CoChat
Sign Up
Cited by 67Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

The road ahead to cure Alzheimer’s disease: development of biological markers and neuroimaging methods for prevention trials across all stages and target populations

Open access
Cavedo, E., Lista, S., Khachaturian, Z., Aisen, P., Amouyel, P., Herholz, K., Jack Jr, C.R., Sperling, R. +23 more·2014·The Journal of Prevention of Alzheimer's Disease
DOI 10.14283/jpad.2014.32PMC PMC4606938
Open this paper in CoChat — free account

Abstract

Alzheimer's disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group's revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard ("core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ 1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1- 40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for “prodromal AD” and "mild cognitive impairment due to AD" include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in regions of interest, such as the hippocampus and in an exploratory fashion, observer and hypothesis-indedendent, throughout the entire brain. Evolving modalities such as diffusion-tensor imaging (DTI) and advanced tractography as well as resting-state functional MRI provide useful additionally useful measures indicating the degree of fiber tract and neural network disintegration (structural, effective and functional connectivity) that may substantially contribute to early detection and the mapping of progression. These modalities require further standardization and validation. The use of molecular in vivo amyloid imaging agents (the fifth validated biomarker), such as the Pittsburgh Compound-B and markers of neurodegeneration, such as fluoro-2-deoxy-D-glucose (FDG) (as the sixth validated biomarker) support the detection of early AD pathological processes and associated neurodegeneration. How to use, interpret, and disclose biomarker results drives the need for optimized standardization. Multimodal AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping fashion. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. AD biomarkers can be combined to increase accuracy or risk. A list of genetic risk factors is increasingly included in secondary prevention trials to stratify and select individuals at genetic risk of AD. Although most of these biomarker candidates are not yet qualified and approved by regulatory authorities for their intended use in drug trials, they are nonetheless applied in ongoing clinical studies for the following functions: (i) inclusion/exclusion criteria, (ii) patient stratification, (iii) evaluation of treatment effect, (iv) drug target engagement, and (v) safety. Moreover, novel promising hypothesis-driven, as well as exploratory biochemical, genetic, electrophysiological, and neuroimaging markers for use in clinical trials are being developed. The current state-of-the-art and future perspectives on both biological and neuroimaging derived biomarker discovery and development as well as the intended application in prevention trials is outlined in the present publication.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.14283/jpad.2014.32

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There exists no effective diagnostic biomarker that can detect the prodromal features of AD before the emergence of cognitive alterations.

    “there exists no effective diagnostic biomarker that can detect the prodromal features of AD before the emergence of cognitive alterations (Cavedo et al., 2014).”

    From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Cavedo et al., 2014

    The Abstract says biological markers can detect AD-related abnormalities years before overt clinical symptoms and that six biomarkers are sufficiently validated for inclusion in diagnostic criteria. The ‘Value of multimodal imaging in prevention trials’ section qualifies this: reliable staging before clinical onset may require a combination of biomarkers. That qualification does not support the categorical claim that no effective diagnostic biomarker exists. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 230 · Cited by 67

Research works printed but not linked: 196

  1. [1]Aisen PS Andrieu S Sampaio C Report of the task force on designing clinical trials in early (predementia) AD Neurology 2011 76 280 286 21178097 PMC3034393
  2. [2]Khachaturian ZS Petersen RC Gauthier S A roadmap for the prevention of dementia: the inaugural Leon Thal Symposium Alzheimers Dement 2008 4 156 163 18631960 PMC2544623
  3. [3]Hampel H Lista S Use of biomarkers and imaging to assess pathophysiology, mechanisms of action and target engagement J Nutr Health Aging 2013 17 54 63 23299381
  4. [4]Hampel H Broich K Enrichment of MCI and early Alzheimer’s disease treatment trials using neurochemical and imaging candidate biomarkers J Nutr Health Aging 2009 13 373 375 19300885
  5. [5]Vellas B Hampel H Rougé-Bugat ME Alzheimer’s disease therapeutic trials: EU/US Task Force report on recruitment, retention, and methodology J Nutr Health Aging 2012 16 339 345 22499454
  6. [6]Group. BDW Biomarkers and surrogate endpoints: preferred definitions and conceptual framework Clin Pharmacol Ther 2001 69 89 95 11240971
  7. [7]Wu L Rosa-Neto P Gauthier S Use of biomarkers in clinical trials of Alzheimer disease: from concept to application Mol Diagn Ther 2011 15 313 325 22188635
  8. [8]Vellas B Aisen PS Sampaio C Prevention trials in Alzheimer’s disease: an EU-US task force report Prog Neurobiol 2011 95 594 600 21925234
  9. [9]Vellas B Pahor M Manini T Designing pharmaceutical trials for sarcopenia in frail older adults: EU/US Task Force recommendations J Nutr Health Aging 2013 17 612 618 23933872 PMC4077187
  10. [10]Hampel H Lista S Khachaturian ZS Development of biomarkers to chart all Alzheimer’s disease stages: the royal road to cutting the therapeutic Gordian Knot Alzheimers Dement 2012 8 312 336 22748938
  11. [11]Hampel H Lista S Teipel SJ Perspective on future role of biological markers in clinical therapy trials of Alzheimer’s disease: a long-range point of view beyond 2020 Biochem Pharmacol 2014 88 426 449 24275164
  12. [12]Teipel SJ Sabri O Grothe M Perspectives for multimodal neurochemical and imaging biomarkers in Alzheimer’s disease J Alzheimers Dis 2013 33 Suppl 1 S329 347 22735677
  13. [13]Ewers M Sperling RA Klunk WE Weiner MW Hampel H Neuroimaging markers for the prediction and early diagnosis of Alzheimer’s disease dementia Trends Neurosci 2011 34 430 442 21696834 PMC3275347
  14. [15]Hampel H Shen Y Walsh DM Biological markers of amyloid beta-related mechanisms in Alzheimer’s disease Exp Neurol 2010 223 334 346 19815015 PMC2896007
  15. [16]Hampel H Blennow K Shaw LM Hoessler YC Zetterberg H Trojanowski JQ Total and phosphorylated tau protein as biological markers of Alzheimer’s disease Experimental gerontology 2010 45 30 40 19853650 PMC2815003
  16. [17]Henriksen K O’Bryant SE Hampel H The future of blood-based biomarkers for Alzheimer’s disease Alzheimer’s and Dementia 2014 10 115 131 PMC4128378 23850333
  17. [18]Hampel H Frank R Broich K Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives Nat Rev Drug Discov 2010 9 560 574 20592748
  18. [19]Lista S Faltraco F Prvulovic D Hampel H Blood and plasma-based proteomic biomarker research in Alzheimer’s disease Prog Neurobiol 2013 101–102 1 17 22743552
  19. [20]Bertram L Hampel H The role of genetics for biomarker development in neurodegeneration Prog Neurobiol 2011 95 501 504 22005514
  20. [21]Zetzsche T Rujescu D Hardy J Hampel H Advances and perspectives from genetic research: development of biological markers in Alzheimer’s disease Expert Rev Mol Diagn 2010 10 667 690 20629514
  21. [22]Lista S Garaci FG Ewers M CSF Aβ1–42 combined with neuroimaging biomarkers in the early detection, diagnosis and prediction of Alzheimer’s disease Alzheimers Dement 2014 10 381 392 23850330
  22. [23]Broich K Weiergräber M Hampel H Biomarkers in clinical trials for neurodegenerative diseases: regulatory perspectives and requirements Prog Neurobiol 2011 95 498 500 21945642
  23. [24]Solomon A Mangialasche F Richard E Advances in the prevention of Alzheimer’s disease and dementia J Intern Med 2014 275 229 250 24605807 PMC4390027
  24. [25]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 workgroups on diagnostic guidelines for Alzheimer’s disease Alzheimer’s & dementia: the journal of the Alzheimer’s Association 2011 7 263 269 PMC3312024 21514250
  25. [26]Albert MS DeKosky ST Dickson D The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging and Alzheimer’s Association Workgroup Alzheimers Dement 2011 7 270 279 21514249 PMC3312027
  26. [27]Dubois B Feldman HH Jacova C Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria Lancet Neurol 2014 13 614 629 24849862
  27. [28]Mills SM Mallmann J Santacruz AM Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial Rev Neurol (Paris) 2013 169 737 743 24016464 PMC3880800
  28. [30]Sperling RA Rentz DM Johnson KA The A4 Study: Stopping AD Before Symptoms Begin? Science Translational Medicine 2014 6 228fs213 PMC4049292 24648338
  29. [31]Sperling RA Jack CR Aisen PS Testing the right target and right drug at the right stage Sci Transl Med 2011 3 111 PMC3752906 22133718
  30. [32]Sperling RA Aisen PS Beckett LA Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Assocation workgroups on diagnostic guidelines for Alzheimer’s disease Alzheimers Dement 2011 7 280 292 21514248 PMC3220946
  31. [33]Reiman EM Langbaum JBS Tariot PN Alzheimer’s Prevention Initiative: a proposal to evaluate presymptomatic treatments as quickly as possible Biomarkers in Medicine 2010 4 3 14 20383319 PMC2850446
  32. [34]Roses AD Welsh-Bohmer KA Burns DK A pharmacogenetics-supported clinical trial to delay onset of mild cognitive impairment due to Alzheimer’s disease The Journal of Nutrition, Health & Aging 2012 841
  33. [35]Reiman EM Langbaum JB Fleisher AS Alzheimer’s Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments J Alzheimers Dis 2011 26 Suppl 3 321 329 21971471 PMC3343739
  34. [36]Norton S Matthews FE Barnes DE Yaffe K Brayne C Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data The Lancet Neurology 2014 13 788 794 25030513
  35. [37]Kivipelto M Ngandu T Laatikainen T Winblad B Soininen H Tuomilehto J Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study Lancet Neurol 2006 5 735 741 16914401
  36. [38]Senjem ML Gunter JL Shiung MM Petersen RC Jack CR Jr Comparison of different methodological implementations of voxel-based morphometry in neurodegenerative disease Neuroimage 2005 26 600 608 15907317 PMC2739382
  37. [39]Baron JC Chetelat G Desgranges B In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer’s disease Neuroimage 2001 14 298 309 11467904
  38. [41]Delacourte A David JP Sergeant N The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease Neurology 1999 52 1158 1165 10214737
  39. [43]Whitwell JL Josephs KA Murray ME MRI correlates of neurofibrillary tangle pathology at autopsy: a voxel-based morphometry study Neurology 2008 71 743 749 18765650 PMC2676950
  40. [44]Josephs KA Whitwell JL Knopman DS Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype Neurology 2008 70 1850 1857 18401022 PMC2779031
  41. [45]Josephs KA Whitwell JL Weigand SD TDP-43 is a key player in the clinical features associated with Alzheimer’s disease Acta Neuropathol 2014 PMC4172544 24659241
  42. [46]Josephs KA Whitwell JL Ahmed Z Beta-amyloid burden is not associated with rates of brain atrophy Ann Neurol 2008 63 204 212 17894374 PMC2735194
  43. [47]Jack CR Jr Lowe VJ Senjem ML 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment Brain 2008 131 665 680 18263627 PMC2730157
  44. [48]Scheltens P Leys D Barkhof F Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates J Neurol Neurosurg Psychiatry 1992 55 967 972 1431963 PMC1015202
  45. [49]Dickerson BC Bakkour A Salat DH The cortical signature of Alzheimer’s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals Cereb Cortex 2009 19 497 510 18632739 PMC2638813
  46. [50]Vemuri P Gunter JL Senjem ML Alzheimer’s disease diagnosis in individual subjects using structural MR images: validation studies Neuroimage 2008 39 1186 1197 18054253 PMC2390889
  47. [51]Jack CR Jr Petersen RC O’Brien PC Tangalos EG MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease Neurology 1992 42 183 188 1734300
  48. [53]Frisoni GB Jack CR Harmonization of magnetic resonance-based manual hippocampal segmentation: A mandatory step for wide clinical use Alzheimers Dement 2011 7 171 174 21414554
  49. [54]Jack CR Jr Barkhof F Bernstein MA Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer’s disease Alzheimers Dement 2011 7 474 485 e474 21784356 PMC3396131
  50. [56]Suppa P Anker U Spies L Fully Automated Atlas-Based Hippocampal Volumetry for Detection of Alzheimer’s Disease in a Memory Clinic Setting J Alzheimers Dis 2014 25201782
  51. [57]Lee JH Kim SH Kim GH Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B Neurology 2011 77 18 25 21593437
  52. [58]Frisoni GB Jagust WJ Subcortical vascular dementia exists! Neurology 2011 77 12 13 21593436
  53. [60]Bakkour A Morris JC Dickerson BC The cortical signature of prodromal AD: regional thinning predicts mild AD dementia Neurology 2009 72 1048 1055 19109536 PMC2677470
  54. [61]Desikan RS Cabral HJ Settecase F Automated MRI measures predict progression to Alzheimer’s disease Neurobiol Aging 2010 31 1364 1374 20570399 PMC2902697
  55. [62]Landau SM Harvey D Madison CM Comparing predictors of conversion and decline in mild cognitive impairment Neurology 2010 75 230 238 20592257 PMC2906178
  56. [63]Apostolova LG Mosconi L Thompson PM Subregional hippocampal atrophy predicts Alzheimer’s dementia in the cognitively normal Neurobiol Aging 2010 31 1077 1088 18814937 PMC2873083
  57. [64]Visser PJ Scheltens P Verhey FR Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment J Neurol 1999 246 477 485 10431775
  58. [65]Fox NC Scahill RI Crum WR Rossor MN Correlation between rates of brain atrophy and cognitive decline in AD Neurology 1999 52 1687 1689 10331700
  59. [66]Fox NC Cousens S Scahill R Harvey RJ Rossor MN Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects Arch Neurol 2000 57 339 344 10714659
  60. [67]Jack CR Jr Petersen RC Grundman M Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI Neurobiol Aging 2008 29 1285 1295 17452062 PMC2768818
  61. [70]Sperling RA Jack CR Jr Black SE Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer’s Association Research Roundtable Workgroup Alzheimers Dement 2011 7 367 385 21784348 PMC3693547
  62. [72]Machulda MM Ward HA Borowski B Comparison of memory fMRI response among normal, MCI, and Alzheimer’s patients Neurology 2003 61 500 506 12939424 PMC2744465
  63. [73]Johnson SC Schmitz TW Moritz CH Activation of brain regions vulnerable to Alzheimer’s disease: the effect of mild cognitive impairment Neurobiol Aging 2006 27 1604 1612 16226349 PMC2627778
  64. [74]Sperling RA Bates JF Chua EF fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease J Neurol Neurosurg Psychiatry 2003 74 44 50 12486265 PMC1738201
  65. [75]Celone KA Calhoun VD Dickerson BC Alterations in Memory Networks in Mild Cognitive Impairment and Alzheimer’s Disease: An Independent Component Analysis J Neurosci 2006 26 10222 10231 17021177 PMC6674636
  66. [76]Hamalainen A Pihlajamaki M Tanila H Increased fMRI responses during encoding in mild cognitive impairment Neurobiol Aging 2007 28 1889 1903 16997428
  67. [77]Dickerson BC Salat DH Greve DN Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD Neurology 2005 65 404 411 16087905 PMC4335677
  68. [78]Lim HK Juh R Pae CU Altered verbal working memory process in patients with Alzheimer’s disease: an fMRI investigation Neuropsychobiology 2008 57 181 187 18654087
  69. [79]Bokde AL Karmann M Born C Altered brain activation during a verbal working memory task in subjects with amnestic mild cognitive impairment J Alzheimers Dis 2010 21 103 118 20413893
  70. [80]Olichney JM Taylor JR Chan S fMRI responses to words repeated in a congruous semantic context are abnormal in mild Alzheimer’s disease Neuropsychologia 2010 48 2476 2487 20433856 PMC2929249
  71. [81]Bokde ALW Lopez-Bayo P Born C Functional Abnormalities of the Visual Processing System in Subjects with Mild Cognitive Impairment: an fMRI study Psychiatr Res: Neuroimaging 2008 163 248 259 18672352
  72. [82]Bokde AL Lopez-Bayo P Meindl T Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment Brain 2006 129 1113 1124 16520329
  73. [83]Forster S Vaitl A Teipel SJ Functional representation of olfactory impairment in early Alzheimer’s disease J Alzheimers Dis 2010 22 581 591 20847402
  74. [85]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 U S A 2004 101 4637 4642 15070770 PMC384799
  75. [86]Sorg C Riedl V Muhlau M Selective changes of resting-state networks in individuals at risk for Alzheimer’s disease Proc Natl Acad Sci U S A 2007 104 18760 18765 18003904 PMC2141850
  76. [87]Gili T Cercignani M Serra L Regional brain atrophy and functional disconnection across Alzheimer’s disease evolution J Neurol Neurosurg Psychiatry 2011 82 58 66 20639384
  77. [88]Sperling RA Laviolette PS O’Keefe K Amyloid deposition is associated with impaired default network function in older persons without dementia Neuron 2009 63 178 188 19640477 PMC2738994
  78. [89]Drzezga A Becker JA Van Dijk KR Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden Brain 2011 134 1635 1646 21490054 PMC3102239
  79. [90]Maillet D Rajah MN Age-related differences in brain activity in the subsequent memory paradigm: A meta-analysis 24973756
  80. [91]Bookheimer SY Strojwas MH Cohen MS Patterns of brain activation in people at risk for Alzheimer’s disease N Engl J Med 2000 343 450 456 10944562 PMC2831477
  81. [93]Mielke MM Okonkwo OC Oishi K Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer’s disease Alzheimers Dement 2012 8 105 113 22404852 PMC3305232
  82. [94]Douaud G Menke RA Gass A Brain Microstructure Reveals Early Abnormalities more than Two Years prior to Clinical Progression from Mild Cognitive Impairment to Alzheimer’s Disease J Neurosci 2013 33 2147 2155 23365250 PMC6571077
  83. [95]Selnes P Aarsland D Bjornerud A Diffusion tensor imaging surpasses cerebrospinal fluid as predictor of cognitive decline and medial temporal lobe atrophy in subjective cognitive impairment and mild cognitive impairment J Alzheimers Dis 2013 33 723 736 23186987
  84. [96]Haller S Nguyen D Rodriguez C Individual prediction of cognitive decline in mild cognitive impairment using support vector machine-based analysis of diffusion tensor imaging data J Alzheimers Dis 2010 22 315 327 20847435
  85. [97]Teipel SJ Reuter S Stieltjes B Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study Psychiatry research 2011 194 363 371 22078796
  86. [100]Kitamura S Kiuchi K Taoka T Longitudinal white matter changes in Alzheimer’s disease: a tractography-based analysis study Brain research 2013 1515 12 18 23583480
  87. [101]Teipel SJ Meindl T Wagner M Longitudinal changes in fiber tract integrity in healthy aging and mild cognitive impairment: a DTI follow-up study J Alzheimers Dis 2010 22 507 522 20847446
  88. [102]Likitjaroen Y Meindl T Friese U Longitudinal changes of fractional anisotropy in Alzheimer’s disease patients treated with galantamine: a 12-month randomized, placebo-controlled, double-blinded study Eur Arch Psychiatry Clin Neurosci 2012 262 341 350 21818628
  89. [103]Catani M Acqua FD de Schotten MT A revised limbic system model for memory, emotion and behaviour Neuroscience and biobehavioral reviews 2013 23850593
  90. [104]Geschwind N Disconnexion syndromes in animals and man I Brain 1965 88 237 294 5318481
  91. [105]Geschwind N Disconnexion syndromes in animals and man. II Brain 1965 88 585 644 5318824
  92. [107]Metzler-Baddeley C Jones DK Belaroussi B Aggleton JP O’Sullivan MJ Frontotemporal connections in episodic memory and aging: a diffusion MRI tractography study J Neurosci 2011 31 13236 13245 21917806 PMC6623273
  93. [108]Metzler-Baddeley C Hunt S Jones DK Leemans A Aggleton JP O’Sullivan MJ Temporal association tracts and the breakdown of episodic memory in mild cognitive impairment Neurology 2012 79 2233 2240 23175726 PMC3542350
  94. [109]Catani M Mesulam MM Jakobsen E A novel frontal pathway underlies verbal fluency in primary progressive aphasia Brain 2013 136 2619 2628 23820597 PMC3722349
  95. [110]Frisoni GB Alzheimer’s disease neuroimaging initiative in Europe Alzheimers Dement 2010 6 280 285 20451877
  96. [111]Cavedo E Redolfi A Angeloni F The Italian Alzheimer’s Disease Neuroimaging Initiative (I-ADNI): Validation of Structural MR Imaging J Alzheimers Dis 2014 24577455
  97. [112]Carrillo MC Bain LJ Frisoni GB Weiner MW Worldwide Alzheimer’s disease neuroimaging initiative Alzheimer’s & dementia: the journal of the Alzheimer’s Association 2012 8 337 342 22748939
  98. [113]Landau SM Breault C Joshi AD Amyloid-beta imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods J Nucl Med 2013 54 70 77 23166389 PMC3747730
  99. [114]Clark CM Pontecorvo MJ Beach TG Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-? plaques: a prospective cohort study The Lancet Neurology 2012 11 669 678 22749065
  100. [115]Chien DT Szardenings AK Bahri S Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808 J Alzheimers Dis 2014 38 171 184 23948934
  101. [116]Villemagne VL Furumoto S Fodero-Tavoletti MT In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease Eur J Nucl Med Mol Imaging 2014 41 816 826 24514874
  102. [117]Bohnen NI Djang DS Herholz K Anzai Y Minoshima S Effectiveness and Safety of 18F-FDG PET in the Evaluation of Dementia: A Review of the Recent Literature J Nucl Med 2012 53 59 71 22173840
  103. [119]Caroli A Prestia A Chen K Summary Metrics to Assess Alzheimer Disease-Related Hypometabolic Pattern with 18F-FDG PET: Head-to-Head Comparison J Nucl Med 2012 53 592 600 22343502 PMC3640308
  104. [120]Shaffer JL Petrella JR Sheldon FC Predicting Cognitive Decline in Subjects at Risk for Alzheimer Disease by Using Combined Cerebrospinal Fluid, MR Imaging, and PET Biomarkers Radiology 2012 PMC3558874 23232293
  105. [124]Schuitemaker A Kropholler MA Boellaard R Microglial activation in Alzheimer’s disease: an (R)-[(1)(1)C]PK11195 positron emission tomography study Neurobiol Aging 2013 34 128 136 22840559
  106. [125]Wiley CA Lopresti BJ Venneti S Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease Arch Neurol 2009 66 60 67 19139300 PMC2666881
  107. [126]Venneti S Lopresti BJ Wiley CA Molecular imaging of microglia/macrophages in the brain Glia 2013 61 10 23 22615180 PMC3580157
  108. [127]Chua SW Kassiou M Ittner LM The translocator protein as a drug target in Alzheimer’s disease Expert Rev Neurother 2014 14 439 448 24625007
  109. [128]Kreisl WC Lyoo CH McGwier M In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease Brain 2013 17 17 PMC3692038 23775979
  110. [129]Owen DR Yeo AJ Gunn RN An 18-kDa Translocator Protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28 J Cereb Blood Flow Metab 2012 32 1 5 22008728 PMC3323305
  111. [131]Horti AG Kuwabara H Holt DP Dannals RF Wong DF Recent PET radioligands with optimal brain kinetics for imaging nicotinic acetylcholine receptors Journal of Labelled Compounds and Radiopharmaceuticals 2013 56 159 166 24285321
  112. [132]Bateman RJ Xiong C Benzinger TL Clinical and biomarker changes in dominantly inherited Alzheimer’s disease The New England journal of medicine 2012 367 795 804 22784036 PMC3474597
  113. [133]Jack CR Jr Knopman DS Jagust WJ Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers Lancet neurology 2013 12 207 216 23332364 PMC3622225
  114. [135]Alexopoulos P Kriett L Haller B Limited agreement between biomarkers of neuronal injury at different stages of Alzheimer’s disease Alzheimer’s & dementia: the journal of the Alzheimer’s Association 2014 24857233
  115. [136]Kendziorra K Wolf H Meyer PM Decreased cerebral alpha4beta2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer’s disease assessed with positron emission tomography European journal of nuclear medicine and molecular imaging 2011 38 515 525 21069319
  116. [137]Villemagne VL Okamura N In vivo tau imaging: obstacles and progress Alzheimer’s & dementia: the journal of the Alzheimer’s Association 2014 10 S254 264 24924676
  117. [138]Okamura N Furumoto S Harada R Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2013 54 1420 1427 23857514
  118. [140]Drzezga A Barthel H Minoshima S Sabri O Potential Clinical Applications of PET/MR Imaging in Neurodegenerative Diseases Journal of nuclear medicine: official publication, Society of Nuclear Medicine 2014 55 47S 55S 24819417
  119. [141]Blennow K Hampel H Weiner M Zetterberg H Cerebrospinal fluid and plasma biomarkers in Alzheimer disease Nat Rev Neurol 2010 6 131 144 20157306
  120. [142]Fagan AM Xiong C Jasielec MS Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer’s disease Sci Transl Med 2014 6 226ra230 PMC4038930 24598588
  121. [143]Mattsson N Andreasson U Persson S The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers Alzheimers Dement 2011 7 386 395 e386 21784349 PMC3710290
  122. [144]Mattsson N Andreasson U Persson S CSF biomarker variability in the Alzheimer’s Association quality control program Alzheimers Dement 2013 9 251 261 23622690 PMC3707386
  123. [145]Carrillo MC Blennow K Soares H Global standardization measurement of cerebral spinal fluid for Alzheimer’s disease: An update from the Alzheimer’s Association Global Biomarkers Consortium Alzheimers Dement 2013 9 137 140 23274154
  124. [146]Leinenbach A Pannee J Dulffer T Mass Spectrometry-Based Candidate Reference Measurement Procedure for Quantification of Amyloid-beta in Cerebrospinal Fluid Clin Chem 2014 24842955
  125. [147]Toledo JB Xie SX Trojanowski JQ Shaw LM Longitudinal change in CSF Tau and Abeta biomarkers for up to 48 months in ADNI Acta Neuropathol 2013 126 659 670 23812320 PMC3875373
  126. [148]Mattsson N Insel P Nosheny R CSF protein biomarkers predicting longitudinal reduction of CSF beta-amyloid42 in cognitively healthy elders Transl Psychiatry 2013 3 e293 23962923 PMC3756294
  127. [150]Zetterberg H Pedersen M Lind K Intra-individual stability of CSF biomarkers for Alzheimer’s disease over two years J Alzheimers Dis 2007 12 255 260 18057559
  128. [151]Blennow K Zetterberg H Minthon L Longitudinal stability of CSF biomarkers in Alzheimer’s disease Neurosci Lett 2007 419 18 22 17482358
  129. [152]Mattsson N Portelius E Rolstad S Longitudinal cerebrospinal fluid biomarkers over four years in mild cognitive impairment J Alzheimers Dis 2012 30 767 778 22475796
  130. [153]Mattsson N Rajendran L Zetterberg H BACE1 inhibition induces a specific cerebrospinal fluid beta-amyloid pattern that identifies drug effects in the central nervous system PLoS ONE 2012 7 e31084 22328928 PMC3273469
  131. [154]Lannfelt L Blennow K Zetterberg H Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer’s disease: a phase IIa, double-blind, randomised, placebo-controlled trial Lancet Neurol 2008 7 779 786 18672400
  132. [155]May PC Dean RA Lowe SL Robust central reduction of amyloid-beta in humans with an orally available, non-peptidic beta-secretase inhibitor J Neurosci 2011 31 16507 16516 22090477 PMC6633289
  133. [156]Portelius E Dean RA Gustavsson MK A novel Abeta isoform pattern in CSF reflects gamma-secretase inhibition in Alzheimer disease Alzheimers Res Ther 2010 2 7 20350302 PMC2876785
  134. [159]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 PMC4204160 24853080
  135. [160]Lee JM Blennow K Andreasen N The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients Clin Chem 2008 54 1617 1623 18703769 PMC2672199
  136. [161]Rosen C Mattsson N Johansson PM Discriminatory Analysis of Biochip-Derived Protein Patterns in CSF and Plasma in Neurodegenerative Diseases Front Aging Neurosci 2011 3 1 21442044 PMC3057441
  137. [162]Thorsell A Bjerke M Gobom J Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer’s disease Brain Res 2010 1362 13 22 20875798
  138. [163]Perrin RJ Craig-Schapiro R Malone JP Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer’s disease PLoS ONE 2011 6 e16032 21264269 PMC3020224
  139. [164]Armstrong A Mattsson N Appelqvist H Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimer’s Disease Neuromolecular Med 2013 PMC3918123 24101586
  140. [166]Kiddle SJ Sattlecker M Proitsi P Candidate blood proteome markers of Alzheimer’s disease onset and progression: a systematic review and replication study J Alzheimers Dis 2014 38 515 531 24121966
  141. [167]O’Bryant SE Xiao G Barber R A serum protein-based algorithm for the detection of Alzheimer disease Archives of Neurology 2010 67 1077 1081 20837851 PMC3069805
  142. [168]O’Bryant SEGX Zhang F Edwards M German D Yin X Como T Reisch J Huebinger HM Graff-Radford N Dickson D Barber RC Hall J O’Suilleabhain P Grammas P Validation of a serum screen for Alzheimer’s disease across assay platforms, species and tissues Journal of Alzheimer’s disease: JAD 2014 in press PMC4400808 25024345
  143. [169]Doecke J Laws SM Faux NG Wilson W Burnham SC Lam CP Mondal A Bedo J Busy AI Brown B De Ruyck K Ellis KA Fowler C Gupta VB Head R Macaulay L Pertile K Rowe CC Rembach A Rodrigues M Rumble R Szoeke C Taddei K Taddei T Trounson B Aimes D Masters CL Martins RN Blood-based protein biomarkers for the diagnosis of Alzheimer’s disease Arch Neurol 2012 published online PMC6287606 22801742
  144. [170]Burnham SC Faux NG Wilson W A blood-based predictor for neocortical Aβ burden in Alzheimer’s disease: Results from the AIBL study Molecular Psychiatry 2014 19 519 526 23628985
  145. [171]Thambisetty M Tripaldi R Riddoch-Contreras J Proteome-based plasma markers of brain amyloid-β deposition in non-demented older individuals Journal of Alzheimer’s Disease 2010 22 1099 1109 PMC3125970 20930274
  146. [172]Hye A Riddoch-Contreras J Baird AL Plasma proteins predict conversion to dementia from prodromal disease Alzheimer’s and Dementia 2014 PMC4240530 25012867
  147. [173]Llano DA Devanarayan V Simon AJ Evaluation of plasma proteomic data for alzheimer disease state classification and for the prediction of progression from mild cognitive impairment to alzheimer disease Alzheimer Disease and Associated Disorders 2013 27 233 243 23023094
  148. [174]Mapstone M Cheema AK Fiandaca MS Plasma phospholipids identify antecedent memory impairment in older adults Nature Medicine 2014 20 415 418 PMC5360460 24608097
  149. [175]Song F Poljak A Crawford J Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals PLoS ONE 2012 7 PMC3372509 22701550
  150. [176]Swaminathan S Risacher SL Yoder KK Association of plasma and cortical amyloid beta is modulated by APOE ε4 status Alzheimer’s and Dementia 2014 10 e9 e18 PMC3750076 23541187
  151. [178]Thambisetty M An Y Kinsey A Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment NeuroImage 2012 59 212 217 21824521 PMC3425349
  152. [180]O’Bryant SEGV Henriksen K Edwards M Jeromin A Lista S Bazenet C Soares H Lovestone S Hampel H Montine T Blennow K Foroud T Carrillo M Graff-Radford N Laske C Breteler M Shaw L Trojanowski JQ Schupf N Rissman R Fagan AM Oberoi P Umek R Weiner MW Grammas P Posner H Martins R Guidelines for the standardization fo preanalytic variables for blood-based biomarker studies in Alzheimer’s disease Alzheimer’s & Dementia 2014 in press PMC4414664 25282381
  153. [181]Bertram L McQueen MB Mullin K Blacker D Tanzi RE Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database Nat Genet 2007 39 17 23 17192785
  154. [183]Goldman JS Hahn SE Catania JW Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors Genet Med 2011 13 597 605 21577118 PMC3326653
  155. [184]Karran E Hardy J Antiamyloid therapy for Alzheimer’s disease--are we on the right road? N Engl J Med 2014 370 377 378 24450897
  156. [185]Kraff O Fischer A Nagel AM Mönninghoff C Ladd ME MRI at 7 tesla and above: Demonstrated and potential capabilities J Magn Reson Imaging 2014 24478137
  157. [186]Rössler M Zarski R Bohl J Ohm TG Stage-dependent and sector-specific neuronal loss in hippocampus during Alzheimer’s disease Acta Neuropathol 2002 103 363 369 11904756
  158. [188]Mueller SG Schuff N Yaffe K Madison C Miller B Weiner MW Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer’s disease Hum Brain Mapp 2010 31 1339 1347 20839293 PMC2943433
  159. [189]Boutet C Chupin M Lehéricy S Marrakchi-Kacem L Epelbaum S Poupon C Wiggins C Vignaud A Hasboun D Defontaines B Hanon O Dubois B Sarazin M Hertz-Pannier L Colliot O Detection of volume loss in hippocampal layers in Alzheimer’s disease using 7 T MRI: A feasibility study NeuroImage Clin 2014 341 348 25161900 PMC4141975
  160. [190]Kerchner GA Berdnik D Shen JC APOE ε4 worsens hippocampal CA1 apical neuropil atrophy and episodic memory Neurology 2014 82 691 697 24453080 PMC3945665
  161. [192]Lee SP Falangola MF Nixon RA Duff K Helpern JA Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer’s disease using MR microscopy without contrast reagents Magn Reson Med 2004 52 538 544 15334572 PMC3962264
  162. [193]Teipel SJ Kaza E Hadlich S Automated detection of amyloid-β-related cortical and subcortical signal changes in a transgenic model of Alzheimer’s disease using high-field MRI J Alzheimers Dis 2011 23 221 237 20966552 PMC3030673
  163. [194]Bertrand A Pasquier A Petiet A Micro-MRI study of cerebral aging: ex vivo detection of hippocampal subfield reorganization, microhemorrhages and amyloid plaques in mouse lemur primates PLoS One 2013 8 e56593 23460806 PMC3584101
  164. [195]Conijn MM Geerlings MI Biessels GJ Cerebral microbleeds on MR imaging: comparison between 1.5 and 7T AJNR Am J Neuroradiol 2011 32 1043 1049 21546463 PMC8013148
  165. [196]Theysohn JM Kraff O Maderwald S 7 tesla MRI of microbleeds and white matter lesions as seen in vascular dementia J Magn Reson Imaging 2011 33 782 791 21448941
  166. [198]van Veluw SJ Heringa SM Kuijf HJ Cerebral cortical microinfarcts at 7Tesla MRI in patients with early Alzheimer’s disease J Alzheimers Dis 2014 39 163 167 24121967
  167. [199]Lopes da Silva F EEG and MEG: relevance to neuroscience Neuron 2013 80 1112 1128 24314724
  168. [200]Keil A Debener S Gratton G Committee report: publication guidelines and recommendations for studies using electroencephalography and magnetoencephalography Psychophysiology 2014 51 1 21 24147581
  169. [201]Hogan MJ Swanwick GR Kaiser J Rowan M Lawlor B Memory-related EEG power and coherence reductions in mild Alzheimer’s disease Int J Psychophysiol 2003 49 147 163 12919717
  170. [202]Drago V Babiloni C Bartrés-Faz D Disease tracking markers for Alzheimer’s disease at the prodromal (MCI) stage J Alzheimers Dis 2011 26 Suppl 3 159 199 21971460
  171. [203]Babiloni C Vecchio F Lizio R Resting state cortical rhythms in mild cognitive impairment and Alzheimer’s disease: electroencephalographic evidence J Alzheimers Dis 2011 26 Suppl 3 201 214 21971461
  172. [204]Stam CJ Jones BF Manshanden I Magnetoencephalographic evaluation of resting-state functional connectivity in Alzheimer’s disease Neuroimage 2006 32 1335 1344 16815039
  173. [205]Stam CJ Montez T Jones BF Disturbed fluctuations of resting state EEG synchronization in Alzheimer’s disease Clin Neurophysiol 2005 116 708 715 15721085
  174. [206]Lee SH Park YM Kim DW Im CH Global synchronization index as a biological correlate of cognitive decline in Alzheimer’s disease Neurosci Res 2010 66 333 339 20025913
  175. [207]Poil SS de Haan W van der Flier WM Mansvelder HD Scheltens P Linkenkaer-Hansen K Integrative EEG biomarkers predict progression to Alzheimer’s disease at the MCI stage Front Aging Neurosci 2013 5 58 24106478 PMC3789214
  176. [208]Zamrini E Maestu F Pekkonen E Magnetoencephalography as a putative biomarker for Alzheimer’s disease Int J Alzheimers Dis 2011 2011 280289 21547221 PMC3087473
  177. [209]Kozauer N Katz R Regulatory innovation and drug development for early-stage Alzheimer’s disease N Engl J Med 2013 368 1169 1171 23484795
  178. [210]Broich KS-WG Weiergräber M Hampel H Regulatory requirements on clinical trials in Alzheimer’s Disease Basel ABP Alzheimer’ Disease–Modernizing Concept Biological Diagnosis and Therapy Karger 2012 168 178
  179. [211]Dubois B Feldman HH Jacova C Revising the definition of Alzheimer’s disease: a new lexicon Lancet neurology 2010 9 1118 1127 20934914
  180. [212]Morris JC Blennow K Froelich L Harmonized diagnostic criteria for Alzheimer’s disease: recommendations J Intern Med 2014 275 204 213 24605805
  181. [213]Hampel HCM Alzheimer’s Disease – Modernizing Concept, Biological Diagnosis and Therapy Adv Biol Psychiatry Basel, Karger 2012 28
  182. [214]Giacobini E Gold G Alzheimer disease therapy--moving from amyloid-β to tau Nat Rev Neurol 2013 9 677 686 24217510
  183. [215]Feldman HH Haas M Gandy S Alzheimer’s disease research and development: a call for a new research roadmap Ann N Y Acad Sci 2014 1313 1 16 24754377
  184. [216]Noel-Storr AH Flicker L Ritchie CW Systematic review of the body of evidence for the use of biomarkers in the diagnosis of dementia Alzheimers Dement 2013 9 e96 e105 23110863
  185. [217]Mattsson N Andreasson U Persson S CSF biomarker variability in the Alzheimer’s Association quality control program Alzheimers Dement 2013 9 251 261 23622690 PMC3707386
  186. [218]NAPA AsAEAWo Workgroup on NAPA’s scientific agenda for a national initiative on Alzheimer’s disease Alzheimers Dement 2012 8 357 371 22748940
  187. [219]Milestones AsAWIo Report on National Alzheimer’s Plan Milestones - FY’ 2014 Alzheimers Dementia 2014 in press
  188. [221]OECD Unlocking Global Collaboration to Accelerate Innovation for Alzheimer’s Disease and Dementia Oxford University 2013
  189. [223]Fowler P Whitwell J Jeffrey L Young J Smith K Kirkland D Cadmium chloride, benzo[a]pyrene and cyclophosphamide tested in the in vitro mammalian cell micronucleus test (MNvit) in the human lymphoblastoid cell line TK6 at Covance laboratories, Harrogate UK in support of OECD draft Test Guideline 487 Mutat Res 2010 702 171 174 20206291
  190. [224]ZK The five-five, ten-ten plan for Alzheimer’s disease Neurobiol Aging 1992 13 197 198 1522938
  191. [226]Khachaturian ZS Camí J Andrieu S Creating a transatlantic research enterprise for preventing Alzheimer’s disease Alzheimers Dement 2009 5 361 366 19560106 PMC3295837
  192. [227]Carrié I van Kan GA Gillette-Guyonnet S Recruitment strategies for preventive trials. The MAPT study (MultiDomain Alzheimer Preventive Trial) J Nutr Health Aging 2012 16 355 359 22499458
  193. [228]Forlenza OV Diniz BS Radanovic M Santos FS Talib LL Gattaz WF Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial The British journal of psychiatry: the journal of mental science 2011 198 351 356 21525519
  194. [229]Craft S Baker LD Montine TJ Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial Arch Neurol 2012 69 29 38 21911655 PMC3260944
  195. [230]Feldman HH Ferris S Winblad B Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: the InDDEx study Lancet Neurol 2007 6 501 512 17509485
  196. [231]Dubois B Chupin M Hampel H Lista S Cavedo E Croisile B Louis Tisserand G Touchon J Bonafe A Ousset PJ Ameur AA Rouaud O Ricolfi F Vighetto A Pasquier P Delmaire C Ceccaldi M Girard N Dufouil C Lehericy S Tonelli I Duveau D Colliot O Garnero L Sarazin M Dormont D And The “Hippocampus Study Group Donepezil Decreases Annual Rate Of Hippocampal Atrophy In Suspected Prodromal Ad 2014 Submitted 25596420

Authors
Cavedo, E., Lista, S., Khachaturian, Z., Aisen, P., Amouyel, P., Herholz, K., Jack Jr, C. R., Sperling, R., Cummings, J., Blennow, K., O’Bryant, S., Frisoni, G. B., Khachaturian, A., Kivipelto, M., Klunk, W., Broich, K., Andrieu, S., Thiebaut de Schotten, M., Mangin, J.-F., Lammertsma, A. A., Johnson, K., Teipel, S., Drzezga, A., Bokde, A., Colliot, O., Bakardjian, H., Zetterberg, H., Dubois, B., Vellas, B., Schneider, L. S., & Hampel, H.
Affiliations
  • Centro San Giovanni di Dio Fatebenefratelli (IT)
  • Inserm (FR)
  • Prevent Alzheimer’s Disease 2020 (US)
  • University of California San Diego (US)
  • University of Manchester (GB)
  • Brigham and Women's Hospital (US)
  • Cleveland Clinic (US)
  • University of Gothenburg (SE)
  • University of North Texas Health Science Center (US)
  • University of Geneva (CH)
  • Karolinska Institutet (SE)
  • University of Pittsburgh (US)
  • Federal Institute for Drugs and Medical Devices (DE)
  • Université Toulouse III - Paul Sabatier (FR)
  • Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
  • Amsterdam University Medical Centers (NL)
  • Harvard University (US)
  • German Center for Neurodegenerative Diseases (DE)
  • University Hospital Cologne (DE)
  • Trinity College Dublin (IE)
  • Centre National de la Recherche Scientifique (FR)
  • Pitié-Salpêtrière Hospital (FR)
  • National Hospital for Neurology and Neurosurgery (GB)
  • University of Southern California (US)
ORCID
Venue
The Journal of Prevention of Alzheimer's Disease
Publisher
Elsevier BV
Published
2014
Volume
1
Issue
3
Pages
1-22
ISSN
2274-5807 (ISSN-L)
DOI
10.14283/jpad.2014.32
PMC
PMC4606938
OpenAlex
W2157357845
Cited by
67
References
230
Citations by year
2025: 3 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 8 · 2018: 10 · 2017: 18 · 2016: 10 · 2015: 2 · 2014: 1
FWCI
7.36
Type
journal article
Language
en
Open access
Locations
  • The Journal of Prevention of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Archive ouverte UNIGE (University of Geneva) (acceptedVersion)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
  • HAL (submittedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
  • DZNE Pub (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
  • Alzheimer's Association
  • Mayo Foundation for Medical Education and Research
  • Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease
  • Université de Lille
  • Science Foundation Ireland (11/RFP.1/NES/3194)
  • Deutsche Forschungsgemeinschaft
  • Agence Nationale de la Recherche (ANR-10-IAIHU06, ANR-13-JSV4-0001, ANR-09-EMER, 10-IAIHU-06, ANR-09-EMER-006, ANR-10)
  • Institut National de la Santé et de la Recherche Médicale (ANR-10-IAIHU-06)
  • AXA Research Fund (ANR-10-IAIHU-06)
  • Knut och Alice Wallenbergs Stiftelse
  • Vetenskapsrådet
  • Université Pierre et Marie Curie
  • Centre hospitalier régional universitaire de Lille
  • Fondation pour la Recherche sur Alzheimer
  • National Institutes of Health (-0001, 5u01ag024904-10, AG12300, U01-AG024904, AG005133, AG024904, AG025204, AG025516, AG011378, ANR-10-IAIHU-06)
  • National Institute on Aging (U01-AG-024904, R01AG043392, P01AG025204, P30AG012300, RF1AG025516, P50AG005133, U01AG006786, U01AG010483, R01AG011378, P50AG005142, R01AG037551, R01AG041851, R37AG025516, R01AG039389)
  • National Heart, Lung, and Blood Institute (U01HL096917)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
Alzheimer's disease, biomarkers, neuroimaging, preclinical Alzheimer's disease, prodromal Alzheimer's disease, mild cognitive impairment, amyloid-beta, tau protein, cerebrospinal fluid biomarkers, hippocampal atrophy, magnetic resonance imaging, diffusion tensor imaging, tractography, resting-state fMRI, neurodegeneration, prevention trials, diagnostic criteria, brain atrophy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review