Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease

Gaël Chételat, Renaud La Joie, Nicolas Villain, Audrey Perrotin, Vincent de La Sayette, Francis Eustache, Rik Vandenberghe, Gaël Chételat, Renaud La Joie, Nicolas Villain, Audrey Perrotin, Vincent de La Sayette, Francis Eustache, Rik Vandenberghe

Abstract

Recent developments of PET amyloid ligands have made it possible to visualize the presence of Aβ deposition in the brain of living participants and to assess the consequences especially in individuals with no objective sign of cognitive deficits. The present review will focus on amyloid imaging in cognitively normal elderly, asymptomatic at-risk populations, and individuals with subjective cognitive decline. It will cover the prevalence of amyloid-positive cases amongst cognitively normal elderly, the influence of risk factors for AD, the relationships to cognition, atrophy and prognosis, longitudinal amyloid imaging and ethical aspects related to amyloid imaging in cognitively normal individuals. Almost ten years of research have led to a few consensual and relatively consistent findings: some cognitively normal elderly have Aβ deposition in their brain, the prevalence of amyloid-positive cases increases in at-risk populations, the prognosis for these individuals is worse than for those with no Aβ deposition, and significant increase in Aβ deposition over time is detectable in cognitively normal elderly. More inconsistent findings are still under debate; these include the relationship between Aβ deposition and cognition and brain volume, the sequence and cause-to-effect relations between the different AD biomarkers, and the individual outcome associated with an amyloid positive versus negative scan. Preclinical amyloid imaging also raises important ethical issues. While amyloid imaging is definitely useful to understand the role of Aβ in early stages, to define at-risk populations for research or for clinical trial, and to assess the effects of anti-amyloid treatments, we are not ready yet to translate research results into clinical practice and policy. More researches are needed to determine which information to disclose from an individual amyloid imaging scan, the way of disclosing such information and the impact on individuals and on society.

Keywords: Amyloid PET imaging; ApoE4; Cognitively normal elderly; Longitudinal studies; Preclinical Alzheimer's disease; Subjective cognitive decline.

Figures

Fig. 1
Fig. 1
Illustration of positive, negative, and intermediate cases within the cognitively normal elderly. These data are issued from the IMAP study (Inserm U1077, Caen, France). Each circle represents the mean neocortical 18F-florbetapir SUVR from an individual. The majority (67%) of healthy controls older than 60 years (HC > 60 yrs) is clearly negative (i.e. their SUVR value is within 2SD of the controls younger than 60 years = HC < 60 yrs). Three cases were clearly positive (i.e. classified as positive both compared to younger controls and using the iterative outlier approach). There were 25% of intermediate cases, i.e. cases classified as positive or negative according to the method.
Fig. 2
Fig. 2
Illustration of the brain distribution of 18F-florbetapir in six cases from the IMAP project (Inserm U1077, Caen, France). The figure shows disproportionate binding of 18F-florbetapir in the caudate nucleus in the asymptomatic and symptomatic mutation carriers for the early-onset familial form of AD compared to both sporadic AD cases and amyloid-positive cognitively normal elderly.

References

    1. Aizenstein H.J., Nebes R.D., Saxton J.A., Price J.C., Mathis C.A., Tsopelas N.D. Frequent amyloid deposition without significant cognitive impairment among the elderly. Archives of Neurology. 2008;65:1509–1517.
    1. Albert M.S., DeKosky S.T., Dickson D., Dubois B., Feldman H.H., Fox N.C. 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. Alzheimer's & Dementia. 2011;7:270–279.
    1. Amariglio R.E., Becker J.A., Carmasin J., Wadsworth L.P., Lorius N., Sullivan C. Subjective cognitive complaints and amyloid burden in cognitively normal older individuals. Neuropsychologia. 2012;50:2880–2886.
    1. Archer H.A., Edison P., Brooks D.J., Barnes J., Frost C., Yeatman T. Amyloid load and cerebral atrophy in Alzheimer's disease: an 11C-PIB positron emission tomography study. Annals of Neurology. 2006;60:145–147.
    1. Bateman R.J., Xiong C., Benzinger T.L.S., Fagan A.M., Goate A., Fox N.C. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. The New England Journal of Medicine. 2012;367:795–804.
    1. Becker J.A., Hedden T., Carmasin J., Maye J., Rentz D.M., Putcha D. Amyloid-β associated cortical thinning in clinically normal elderly. Annals of Neurology. 2011;69:1032–1042.
    1. Berti V., Nacmias B., Bagnoli S., Sorbi S. Alzheimer's disease: genetic basis and amyloid imaging as endophenotype. The Quarterly Journal of Nuclear Medicine and Molecular Imaging. 2011;55:225–236.
    1. Blennow K., Zetterberg H. Is it time for biomarker-based diagnostic criteria for prodromal Alzheimer's disease? Alzheimer's Research & Therapy. 2010;2:8.
    1. Bourgeat P., Chételat G., Villemagne V.L., Fripp J., Raniga P., Pike K. Beta-amyloid burden in the temporal neocortex is related to hippocampal atrophy in elderly subjects without dementia. Neurology. 2010;74:121–127.
    1. Braak H., Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiology of Aging. 1997;18:351–357.
    1. Chételat G. Alzheimer disease: Aβ-independant processes - rethinking preclinical AD. Nature Reviews Neurology. 2013;9:123–124.
    1. Chételat G., Desgranges B., Landeau B., Mézenge F., Poline J.B., de la Sayette V. Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer's disease. Brain. 2008;131:60–71.
    1. Chételat G., Villemagne V.L., Bourgeat P., Pike K.E., Jones G., Ames D. Relationship between atrophy and beta-amyloid deposition in Alzheimer disease. Annals of Neurology. 2010;67:317–324.
    1. Chételat G., Villemagne V.L., Pike K.E., Baron J.-C., Bourgeat P., Jones G. Larger temporal volume in elderly with high versus low beta-amyloid deposition. Brain. 2010;133:3349–3358.
    1. Chételat G., Villemagne V.L., Pike K.E., Ellis K.A., Bourgeat P., Jones G. Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease. Brain. 2011;134:798–807.
    1. Chételat G., Villemagne V.L., Villain N., Jones G., Ellis K.A., Ames D. Accelerated cortical atrophy in cognitively normal elderly with high β-amyloid deposition. Neurology. 2012;78:477–484.
    1. Choi S.R., Golding G., Zhuang Z., Zhang W., Lim N., Hefti F. Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain. Journal of Nuclear Medicine. 2009;50:1887–1894.
    1. Craig-Schapiro R., Fagan A.M., Holtzman D.M. Biomarkers of Alzheimer's disease. Neurobiology of Disease. 2009;35:128–140.
    1. Crystal H., Dickson D., Fuld P., Masur D., Scott R., Mehler M. Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology. 1988;38:1682–1687.
    1. Dickerson B.C., Bakkour A., Salat D.H., Feczko E., Pacheco J., Greve D.N. 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. Cerebral Cortex. 2009;19:497–510.
    1. Doraiswamy P.M., Sperling R.A., Coleman R.E., Johnson K.A., Reiman E.M., Davis M.D. Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline A multicenter study. Neurology. 2012;79(16):1636–1644. (Epub 2012 Jul 11)
    1. Draper B., Peisah C., Snowdon J., Brodaty H. Early dementia diagnosis and the risk of suicide and euthanasia. Alzheimer's & Dementia. 2010;6:75–82.
    1. Dubois B., Feldman H.H., Jacova C., Dekosky S.T., Barberger-Gateau P., Cummings J. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurology. 2007;6:734–746.
    1. Dubois B., Feldman H.H., Jacova C., Cummings J.L., Dekosky S.T., Barberger-Gateau P. Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurology. 2010;9:1118–1127.
    1. Edison P., Hinz R., Brooks D.J. Technical aspects of amyloid imaging for Alzheimer's disease. Alzheimer's Research & Therapy. 2011;3:25.
    1. Edison P., Hinz R., Ramlackhansingh A., Thomas J., Gelosa G., Archer H.A. Can target-to-pons ratio be used as a reliable method for the analysis of [11C]PIB brain scans? NeuroImage. 2012;60:1716–1723.
    1. Fjell A.M., Walhovd K.B. Neuroimaging results impose new views on Alzheimer's disease–the role of amyloid revised. Molecular Neurobiology. 2012;45:153–172.
    1. Fleisher A.S., Chen K., Liu X., Roontiva A., Thiyyagura P., Ayutyanont N. Using positron emission tomography and florbetapir F18 to image cortical amyloid in patients with mild cognitive impairment or dementia due to Alzheimer disease. Archives of Neurology. 2011;68:1404–1411.
    1. Fleisher A.S., Chen K., Quiroz Y.T., Jakimovich L.J., Gomez M.G., Langois C.M. Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. Lancet Neurology. 2012;11:1057–1065.
    1. Fleisher A.S., Chen K., Liu X., Ayutyanont N., Roontiva A., Thiyyagura P. Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiology of Aging. 2013;34:1–12.
    1. Frisoni G.B., Fox N.C., Jack C.R., Scheltens P., Thompson P.M. The clinical use of structural MRI in Alzheimer disease. Nature Reviews. Neurology. 2010;6:67–77.
    1. 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.
    1. Hatashita S., Yamasaki H. Clinically different stages of Alzheimer's disease associated by amyloid deposition with [11C]-PIB PET imaging. Journal of Alzheimer's Disease. 2010;21:995–1003.
    1. Head D., Bugg J.M., Goate A.M., Fagan A.M., Mintun M.A., Benzinger T. Exercise engagement as a moderator of the effects of APOE genotype on amyloid deposition. Archives of Neurology. 2012;69:636–643.
    1. Hedden T., Van Dijk K.R.A., Becker J.A., Mehta A., Sperling R.A., Johnson K.A. Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. Journal of Neuroscience. 2009;29:12686–12694.
    1. Herholz K., Ebmeier K. Clinical amyloid imaging in Alzheimer's disease. Lancet Neurology. 2011;10:667–670.
    1. Herrup K. Commentary on « Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. » Addressing the challenge of Alzheimer's disease in the 21st century. Alzheimer's & Dementia. 2011;7:335–337.
    1. Hua X., Hibar D.P., Lee S., Toga A.W., Jack C.R., Jr., Weiner M.W. Sex and age differences in atrophic rates: an ADNI study with n = 1368 MRI scans. Neurobiology of Aging. 2010;31:1463–1480.
    1. Jack C.R., Lowe V.J., Senjem M.L., Weigand S.D., Kemp B.J., Shiung M.M. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. Brain. 2008;131:665–680.
    1. Jack C.R., Lowe V.J., Weigand S.D., Wiste H.J., Senjem M.L., Knopman D.S. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease. Brain. 2009;132:1355–1365.
    1. Jack C.R., Knopman D.S., Jagust W.J., Shaw L.M., Aisen P.S., Weiner M.W. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurology. 2010;9:119–128.
    1. Jack C.R., Jr., Knopman D.S., Weigand S.D., Wiste H.J., Vemuri P., Lowe V. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Annals of Neurology. 2012;71:765–775.
    1. Jagust W.J., Bandy D., Chen K., Foster N.L., Landau S.M., Mathis C.A. The Alzheimer's Disease Neuroimaging Initiative positron emission tomography core. Alzheimer's & Dementia. 2010;6:221–229.
    1. Johnson K.A., Minoshima S., Bohnen N.I., Donohoe K.J., Foster N.L., Herscovitch P. 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. Alzheimer's & Dementia. 2013;9(1):E1–E16.
    1. Kantarci K., Lowe V., Przybelski S.A., Weigand S.D., Senjem M.L., Ivnik R.J. APOE modifies the association between Aβ load and cognition in cognitively normal older adults. Neurology. 2012;78:232–240.
    1. Karlawish J. Addressing the ethical, policy, and social challenges of preclinical Alzheimer disease. Neurology. 2011;77:1487–1493.
    1. Katzman R., Terry R., DeTeresa R., Brown T., Davies P., Fuld P. Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Annals of Neurology. 1988;23:138–144.
    1. Klunk W.E. Amyloid imaging as a biomarker for cerebral β-amyloidosis and risk prediction for Alzheimer dementia. Neurobiology of Aging. 2011;32(Suppl. 1):S20–S36.
    1. Klunk W.E., Engler H., Nordberg A., Wang Y., Blomqvist G., Holt D.P. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Annals of Neurology. 2004;55:306–319.
    1. Klunk W.E., Price J.C., Mathis C.A., Tsopelas N.D., Lopresti B.J., Ziolko S.K. Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. Journal of Neuroscience. 2007;27:6174–6184.
    1. Knight W.D., Okello A.A., Ryan N.S., Turkheimer F.E., Rodríguez Martinez de Llano S., Edison P. Carbon-11-Pittsburgh compound B positron emission tomography imaging of amyloid deposition in presenilin 1 mutation carriers. Brain. 2011;134:293–300.
    1. Knopman D.S., Jack C.R., Jr., Wiste H.J., Weigand S.D., Vemuri P., Lowe V. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology. 2012;78:1576–1582.
    1. Knopman, D.S., Jack, C.R., Wiste, H.J., Weigand, S.D., Vemuri, P., Lowe, V.J., Kantarci, K., Gunter, J.L., Senjem, M.L., Mielke, M.M., Roberts, R.O., Boeve, B.F., Petersen, R.C., in press. Brain injury biomarkers are not dependent on β-amyloid in normal elderly. Annals of Neurology. .
    1. Koivunen J., Scheinin N., Virta J.R., Aalto S., Vahlberg T., Någren K. Amyloid PET imaging in patients with mild cognitive impairment A 2-year follow-up study. Neurology. 2011;76:1085–1090.
    1. La Joie R., Perrotin A., Barré L., Hommet C., Mézenge F., Ibazizene M. Region-specific hierarchy between atrophy, hypometabolism, and β-amyloid (Aβ) load in Alzheimer's disease dementia. Journal of Neuroscience. 2012;32:16265–16273.
    1. Landau S.M., Marks S.M., Mormino E.C., Rabinovici G.D., Oh H., O'Neil J.P. Association of lifetime cognitive engagement and low β-amyloid deposition. Archives of Neurology. 2012;69:623–629.
    1. Leow A.D., Yanovsky I., Parikshak N., Hua X., Lee S., Toga A.W. Alzheimer's disease neuroimaging initiative: a one-year follow up study using tensor-based morphometry correlating degenerative rates, biomarkers and cognition. NeuroImage. 2009;45:645–655.
    1. Liang K.Y., Mintun M.A., Fagan A.M., Goate A.M., Bugg J.M., Holtzman D.M. Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Annals of Neurology. 2010;68:311–318.
    1. Lowe V.J., Kemp B.J., Jack C.R., Senjem M., Weigand S., Shiung M. Comparison of 18F-FDG and PiB PET in cognitive impairment. Journal of Nuclear Medicine. 2009;50:878–886.
    1. Marchant N.L., Reed B.R., DeCarli C.S., Madison C.M., Weiner M.W., Chui H.C. Cerebrovascular disease, beta-amyloid, and cognition in aging. Neurobiology of Aging. 2012;33 (1006.e25-36)
    1. Masters C.L., Cappai R., Barnham K.J., Villemagne V.L. Molecular mechanisms for Alzheimer's disease: implications for neuroimaging and therapeutics. Journal of Neurochemistry. 2006;97:1700–1725.
    1. Mattsson N., Brax D., Zetterberg H. J Alzheimers Dis; Int: 2010. To Know or Not to Know: Ethical Issues Related to Early Diagnosis of Alzheimer's Disease. (2010)
    1. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E.M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984;34:939–944.
    1. McKhann G.M., Knopman D.S., Chertkow H., Hyman B.T., Jack C.R., Jr., Kawas C.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. 2011;7:263–269.
    1. Mielke M.M., Wiste H.J., Weigand S.D., Knopman D.S., Lowe V.J., Roberts R.O. Indicators of amyloid burden in a population-based study of cognitively normal elderly. Neurology. 2012;79:1570–1577.
    1. Mintun M.A., Larossa G.N., Sheline Y.I., Dence C.S., Lee S.Y., Mach R.H. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67:446–452.
    1. Mormino E.C., Kluth J.T., Madison C.M., Rabinovici G.D., Baker S.L., Miller B.L. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain. 2009;132:1310–1323.
    1. Mormino E.C., Brandel M.G., Madison C.M., Rabinovici G.D., Marks S., Baker S.L. Not quite PIB-positive, not quite PIB-negative: slight PIB elevations in elderly normal control subjects are biologically relevant. NeuroImage. 2012;59:1152–1160.
    1. Morris J.C., Roe C.M., Grant E.A., Head D., Storandt M., Goate A.M. Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Archives of Neurology. 2009;66:1469–1475.
    1. Morris J.C., Roe C.M., Xiong C., Fagan A.M., Goate A.M., Holtzman D.M. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Annals of Neurology. 2010;67:122–131.
    1. Mosconi L., Rinne J.O., Tsui W.H., Berti V., Li Y., Wang H. Increased fibrillar amyloid-{beta} burden in normal individuals with a family history of late-onset Alzheimer's. Proceedings of the National Academy of Sciences of the United States of America. 2010;107:5949–5954.
    1. Nelissen N., Vandenbulcke M., Fannes K., Verbruggen A., Peeters R., Dupont P. Abeta amyloid deposition in the language system and how the brain responds. Brain. 2007;130:2055–2069.
    1. Oh H., Madison C., Haight T.J., Markley C., Jagust W.J. Effects of age and β-amyloid on cognitive changes in normal elderly people. Neurobiology of Aging. 2012;33:2746–2755.
    1. Oh, H., Habeck, C., Madison, C., Jagust, W., in press. Covarying alterations in Aβ deposition, glucose metabolism, and gray matter volume in cognitively normal elderly. Human Brain Mapping. .
    1. Okello A., Koivunen J., Edison P., Archer H.A., Turkheimer F.E., Någren K. Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology. 2009;73:754–760.
    1. Perrotin A., Mormino E.C., Madison C.M., Hayenga A.O., Jagust W.J. Subjective cognition and amyloid deposition imaging: a Pittsburgh Compound B positron emission tomography study in normal elderly individuals. Archives of Neurology. 2012;69:223–229.
    1. Petersen R.C. Alzheimer's disease: progress in prediction. Lancet Neurology. 2010;9:4–5.
    1. Pike K.E., Savage G., Villemagne V.L., Ng S., Moss S.A., Maruff P. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain. 2007;130:2837–2844.
    1. Pike K.E., Ellis K.A., Villemagne V.L., Good N., Chételat G., Ames D. Cognition and beta-amyloid in preclinical Alzheimer's disease: data from the AIBL study. Neuropsychologia. 2011;49:2384–2390.
    1. Price J.L., Morris J.C. Tangles and plaques in nondemented aging and « preclinical » Alzheimer's disease. Annals of Neurology. 1999;45:358–368.
    1. Prvulovic D., Hampel H. Ethical considerations of biomarker use in neurodegenerative diseases — a case study of Alzheimer's disease. Progress in Neurobiology. 2011;95:517–519.
    1. Quigley H., Colloby S.J., O'Brien J.T. PET imaging of brain amyloid in dementia: a review. International Journal of Geriatric Psychiatry. 2011;26:991–999.
    1. Reiman E.M., Chen K., Liu X., Bandy D., Yu M., Lee W. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:6820–6825.
    1. Reiman E.M., Quiroz Y.T., Fleisher A.S., Chen K., Velez-Pardo C., Jimenez-Del-Rio M. 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 Neurology. 2012;11:1048–1056.
    1. Rentz D.M., Locascio J.J., Becker J.A., Moran E.K., Eng E., Buckner R.L. Cognition, reserve, and amyloid deposition in normal aging. Annals of Neurology. 2010;67:353–364.
    1. Rentz D.M., Amariglio R.E., Becker J.A., Frey M., Olson L.E., Frishe K. Face-name associative memory performance is related to amyloid burden in normal elderly. Neuropsychologia. 2011;49:2776–2783.
    1. Resnick S.M., Sojkova J. Amyloid imaging and memory change for prediction of cognitive impairment. Alzheimer's Research & Therapy. 2011;3:3.
    1. Resnick S.M., Sojkova J., Zhou Y., An Y., Ye W., Holt D.P. Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology. 2010;74:807–815.
    1. Rinne J.O., Någren K. Positron emission tomography in at risk patients and in the progression of mild cognitive impairment to Alzheimer's disease. Journal of Alzheimer's Disease. 2010;19:291–300.
    1. Roberts J.S., Tersegno S.M. Estimating and disclosing the risk of developing Alzheimer's disease: challenges, controversies and future directions. Future Neurology. 2010;5:501–517.
    1. Rodrigue K.M., Kennedy K.M., Devous M.D., Sr., Rieck J.R., Hebrank A.C., Diaz-Arrastia R. β-Amyloid burden in healthy aging: regional distribution and cognitive consequences. Neurology. 2012;78:387–395.
    1. Rowe C.C., Ng S., Ackermann U., Gong S.J., Pike K., Savage G. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68:1718–1725.
    1. Rowe C.C., Ellis K.A., Rimajova M., Bourgeat P., Pike K.E., Jones G. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiology of Aging. 2010;31:1275–1283.
    1. Scheinin N.M., Aalto S., Koikkalainen J., Lötjönen J., Karrasch M., Kemppainen N. Follow-up of [11C]PIB uptake and brain volume in patients with Alzheimer disease and controls. Neurology. 2009;73:1186–1192.
    1. Scheinin N.M., Aalto S., Kaprio J., Koskenvuo M., Räihä I., Rokka J. Early detection of Alzheimer disease: 11C-PiB PET in twins discordant for cognitive impairment. Neurology. 2011;77:453–460.
    1. Schott J.M., Bartlett J.W., Fox N.C., Barnes J. Increased brain atrophy rates in cognitively normal older adults with low cerebrospinal fluid Aβ1-42. Annals of Neurology. 2010;68:825–834.
    1. Small G.W., Kepe V., Ercoli L.M., Siddarth P., Bookheimer S.Y., Miller K.J. PET of brain amyloid and tau in mild cognitive impairment. The New England Journal of Medicine. 2006;355:2652–2663.
    1. Sojkova J., Zhou Y., An Y., Kraut M.A., Ferrucci L., Wong D.F. Longitudinal patterns of β-amyloid deposition in nondemented older adults. Archives of Neurology. 2011;68:644–649.
    1. Sperling R.A., Laviolette P.S., O'Keefe K., O'Brien J., Rentz D.M., Pihlajamaki M. Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron. 2009;63:178–188.
    1. Sperling R.A., Aisen P.S., Beckett L.A., Bennett D.A., Craft S., Fagan A.M. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging and the Alzheimer's Association workgroup. Alzheimer's & Dementia. 2011
    1. Sperling R.A., Johnson K.A., Doraiswamy P.M., Reiman E.M., Fleisher A.S., Sabbagh M.N. Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiology of Aging. 2013;34:822–831.
    1. Stern Y. What is cognitive reserve? Theory and research application of the reserve concept. Journal of International Neuropsychological Society. 2002;8:448–460.
    1. 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. Archives of Neurology. 2009;66:1476–1481.
    1. Storandt M., Head D., Fagan A.M., Holtzman D.M., Morris J.C. Toward a multifactorial model of Alzheimer disease. Neurobiology of Aging. 2012;33:2262–2271.
    1. Tosun D., Schuff N., Mathis C.A., Jagust W., Weiner M.W. Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment. Brain. 2011;134:1077–1088.
    1. Tosun D., Schuff N., Shaw L.M., Trojanowski J.Q., Weiner M.W. Relationship between CSF biomarkers of Alzheimer's disease and rates of regional cortical thinning in ADNI data. Journal of Alzheimer's Disease. 2011;26(Suppl. 3):77–90.
    1. 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. 2013;2:497–511. (this issue)
    1. Vandenberghe R., Van Laere K., Ivanoiu A., Salmon E., Bastin C., Triau E. 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Annals of Neurology. 2010;68:319–329.
    1. Villain N., Chételat G., Grassiot B., Bourgeat P., Jones G., Ellis K.A. Regional dynamics of amyloid-β deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PiB-PET longitudinal study. Brain. 2012;135:2126–2139.
    1. Villemagne V.L., Ataka S., Mizuno T., Brooks W.S., Wada Y., Kondo M. High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. Archives of Neurology. 2009;66:1537–1544.
    1. Villemagne V.L., Pike K.E., Chételat G., Ellis K.A., Mulligan R.S., Bourgeat P. Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Annals of Neurology. 2011;69:181–192.
    1. Villemagne V.L., Mulligan R.S., Pejoska S., Ong K., Jones G., O'Keefe G. Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer's disease. European Journal of Nuclear Medicine and Molecular Imaging. 2012;39:983–989.
    1. Vlassenko A.G., Mintun M.A., Xiong C., Sheline Y.I., Goate A.M., Benzinger T.L.S. Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C]Pittsburgh compound B data. Annals of Neurology. 2011;70:857–861.
    1. Weiner M.W., Aisen P.S., Jack C.R., Jagust W.J., Trojanowski J.Q., Shaw L. The Alzheimer's disease neuroimaging initiative: progress report and future plans. Alzheimer's & Dementia. 2010;6:202–211.e7.
    1. Whitwell J.L., Wiste H.J., Weigand S.D., Rocca W.A., Knopman D.S., Roberts R.O. Comparison of imaging biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging. Archives of Neurology. 2012;69:614–622.
    1. Wilson J.M.G., Jungner G. 1968. Principles and Practice of Screening for Disease.
    1. Wong D.F., Rosenberg P.B., Zhou Y., Kumar A., Raymont V., Ravert H.T. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (flobetapir F 18) Journal of Nuclear Medicine. 2010;51:913–920.
    1. Xiong C., Roe C.M., Buckles V., Fagan A., Holtzman D., Balota D. Role of family history for Alzheimer biomarker abnormalities in the adult children study. Archives of Neurology. 2011;68:1313–1319.

Source: PubMed

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