Jump to ContentJump to Main Navigation
Show Summary Details

Translational Neuroscience

Editor-in-Chief: Šimic, Goran

IMPACT FACTOR 2015: 1.012

SCImago Journal Rank (SJR) 2015: 0.704
Source Normalized Impact per Paper (SNIP) 2015: 0.286
Impact per Publication (IPP) 2015: 1.155

Open Access
See all formats and pricing

Amyloid imaging in Alzheimer’s disease: a potential new era of personalized medicine?

1Translational Neuroimaging Laboratory (TNL), McGill Centre for Studies in Aging (MCSA), Douglas Mental Health University Institute, Montreal, H4H 1R3, Quebec, Canada

2Alzheimer’s Disease Research Unit, MCSA, Douglas Mental Health University Institute, Montreal, H4H 1R3, Quebec, Canada

3Department of Biochemistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil

© 2014 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)

Citation Information: Translational Neuroscience. Volume 5, Issue 1, Pages 51–56, ISSN (Online) 2081-6936, DOI: https://doi.org/10.2478/s13380-014-0205-y, March 2014

Publication History

Published Online:


Recent advances along clinical and neuropathological lines, as well as in our ability to detect the deposition of β-amyloid (Aβ) in vivo using positron emission tomography (PET), have helped redefine Alzheimer’s disease (AD) as a dynamic clinicobiological entity. On the basis of these advances, AD is now conceptualized as a continuum comprising asymptomatic, minimally symptomatic, and dementia phases, with detection of brain Aβ — in particular, via PET amyloid imaging — central to the diagnostic process. In this respect, [18F]florbetapir (Amyvid™) and [18F]flutemetamol (Vizamyl™) have recently received approval for clinical use from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), with additional radiofluorinated tracers for detection of Aβ in phase III trials. Recent initiatives such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) suggest that Aβ production, oligomerization and aggregation begins many years, possibly decades, before detectable cognitive impairment, with Aβ shown to associate with cognitive decline and conversion to dementia. While personalized medicine has now emerged as a prospect for the field, the recent decision by the Centers for Medicare & Medicaid Services (CMS) — who declined to cover the cost of amyloid PET imaging citing insufficient evidence to support its clinical utility — highlights that such a move may be premature.

Keywords: Alzheimer’s disease; [11C]PIB [18F]florbetapen; [18F]florbetapir; [18F]flutemetamol; [18F]NAV4694; Amyloid cascade hypothesis; Personalized medicine

  • [1] McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E.M., Clinical diagnosis of Alzheimer’s disease: report of the NINCDSADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease, Neurology, 1984, 34, 939–94 http://dx.doi.org/10.1212/WNL.34.7.939 [Crossref]

  • [2] Dubois B., Feldman H.H., Jacova C., Cummings J.L., Dekosky S.T., Barberger-Gateau P., et al., Revising the definition of Alzheimer’s disease: a new lexicon, Lancet Neurol., 2010, 9, 1118–1127 http://dx.doi.org/10.1016/S1474-4422(10)70223-4 [Crossref]

  • [3] Dubois B., Feldman H.H., Jacova C., Dekosky S.T., Barberger-Gateau P., Cummings J., et al., Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria, Lancet Neurol., 2007, 6, 734–746 http://dx.doi.org/10.1016/S1474-4422(07)70178-3 [Crossref]

  • [4] Sperling R.A., Aisen P.S., Beckett L.A., Bennett D.A., Craft S., Fagan A.M., et al., 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, Alzheimers Dement., 2011, 7, 280–292 http://dx.doi.org/10.1016/j.jalz.2011.03.003 [Crossref]

  • [5] Albert M.S., DeKosky S.T., Dickson D., Dubois B., Feldman H.H., Fox N.C., et al., The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease, Alzheimers Dement., 2011, 7, 270–279 http://dx.doi.org/10.1016/j.jalz.2011.03.008 [Crossref]

  • [6] McKhann G.M., Knopman D.S., Chertkow H., Hyman B.T., Jack C.R., Jr., Kawas C.H., et al., The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease, Alzheimers Dement., 2011, 7, 263–269 http://dx.doi.org/10.1016/j.jalz.2011.03.005 [Crossref]

  • [7] Varma A.R., Snowden J.S., Lloyd J.J., Talbot P.R., Mann D.M., Neary D., Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer’s disease and frontotemporal dementia, J. Neurol. Neurosurg. Psychiatry, 1999, 66, 184–188 http://dx.doi.org/10.1136/jnnp.66.2.184 [Crossref]

  • [8] Kazee A.M., Eskin T.A., Lapham L.W., Gabriel K.R., McDaniel K.D., Hamill R.W., Clinicopathologic correlates in Alzheimer disease: assessment of clinical and pathologic diagnostic criteria, Alzheimer Dis. Assoc. Disord., 1993, 7, 152–164 http://dx.doi.org/10.1097/00002093-199307030-00004 [Crossref]

  • [9] Biomarkers Definitions Working G., Biomarkers and surrogate endpoints: preferred definitions and conceptual framework, Clin. Pharmacol. Ther., 2001, 69, 89–95 http://dx.doi.org/10.1067/mcp.2001.113989 [Crossref]

  • [10] Hardy J., Selkoe D.J., The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics, Science, 2002, 297, 353–356 http://dx.doi.org/10.1126/science.1072994 [Crossref]

  • [11] Fagan A.M., Mintun M.A., Shah A.R., Aldea P., Roe C.M., Mach R.H., et al., Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer’s disease, EMBO Mol. Med., 2009, 1, 371–380 http://dx.doi.org/10.1002/emmm.200900048 [Crossref]

  • [12] Morris J.C., Roe C.M., Xiong C., Fagan A.M., Goate A.M., Holtzman D.M., et al., APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging, Ann. Neurol., 2010, 67, 122–131 http://dx.doi.org/10.1002/ana.21843 [Crossref]

  • [13] Fagan A.M., Mintun M.A., Mach R.H., Lee S.Y., Dence C.S., Shah A.R., et al., Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans, Ann. Neurol., 2006, 59, 512–519 http://dx.doi.org/10.1002/ana.20730 [Crossref]

  • [14] Koivunen J., Pirttila T., Kemppainen N., Aalto S., Herukka S.K., Jauhianen A.M., et al., PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment, Dement. Geriatr. Cogn. Disord., 2008, 26, 378–383 http://dx.doi.org/10.1159/000163927 [Crossref]

  • [15] Forsberg A., Almkvist O., Engler H., Wall A., Langstrom B., Nordberg A., High PIB retention in Alzheimer’s disease is an early event with complex relationship with CSF biomarkers and functional parameters, Curr. Alzheimer Res., 2010, 7, 56–66 http://dx.doi.org/10.2174/156720510790274446 [Crossref]

  • [16] Landau S.M., Lu M., Joshi A.D., Pontecorvo M., Mintun M.A., Trojanowski J.Q., et al., Comparing positron emission tomography imaging and cerebrospinal fluid measurements of beta-amyloid, Ann. Neurol., 2013, 74, 826–836 http://dx.doi.org/10.1002/ana.23908 [Crossref]

  • [17] Mattsson N., Blennow K., Zetterberg H., Inter-laboratory variation in cerebrospinal fluid biomarkers for Alzheimer’s disease: united we stand, divided we fall, Clin. Chem. Lab. Med., 2010, 48, 603–607 http://dx.doi.org/10.1515/CCLM.2010.131 [Crossref]

  • [18] Nordberg A., Carter S.F., Rinne J., Drzezga A., Brooks D.J., Vandenberghe R., et al., A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease, Eur. J. Nucl. Med. Mol. Imaging, 2013, 40, 104–114 http://dx.doi.org/10.1007/s00259-012-2237-2 [Crossref]

  • [19] Vandenberghe R., Adamczuk K., Dupont P., Laere K.V., Chételat G., Amyloid PET in clinical practice: its place in the multidimensional space of Alzheimer’s disease, Neuroimage. Clin., 2013, 2, 497–511 http://dx.doi.org/10.1016/j.nicl.2013.03.014 [Crossref]

  • [20] Cohen A.D., Rabinovici G.D., Mathis C.A., Jagust W.J., Klunk W.E., Ikonomovic M.D., Using Pittsburgh Compound B for in vivo PET imaging of fibrillar amyloid-beta, Adv. Pharmacol., 2012, 64, 27–81 http://dx.doi.org/10.1016/B978-0-12-394816-8.00002-7 [Crossref]

  • [21] Price J.C., Klunk W.E., Lopresti B.J., Lu X., Hoge J.A., Ziolko S.K., et al., Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B, J. Cereb. Blood Flow Metab., 2005, 25, 1528–1547 http://dx.doi.org/10.1038/sj.jcbfm.9600146 [Crossref]

  • [22] Lockhart A., Lamb J.R., Osredkar T., Sue L.I., Joyce J.N., Ye L., et al., PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptiderelated cerebral amyloidosis, Brain, 2007, 130, 2607–2615 http://dx.doi.org/10.1093/brain/awm191 [Crossref]

  • [23] Maezawa I., Hong H.S., Liu R., Wu C.Y., Cheng R.H., Kung M.P., et al., Congo red and thioflavin-T analogs detect Abeta oligomers, J. Neurochem., 2008, 104, 457–468

  • [24] Kemppainen N.M., Aalto S., Wilson I.A., Nagren K., Helin S., Bruck A., et al., PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment, Neurology, 2007, 68, 1603–1606 http://dx.doi.org/10.1212/01.wnl.0000260969.94695.56 [Crossref]

  • [25] Klunk W.E., Engler H., Nordberg A., Wang Y., Blomqvist G., Holt D.P., et al., Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B, Ann. Neurol., 2004, 55, 306–319 http://dx.doi.org/10.1002/ana.20009 [Crossref]

  • [26] Forsberg A., Engler H., Almkvist O., Blomquist G., Hagman G., Wall A., et al., PET imaging of amyloid deposition in patients with mild cognitive impairment, Neurobiol. Aging, 2008, 29, 1456–1465 http://dx.doi.org/10.1016/j.neurobiolaging.2007.03.029 [Crossref]

  • [27] Okello A., Koivunen J., Edison P., Archer H.A., Turkheimer F.E., Nagren K., et al., Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study, Neurology, 2009, 73, 754–760 http://dx.doi.org/10.1212/WNL.0b013e3181b23564 [Crossref]

  • [28] Jagust W.J., Bandy D., Chen K., Foster N.L., Landau S.M., Mathis C.A., et al., The Alzheimer’s Disease Neuroimaging Initiative positron emission tomography core, Alzheimers Dement., 2010, 6, 221–229 http://dx.doi.org/10.1016/j.jalz.2010.03.003 [Crossref]

  • [29] Resnick S.M., Sojkova J., Amyloid imaging and memory change for prediction of cognitive impairment, Alzheimers Res.Ther., 2011, 3, 3 http://dx.doi.org/10.1186/alzrt62 [Crossref]

  • [30] Rowe C.C., Ellis K.A., Rimajova M., Bourgeat P., Pike K.E., Jones G., et al., Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, Neurobiol. Aging, 2010, 31, 1275–1283 http://dx.doi.org/10.1016/j.neurobiolaging.2010.04.007 [Crossref]

  • [31] Mintun M.A., Larossa G.N., Sheline Y.I., Dence C.S., Lee S.Y., Mach R.H., et al., [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease, Neurology, 2006, 67, 446–452 http://dx.doi.org/10.1212/01.wnl.0000228230.26044.a4 [Crossref]

  • [32] Rowe C.C., Ng S., Ackermann U., Gong S.J., Pike K., Savage G., et al., Imaging beta-amyloid burden in aging and dementia, Neurology, 2007, 68, 1718–1725 http://dx.doi.org/10.1212/01.wnl.0000261919.22630.ea [Crossref]

  • [33] Ng S.Y., Villemagne V.L., Masters C.L., Rowe C.C., Evaluating atypical dementia syndromes using positron emission tomography with carbon 11 labeled Pittsburgh Compound B, Arch. Neurol., 2007, 64, 1140–1144 http://dx.doi.org/10.1001/archneur.64.8.1140 [Crossref]

  • [34] Rabinovici G.D., Furst A.J., O’Neil J.P., Racine C.A., Mormino E.C., Baker S.L., et al., 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration, Neurology, 2007, 68, 1205–1212 http://dx.doi.org/10.1212/01.wnl.0000259035.98480.ed [Crossref]

  • [35] Rowe C.C., Ackerman U., Browne W., Mulligan R., Pike K.L., O’Keefe G., et al., Imaging of amyloid beta in Alzheimer’s disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism, Lancet Neurol., 2008, 7, 129–135 http://dx.doi.org/10.1016/S1474-4422(08)70001-2 [Crossref]

  • [36] Clark C.M., Pontecorvo M.J., Beach T.G., Bedell B.J., Coleman R.E., Doraiswamy P.M., et al., 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 http://dx.doi.org/10.1016/S1474-4422(12)70142-4 [Crossref]

  • [37] Wolk D.A., Grachev I.D., Buckley C., Kazi H., Grady M.S., Trojanowski J.Q., et al., Association between in vivo fluorine 18-labeled flutemetamol amyloid positron emission tomography imaging and in vivo cerebral cortical histopathology, Arch. Neurol., 2011, 68, 1398–1403 http://dx.doi.org/10.1001/archneurol.2011.153 [Crossref]

  • [38] Cselenyi Z., Jonhagen M.E., Forsberg A., Halldin C., Julin P., Schou M., et al., Clinical validation of 18F-AZD4694, an amyloid-beta-specific PET radioligand, J. Nucl. Med., 2012, 53, 415–424 http://dx.doi.org/10.2967/jnumed.111.094029 [Crossref]

  • [39] Ikonomovic M.D., Klunk W.E., Abrahamson E.E., Mathis C.A., Price J.C., Tsopelas N.D., et al., Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease, Brain, 2008, 131, 1630–1645 http://dx.doi.org/10.1093/brain/awn016 [Crossref]

  • [40] Clark C.M., Schneider J.A., Bedell B.J., Beach T.G., Bilker W.B., Mintun M.A., et al., Use of florbetapir-PET for imaging beta-amyloid pathology, JAMA, 2011, 305, 275–283 http://dx.doi.org/10.1001/jama.2010.2008 [Crossref]

  • [41] Zimmer E., Parent M., Leuzy A., Rowley J., Cheewakriengkrai L., Shin M., et al., [18F]NAV4694 shows higher binding and wider dynamic range compared with [11C]PiB in Alzheimer’s disease postmortem tissue, Alzheimers Dement., 2013, 9, P22–P23 http://dx.doi.org/10.1016/j.jalz.2013.05.026 [Crossref]

  • [42] Johnson K.A., Minoshima S., Bohnen N.I., Donohoe K.J., Foster N.L., Herscovitch P., et al., Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association, Alzheimers Dement., 2013, 9, e-1–16 http://dx.doi.org/10.1016/j.jalz.2013.01.002 [Crossref]

  • [43] Johnson K.A., Fox N.C., Sperling R.A., Klunk W.E., Brain imaging in Alzheimer disease, Cold Spring Harb. Perspect. Med., 2012, 2, a006213 http://dx.doi.org/10.1101/cshperspect.a006213 [Crossref]

  • [44] Olson S., Institute of Medicine (U.S.). Roundtable on translating genomic-based research for health., Institute of Medicine (U.S.). Board on Health Sciences Policy., Integrating large-scale genomic information into clinical practice: workshop summary, National Academies Press, Washington, D.C., 2012

  • [45] Hood L., Flores M., A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory, N. Biotechnol., 2012, 29, 613–624 http://dx.doi.org/10.1016/j.nbt.2012.03.004 [Crossref]

  • [46] Snyderman R., Personalized health care: from theory to practice, Biotechnol. J., 2012, 7, 973–979 http://dx.doi.org/10.1002/biot.201100297 [Crossref]

  • [47] Weiner M.W., Veitch D.P., Aisen P.S., Beckett L.A., Cairns N.J., Green R.C., et al., The Alzheimer’s Disease Neuroimaging Initiative: a review of papers published since its inception, Alzheimers Dement., 2012, 8, S1–68 http://dx.doi.org/10.1016/j.jalz.2011.09.172 [Crossref]

  • [48] Ellis K.A., Bush A.I., Darby D., De Fazio D., Foster J., Hudson P., et al., The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer’s disease, Int. Psychogeriatr., 2009, 21, 672–687 http://dx.doi.org/10.1017/S1041610209009405 [Crossref]

  • [49] Pike K.E., Savage G., Villemagne V.L., Ng S., Moss S.A., Maruff P., et al., Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease, Brain, 2007, 130, 2837–2844 http://dx.doi.org/10.1093/brain/awm238 [Crossref]

  • [50] Jack C.R., Jr., Lowe V.J., Senjem M.L., Weigand S.D., Kemp B.J., Shiung M.M., et al., 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment, Brain, 2008, 131, 665–680 http://dx.doi.org/10.1093/brain/awm336 [Crossref]

  • [51] Aizenstein H.J., Nebes R.D., Saxton J.A., Price J.C., Mathis C.A., Tsopelas N.D., et al., Frequent amyloid deposition without significant cognitive impairment among the elderly, Arch. Neurol., 2008, 65, 1509–1517 http://dx.doi.org/10.1001/archneur.65.11.1509 [Crossref]

  • [52] Mormino E.C., Kluth J.T., Madison C.M., Rabinovici G.D., Baker S.L., Miller B.L., et al., Episodic memory loss is related to hippocampalmediated beta-amyloid deposition in elderly subjects, Brain, 2009, 132, 1310–1323 http://dx.doi.org/10.1093/brain/awn320 [Crossref]

  • [53] Storandt M., Mintun M.A., Head D., Morris J.C., Cognitive decline and brain volume loss as signatures of cerebral amyloid-beta peptide deposition identified with Pittsburgh compound B: cognitive decline associated with Abeta deposition, Arch. Neurol., 2009, 66, 1476–1481 http://dx.doi.org/10.1001/archneurol.2009.272 [Crossref]

  • [54] Villemagne V.L., Pike K.E., Chetelat G., Ellis K.A., Mulligan R.S., Bourgeat P., et al., Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease, Ann. Neurol., 2011, 69, 181–192 http://dx.doi.org/10.1002/ana.22248 [Crossref]

  • [55] Landau S.M., Mintun M.A., Joshi A.D., Koeppe R.A., Petersen R.C., Aisen P.S., et al., Amyloid deposition, hypometabolism, and longitudinal cognitive decline, Ann. Neurology, 2012, 72, 578–586 [Crossref]

  • [56] Jack C.R., Jr., Wiste H.J., Vemuri P., Weigand S.D., Senjem M.L., Zeng G., et al., Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease, Brain, 2010, 133, 3336–3348 http://dx.doi.org/10.1093/brain/awq277 [Crossref]

  • [57] Wolk D.A., Price J.C., Saxton J.A., Snitz B.E., James J.A., Lopez O.L., et al., Amyloid imaging in mild cognitive impairment subtypes, Ann. Neurol., 2009, 65, 557–568 http://dx.doi.org/10.1002/ana.21598 [Crossref]

  • [58] Trzepacz P.T., Yu P., Sun J., Schuh K., Case M., Witte M.M., et al., Comparison of neuroimaging modalities for the prediction of conversion from mild cognitive impairment to Alzheimer’s dementia, Neurobiol. Aging, 2014, 35, 143–151 http://dx.doi.org/10.1016/j.neurobiolaging.2013.06.018 [Crossref]

  • [59] Green R.C., Roberts J.S., Cupples L.A., Relkin N.R., Whitehouse P.J., Brown T., et al., Disclosure of APOE genotype for risk of Alzheimer’s disease, N. Engl. J. Med., 2009, 361, 245–254 http://dx.doi.org/10.1056/NEJMoa0809578 [Crossref]

  • [60] Steinbrook R., The Centers for Medicare & Medicaid Services and amyloid-beta positron emission tomography for Alzheimer disease, JAMA Intern. Med., 2014, 174, 135 http://dx.doi.org/10.1001/jamainternmed.2013.11705 [Crossref]

  • [61] Pearson S.D., Ollendorf D.A., Colby J.A., Amyloid-beta positron emission tomography in the diagnostic evaluation of Alzheimer disease: summary of primary findings and conclusions, JAMA Intern. Med., 2014, 174, 133–134 http://dx.doi.org/10.1001/jamainternmed.2013.11711 [Crossref]

  • [62] Doraiswamy P.M., Sperling R.A., Coleman R.E., Johnson K.A., Reiman E.M., Davis M.D., et al., Amyloid-beta assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study, Neurology, 2012, 79, 1636–1644 http://dx.doi.org/10.1212/WNL.0b013e3182661f74 [Crossref]

  • [63] Garber K., First FDA-approved beta-amyloid diagnostic hits the market, Nat. Biotechnol., 2012, 30, 575 http://dx.doi.org/10.1038/nbt0712-575 [Crossref]

  • [64] Leuzy A., Gauthier S., Ethical issues in Alzheimer’s disease: an overview, Expert Rev. Neurother., 2012, 12, 557–567 http://dx.doi.org/10.1586/ern.12.38 [Crossref]

  • [65] Lineweaver T.T., Bondi M.W., Galasko D., Salmon D.P., Effect of knowledge of APOE genotype on subjective and objective memory performance in healthy older adults, Am. J. Psychiatry, 2014, 171, 201–208 http://dx.doi.org/10.1176/appi.ajp.2013.12121590 [Crossref]

  • [66] Karlawish J., Green R.C., Minding the aging brain: are we ready for personalized medicine?, Am. J. Psychiatry, 2014, 171, 137–139 http://dx.doi.org/10.1176/appi.ajp.2013.13111536 [Crossref]

Comments (0)

Please log in or register to comment.