivity of water. Radiology . 2001;219:101-107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  185. Bozzali M. , Falini A., Franceschi M., et al. White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging . J Neurol Neurosurg Psychiatry. 2002;72:742-746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  186. Yoshiura T. , Mihara F., Ogomori K., et al. Diffusion tensor in posterior cingulate gyrus: correlation with cognitive decline in Alzheimer's disease. Neuroreport. 2002;13:2299-2302. [DOI] [PubMed] [Google Scholar]
  187. Kantarci K. , Petersen RC, Boeve BF, et al. DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment . Neurology. 2005;64: 902-904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  188. Sandson TA , O'Connor M., Sperling RA, et al. Non-invasive perfusion MRI in Alzheimer's disease: a preliminary report. Neurology. 1996;47:1339-1342. [DOI] [PubMed] [Google Scholar]
  189. Alsop DC, Detre JA, Grossman M. Assessment of cerebral blood flow in Alzheimer's disease by spin-labeled magnetic resonance imaging. Ann Neurol. 2000. ;47: 93-100. [PubMed] [Google Scholar]
  190. Dickerson BC, Salat DH, Greve DN, et al. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology. 2005;65:404-411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  191. Dickerson BC, Sperling RA Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer's disease: insights from functional MRI studies. Neuropsychologia . 2008;46:1624-1635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  192. Bookheimer SY, Strojwas MH, Cohen MS, et al. Patterns of brain activation in people at risk for Alzheimer's disease. N Engl J Med. 2000;343:450-456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  193. Rombouts SA , Barkhof F., Van Meel CS, Scheltens P. Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2002. ;73:665-671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  194. Kircher TT , Erb M., Grodd W., Leube DT Cortical activation during cholinesterase-inhibitor treatment in Alzheimer disease: preliminary findings from a pharmaco-fMRI study. Am J Geriatr Psychiatry . 2005;13:1006-1013. [DOI] [PubMed] [Google Scholar]
  195. Greicius MD , Srivastava G., Reiss AL, Menon V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA. 2004. ;101: 4637-4642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  196. Matsuda H. Role of neuroimaging in Alzheimer's disease, with emphasis on brain perfusion SPECT. J Nucl Med. 2007;48:1289-1300. [DOI] [PubMed] [Google Scholar]
  197. Matsuda H., Kanetaka H., Ohnishi T., et al. Brain SPET abnormalities in Alzheimer's disease before and after atrophy correction. Eur J Nucl Med Mol Imaging. 2002;29:1502-1505. [DOI] [PubMed] [Google Scholar]
  198. Jagust W., Thisted R., Devous MD, et al. SPECT perfusion imaging in the diagnosis of Alzheimer's disease: a clinical-pathologic study. Neurology. 2001. ;56: 950-956. [DOI] [PubMed] [Google Scholar]
  199. Colloby SJ, Fenwick JD, Williams ED, et al. A comparison of (99m)Tc-HMPAO SPET changes in dementia with Lewy bodies and Alzheimer's disease using statistical parametric mapping. Eur J Nucl Med Mol Imaging. 2002;29:615-622. [DOI] [PubMed] [Google Scholar]
  200. Bonte FJ, Harris TS, Roney CA, Hynan LS Differential diagnosis between Alzheimer's and frontotemporal disease by the posterior cingulate sign. J Nucl Med. 2004. ;45:771-774. [PubMed] [Google Scholar]
  201. Caroli A., Testa C., Geroldi C., et al. Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment. J Neurol. 2007;254:1698-1707. [DOI] [PubMed] [Google Scholar]
  202. Mosconi L. Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD. Eur J Nucl Med Mol Imaging. 2005;32:486-510. [DOI] [PubMed] [Google Scholar]
  203. Mosconi L. , Brys M., Glodzik-Sobanska L., et al. Early detection of Alzheimer's disease using neuroimaging. Exp Gerontol. 2007;42:129-138. [DOI] [PubMed] [Google Scholar]
  204. Mosconi L. , Tsui WH, Santi S., et al. Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis. Neurology . 2005;64:1860-1867. [DOI] [PubMed] [Google Scholar]
  205. Santi S., Leon MJ, Rusinek H., et al. Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging. 2001;22:529-539. [DOI] [PubMed] [Google Scholar]
  206. Chetelat G. , Desgranges B., de la Sayette V., et al. Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer's disease? Neurology. 2003;60:1374-1377. [DOI] [PubMed] [Google Scholar]
  207. Minoshima S., Foster NL, Sima AA, et al. Alzheimer's disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation . Ann Neurol. 2001;50:358-365. [DOI] [PubMed] [Google Scholar]
  208. Foster NL, Heidebrink JL, Clark CM, et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease. Brain. 2007;130: 2616-2635. [DOI] [PubMed] [Google Scholar]
  209. Mosconi L. , Tsui WH, Herholz K., et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias . J Nucl Med. 2008;49:390-398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  210. Shoghi-Jadid K., Small D., Agdeppa ED, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brain of living patients with Alzheimer disease . Am J Geriatr Psychiatry . 2002;10:24-35. [PubMed] [Google Scholar]
  211. Klunk WE, Engler H., Nordberg A., et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Ann Neurol. 2004;55:306-319. [DOI] [PubMed] [Google Scholar]
  212. Verhoeff NP , Wilson AA, Takeshita S., et al. In vivo imaging of Alzheimer disease beta-amyloid with [11C]SB13 PET. Am Geriatr Psychiatry. 2004;12:584-595. [DOI] [PubMed] [Google Scholar]
  213. Kudo Y., Okamura N., Forumoto S., et al. 2-(2-[2-Dimethylaminothiazol-5-yl]-ethenyl)-6-(2-[fluoro]ethoxy) benzoxazole: a novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer's disease patients. J Nucl Med. 2007;49:554-561. [DOI] [PubMed] [Google Scholar]
  214. Nordberg A. Amyloid imaging in Alzheimer's disease. Curr Opin Neurol. 2007;20:398-402. [DOI] [PubMed] [Google Scholar]
  215. Rabinovici GD, Furst AJ, O'Neil JP, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology. 2007;68:1205-1212. [DOI] [PubMed] [Google Scholar]
  216. Lockhart A. , Lamb JR, Osredkar T., et al. PIB is a nonspecific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Brain. 2007;130: 2607-2615. [DOI] [PubMed] [Google Scholar]
  217. Nordberg A. , Lundqvist H., Hartvig P., et al. Kinetic analysis of regional (S)-11C-nicotine binding in normal and Alzheimer brains - in vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord. 1995;9:21-27. [DOI] [PubMed] [Google Scholar]
  218. Rosén I. Electroencephalography as a diagnostic tool in dementia. Dement Geriatr Cogn Disord. 1997;8:110-116. [DOI] [PubMed] [Google Scholar]
  219. Jeong J. EEG dynamics in patients with Alzheimer's disease. Clin Neurophysiol . 2004;115:1490-505. [DOI] [PubMed] [Google Scholar]
  220. Adler G. The EEG as an indicator of cholinergic deficit in Alzheimer's disease . Fortschr Neurol Psychiatr. 2000;68:352-356. [DOI] [PubMed] [Google Scholar]
  221. Hooijer C. , Jonker C., Posthuma J., Visser SL Reliability, validity and follow-up of the EEG in senile dementia: sequelae of sequential measurement . Electroencephalogr Clin Neurophysiol. 1990. ;76:400-412. [DOI] [PubMed] [Google Scholar]
  222. Rosén I., Gustafson L., Risberg J. Multichannel EEG frequency analysis and somatosensory-evoked potentials in patients with different types of organic dementia. Dementia . 1993;4:43-49. [DOI] [PubMed] [Google Scholar]
  223. Jelic V., Shigeta M., Julin P., et al. Quantitative electroencephalography power and coherence in Alzheimer's disease and mild cognitive impairment. Dementia. 1996;7:314-323. [DOI] [PubMed] [Google Scholar]
  224. Olichney JM , Hillert DG Clinical applications of cognitive event-related potentials in Alzheimer's disease. Phys Med Rehabil Clin N Am. 2004;15:205-233. [DOI] [PubMed] [Google Scholar]
  225. Swanwick GR , Rowan MJ, Coen RF, et al. Prognostic value of electrophysiological markers in Alzheimer's disease. Am J Geriatr Psychiatry. 1999;7:335-338. [PubMed] [Google Scholar]
  226. Ford JM, Askari N., Mathalon DH, et al. Event-related brain potential evidence of spared knowledge in Alzheimer's disease. Psychol Aging. 2001;16:161-176. [DOI] [PubMed] [Google Scholar]
  227. Yokoyama Y. , Nakashima K., Shimoyama R., et al. Distribution of event-related potentials in patients with dementia. Electromyogr Clin Neurophysiol . 1995;35: 431-437. [PubMed] [Google Scholar]
  228. Pfefferbaum A., Wenegrat BG, Ford JM, et al. Clinical application of the P3 component of event-related potentials: II. dementia, depression and schizophrenia. Electroencephalogr Clin Neurophysiol. 1984;59:104-124. [DOI] [PubMed] [Google Scholar]
  229. Polich J., Pitzer A. P300 and Alzheimer's disease: odd-ball task difficulty and modality effects . Electroencephalogr Clin Neurophysiol. 1999. ;50:281-287. [PubMed] [Google Scholar]
  230. Iragui V., Kutas M., Salmon DP Event-related brain potentials during semantic categorization in normal aging and senile dementia of the Alzheimer's type. Electroencephalogr Clin Neurophysiol. 1996;100:392-406. [PubMed] [Google Scholar]
  231. Ford JM, Woodward SH, Sullivan EV, et al. N400 evidence of abnormal responses to speech in Alzheimer's disease. Electroencephalogr Clin Neurophysiol. 1996;99: 235-246. [DOI] [PubMed] [Google Scholar]
  232. Growdon JH, Corkin S. Neurochemical approaches to the treatment of senile dementia. Proc Annu Meet Am Psychopathol Assoc. 1980;69:281-296. [PubMed] [Google Scholar]
  233. Scarpini E. , Scheltens P., Feldman H. Treatment of Alzheimer's disease: current status and new perspectives. Lancet Neurol . 2003;2:539-547. [DOI] [PubMed] [Google Scholar]
  234. Klafki HW, Staufenbiel M., Kornhuber J., Wiltfang J. Therapeutic approaches to Alzheimer's disease. Brain . 2006;129:2840-2855. [DOI] [PubMed] [Google Scholar]
  235. Rogers SL, Farlow MR, Doody RS, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology. 1998;50:136-145. [DOI] [PubMed] [Google Scholar]
  236. Rösler M., Anand R., Cicin-Sain A., et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. BMJ. 1999;318:633-638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  237. Raskind MA , Peskind ER, Wessel T., Yuan W. Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology. 2000;54: 2261-2268. [DOI] [PubMed] [Google Scholar]
  238. Samochocki M., Höffle A., Fehrenbacher A., et al. Galantamine is an allosterically potentiating ligand of neuronal nicotinic but not of muscarinic acetylcholine receptors . J Pharmacol Exp Ther . 2003;305:1024-1036. [DOI] [PubMed] [Google Scholar]
  239. Doody RS, Dunn JK, Clark CM, et al. Chronic donepezil treatment is associated with slowed cognitive decline in Alzheimer's disease. Dement Geriatr Cogn Disord . 2001;12:295-300. [DOI] [PubMed] [Google Scholar]
  240. Birks J., Iakovidou V., Tsolaki M. Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2000; CD00 1191. [DOI] [PubMed] [Google Scholar]
  241. Birks JS, Harvey R. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2003; CD00 1190. [DOI] [PubMed] [Google Scholar]
  242. Loy C. , Schneider L. Galantamine for Alzheimer's disease . Cochrane Database Syst Rev. 2004; CD00 1747. [DOI] [PubMed] [Google Scholar]
  243. Bullock R. , Touchon J., Bergman H., et al. Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year period . Curr Med Res Opin. 2005;21:1317-1327. [DOI] [PubMed] [Google Scholar]
  244. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006; CD00 5593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  245. Burns A., O'Brien J., Auriacombe S., et al. Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology. J Psychopharmacol . 2006;20:732-755. [DOI] [PubMed] [Google Scholar]
  246. Gotti C., Riganti L., Vailati S., Clementi F. Brain neuronal nicotinic receptors as new targets for drug discovery . Curr Pharm Des. 2006;12:407-428. [DOI] [PubMed] [Google Scholar]
  247. Palmer GC Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies . Curr Drug Targets. 2001;2:241-271. [DOI] [PubMed] [Google Scholar]
  248. Parsons CG , Stöffler A., Danysz W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system-too little activation is bad, too much is even worse. Neuropharmacology . 2007;53:699-723. [DOI] [PubMed] [Google Scholar]
  249. Johnson JW , Kotermanski SE Mechanism of action of memantine . Curr Opin Pharmacol. 2006;6:61-67. [DOI] [PubMed] [Google Scholar]
  250. Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291:317-324. [DOI] [PubMed] [Google Scholar]
  251. McShane R. , Areosa Sastre A., Minakaran N. Memantine for dementia . Cochrane Database Syst Rev. 2006; CD00 3154. [DOI] [PubMed] [Google Scholar]
  252. Porsteinsson AP, Grossberg GT, Mintzer J., Olin JT, for the Memantine Mem-Md-12 Study Group. Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial . Curr Alzheimer Res. 2008;5:83-89. [DOI] [PubMed] [Google Scholar]
  253. Gauthier S. , Feldman H., Hecker J., et al. Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. Int Psychogeriatr. 2002;14:389-404. [DOI] [PubMed] [Google Scholar]
  254. Cummings JL , Koumaras B., Chen M., et al. Effects of rivastigmine treatment on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable Alzheimer's disease: a 26-week, multicenter, open-label study. Am J Geriatr Pharmacother. 2005;3:137-148. [DOI] [PubMed] [Google Scholar]
  255. Herrmann N. , Rabheru K., Wang J., Binder C. Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials . Am J Geriatr Psychiatry. 2005;13:527-534. [DOI] [PubMed] [Google Scholar]
  256. Gauthier S. , Wirth Y., Möbius HJ Effects of memantine on behavioural symptoms in Alzheimer's disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies . Int J Geriatr Psychiatry. 2005;20:459-464. [DOI] [PubMed] [Google Scholar]
  257. Cummings JL , Schneider E., Tariot PN, et al. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology. 2006;67:57-63. [DOI] [PubMed] [Google Scholar]
  258. Borson S., Raskind MA Clinical features and pharmacologic treatment of behavioral symptoms of Alzheimer's disease. Neurology. 1997;48:17-24. [DOI] [PubMed] [Google Scholar]
  259. Knopman DS Part VII. Treatment of neuropsychiatric symptoms in Alzheimer's disease. Dis Mon. 2000;46: 761-766. [DOI] [PubMed] [Google Scholar]
  260. Daiello LA Atypical antipsychotics for the treatment of dementia-related behaviors: an update. Med Health R I. 2007;90:191-194. [PubMed] [Google Scholar]
  261. Ballard C., Lana MM, Theodoulou M., et al. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial). PLoS Med. 2008;5:e76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  262. Meyers BS, Mei-Tal V. Psychiatric reactions during tricyclic treatment of the elderly reconsidered . J Clin Psychopharmacol. 1983;3:2-6. [PubMed] [Google Scholar]
  263. Nyth AL, Gottfries CG, Lyby K., et al. A controlled multicenter clinical study of citalopram and placebo in elderly patients with and without concomitant dementia. Acta Psychiatrica Scandinavica. 1992;86: 138-145. [DOI] [PubMed] [Google Scholar]
  264. Petracca GM , Chemerinski E., Starkstein SE A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease. Int. Psychogeriatrics. 2001;13:233-240. [DOI] [PubMed] [Google Scholar]
  265. Lyketsos CG , DelCampo L., Steinberg M., et al. Treating depression in Alzheimer Disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry. 2003;60: 737-746. [DOI] [PubMed] [Google Scholar]
  266. Grau-Veciana JM Treatment of non cognitive symptoms of Alzheimer's disease. Rev Neurol. 2006;42: 482-488. [PubMed] [Google Scholar]
  267. Mittelman MS, Ferris SH, Shulman E., et al. A family intervention to delay nursing home placement of patients with Alzheimer disease. A randomized controlled trial. JAMA. 1996;276:1725-1731. [PubMed] [Google Scholar]
  268. De Vreese LP, Neri M., Fioravanti M., et al. Memory rehabilitation in Alzheimer's disease: a review of progress. Int J Geriatr Psychiatry. 2001;16:794-809. [DOI] [PubMed] [Google Scholar]
  269. Fossey J., Ballard C., Juszczak E., et al. Effect of enhanced psychosocial care on antipsychotic use in nursing home residents with severe dementia: cluster randomised trial. BMJ. 2006;332:756-761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  270. Grossberg GT The ABC of Alzheimer's disease: behavioral symptoms and their treatment. Int Psychogeriatr. 2002;14:27-49. [DOI] [PubMed] [Google Scholar]
  271. Wilson BA, Evans JJ, Emslie H., Malinek V. Evaluation of NeuroPage: a new memory aid. J Neurol Neurosurg Psychiatry. 1997;63:113-115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  272. Clare L., Wilson BA, Carter G., et al. Intervening with everyday memory problems in dementia of Alzheimer type: an errorless learning approach. J Clin Exp Neuropsychol . 2000;22:132-146. [DOI] [PubMed] [Google Scholar]
  273. Spector A. , Thorgrimsen L., Woods B., et al. Efficacy of an evidence -based cognitive stimulation therapy programme for people with dementia Randomised controlled trial. Br J Psychiatry. 2003;183:248-254. [DOI] [PubMed] [Google Scholar]
  274. Berry E., Kapur N., Williams L., et al. The use of a wearable camera, SenseCam, as a pictorial diary to improve autobiographical memory in a patient with limbic encephalitis: a preliminary report. Neuropsychol Rehabil. 2007;17:582-601. [DOI] [PubMed] [Google Scholar]
  275. Woods RT Discovering the person with Alzheimer's disease: cognitive, emotional and behavioural aspects. Aging Ment Health. 2001. ;5:S7-S16. [PubMed] [Google Scholar]
  276. Kitwood T. , Bredin K. Towards a theory of dementia care: personhood and well-being. Ageing Soc. 1992. ;12: 269-287. [DOI] [PubMed] [Google Scholar]
  277. McGeer PL, McGeer EG NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging. 2007;28:639-647. [DOI] [PubMed] [Google Scholar]
  278. Mintzer JE , Wilcock GK, Black SE, et al. P2-412 MPC-7869 (R-flurbiprofen), a selective Ab42-lowering agent, delays time to clinically significant psychiatric events in Alzheimer's disease (AD): Analysis from a 12-month phase 2 trial . Alz Dem. 2007;3:99-100. [Google Scholar]
  279. Wilcock GK , Black SE, Hendrix SB, et al. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurol. 2008;7:483-493. [DOI] [PubMed] [Google Scholar]
  280. Weggen S., Rogers M., Eriksen J. NSAIDs: small molecules for prevention of Alzheimer's disease or precursors for future drug development? Trends Pharmacol Sci. 2007;28:536-543. [DOI] [PubMed] [Google Scholar]
  281. Rockwood K. Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer's disease. Acta Neurol Scand Suppl. 2006;185:71-77. [DOI] [PubMed] [Google Scholar]
  282. Zhou B., Teramukai S., Fukushima M. Prevention and treatment of dementia or Alzheimer's disease by statins: a meta-analysis. Dement Geriatr Cogn Disord. 2007;23: 194-201. [DOI] [PubMed] [Google Scholar]
  283. Li G., Larson EB, Sonnen JA, et al. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology. 2007;69:878-885. [DOI] [PubMed] [Google Scholar]
  284. Arvanitakis Z., Schneider JA, Wilson RS, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology . 2008;70:1795-1802. [DOI] [PubMed] [Google Scholar]
  285. Wolozin B. , Manger J., Bryant R., et al. Re-assessing the relationship between cholesterol, statins and Alzheimer's disease. Acta Neurol Scand Suppl. 2006;185:63-70. [DOI] [PubMed] [Google Scholar]
  286. Ostrowski SM, Wilkinson BL, Golde TE, Landreth G. Statins reduce amyloid-beta production through inhibition of protein isoprenylation. J Biol Chem. 2007;282: 26832-26844. [DOI] [PubMed] [Google Scholar]
  287. Parsons RB , Farrant JK, Price GC, et al. Regulation of the lipidation of beta-secretase by statins. Biochem Soc Trans . 2007;35:577-582. [DOI] [PubMed] [Google Scholar]
  288. Jaffe AB, Toran-Allerand CD, Greengard P., et al. Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. J Biol Chem. 1994;269:13065-13068. [PubMed] [Google Scholar]
  289. Yaffe K., Sawaya G., Lieberburg I., et al. Estrogen therapy in postmenopausal women. Effects on cognitive function and dementia. JAMA. 1998;279:688-695. [DOI] [PubMed] [Google Scholar]
  290. Hogervorst E., Williams J., Budge M., et al. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis. Neuroscience. 2000. ;101: 485-512. [DOI] [PubMed] [Google Scholar]
  291. LeBlanc ES, Janowsky J., Chan BKS, et al. Hormone replacement therapy and cognition. Systematic review and meta-analysis. JAMA. 2001;285:1489-1499. [DOI] [PubMed] [Google Scholar]
  292. Nathan BP, Barsukova AG, Shen F., et al. Estrogen facilitates neurite extension via apolipoprotein E in cultured adult mouse cortical neurons. Endocrinology. 2004;145:3065-3073. [DOI] [PubMed] [Google Scholar]
  293. Shumaker SA, Legault C., Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289:2651-2662. [DOI] [PubMed] [Google Scholar]
  294. Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: The Cache County Study. Arch Neurol. 2004;61:82-88. [DOI] [PubMed] [Google Scholar]
  295. Maxwell CJ , Hicks MS, Hogan DB, et al. Supplemental use of antioxidant vitamins and subsequent decline and dementia. Dement Geriatr Cogn Disord . 2005;20: 45-51. [DOI] [PubMed] [Google Scholar]
  296. Gray SL, Anderson ML, Crane PK, et al. Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in older adults. J Am Geriatr Soc. 2008;56:291-295. [DOI] [PubMed] [Google Scholar]
  297. Postina R. , Schroeder A., Dewachter I., et al. A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest. 2004;113: 1456-1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  298. Fisher A. M1 muscarinic agonists target major hallmarks of Alzheimer's disease-an update . Curr Alzheimer Res. 2007;4:577-580. [DOI] [PubMed] [Google Scholar]
  299. Fahrenholz F., Postina R. Alpha-secretase activation-an approach to Alzheimer's disease therapy. Neurodegener Dis. 2006;3:255-261. [DOI] [PubMed] [Google Scholar]
  300. Laird FM, Cai H., Savonenko AV, et al. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci. 2005;25:11693-11709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  301. Ghosh AK, Kumaragurubaran N., Hong L., et al. Memapsin 2 (beta-secretase) inhibitors: drug development. Curr Alzheimer Res. 2008;5:121-131. [DOI] [PubMed] [Google Scholar]
  302. Iserloh U. , Pan J., Stamford AW, et al. Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor. Bioorg Med Chem Lett. 2008;18:418-422. [DOI] [PubMed] [Google Scholar]
  303. Imbimbo BP Therapeutic potential of gamma-secretase inhibitors and modulators. Curr Top Med Chem. 2008;8:54-61. [DOI] [PubMed] [Google Scholar]
  304. Icad 2008. Alzheimer's Association International Conference on Alzheimer's Disease: Abstract 03-04-01. Presented July 29, 2008. [Google Scholar]
  305. Gervais F. , Chalifour R., Garceau D., Kong X., Laurin J., Mclaughlin J., Morissette C., Paquette J. Glycosaminoglycan mimetics: a therapeutic approach to cerebral amyloid angiopathy. Amyloid. 2001;8:28-35. [PubMed] [Google Scholar]
  306. Aisen PS, Saumier D., Briand R., et al. A Phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurology. 2006;67:1757-1763. [DOI] [PubMed] [Google Scholar]
  307. Aisen PS, Gauthier S., Vellas B., et al. Alzhemed: A Potential Treatment for Alzheimer's Disease. Curr Alz Res. 2007;4:473-478. [DOI] [PubMed] [Google Scholar]
  308. Necula M., Kayed R., Milton S., Glabe CG Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct. J Biol Chem. 2007;282: 10311-10324. [DOI] [PubMed] [Google Scholar]
  309. Santa-Maria I., Hernández F., Del Rio J., et al. Tramiprosate, a drug of potential interest for the treatment of Alzheimer's disease, promotes an abnormal aggregation of tau. Mol Neurodegener. 2007;2:17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  310. Schenk D., Barbour R., Dunn W., et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999. ;400: 173-177. [DOI] [PubMed] [Google Scholar]
  311. Gilman S., Koller M., Black RS, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64:1553-1562. [DOI] [PubMed] [Google Scholar]
  312. Brody DL, Holtzman DM Active and Passive Immunotherapy for Neurodegenerative Disorders. Annu Rev Neurosci. 2008;31:175-193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  313. Dodart JC, Bales KR, Gannon KS, et al. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat Neurosci. 2002;5:452-457. [DOI] [PubMed] [Google Scholar]
  314. Takashima A. GSK-3 is essential in the pathogenesis of Alzheimer's disease. J Alzheimers Dis. 2006. ;9: 309-317. [DOI] [PubMed] [Google Scholar]
  315. Avila J., Hernández F. GSK-3 inhibitors for Alzheimer's disease. Expert Rev Neurother . 2007;7:1527-1533. [DOI] [PubMed] [Google Scholar]
  316. Hong M., Chen DC, Klein PS, Lee VM Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3 . J Biol Chem. 1997;272:25326-25332. [DOI] [PubMed] [Google Scholar]
  317. Phiel CJ, Wilson CA, Lee VM, Klein PS GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides . Nature. 2003;423:435-439. [DOI] [PubMed] [Google Scholar]
  318. Feyt C., Kienlen-Campard P., Leroy K., et al. Lithium chloride increases the production of amyloid-beta peptide independently from its inhibition of glycogen synthase kinase 3. J Biol Chem. 2005;280:33220-33227. [DOI] [PubMed] [Google Scholar]
  319. Forlenza OV , Spink JM, Dayanandan R., et al. Muscarinic agonists reduce tau phosphorylation in non-neuronal cells via GSK-3beta inhibition and in neurons. J Neural Transm. 2000;107:1201-1212. [DOI] [PubMed] [Google Scholar]
  320. Tuszynski MH Nerve growth factor gene therapy in Alzheimer disease. Alzheimer Dis Assoc Disord. 2007;21: 179-189. [DOI] [PubMed] [Google Scholar]
  321. Eriksdotter Jönhagen M., Nordberg A., et al. Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease . Dement Geriatr Cogn Disord. 1998;9:246-257. [DOI] [PubMed] [Google Scholar]
  322. Tuszynski MH , Thal L., Pay M., et al. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med . 2005;11:551-555. [DOI] [PubMed] [Google Scholar]
  323. Terry AV Jr, Buccafusco JJ The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003;306: 821-827. [DOI] [PubMed] [Google Scholar]
  324. Seabrook GR , Ray WJ, Shearman M., Hutton M. Beyond amyloid: the next generation of Alzheimer's diseasse therapeutics. Mol Interv. 2007;7:261-270. [DOI] [PubMed] [Google Scholar]

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