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Erschienen in: Current Neurology and Neuroscience Reports 11/2014

01.11.2014 | Neuroimaging (DJ Brooks, Section Editor)

The Relationship between Amyloid Deposition, Neurodegeneration, and Cognitive Decline in Dementia

verfasst von: Rik Vandenberghe

Erschienen in: Current Neurology and Neuroscience Reports | Ausgabe 11/2014

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Abstract

Amyloid imaging has been clinically approved for measuring β amyloid plaque load in patients being evaluated for Alzheimer's disease or other causes of cognitive decline. Here we explore a multidimensional approach to cognitive decline, where we situate amyloid plaque burden among a number of other relevant dimensions, such as aging, volume loss, other proteinopathies such as TDP43 and Lewy bodies, and functional reorganisation of cognitive brain systems. The multidimensional model incorporates a 'pure AD' trajectory, corresponding to e.g. monogenic Alzheimer's disease, but leaves room for other combinations of biomarker abnormalities (e.g. volume loss without amyloid positivity) and other trajectories. More tools will become available in the future that allow one to carve out a causal-mechanistic space for explaing cognitive decline in a personalized manner, enhancing progress towards more efficacious interventions.
Literatur
1.
Zurück zum Zitat Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt D, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Ann Neurol. 2004;55:306–19.PubMedCrossRef Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt D, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Ann Neurol. 2004;55:306–19.PubMedCrossRef
2.••
Zurück zum Zitat Clark C, Pontecorvo M, Beach T, Bedell B, Coleman R, Doraiswamy P, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol. 2012;11:669–78. This pivotal paper establishes the validity of 18 F-florbetapir as a marker of neuritic amyloid plaque density. Clark C, Pontecorvo M, Beach T, Bedell B, Coleman R, Doraiswamy P, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol. 2012;11:669–78. This pivotal paper establishes the validity of 18 F-florbetapir as a marker of neuritic amyloid plaque density.
4.
Zurück zum Zitat Vandenberghe R, Adamczuk K, Dupont P, Van Laere K, Chételat G. Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease. Neuroimage Clin. 2013;2:497–511.PubMedPubMedCentralCrossRef Vandenberghe R, Adamczuk K, Dupont P, Van Laere K, Chételat G. Amyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease. Neuroimage Clin. 2013;2:497–511.PubMedPubMedCentralCrossRef
5.
Zurück zum Zitat Rinne J, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, et al. (11)C-PIB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010;9:363–72.PubMedCrossRef Rinne J, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, et al. (11)C-PIB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010;9:363–72.PubMedCrossRef
6.
Zurück zum Zitat Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69:198–207.PubMedCrossRef Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69:198–207.PubMedCrossRef
7.
Zurück zum Zitat Salloway S, Sperling R, Fox NC, Blennow K, Klunk WE, Raskind M, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370:322–33.PubMedPubMedCentralCrossRef Salloway S, Sperling R, Fox NC, Blennow K, Klunk WE, Raskind M, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370:322–33.PubMedPubMedCentralCrossRef
8.
Zurück zum Zitat Vandenberghe R, Van Laere K, Ivanoiu A, Salmon E, Bastin C, Triau E, et al. 18 F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol. 2010;68:319–29.PubMedCrossRef Vandenberghe R, Van Laere K, Ivanoiu A, Salmon E, Bastin C, Triau E, et al. 18 F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol. 2010;68:319–29.PubMedCrossRef
9.
Zurück zum Zitat Doraiswamy PM, Sperling RA, Coleman RE, Johnson KA, Reiman EM, Davis MD, et al. Amyloid-β assessed by florbetapir F18 PET and 18-month cognitive decline: a multicenter study. Neurology. 2012;79:1636–44.PubMedPubMedCentralCrossRef Doraiswamy PM, Sperling RA, Coleman RE, Johnson KA, Reiman EM, Davis MD, et al. Amyloid-β assessed by florbetapir F18 PET and 18-month cognitive decline: a multicenter study. Neurology. 2012;79:1636–44.PubMedPubMedCentralCrossRef
10.
Zurück zum Zitat Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS, et al. Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol. 2013;74:199–208.PubMedPubMedCentral Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS, et al. Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol. 2013;74:199–208.PubMedPubMedCentral
11.••
Zurück zum Zitat Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease centers, 2005–2010. J Neuropathol Exp Neurol. 2012;71:266–73. This clinicopathological paper provides critical information about the accuracy of a clincal diagnosis of clinically probable or possible AD in a prospective multicentre academic memory clinic based series collected between 2005 and 2010 (n = 919). Compared to the standard-of-truth (neuritic plaque density and neurofibrillary tangle stage), the positive predictive value of a diagnosis of clinically probable AD ranged between 62 and 84 %; specificity between 60 % to 71 %, with a sensitivity around 73 %.PubMedPubMedCentralCrossRef Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease centers, 2005–2010. J Neuropathol Exp Neurol. 2012;71:266–73. This clinicopathological paper provides critical information about the accuracy of a clincal diagnosis of clinically probable or possible AD in a prospective multicentre academic memory clinic based series collected between 2005 and 2010 (n = 919). Compared to the standard-of-truth (neuritic plaque density and neurofibrillary tangle stage), the positive predictive value of a diagnosis of clinically probable AD ranged between 62 and 84 %; specificity between 60 % to 71 %, with a sensitivity around 73 %.PubMedPubMedCentralCrossRef
12.
Zurück zum Zitat Vandenberghe R, Adamczuk K, Van Laere K. The interest of amyloid PET imaging in the diagnosis of Alzheimer's disease. Curr Opin Neurol. 2013;26:646–55.PubMedCrossRef Vandenberghe R, Adamczuk K, Van Laere K. The interest of amyloid PET imaging in the diagnosis of Alzheimer's disease. Curr Opin Neurol. 2013;26:646–55.PubMedCrossRef
13.
Zurück zum Zitat Edison P, Rowe CC, Rinne JO, Nq S, Ahmed I, Kemmpainen N, et al. Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry. 2008;79:1331–8.PubMedCrossRef Edison P, Rowe CC, Rinne JO, Nq S, Ahmed I, Kemmpainen N, et al. Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry. 2008;79:1331–8.PubMedCrossRef
14.
Zurück zum Zitat Gomperts SN. Imaging the role of amyloid in PD dementia and dementia with Lewy bodies. Curr Neurol Neurosci Rep. 2014;14:472.PubMedCrossRef Gomperts SN. Imaging the role of amyloid in PD dementia and dementia with Lewy bodies. Curr Neurol Neurosci Rep. 2014;14:472.PubMedCrossRef
15.
Zurück zum Zitat Kantarci K, Lowe VJ, Boeve BF, Weigand SD, Senjem ML, Przybelski SA, et al. Multimodality imaging characteristics of dementia with Lewy bodies. Neurobiol Aging. 2012;33:2091–105.PubMedPubMedCentralCrossRef Kantarci K, Lowe VJ, Boeve BF, Weigand SD, Senjem ML, Przybelski SA, et al. Multimodality imaging characteristics of dementia with Lewy bodies. Neurobiol Aging. 2012;33:2091–105.PubMedPubMedCentralCrossRef
16.
Zurück zum Zitat Bettens K, Sleegers K, Van Broeckhoven C. Current status on Alzheimer disease molecular genetics: from past, to present, to future. Hum Mol Genet. 2010;19:R4–R11.PubMedPubMedCentralCrossRef Bettens K, Sleegers K, Van Broeckhoven C. Current status on Alzheimer disease molecular genetics: from past, to present, to future. Hum Mol Genet. 2010;19:R4–R11.PubMedPubMedCentralCrossRef
17.
Zurück zum Zitat Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C, et al. Age, neuropathology, and dementia. N Engl J Med. 2009;360:2302–9.PubMedCrossRef Savva GM, Wharton SB, Ince PG, Forster G, Matthews FE, Brayne C, et al. Age, neuropathology, and dementia. N Engl J Med. 2009;360:2302–9.PubMedCrossRef
18.
Zurück zum Zitat Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207–16.PubMedPubMedCentralCrossRef Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207–16.PubMedPubMedCentralCrossRef
19.
Zurück zum Zitat Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002;297:353–6.PubMedCrossRef Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002;297:353–6.PubMedCrossRef
20.
Zurück zum Zitat Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron. 2003;39:409–21.PubMedCrossRef Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron. 2003;39:409–21.PubMedCrossRef
21.
Zurück zum Zitat Silbert LC, Quinn JF, Moore MM, Corbridge E, Ball MJ, Murdoch G, et al. Changes in premorbid brain volume predict Alzheimer's disease pathology. Neurology. 2003;61:487–92.PubMedCrossRef Silbert LC, Quinn JF, Moore MM, Corbridge E, Ball MJ, Murdoch G, et al. Changes in premorbid brain volume predict Alzheimer's disease pathology. Neurology. 2003;61:487–92.PubMedCrossRef
22.
Zurück zum Zitat Jagust WJ, Zheng L, Harvey DJ, Mack WJ, Vinters HV, Weiner MW, et al. Neuropathological basis of magnetic resonance images in aging and dementia. Ann Neurol. 2008;63:72–80.PubMedPubMedCentralCrossRef Jagust WJ, Zheng L, Harvey DJ, Mack WJ, Vinters HV, Weiner MW, et al. Neuropathological basis of magnetic resonance images in aging and dementia. Ann Neurol. 2008;63:72–80.PubMedPubMedCentralCrossRef
23.
Zurück zum Zitat Josephs KA, Whitwell JL, Ahmed Z, Shiung MM, Weigand SD, Knopman DS, et al. Beta-amyloid burden is not associated with rates of brain atrophy. Ann Neurol. 2008;63:204–12.PubMedPubMedCentralCrossRef Josephs KA, Whitwell JL, Ahmed Z, Shiung MM, Weigand SD, Knopman DS, et al. Beta-amyloid burden is not associated with rates of brain atrophy. Ann Neurol. 2008;63:204–12.PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Sabuncu MR, Desikan RS, Sepulcre J, Yeo BTT, Liu H, Schmansky NJ, et al. The dynamics of cortical and hippocampal atrophy in Alzheimer disease. Arch Neurol. 2011;68:1040–8.PubMedPubMedCentralCrossRef Sabuncu MR, Desikan RS, Sepulcre J, Yeo BTT, Liu H, Schmansky NJ, et al. The dynamics of cortical and hippocampal atrophy in Alzheimer disease. Arch Neurol. 2011;68:1040–8.PubMedPubMedCentralCrossRef
25.••
Zurück zum Zitat Erten-Lyons D, Dodge HH, Woltjer R, Silbert LC, Howieson DB, Kramer P, et al. Neuropathologic basis of age-associated brain atrophy. JAMA Neurol. 2013;70:616–22. From the Oregon Brain and Aging study, different measures (ventricular, total brain and hippocampal) were derived from longitudinal structural MRIs obtained in 70 cognitively intact older adults. These were correlated with clinical status, APOE status and neuropathological measures (NFT, neuritic plaques, different types of vascular lesions). Strongest correlations were obtained for ventricular and total brain measures. The correlations between these structural measures and cognition remained even after controlling for the degree of neuropathology. Hippocampal volume correlated only with the degree of amyloid angiopathy.PubMedPubMedCentralCrossRef Erten-Lyons D, Dodge HH, Woltjer R, Silbert LC, Howieson DB, Kramer P, et al. Neuropathologic basis of age-associated brain atrophy. JAMA Neurol. 2013;70:616–22. From the Oregon Brain and Aging study, different measures (ventricular, total brain and hippocampal) were  derived from longitudinal structural MRIs obtained in 70 cognitively intact older adults. These  were correlated with clinical status, APOE status and neuropathological measures (NFT, neuritic plaques, different types of vascular lesions). Strongest correlations were obtained for ventricular and total brain measures. The correlations between these structural measures and cognition remained even after controlling for the degree of neuropathology. Hippocampal volume correlated only with the degree of amyloid angiopathy.PubMedPubMedCentralCrossRef
26.
Zurück zum Zitat MC Donohue, H Jacqmin-Gadda, M Le Goff, RG Thomas, R Raman, AC Gamst, et al. Estimating long-term multivariate progression from short-term data. Alzheimers Dement. in press, 2014. MC Donohue, H Jacqmin-Gadda, M Le Goff, RG Thomas, R Raman, AC Gamst, et al. Estimating long-term multivariate progression from short-term data. Alzheimers Dement. in press, 2014.
27.•
Zurück zum Zitat M Bilgel, Y An, A Lang, J Prince, L Ferrucci, B Jedynak, and SM Resnick. Trajectories of Alzheimer disease-related cognitive measures in a longitudinal sample. Alzheimers Dement. in press, 2014. Ultimately, efficacy of any intervention must be proven in terms of clinical parameters. From almost 900 BLSA participants, some of the most commonly used neuropsychological episodic memory measures were analyzed for their sensitivity to detect decline in the preclinical AD stage. The importance of this work lies in the high familiarity worldwide of the test parameters examined and the novel insight into the relative sensitivity of encoding versus retrieval parameters M Bilgel, Y An, A Lang, J Prince, L Ferrucci, B Jedynak, and SM Resnick. Trajectories of Alzheimer disease-related cognitive measures in a longitudinal sample. Alzheimers Dement. in press, 2014. Ultimately, efficacy of any intervention must be proven in terms of clinical parameters. From almost 900 BLSA participants, some of the most commonly used neuropsychological episodic memory measures were analyzed for their sensitivity to detect decline in the preclinical AD stage. The importance of this work lies in the high familiarity worldwide of the test parameters examined and the novel insight into the relative sensitivity of encoding versus retrieval parameters
28.
Zurück zum Zitat Dickerson BC, Bakkour A, Salat DH, Feczko E, Pacheco J, Greve DN, et al. 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.PubMedPubMedCentralCrossRef Dickerson BC, Bakkour A, Salat DH, Feczko E, Pacheco J, Greve DN, et al. 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.PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Vlassenko AG, Mintun MA, Xiong C, Sheline YI, Goate AM, Benzinger TLS, et al. Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C]Pittsburgh compound B data. Ann Neurol. 2011;70:857–61.PubMedPubMedCentralCrossRef Vlassenko AG, Mintun MA, Xiong C, Sheline YI, Goate AM, Benzinger TLS, et al. Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C]Pittsburgh compound B data. Ann Neurol. 2011;70:857–61.PubMedPubMedCentralCrossRef
30.
Zurück zum Zitat Villain N, Chételat G, Grassiot B, Bourgeat P, Jones G, Ellis KA, et al. Regional dynamics of amyloid-β deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PIB-PET longitudinal study. Brain. 2012;135:2126–39.PubMedCrossRef Villain N, Chételat G, Grassiot B, Bourgeat P, Jones G, Ellis KA, et al. Regional dynamics of amyloid-β deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PIB-PET longitudinal study. Brain. 2012;135:2126–39.PubMedCrossRef
31.
Zurück zum Zitat Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67.PubMedCrossRef Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67.PubMedCrossRef
32.
Zurück zum Zitat Jack CR, Wiste HJ, Knopman DS, Vemuri P, Mielke MM, Weigand SD, et al. Rates of β-amyloid accumulation are independent of hippocampal neurodegeneration. Neurology. 2014;82:1605–12.PubMedPubMedCentralCrossRef Jack CR, Wiste HJ, Knopman DS, Vemuri P, Mielke MM, Weigand SD, et al. Rates of β-amyloid accumulation are independent of hippocampal neurodegeneration. Neurology. 2014;82:1605–12.PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat Chételat G, Villemagne VL, Villain N, Jones G, Ellis KA, Ames D, et al. Accelerated cortical atrophy in cognitively normal elderly with high β-amyloid deposition. Neurology. 2012;78:477–84.PubMedCrossRef Chételat G, Villemagne VL, Villain N, Jones G, Ellis KA, Ames D, et al. Accelerated cortical atrophy in cognitively normal elderly with high β-amyloid deposition. Neurology. 2012;78:477–84.PubMedCrossRef
34.••
Zurück zum Zitat Bateman RJ, Xiong C, Benzinger TLS, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367:795–804. From the Dominantly Inherited Alzheimer Network, multimodal cross-sectional data were analyzed from 50 symptomatic and 50 asymptomatic mutation carriers and 100 noncarrier siblings. This study provides critical empirical evidence for the orderly sequence of changes in in vivo biomarkers in monogenic AD up to 30 years prior to expected disease onset.PubMedPubMedCentralCrossRef Bateman RJ, Xiong C, Benzinger TLS, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367:795–804. From the Dominantly Inherited Alzheimer Network, multimodal cross-sectional data were analyzed from 50 symptomatic and 50 asymptomatic mutation carriers and 100 noncarrier siblings. This study provides critical empirical evidence for the orderly sequence of changes in in vivo biomarkers in monogenic AD up to 30 years prior to expected disease onset.PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Fleisher AS, Chen K, Quiroz YT, Jakimovich LJ, Gomez MG, Langois CM, et al. Florbetapir PET analysis of amyloid-β deposition in the Presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. Lancet Neurol. 2012;11:1057–65.PubMedCrossRef Fleisher AS, Chen K, Quiroz YT, Jakimovich LJ, Gomez MG, Langois CM, et al. Florbetapir PET analysis of amyloid-β deposition in the Presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. Lancet Neurol. 2012;11:1057–65.PubMedCrossRef
36.•
Zurück zum Zitat Reiman EM, Quiroz YT, Fleisher AS, Chen K, Velez-Pardo C, Jimenez-Del-Rio M, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the Presenilin 1 E280A kindred: a case–control study. Lancet Neurol. 2012;11:1048–56. From the Columbian Alzheimer Prevention Initiative registry, 20 PS1 mutation carriers and 20 noncarrier siblings between 18 and 26 years of age underwent task-related fMRI, structural MRI and CSF. This study provides essential insight in the functional organization of cognitive brain systems prior to clinical disease expression.PubMedCrossRef Reiman EM, Quiroz YT, Fleisher AS, Chen K, Velez-Pardo C, Jimenez-Del-Rio M, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the Presenilin 1 E280A kindred: a case–control study. Lancet Neurol. 2012;11:1048–56. From the Columbian Alzheimer Prevention Initiative registry, 20 PS1 mutation carriers and 20 noncarrier siblings between 18 and 26 years of age underwent task-related fMRI, structural MRI and CSF. This study provides essential insight in the functional organization of cognitive brain systems prior to clinical disease expression.PubMedCrossRef
37.
Zurück zum Zitat Fagan AM, Xiong C, Jasielec MS, Bateman RJ, Goate AM, Benzinger TLS, et al. Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease. Sci Transl Med. 2014;6:226–30.CrossRef Fagan AM, Xiong C, Jasielec MS, Bateman RJ, Goate AM, Benzinger TLS, et al. Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease. Sci Transl Med. 2014;6:226–30.CrossRef
38.
Zurück zum Zitat B Kaur, JJ Himali, S Seshadri, AS Beiser, R Au, AC McKee, et al. Association between neuropathology and brain volume in the Framingham Heart Study. Alzheimer Dis Assoc Disord. in press, 2014. B Kaur, JJ Himali, S Seshadri, AS Beiser, R Au, AC McKee, et al. Association between neuropathology and brain volume in the Framingham Heart Study. Alzheimer Dis Assoc Disord. in press, 2014.
39.
Zurück zum Zitat Fotuhi M, Do D, Jack C. Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol. 2012;8:189–202.PubMed Fotuhi M, Do D, Jack C. Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol. 2012;8:189–202.PubMed
40.••
Zurück zum Zitat Wilson RS, Yu L, Trojanowski JQ, Chen EY, Boyle PA, Bennett DA, et al. TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurol. 2013;70:1418–24. In a consecutive series of 130 cases with annual cognitive assessments for more than 10 years, postmortem measures of TDP43 explained as much variability in the rate of the cognitive decline as neurofibrillary tangles. This is of high importance as it points to high clinical relevance of other proteinopathies apart from the classical AD hallmark lesions.PubMedCrossRef Wilson RS, Yu L, Trojanowski JQ, Chen EY, Boyle PA, Bennett DA, et al. TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurol. 2013;70:1418–24. In a consecutive series of 130 cases with annual cognitive assessments for more than 10 years, postmortem measures of TDP43 explained as much variability in the rate of the cognitive decline as neurofibrillary tangles. This is of high importance as it points to high clinical relevance of other proteinopathies apart from the classical AD hallmark lesions.PubMedCrossRef
41.
Zurück zum Zitat Gomez-Isla T, Price JL, McKeel DW, Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J Neurosci. 1996;16:4491–500.PubMed Gomez-Isla T, Price JL, McKeel DW, Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J Neurosci. 1996;16:4491–500.PubMed
42.
Zurück zum Zitat Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59.PubMedCrossRef Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82:239–59.PubMedCrossRef
43.
Zurück zum Zitat Hyman BT, Gomez-Isla T. Alzheimer's disease is a laminar, regional, and neural system specific disease, not a global brain disease. Neurobiol Aging. 1994;15:353–4.PubMedCrossRef Hyman BT, Gomez-Isla T. Alzheimer's disease is a laminar, regional, and neural system specific disease, not a global brain disease. Neurobiol Aging. 1994;15:353–4.PubMedCrossRef
44.
Zurück zum Zitat Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70:960–9.PubMedCrossRef Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70:960–9.PubMedCrossRef
45.
Zurück zum Zitat DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol. 1990;27:457–64.PubMedCrossRef DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol. 1990;27:457–64.PubMedCrossRef
46.
Zurück zum Zitat Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30:572–80.PubMedCrossRef Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30:572–80.PubMedCrossRef
47.
Zurück zum Zitat Davis DG, Schmitt FA, Wekstein DR, Markesberry WR. Alzheimer neuropathologic alterations in aged cognitively intact subjects. J Neuropathol Exp Neurol. 1999;58:376–88.PubMedCrossRef Davis DG, Schmitt FA, Wekstein DR, Markesberry WR. Alzheimer neuropathologic alterations in aged cognitively intact subjects. J Neuropathol Exp Neurol. 1999;58:376–88.PubMedCrossRef
48.
Zurück zum Zitat Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 2006;27:1372–84.PubMedCrossRef Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 2006;27:1372–84.PubMedCrossRef
49.
Zurück zum Zitat Kovacs GG, Milenkovic I, Wöhrer A, Höftberger R, Gelpi E, Haberler C, et al. Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol. 2013;126:365–84.PubMedCrossRef Kovacs GG, Milenkovic I, Wöhrer A, Höftberger R, Gelpi E, Haberler C, et al. Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol. 2013;126:365–84.PubMedCrossRef
50.
Zurück zum Zitat Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer's disease: The Nun study. JAMA. 1997;277:813–7.PubMedCrossRef Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer's disease: The Nun study. JAMA. 1997;277:813–7.PubMedCrossRef
51.
Zurück zum Zitat Schneider JA, Arvanitakis Z, Yu L, Boyle PA, Leurgans SE, Bennett DA. Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain. 2012;135:3005–14.PubMedPubMedCentralCrossRef Schneider JA, Arvanitakis Z, Yu L, Boyle PA, Leurgans SE, Bennett DA. Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain. 2012;135:3005–14.PubMedPubMedCentralCrossRef
52.
Zurück zum Zitat Kovacs G. Current concepts of neurodegenerative diseases. Eur Med J Neurol. 2014;1:78–86. Kovacs G. Current concepts of neurodegenerative diseases. Eur Med J Neurol. 2014;1:78–86.
53.
Zurück zum Zitat Boyle PA, Wilson RS, Yu L, Barr AM, Honer WG, Schneider JA, et al. Much of late life cognitive decline is not due to common neurodegenerative pathologies. Ann Neurol. 2013;74:478–89.PubMed Boyle PA, Wilson RS, Yu L, Barr AM, Honer WG, Schneider JA, et al. Much of late life cognitive decline is not due to common neurodegenerative pathologies. Ann Neurol. 2013;74:478–89.PubMed
54.
Zurück zum Zitat Iacono D, Resnick SM, O'Brien R, Zonderman AB, An Y, Pletnikova O, et al. Mild cognitive impairment and asymptomatic Alzheimer disease subjects: equivalent β-amyloid and tau loads with divergent cognitive outcomes. J Neuropathol Exp Neurol. 2014;73:295–304.PubMedPubMedCentralCrossRef Iacono D, Resnick SM, O'Brien R, Zonderman AB, An Y, Pletnikova O, et al. Mild cognitive impairment and asymptomatic Alzheimer disease subjects: equivalent β-amyloid and tau loads with divergent cognitive outcomes. J Neuropathol Exp Neurol. 2014;73:295–304.PubMedPubMedCentralCrossRef
55.
Zurück zum Zitat Dickerson BC, Sperling RA. Large-scale functional brain network abnormalities in Alzheimer's disease: insights from functional neuroimaging. Behav Neurol. 2009;21:63–75.PubMedPubMedCentralCrossRef Dickerson BC, Sperling RA. Large-scale functional brain network abnormalities in Alzheimer's disease: insights from functional neuroimaging. Behav Neurol. 2009;21:63–75.PubMedPubMedCentralCrossRef
56.
Zurück zum Zitat Quiroz YT, Budson AE, Celone K, Ruiz A, Newmark R, Castrillón G, et al. Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease. Ann Neurol. 2010;68:865–75.PubMedPubMedCentralCrossRef Quiroz YT, Budson AE, Celone K, Ruiz A, Newmark R, Castrillón G, et al. Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease. Ann Neurol. 2010;68:865–75.PubMedPubMedCentralCrossRef
58.
Zurück zum Zitat Vandenbulcke M, Peeters R, Dupont P, Van Hecke P, Vandenberghe R. Word reading and posterior temporal dysfunction in amnestic mild cognitive impairment. Cereb Cortex. 2007;17:542–51.PubMedCrossRef Vandenbulcke M, Peeters R, Dupont P, Van Hecke P, Vandenberghe R. Word reading and posterior temporal dysfunction in amnestic mild cognitive impairment. Cereb Cortex. 2007;17:542–51.PubMedCrossRef
59.
Zurück zum Zitat Nelissen N, Vandenbulcke M, Fannes K, Verbruggen A, Peeters R, Dupont P, et al. Aβ amyloid deposition in the language system and how the brain responds. Brain. 2007;130:2055–69.PubMedCrossRef Nelissen N, Vandenbulcke M, Fannes K, Verbruggen A, Peeters R, Dupont P, et al. Aβ amyloid deposition in the language system and how the brain responds. Brain. 2007;130:2055–69.PubMedCrossRef
60.
Zurück zum Zitat Becker JT, Mintun MA, Aleva K, Wiseman MB, Nichols T, DeKosky ST. Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimer's disease. Neurology. 1996;46:692–700.PubMedCrossRef Becker JT, Mintun MA, Aleva K, Wiseman MB, Nichols T, DeKosky ST. Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimer's disease. Neurology. 1996;46:692–700.PubMedCrossRef
61.
Zurück zum Zitat Grady CL, McIntosh AR, Beig S, Keightley ML, Burian H, Black SE. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. J Neurosci. 2003;23:986–93.PubMed Grady CL, McIntosh AR, Beig S, Keightley ML, Burian H, Black SE. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. J Neurosci. 2003;23:986–93.PubMed
62.
Zurück zum Zitat Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67:446–52.PubMedCrossRef Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67:446–52.PubMedCrossRef
63.
Zurück zum Zitat Pike KE, Savage G, Villemagne VL, Ng S, Moss SA, Maruff P, et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain. 2007;130:2837–44.PubMedCrossRef Pike KE, Savage G, Villemagne VL, Ng S, Moss SA, Maruff P, et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain. 2007;130:2837–44.PubMedCrossRef
64.
Zurück zum Zitat Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008;65:1509–17.PubMedPubMedCentralCrossRef Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008;65:1509–17.PubMedPubMedCentralCrossRef
65.
Zurück zum Zitat Adamczuk K, De Weer AS, Nelissen N, Chen K, Sleegers K, Bettens K, et al. Polymorphism of brain derived neurotrophic factor influences β amyloid load in cognitively intact apolipoprotein e ε4 carriers. Neuroimage Clin. 2013;2:512–20.PubMedPubMedCentralCrossRef Adamczuk K, De Weer AS, Nelissen N, Chen K, Sleegers K, Bettens K, et al. Polymorphism of brain derived neurotrophic factor influences β amyloid load in cognitively intact apolipoprotein e ε4 carriers. Neuroimage Clin. 2013;2:512–20.PubMedPubMedCentralCrossRef
66.•
Zurück zum Zitat Fleisher AS, Chen K, Liu X, Ayutyanont N, Roontiva A, Thiyyagura P, et al. Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiol Aging. 2013;34:1–12. Based on a pooled analysis of 245 subjects who had undergone 18 F-florbetapir and APOE genotyping, reliable age-dependent estimates are obtained for linear amyloid increase and for amyloid-positivity as a function of age and APOE.PubMedCrossRef Fleisher AS, Chen K, Liu X, Ayutyanont N, Roontiva A, Thiyyagura P, et al. Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiol Aging. 2013;34:1–12. Based on a pooled analysis of 245 subjects who had undergone 18 F-florbetapir and APOE genotyping, reliable age-dependent estimates are obtained for linear amyloid increase and for amyloid-positivity as a function of age and APOE.PubMedCrossRef
67.
Zurück zum Zitat Yeo BTT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:1125–65.PubMedCrossRef Yeo BTT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:1125–65.PubMedCrossRef
68.
Zurück zum Zitat Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, et al. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005;25:7709–17.PubMedCrossRef Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, et al. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005;25:7709–17.PubMedCrossRef
69.
Zurück zum Zitat Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009;62:42–52.PubMedPubMedCentralCrossRef Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron. 2009;62:42–52.PubMedPubMedCentralCrossRef
70.
Zurück zum Zitat Zhou J, Gennatas ED, Kramer JH, Miller BL, Seeley WW. Predicting regional neurodegeneration from the healthy brain functional connectome. Neuron. 2012;73:1216–27.PubMedPubMedCentralCrossRef Zhou J, Gennatas ED, Kramer JH, Miller BL, Seeley WW. Predicting regional neurodegeneration from the healthy brain functional connectome. Neuron. 2012;73:1216–27.PubMedPubMedCentralCrossRef
71.
Zurück zum Zitat Myers N, Pasquini L, Göttler J, Grimmer T, Koch K, Ortner M, et al. Within-patient correspondence of amyloid-β and intrinsic network connectivity in Alzheimer's disease. Brain. 2014;137:2052–64.PubMedPubMedCentralCrossRef Myers N, Pasquini L, Göttler J, Grimmer T, Koch K, Ortner M, et al. Within-patient correspondence of amyloid-β and intrinsic network connectivity in Alzheimer's disease. Brain. 2014;137:2052–64.PubMedPubMedCentralCrossRef
72.
Zurück zum Zitat Vlassenko AG, Vaishnavi SN, Couture L, Sacco D, Shannon BJ, Mach RH, et al. Spatial correlation between brain aerobic glycolysis and amyloid-β deposition. Proc Natl Acad Sci U S A. 2010;107:17763–7.PubMedPubMedCentralCrossRef Vlassenko AG, Vaishnavi SN, Couture L, Sacco D, Shannon BJ, Mach RH, et al. Spatial correlation between brain aerobic glycolysis and amyloid-β deposition. Proc Natl Acad Sci U S A. 2010;107:17763–7.PubMedPubMedCentralCrossRef
73.
Zurück zum Zitat Mathis CA, Kuller LH, Klunk WE, Snitz BE, Price JC, Weissfeld LA, et al. In vivo assessment of amyloid-β deposition in nondemented very elderly subjects. Ann Neurol. 2013;73:751–61.PubMedPubMedCentralCrossRef Mathis CA, Kuller LH, Klunk WE, Snitz BE, Price JC, Weissfeld LA, et al. In vivo assessment of amyloid-β deposition in nondemented very elderly subjects. Ann Neurol. 2013;73:751–61.PubMedPubMedCentralCrossRef
74.
Zurück zum Zitat G Chételat, R La Joie, N Villain, A Perrotin, V de La Sayette, F Eustache, and R Vandenberghe. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease. NeuroImage: Clinical. 2013 G Chételat, R La Joie, N Villain, A Perrotin, V de La Sayette, F Eustache, and R Vandenberghe. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease. NeuroImage: Clinical. 2013
75.
Zurück zum Zitat Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–29.PubMedCrossRef Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–29.PubMedCrossRef
76.
Zurück zum Zitat Altmann A, Tian L, Henderson VW, Greicius MD, Alzheimer's Disease Neuroimaging Initiative Investigators. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol. 2014;75:563–73.PubMedCrossRef Altmann A, Tian L, Henderson VW, Greicius MD, Alzheimer's Disease Neuroimaging Initiative Investigators. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol. 2014;75:563–73.PubMedCrossRef
77.
Zurück zum Zitat Morris JC, Roe CM, Xiong C, Fagan AM, Goate AM, Holtzman DM, et al. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol. 2010;67:122–31.PubMedPubMedCentralCrossRef Morris JC, Roe CM, Xiong C, Fagan AM, Goate AM, Holtzman DM, et al. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol. 2010;67:122–31.PubMedPubMedCentralCrossRef
78.
Zurück zum Zitat Thambisetty M, An Y, Nalls M, Sojkova J, Swaminathan S, Zhou Y, et al. Effect of complement CR1 on brain amyloid burden during aging and its modification by APOE genotype. Biol Psychiatry. 2013;73:422–8.PubMedPubMedCentralCrossRef Thambisetty M, An Y, Nalls M, Sojkova J, Swaminathan S, Zhou Y, et al. Effect of complement CR1 on brain amyloid burden during aging and its modification by APOE genotype. Biol Psychiatry. 2013;73:422–8.PubMedPubMedCentralCrossRef
79.
Zurück zum Zitat Sperling RA, Aisen P, Beckett LA, Bennett DA, Craft S, Fagan AM, 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;7:280–92.PubMedPubMedCentralCrossRef Sperling RA, Aisen P, Beckett LA, Bennett DA, Craft S, Fagan AM, 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;7:280–92.PubMedPubMedCentralCrossRef
80.
Zurück zum Zitat Vandenberghe R, Nelissen N, Salmon E, Ivanoiu A, Hasselbalch S, Andersen A, et al. Binary classification of 18 F-flutemetamol PET using machine learning: Comparison with visual reads and structural MRI. Neuroimage. 2012;64C:517–25. Vandenberghe R, Nelissen N, Salmon E, Ivanoiu A, Hasselbalch S, Andersen A, et al. Binary classification of 18 F-flutemetamol PET using machine learning: Comparison with visual reads and structural MRI. Neuroimage. 2012;64C:517–25.
81.
Zurück zum Zitat Jack CR, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, et al. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol. 2012;71:765–75.PubMedPubMedCentralCrossRef Jack CR, Knopman DS, Weigand SD, Wiste HJ, Vemuri P, Lowe V, et al. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann Neurol. 2012;71:765–75.PubMedPubMedCentralCrossRef
82.
Zurück zum Zitat Knopman DS, Jack Jr CR, Wiste HJ, Weigand SD, Vemuri P, Lowe VJ, et al. Brain injury biomarkers are not dependent on β-amyloid in normal elderly. Ann Neurol. 2013;73:472–80.PubMedPubMedCentralCrossRef Knopman DS, Jack Jr CR, Wiste HJ, Weigand SD, Vemuri P, Lowe VJ, et al. Brain injury biomarkers are not dependent on β-amyloid in normal elderly. Ann Neurol. 2013;73:472–80.PubMedPubMedCentralCrossRef
83.
Zurück zum Zitat Becker JA, Hedden T, Carmasin J, Maye J, Rentz DM, Putcha D, et al. Amyloid-β associated cortical thinning in clinically normal elderly. Ann Neurol. 2011;69:1032–42.PubMedPubMedCentralCrossRef Becker JA, Hedden T, Carmasin J, Maye J, Rentz DM, Putcha D, et al. Amyloid-β associated cortical thinning in clinically normal elderly. Ann Neurol. 2011;69:1032–42.PubMedPubMedCentralCrossRef
84.
Zurück zum Zitat Sheline YI, Raichle ME, Snyder AZ, Morris JC, Head D, Wang S, et al. Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol Psychiatry. 2010;67:584–7.PubMedPubMedCentralCrossRef Sheline YI, Raichle ME, Snyder AZ, Morris JC, Head D, Wang S, et al. Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol Psychiatry. 2010;67:584–7.PubMedPubMedCentralCrossRef
85.
Zurück zum Zitat Knopman DS. CR Jack, Jr, H. J. Wiste, S. D. Weigand, P. Vemuri, V. Lowe, et al. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology. 2012;78:1576–82.PubMedPubMedCentralCrossRef Knopman DS. CR Jack, Jr, H. J. Wiste, S. D. Weigand, P. Vemuri, V. Lowe, et al. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology. 2012;78:1576–82.PubMedPubMedCentralCrossRef
86.
Zurück zum Zitat Lim YY, Villemagne VL, Laws SM, Ames D, Pietrzak RH, Ellis KA, et al. BDNF val66met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease. Neurobiol Aging. 2013;34:2457–64.PubMedCrossRef Lim YY, Villemagne VL, Laws SM, Ames D, Pietrzak RH, Ellis KA, et al. BDNF val66met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease. Neurobiol Aging. 2013;34:2457–64.PubMedCrossRef
87.
Zurück zum Zitat Nordberg A, Carter SF, Rinne J, Drzezga A, Brooks DJ, Vandenberghe R, et al. A European multicentre PET study of fibrillar amyloid in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2013;40:104–14.PubMedPubMedCentralCrossRef Nordberg A, Carter SF, Rinne J, Drzezga A, Brooks DJ, Vandenberghe R, et al. A European multicentre PET study of fibrillar amyloid in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2013;40:104–14.PubMedPubMedCentralCrossRef
88.
Zurück zum Zitat Jack CR, Wiste HJ, Vemuri P, Weigand SD, Senjem ML, 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;133:3336–48.PubMedPubMedCentralCrossRef Jack CR, Wiste HJ, Vemuri P, Weigand SD, Senjem ML, 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;133:3336–48.PubMedPubMedCentralCrossRef
89.
Zurück zum Zitat Villemagne VL, Pike KE, Chételat G, Ellis KA, Mulligan RS, Bourgeat P, et al. Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69:181–92.PubMedPubMedCentralCrossRef Villemagne VL, Pike KE, Chételat G, Ellis KA, Mulligan RS, Bourgeat P, et al. Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol. 2011;69:181–92.PubMedPubMedCentralCrossRef
90.
Zurück zum Zitat Rowe CC, Bourgeat P, Ellis KA, Brown B, Lim YY, Mulligan R, et al. Predicting Alzheimer disease with β-amyloid imaging: results from the Australian Imaging, Biomarkers, and Lifestyle study of ageing. Ann Neurol. 2013;74:905–13.PubMedCrossRef Rowe CC, Bourgeat P, Ellis KA, Brown B, Lim YY, Mulligan R, et al. Predicting Alzheimer disease with β-amyloid imaging: results from the Australian Imaging, Biomarkers, and Lifestyle study of ageing. Ann Neurol. 2013;74:905–13.PubMedCrossRef
91.
Zurück zum Zitat Duara R, Loewenstein DA, Shen Q, Barker W, Potter E, Varon D, et al. Amyloid positron emission tomography with (18)F-flutemetamol and structural magnetic resonance imaging in the classification of mild cognitive impairment and Alzheimer's disease. Alzheimers Dement. 2013;9:295–301.PubMedCrossRef Duara R, Loewenstein DA, Shen Q, Barker W, Potter E, Varon D, et al. Amyloid positron emission tomography with (18)F-flutemetamol and structural magnetic resonance imaging in the classification of mild cognitive impairment and Alzheimer's disease. Alzheimers Dement. 2013;9:295–301.PubMedCrossRef
92.
Zurück zum Zitat Jack Jr CR, Wiste HJ, Lesnick TG, Weigand SD, Knopman DS, Vemuri P, et al. Brain β-amyloid load approaches a plateau. Neurology. 2013;80:890–6.PubMedPubMedCentralCrossRef Jack Jr CR, Wiste HJ, Lesnick TG, Weigand SD, Knopman DS, Vemuri P, et al. Brain β-amyloid load approaches a plateau. Neurology. 2013;80:890–6.PubMedPubMedCentralCrossRef
Metadaten
Titel
The Relationship between Amyloid Deposition, Neurodegeneration, and Cognitive Decline in Dementia
verfasst von
Rik Vandenberghe
Publikationsdatum
01.11.2014
Verlag
Springer US
Erschienen in
Current Neurology and Neuroscience Reports / Ausgabe 11/2014
Print ISSN: 1528-4042
Elektronische ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-014-0498-9

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