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Cited by 81Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Alzheimer Disease

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Caselli, Richard J., Beach, Thomas G., Knopman, David S., Graff-Radford, Neill R.·2017·Mayo Clinic Proceedings
DOI 10.1016/j.mayocp.2017.02.011PMC PMC5536337
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Abstract

Alzheimer disease (AD) was originally conceived as a rare disease that caused presenile dementia but has come to be understood as the most prevalent cause of dementia at any age worldwide. It has an extended preclinical phase characterized by sequential changes in imaging and cerebrospinal fluid biomarkers with subtle memory decline beginning more than a decade before the emergence of symptomatic memory loss heralding the beginning of the mild cognitive impairment stage. The apolipoprotein E ε4 allele is a prevalent and potent risk factor for AD that has facilitated research into its preclinical phase. Cerebral Aβ levels build from preclinical through early dementia stages followed by hyperphosphorylated tau-related pathology, the latter driving cognitive deficits and dementia severity. Structural and molecular imaging can now recapitulate the neuropathology of AD antemortem. Autosomal dominant forms of early-onset familial AD gave rise to the amyloid hypothesis of AD, which, in turn, has led to therapeutic trials of immunotherapy designed to clear cerebral amyloid, but to date results have been disappointing. Genome-wide association studies have identified multiple additional risk factors, but to date none have yielded an effective alternate therapeutic target. Current and future trials aimed at presymptomatic individuals either harboring cerebral amyloid or at genetically high risk offer the hope that earlier intervention might yet succeed where trials in patients with established dementia have failed. A major looming challenge will be that of expensive, incompletely effective disease-modifying therapy: who and when to treat, and how to pay for it.

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  • Clinical features lack specificity for a pathologic process, but rather indicate brain regions or systems affected by the disease process.

    “clinical features lack specificity for a pathologic process, but rather indicate brain regions or systems affected by the disease process [3, 4].”

    From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [4]

    The Clinical Background section says that variant Alzheimer syndromes reflect different pathological topography, with visual impairment linked to involvement of visual cortices. That supports the point that clinical features can indicate affected brain regions. The copy does not establish the broader claim that clinical features generally lack specificity for the underlying pathologic process. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Alzheimer's pathology can be found in cognitively normal patients at autopsy, and this preclinical phase can also be observed in patients with mild cognitive impairment that do not meet criteria for clinical AD.

    “Alzheimer’s pathology can be found in cognitively normal patients at the time of autopsy, and this preclinical phase can also be observed in patients with mild cognitive impairment that do not meet the criteria for clinical AD [4, 23].”

    From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [4]

    Section VII, Possible Solutions, reports AD pathology at autopsy in people who appeared cognitively normal. Section II, Clinical Background, also reports AD pathology in patients diagnosed with MCI, but the paper distinguishes symptomatic MCI from the preclinical phase, when no symptoms are evident. It therefore does not support calling MCI part of that preclinical phase. Page numbers are not available in our copy. (LLM, conf=0.88)

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References 158 · Cited by 81

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  1. [2]Katzman R The prevalence and malignancy of Alzheimer disease. A Major Killer Arch Neurol 1976 33 4 217 218 1259639
  2. [3]Terry RD My own experience in early research on Alzheimer disease J Alzheimers Dis 2006 9 3 suppl 117 119 17004364
  3. [4]Petersen RC Smith GE Ivnik RJ Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals JAMA 1995 273 16 1274 1278 7646655
  4. [5]Petersen RC Smith GE Waring SC Mild cognitive impairment: clinical characterization and outcome Arch Neurol 1999 56 3 303 308 10190820
  5. [7]Petersen RC Doody R Kurz A Current concepts in mild cognitive impairment Arch Neurol 2001 58 12 1985 1992 11735772
  6. [8]Winblad B Palmer K Kivipelto M Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment J Intern Med 2004 256 3 240 246 15324367
  7. [9]Ganguli M Dodge HH Shen C Mild cognitive impairment, amnestic type: an epidemiologic study Neurology 2004 63 1 115 121 15249620
  8. [10]Morris JC Storandt M Miller JP Mild cognitive impairment represents early-stage Alzheimer disease Arch Neurol 2001 58 3 397 405 11255443
  9. [11]Jicha GA Parisi JE Dickson DW Neuropathologic outcome of mild cognitive impairment following progression to dementia Arch Neurol 2006 63 5 674 681 16682537
  10. [13]McKhann GM Knopman DS Chertkow H The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workshops on diagnostic guidelines for Alzheimer’s disease Alz Dem 2011 7 3 263 269 PMC3312024 21514250
  11. [14]Tang-Wai DF Graff-Radford NR Boeve BF Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy Neurology 2004 63 7 1168 1174 15477533
  12. [15]Gorno-Tempini ML Brambati SM Ginex V The logopenic/phonological variant of primary progressive aphasia Neurology 2008 71 16 1227 1234 18633132 PMC2676989
  13. [16]Caselli RJ Stelmach GE Caviness JN A kinematic study of progressive apraxia with and without dementia Mov Disord 1999 14 2 276 287 10091622
  14. [18]Johnson JK Head E Kim R Clinical and pathological evidence for a frontal variant of Alzheimer disease Arch Neurol 1999 56 10 1233 1239 10520939
  15. [19]Khachaturian ZS Diagnosis of Alzheimer’s disease Arch Neurol 1985 42 11 1097 1105 2864910
  16. [20]Mirra SS Heyman A McKeel D The Consortium to establish a Registry for Alzheimer’s Disease (CERAD) Part II. Standardization of the neuropathological assessment of Alzheimer’s disease Neurology 1991 41 4 479 486 2011243
  17. [22]Braak H Braak E Staging of Alzheimer’s disease-related neurofibrillary changes Neurobiol Aging 1995 16 3 271 284 7566337
  18. [23]NIA and Reagan Institute Working Group Consensus Recommendations for the postmortem diagnosis of Alzheimer’s disease Neurobiol Aging 1997 18 suppl 4 S1 S2 9330978
  19. [24]Thal DR Rub U Orantes M Braak H Phases of AB-deposition in the human brain and its relevance for the development of AD Neurology 2002 58 12 1791 1800 12084879
  20. [25]Thal DR Arendt T Waldmann G Holzer M Zedlick D Rub U Schober R Progression of neurofibrillary changes and PHF-tau in end-stage Alzheimer’s disease is different from plaque and cortical microglial pathology Neurobiol Aging 1998 19 6 517 525 10192210
  21. [26]Dugger BN Davis K Malek-Ahmadi M Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment BMC Neurol 2015 8 20 15 146 10.1186/s12883-015-0403-4 Accessed December 20, 2016 26289075 PMC4545878 · DOI
  22. [27]Kawas CH Kim RC Sonnen JA Bullain SS Trieu T Corrada MM Multiple pathologies are common and related to dementia in the oldest-old: the 90+ study Neurology 2015 85 6 535 542 26180144 PMC4540246
  23. [28]Zheng L Vinters HV Mack WJ Differential effects of ischemic vascular disease and Alzheimer’s disease on brain atrophy and cognition J Cereb Blood Flow Metab 2016 36 1 204 215 26126864 PMC4758550
  24. [29]White LR Edland SD Hemmy LS Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies Neurology 2016 86 11 1000 1008 26888993 PMC4799714
  25. [30]Ringman JM Monsell S Ng DW Neuropathology of autosomal dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database J Neuropathol Exp Neurol 2016 75 3 284 290 26888304 PMC4934612
  26. [31]Arvanitakis Z Capuano AW Leurgans SE Bennett DA Schneider JA Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross sectional study Lancet Neurol 2016 15 9 934 943 27312738 PMC4969105
  27. [32]Beach TG Adler CH Sue LI Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program Neuropathology 2015 35 4 354 389 25619230 PMC4593391
  28. [34]Gurland BJ Wilder DE Lantigua R Rates of dementia in three ethnoracial groups Int J Geriatr Psychiatry 1999 14 6 481 493 10398359
  29. [35]Glymour MM Manly JJ Lifecourse social conditions and racial and ethnic patterns of cognitive aging Neuropsychol Rev 2008 18 3 223 254 18815889
  30. [36]Graff-Radford NR Besser LM Crook JE Kukull WA Dickson DW Neuropathologic differences by race from the National Alzheimer’s Coordinating Center Alz Dem 2016 12 6 669 677 PMC4903907 27094726
  31. [40]St George-Hyslop PH Tanzi RE Polinsky RJ The genetic defect causing familial Alzheimer’s disease maps on chromosome 21 Science 1987 235 4791 885 890 2880399
  32. [41]Schellenberg GD Bird TD Wijsman EM Genetic linkage evidence for a familial Alzheimer’s disease locus on chromosome 14 Science 1992 258 5028 668 671 1411576
  33. [43]DeStrooper B Saftog B Craessaerts K Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein Nature 1998 391 6665 387 390 9450754
  34. [45]Tharp WG Sarkar IN Origins of amyloid-B BMC Genomics 2013 4 30 14 290 10.1186/1471-2164-14-290 Accessed December 30, 2016 23627794 PMC3660159 · DOI
  35. [46]von Kock CS Zheng H Chen H Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice Neurobiol Aging 1997 18 6 661 669 9461064
  36. [47]Joshi P Liang JO DiMonte K Sullivan J Pimplikar SW Amyloid precursor protein is required for convergent-extension movements during zebrafish development Dev Biol 2009 335 1 1 11 19664615
  37. [48]Spalding KL Bergmann O Alkass K Dynamics of hippocampal neurogenesis in adult humans Cell 2013 153 6 1219 1227 23746839 PMC4394608
  38. [49]Dennis CV Suh LS Rodriguez ML Kril JJ Sutherland GT Human adult neurogenesis across the ages: an immunohistochemical study Neuropathol Appl Neurobiol 2016 12 42 7 621 638 10.1111/nan.12337 Epub 2016 Aug 28 Accessed December 30, 2016 27424496 PMC5125837 · DOI
  39. [50]Demars MP Batholomew A Strakova Z Lazarov O Soluble amyloid precursor protein: a novel proliferation factor of adult progenitor cells of ectodermal and mesodermal origin Stem Cell Res Ther 2011 8 30 2 4 36 10.1186/scrt77 Accessed January 3, 2017 21878106 PMC3219067 · DOI
  40. [51]Freude KK Penjwini M Davis JL LaFerla FM Blurton-Jones M Soluble amyloid precursor protein induces rapid neural differentiation of human embryonic stem cells J Biol Chem 286 27 24264 24274 PMC3129207 21606494
  41. [52]Pimplikar SW Ghosal K Amyloid precursor protein: more than just neurodegeneration Stem Cell Res Ther 10 14 2 5 39 10.1186/scrt80 PMC3308036 22000643 · DOI
  42. [53]Cirrito JR Yamada KA Finn MB Synaptic activity regulates interstitial fluid amyloid- β levels in vivo Neuron 2005 48 913 922 16364896
  43. [55]Wang Y Cella M Mallinson K TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model Cell 2015 160 6 1061 1071 25728668 PMC4477963
  44. [57]Clavaguera F Akatsu H Fraser G Brain homogenates from human tauopathies induce tau inclusions in mouse brain Proc Natl Acad Sci USA 2013 110 23 9535 9540 23690619 PMC3677441
  45. [59]Edgren G Hjalgrim H Rostgaard K Transmission of neurodegenerative disorders through blood transfusion: a cohort study Ann Intern Med 2016 165 5 316 24 27368068
  46. [61]Orgogozo JM Gilman S Dartigues JF Subacute meningoencephalitis in a subset of patients with AD after AB42 immunization Neurology 2003 61 1 46 54 12847155
  47. [64]Patton RL Kalback WM Esh CL Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer's disease patients: a biochemical analysis Am J Pathol 2006 169 3 1048 1063 16936277 PMC1698828
  48. [65]Siemers ER Sundell KL Carlson C Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer’s disease patients Alz Dem 2016 12 2 110 120 26238576
  49. [66]Karran E Hardy J A critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease Ann Neurol 2014 76 2 185 205 24853080 PMC4204160
  50. [67]Hyman BT Marzloff K Arriagada PV The lack of accumulation of senile plaques or amyloid burden in Alzheimer’s disease suggests a dynamic balance between amyloid deposition and resolution J Neuropathol Exp Neurol 1993 52 6 594 600 8229078
  51. [68]Hyman BT Amyloid-dependent and amyloid-independent stages of Alzheimer disease Arch Neurol 2011 68 8 1062 1064 21482918
  52. [69]Sankaranarayanan S Barten DM Vana L Passive immunization with phosphor-tau antibodies reduces tau pathology and functional deficits in two distinct mouse tauopathy models PLoS One 2015 5 1 10 5 e0125614 10.1371/journal.pone.0125614 25933020 PMC4416899 · DOI
  53. [72]Corder EH Saunders AM Strittmatter WJ Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families Science 1993 261 5123 921 923 8346443
  54. [73]Saunders AM Strittmatter WJ Schmechel D Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease Neurology 1993 43 8 1467 1472 8350998
  55. [75]Caselli RJ Walker D Sue L Sabbagh M Beach T Amyloid load in nondemented brains correlates with APOE e4 Neurosci Lett 2010 473 3 168 171 20153809 PMC2851172
  56. [76]Reiman EM Caselli RJ Yun LS Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E New Engl J Med 1996 334 12 752 8 8592548
  57. [77]Reiman EM Caselli RJ Chen K Alexander GE Bandy D Frost J Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease Proc Natl Acad Sci U S A 2001 98 6 3334 9 11248079 PMC30654
  58. [79]Den Heijer T Oudkerk M Launer LJ van Duijn CM Hofman A Breteler MM Hippocampal, amygdalar, and global brain atrophy in different apolipoprotein E genotypes Neurology 2002 59 5 746 748 12221169
  59. [80]Caselli RJ Dueck AC Osborne D Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect New Engl J Med 2009 361 3 255 63 19605830 PMC2928998
  60. [81]Caselli RJ Locke DE Dueck AC The neuropsychology of normal aging and preclinical Alzheimer's disease Alzheimers Dement 2014 10 1 84 92 23541188 PMC3700591
  61. [82]Snowdon DA Kemper SJ Mortimer JA Greiner LH Wekstein DR Markesbery WR Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life. Findings from the Nun Study JAMA 1996 275 7 528 532 8606473
  62. [83]Reiman EM Chen KW Alexander GE Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia Proc Natl Acad Sci U S A 2004 101 1 284 289 14688411 PMC314177
  63. [87]Fleisher AS Chen K Liu X Apolipoprotein E e4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease Neurobiol Aging 2013 34 1 1 2 22633529
  64. [89]Sevigny J Chiao P Bussiere T The antibody aducanumab reduces AB plaques in Alzheimer’s disease Nature 2016 537 7618 50 58 27582220
  65. [90]Sperling RA Aisen PS Beckett LA Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease Alz Dem 2011 7 280 292 PMC3220946 21514248
  66. [92]Nelson PT Head E Schmitt FA Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies Acta Neuropathol 2011 12 5 571 587 PMC3179861 21516511
  67. [94]Reiman EM Quiroz YT Fleisher AS Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer’s disease in the presenilin 1 E280A kindred: a case-control study Lancet Neurol 2012 11 12 1048 1056 23137948 PMC4181671
  68. [96]Jack CR Jr Petersen RC O’Brien PC Tangalos EG MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease Neurology 1992 42 1 183 188 1734300
  69. [98]Yu P Sun J Wolz R Operationalizing hippocampal volume as an enrichment biomarker for amnestic mild cognitive impairment trials: effect of algorithm, test-retest variability, and cut point on trial cost, duration, and sample size Neurobiol Aging 2014 35 4 808 818 24211008 PMC4201941
  70. [99]Knopman DS Jack CR Jr Wiste HJ Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia Neurology 2016 87 691 698 27421543 PMC4999168
  71. [100]Klunk WE Engler H Nordberg A Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound–B Ann Neurol 2004 55 3 306 319 14991808
  72. [101]Wong DF Rosenberg PB Zhou Y In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir F18) J Nucl Med 2010 51 6 913 920 20501908 PMC3101877
  73. [102]Vandenberghe R Van Laere K Ivanoiu A 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial Ann Neurol 2010 68 3 319 329 20687209
  74. [103]Clark CM Pontecorvo MJ Beach TG Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study Lancet Neurol 2012 11 669 678 22749065
  75. [106]Beach TG Schneider JA Sue LI Theoretical impact of Florbetapir (18F) amyloid imaging on diagnosis of alzheimer dementia and detection of preclinical cortical amyloid J Neuropathol Exp Neurol 2014 73 948 953 25192053 PMC4169306
  76. [108]Johnson KA Schultz A Betensky RA Tau positron emission tomographic imaging in aging and early Alzheimer disease Ann Neurol 2016 79 1 110 119 26505746 PMC4738026
  77. [109]Ossenkoppele R Schonhaut DR Scholl M Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease Brain 2016 139 Pt5 1551 1567 26962052 PMC5006248
  78. [110]Hoffman JM Welsh-Bohmer KA Hanson M FDG-PET imaging in patients with pathologically verified dementia J Nucl Med 2000 41 1920 1928 11079505
  79. [111]Olsson B Lautner R Andreasson U CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis Lancet Neurology 2016 15 7 673 684 27068280
  80. [112]Bateman RJ Wen G Morris JC Holtzman DM Fluctuations of CSF amyloid-beta levels: implications for a diagnostic and therapeutic biomarker Neurology 2007 68 9 666 669 17325273
  81. [113]Mattson N Andreasson U Persson S The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers Alz Dem 2011 7 4 386 395 PMC3710290 21784349
  82. [114]Freer R Sormanni P Vecchi G Ciryam P Dobson CM Vendruscolo M A protein homeostasis signature in healthy brains recapitulates tissue vulnerability to Alzheimer’s disease Sci Adv 2016 8 10 2 8 e1600947 10.1126/sciadv.1600947 Accessed August 23, 2016 27532054 PMC4980108 · DOI
  83. [115]Gatz M Reynolds CA Fratiglioni L Role of genes and environments for explaining Alzheimer disease Arch Gen Psychiatry 2006 63 2 168 174 16461860
  84. [116]Van Cauwenberghe C Van Broeckhoven C Sleegers K The genetic landscape of Alzheimer disease: clinical implications and perspectives Genet Med 2016 18 5 421 430 26312828 PMC4857183
  85. [117]Head E Lott IT Down syndrome and beta-amyloid deposition Curr Opin Neurol 2004 17 2 95 100 15021233
  86. [118]Szaruga M Veugelen S Benurwar M Qualitative changes in human gamm-secretase underlie familial Alzheimer’s disease J Exp Med 2015 212 12 2003 2013 26481686 PMC4647268
  87. [119]Gerdes LU Klausen IC Sihm I Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world Genet Epidemiol 1992 9 3 155 167 1381696
  88. [120]Corbo RM Scacchi R Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele? Ann Hum Genet 1999 63 Pt. 4 301 310 10738542
  89. [122]Huang Y Mahley RW Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer’s diseases Neurobiol Dis 2014 72 Pt. A 3 12 25173806 PMC4253862
  90. [123]Genin E Hannequin D Wallon D APOE and Alzheimer disease: a major gene with semi-dominant inheritance Mol Psychiatry 2011 16 9 903 907 21556001 PMC3162068
  91. [124]Roses AD Lutz MW Amrine-Madsen H A TOMM40 variable length polymorphism predicts the age of late-onset Alzheimer’s disease Pharmacogenomics Journal 2009 10 10 5 375 84 10.1038/tpj.2009.69 20029386 PMC2946560 · DOI
  92. [125]Nalbantoglu J Gilfix BM Bertrand P Predictive value of apolipoprotein E genotyping in Alzheimer's disease: results of an autopsy series and an analysis of several combined studies Ann Neurol 1994 36 6 889 895 7998776
  93. [127]Pomeraniec IJ Bond AE Lopes MB Jane JA Sr Concurrent Alzheimer’s pathology in patients with clinical normal pressure hydrocephalus: correlation with high-volume lumbar puncture results, cortical brain biopsies, and outcomes J Neurosurg 2016 124 2 382 388 26339853
  94. [128]Caselli RJ Woodruff BK The clinical impact of amyloid PET: is it worth the cost? JAMA Neurol 2016 73 12 1396 1398 27802483
  95. [129]Green RC Roberts JS Cupples LA Disclosure of APOE genotype for risk of Alzheimer’s disease New Engl J Med 2009 361 3 245 254 19605829 PMC2778270
  96. [130]Caselli RJ Langbaum J Marchant GE Public perceptions of presymptomatic testing for Alzheimer disease Mayo Clin Proc 2014 89 10 1389 96 25171823 PMC4369785
  97. [131]Rogers SL Farlow MR Doody RS A 24-week, double-blind, placebo controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group Neurology 1998 50 1 136 145 9443470
  98. [132]Rosler M Anand R Cicin-Sain A Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial BMJ 1999 318 7184 633 638 10066203 PMC27767
  99. [133]Raskind MA Peskind ER Wessel T Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group Neurology 2000 54 12 2261 2268 10881250
  100. [134]Reisberg B Doody R Stoffler A Memantine in moderate-to-severe Alzheimer's disease New Engl J Med 2003 348 14 1333 1341 12672860
  101. [135]Aisen PS Schaefer KA Grundman M Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial JAMA 2003 289 21 2819 2826 12783912
  102. [136]Shumaker SA Legault C Rapp SR 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 20 2651 2662 12771112
  103. [137]Petersen RC Thomas RG Grundman M Vitamin E and donepezil for the treatment of mild cognitive impairment New Engl J Med 2005 352 23 2379 2388 15829527
  104. [138]Aisen PS Schneider LS Sano M High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial JAMA 2008 300 15 1774 1783 18854539 PMC2684821
  105. [139]DeKosky ST Williamson JD Fitzpatrick AL Ginkgo biloba for prevention of dementia: a randomized controlled trial JAMA 2008 300 19 2253 2262 19017911 PMC2823569
  106. [140]Feldman HH Doody RS Kivipelto M Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe Neurology 2010 74 12 956 964 20200346
  107. [141]Scarmeas N Stern Y Tang MX Mediterranean diet and risk for Alzheimer's disease Ann Neurol 2006 59 6 912 921 16622828 PMC3024594
  108. [142]Geda YE Roberts RO Knopman DS Physical exercise, aging, and mild cognitive impairment: a population-based study Arch Neurol 2010 67 1 80 86 20065133 PMC2919839
  109. [145]Stern Y Albert S Tang MX Tsai WY Rate of memory decline in AD is related to education and occupation: cognitive reserve? Neurology 1999 53 9 1942 1947 10599762
  110. [146]Bennett DA Arnold SE Valenzuela MJ Brayne C Schneider JA Cognitive and social lifestyle: links to neuropathology and cognition in later life Acta Neuropathol 2014 127 1 137 150 24356982 PMC4054865
  111. [147]Caselli RJ Dueck AC Locke DE Baxter LC Woodruff BK Geda YE Sex-based memory advantages and cognitive aging: a challenge to the cognitive reserve construct? J Int Neuropsychol Soc 2015 21 2 95 104 25665170 PMC4785799
  112. [148]Cummings J Isaacson S Mills R Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial Lancet 2014 383 9916 533 540 24183563
  113. [149]Schneider LS Dagerman K Insel PS Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials Am J Geriatr Psychiatry 2006 14 3 191 210 16505124
  114. [150]Schneider LS Tariot PN Dagerman KS Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease New Engl J Med 2006 355 15 1525 1538 17035647
  115. [151]Kurlan R Cummings J Raman R Thal L for the ADCS Quetiapine for agitation or psychosis in patients with dementia and parkinsonism Neurology 2007 68 17 1356 1363 17452579
  116. [152]Wang PS Schneeweiss S Avorn J Risk of death in elderly users of conventional vs. atypical antipsychotic medications New Engl J Med 2005 353 22 2335 2341 16319382

Authors
Caselli, R. J., Beach, T. G., Knopman, D. S., & Graff-Radford, N. R.
Affiliations
  • Mayo Clinic (US)
  • Banner Sun Health Research Institute (US)
Corresponding author
Caselli, Richard J.
ORCID
Venue
Mayo Clinic Proceedings
Publisher
Elsevier BV
Published
2017-06
Volume
92
Issue
6
Pages
978-994
ISSN
0025-6196 (ISSN-L)
DOI
10.1016/j.mayocp.2017.02.011
PMC
PMC5536337
OpenAlex
W2732154503
Cited by
81
References
158
Citations by year
2026: 1 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 13 · 2019: 9 · 2018: 16 · 2017: 6
FWCI
1.48
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Mayo Clinic Proceedings (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG044372, U01AG006786, R01AG031581, P30AG019610, R21AG044723, R01AG041851, P50AG016574)
  • National Institute of Neurological Disorders and Stroke (R21NS093222, U24NS072026)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, preclinical Alzheimer's disease, mild cognitive impairment, APOE ε4, amyloid-beta, tau hyperphosphorylation, cerebrospinal fluid biomarkers, anti-amyloid therapy, disease-modifying therapy, presymptomatic treatment, dementia risk factors, genome-wide association study
MeSH terms
Aging, Alzheimer Disease, Apolipoproteins E, Brain, Humans, Magnetic Resonance Imaging

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