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24 - Functional imaging of Alzheimer's disease

from Section IV - Cognitive Disorders

Published online by Cambridge University Press:  10 January 2011

By
Vanessa Taler  and
Andrew J. Saykin
Edited by
Martha E. Shenton  and
Bruce I. Turetsky
Vanessa Taler
Affiliation:
Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis, IN, USA
Andrew J. Saykin
Affiliation:
Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis, IN, USA
Martha E. Shenton
Affiliation:
VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School
Bruce I. Turetsky
Affiliation:
University of Pennsylvania
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Summary

Alzheimer's disease

Background

Alzheimer's disease (AD) is a devastating progressive neurodegenerative disorder that is the most common cause of age-related dementia, accounting for between 60 and 80% of cases of dementia. In 2008, around 5.2 million Americans had AD, with an approximate annual cost of $100 billion. It is estimated that between 11 and 16 million people will be diagnosed with AD in the United States by 2050 (Alzheimer's Association, 2008).

Neuropathological alterations in AD include synaptic loss and cortical atrophy, buildup of beta-amyloid fragments into the “senile” plaques between neurons identified a century ago, and of tau protein into the hallmark neurofibrillary tangles within dead or dying neurons. Cholinergic and glutaminergic pathways are prominently involved in the pathophysiology of AD. While the genetic bases of sporadic late-onset AD are not yet well understood, there are several genetic factors that have been identified as playing a role in the disease. A small number of AD cases (<5%) are familial in nature and caused by rare mutations in the amyloid precursor protein (APP) or presenilin (PSEN) genes. Presence of the ε4 allele of the apolipoprotein-E (APOE) gene confers increased risk of the more prominent late-onset form of AD, and many studies aiming to identify risk markers for AD focus on these genes.

Keywords

Alzheimer's diseasebeta-amyloidcognitive tasksPETmild cognitive impairmentfunctional neuroimagingcortical activationfMRISPECT
Type
Chapter
Information
Understanding Neuropsychiatric Disorders
Insights from Neuroimaging
 , pp. 332 - 350
Publisher: Cambridge University Press
Print publication year: 2010

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References

Aizenstein, H J, Nebes, R D, Saxton, J A, et al. 2008. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol 65, 1509–17.Google Scholar
Allen, G, Barnard, H, McColl, R, Hester, A L, Fields, J A and Weiner, M F. 2007. Reduced hippocampal functional connectivity in Alzheimer disease. Arch Neurol 64, 1482–7.Google Scholar
Almkvist, O, Axelman, K, Basun, H et al. 2003. Clinical findings in nondemented mutation carriers predisposed to Alzheimer's disease: A model of mild cognitive impairment. Acta Neurol Scand Suppl 179, 77–82.Google Scholar
Alzheimer's Association, . 2008. Alzheimer's disease facts and figures. Alzheimer's Dementia 4, 110–33.Google Scholar
Arnaiz, E, Jelic, V, Almkvist, O, et al. 2001. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. Neuroreport 12, 851–5.Google Scholar
Bäckman, L, Andersson, J L, Nyberg, L, Winblad, B, Nordberg, A and Almkvist, O. 1999. Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease. Neurology 52, 1861–70.Google Scholar
Bacskai, B J, Frosch, M P, Freeman, S H, et al. 2007. Molecular imaging with Pittsburgh Compound B confirmed at autopsy: A case report. Arch Neurol 64, 431–4.Google Scholar
Bai, F, Zhang, Z, Watson, D R, et al. 2009. Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment. Biol Psychiatry 65, 951–8.Google Scholar
Bartrés-Faz, D, Serra-Grabulosa, J M, Sun, F T, et al. 2008. Functional connectivity of the hippocampus in elderly with mild memory dysfunction carrying the APOE epsilon4 allele. Neurobiol Aging 29, 1644–53.Google Scholar
Bassett, S S, Yousem, D M, Cristinzio, C, et al. 2006. Familial risk for Alzheimer's disease alters fMRI activation patterns. Brain 129, 1229–39.Google Scholar
Basun, H, Bogdanovic, N, Ingelsson, M, et al. 2008. Clinical and neuropathological features of the arctic APP gene mutation causing early-onset Alzheimer disease. Arch Neurol 65, 499–505.Google Scholar
Becker, J T, Mintun, M A, Aleva, K, Wiseman, M B, Nichols, T and Dekosky, S T. 1996a. Alterations in functional neuroanatomical connectivity in Alzheimer's disease. Positron emission tomography of auditory verbal short-term memory. Ann N Y Acad Sci 777, 239–42.Google Scholar
Becker, J T, Mintun, M A, Aleva, K, Wiseman, M B, Nichols, T and Dekosky, S T. 1996b. Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimer's disease. Neurology 46, 692–700.Google Scholar
Bentley, P, Driver, J and Dolan, R J 2008. Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health. Brain 131, 409–24.Google Scholar
Bokde, A L, Lopez-Bayo, P, Meindl, T, et al. 2006. Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment Brain 129, 1113–24.Google Scholar
Bondi, M W, Houston, W S, Eyler, L T and Brown, G G. 2005. fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer's disease. Neurology 64, 501–8.Google Scholar
Bookheimer, S Y, Strojwas, M H, Cohen, M S, et al. 2000. Patterns of brain activation in people at risk for Alzheimer's disease. N Engl J Med 343, 450–6.Google Scholar
Borghesani, P R, Johnson, L C, Shelton, A L, et al. 2008. Altered medial temporal lobe responses during visuospatial encoding in healthy APOEε4 carriers. Neurobiol Aging 29, 981–91.Google Scholar
Bosscher, L and Scheltens, P H. 2001. MRI of the Temporal Lobe. Evidence-Based Dementia. Oxford: Blackwell.
Bradley, K M, O'sullivan, V T, Soper, N D, et al. 2002. Cerebral perfusion SPECT correlated with Braak pathological stage in Alzheimer's disease. Brain 125, 1772–81.Google Scholar
Buckner, R L, Snyder, A Z, Sanders, A L, Raichle, M E and Morris, J C. 2000. Functional brain imaging of young, nondemented, and demented older adults. J Cogn Neurosci 12 (Suppl. 2), 24–34.Google Scholar
Burggren, A C, Small, G W, Sabb, F W and Bookheimer, S. 2002. Specificity of brain activation patterns in people at genetic risk for Alzheimer disease. Am J Geriatr Psychiatry 10, 44–51.Google Scholar
Caselli, R J, Chen, K, Lee, W, Alexander, G E and Reiman, E M. 2008. Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. Arch Neurol 65, 1231–6.Google Scholar
Celone, K A, Calhoun, V D, Dickerson, B C, et al. 2006. Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: An independent component analysis. J Neurosci 26, 10 222–31.Google Scholar
Chételat, G, Desgranges, B, Sayette, V, et al. 2003. Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment. Brain 126, 1995–67.Google Scholar
Chételat, G, Eustache, F, Viader, F, et al. 2005. FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment Neurocase 11, 14–25.Google Scholar
Craig-Schapiro, R, Fagan, A M and Holtzman, D M. 2009. Biomarkers of Alzheimer's disease. Neurobiol Dis 35, 128–40.Google Scholar
D'Esposito, M, Deouell, L Y and Gazzaley, A. 2003. Alterations in the BOLD fMRI signal with ageing and disease: A challenge for neuroimaging. Nat Rev Neurosci 4, 863–72.Google Scholar
Leon, M, Golomb, J, George, A E, et al. 1993. The radiologic prediction of Alzheimer disease: The atrophic hippocampal formation. Am J Neuroradiol 13, 897–906.Google Scholar
Leon, M J, Convit, A, Wolf, O T, et al. 2001. Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET). Proc Natl Acad Sci U S A 98, 10 966–71.Google Scholar
Leon, M J, George, A E, Stylopoulos, L A, Smith, G and Miller, D C. 1989. Early marker for Alzheimer's disease: The atrophic hippocampus. Lancet 2, 672–3.Google Scholar
Desgranges, B, Baron, J C, Sayette, V, et al. 1998. The neural substrates of memory systems impairment in Alzheimer's disease. A PET study of resting brain glucose utilization. Brain 121, 611–31.Google Scholar
Desikan, R S, Fischl, B, Cabral, H J, et al. 2008. MRI measures of temporoparietal regions show differential rates of atrophy during prodromal AD. Neurology 71, 819–25.Google Scholar
Devanand, D P, Habeck, C G, Tabert, M H, et al. 2006. PET network abnormalities and cognitive decline in patients with mild cognitive impairment. Neuropsychopharmacology 31, 1327–34.Google Scholar
Dickerson, B C, Bakkour, A, Salat, D H, et al. 2007a. The cortical signature of Alzheimer's disease (AD): A high throughput in vivo MRI-based quantitative biomarker. In Massachusetts Alzheimer's Disease Research Center 20th Annual Scientific Poster Symposium, Boston, MA.
Dickerson, B C, Miller, S L, Greve, D N, et al. 2007b. Prefrontal–hippocampal–fusiform activity during encoding predicts intraindividual differences in free recall ability: An event-related functional–anatomic MRI study. Hippocampus 17, 1060–70.Google Scholar
Dickerson, B C, Salat, D H, Bates, J F, et al. 2004. Medial temporal lobe function and structure in mild cognitive impairment. Ann Neurol 56, 27–35.Google Scholar
Dickerson, B C, Salat, D H, Greve, D N, et al. 2005. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65, 404–11.Google Scholar
Dickerson, B C and Sperling, R A. 2005. Neuroimaging biomarkers for clinical trials of disease-modifying therapies in Alzheimer's disease. NeuroRX 2, 348–60.Google Scholar
Drzezga, A, Grimmer, T, Riemenschneider, M, et al. 2005. Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET. J Nucl Med 46, 1625–32.Google Scholar
Filbey, F M, Slack, K J, Sunderland, T P and Cohen, R M. 2006. Functional magnetic resonance imaging and magnetoencephalography differences associated with APOEepsilon4 in young healthy adults. Neuroreport 17, 1585–90.Google Scholar
Fleisher, A S, Houston, W S, Eyler, L T, et al. 2005. Identification of Alzheimer disease risk by functional magnetic resonance imaging. Arch Neurol 62, 1881–8.Google Scholar
Forsberg, A, Engler, H, Almkvist, O, et al. 2008. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 29, 1456–65.Google Scholar
Fox, N C, Kennedy, A M, Harvey, R J, et al. 1997. Clinicopathological features of familial Alzheimer's disease associated with the M139V mutation in the presenilin 1 gene. Pedigree but not mutation specific age at onset provides evidence for a further genetic factor. Brain 120, 491–501.Google Scholar
Fox, N C, Warrington, E K, Stevens, J M and Rossor, M N. 1996. Atrophy of the hippocampal formation in early familial Alzheimer's disease. A longitudinal MRI study of at-risk members of a family with an amyloid precursor protein 717Val-Gly mutation. Ann N Y Acad Sci 777, 226–32.Google Scholar
Goekoop, R, Scheltens, P, Barkhof, F and Rombouts, S A. 2006. Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation – A pharmacological fMRI study. Brain 129, 141–57.Google Scholar
Grady, C L, Furey, M L, Pietrini, P, Horwitz, B and Rapoport, S I. 2001. Altered brain functional connectivity and impaired short-term memory in Alzheimer's disease. Brain 124, 739–56.Google Scholar
Grady, C L, Mcintosh, A R, Beig, S, Keightley, M L, Burlan, H and Black, S E. 2003. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. J Neurosci 23, 986–93.Google Scholar
Graham, J E, Rockwood, K, Beattie, B L, et al. 1997. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 349, 1793–6.Google Scholar
Greicius, M D, Srivastava, G, Reiss, A L and Menon, V. 2004. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI. Proc Natl Acad Sci U S A 101, 4637–42.Google Scholar
Grön, G, Brandenburg, I, Wunderlich, A P and Riepe, M W. 2006. Inhibition of hippocampal function in mild cognitive impairment: Targeting the cholinergic hypothesis. Neurobiol Aging 27, 78–87.Google Scholar
Grossman, M, Koenig, P, Glosser, G, et al. 2003. Neural basis for semantic memory difficulty in Alzheimer's disease: An fMRI study. Brain 126, 292–311.Google Scholar
Guye, M, Bartolomei, F and Ranjeva, J P. 2008. Imaging structural and functional connectivity: Towards a unified definition of human brain organization? Curr Opin Neurol 21, 393–403.Google Scholar
Han, S D, Houston, W S, Jak, A J, et al. 2007. Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response. Neurobiol Aging 28, 238–47.Google Scholar
He, Y, Wang, L, Zang, Y, et al. 2007. Regional coherence changes in the early stages of Alzheimer's disease: A combined structural and resting-state functional MRI study. Neuroimage 35, 488–500.Google Scholar
Higuchi, M, Arai, H, Nakagawa, T, et al. 1997. Regional cerebral glucose utilization is modulated by the dosage of apolipoprotein E type 4 allele and alpha1-antichymotrypsin type A allele in Alzheimer's disease. Neuroreport 8, 2639–43.Google Scholar
Hirao, K, Ohnishi, T, Matsuda, H, et al. 2006. Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer's disease using brain perfusion single-photon emission computed tomography. Nucl Med Commun 27, 151–6.Google Scholar
Hoffman, J M, Welsh-Bohmer, K A, Hanson, M, et al. 2000. FDG PET imaging in patients with pathologically verified dementia. J Nucl Med 41, 1920–8.Google Scholar
Høgh, P, Knudsen, G M, Kjaer, K H, Jørgensen, O S, Paulson, O B and Waldemar, G. 2001. Single photon emission computed tomography and apolipoprotein E in Alzheimer's disease: Impact of the epsilon4 allele on regional cerebral blood flow. J Geriatr Psychiatry Neurol 14, 42–51.Google Scholar
Horwitz, B, Grady, C L, Schlageter, N L, Duara, R and Rapoport, S I. 1987. Intercorrelations of regional cerebral glucose metabolic rates in Alzheimer's disease. Brain Res 407, 294–306.Google Scholar
Ikonomovic, M D, Klunk, W E, Ambrahamson, E E, et al. 2008. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain 131, 1630–45.Google Scholar
Jack, C R, Petersen, R C, Xu, Y C, et al. 1999. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 52, 1397–403.Google Scholar
Jack, C R J, Petersen, R C, Xu, Y C, et al. 1997. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology 49, 786–94.Google Scholar
Johnson, K A, Jones, K, Holman, B L, et al. 1998. Preclinical prediction of Alzheimer's disease using SPECT. Neurology 50, 1563–71.Google Scholar
Johnson, K A, Lopera, F, Jones, K, et al. 2001. Presenilin-1-associated abnormalities in regional cerebral perfusion. Neurology 56, 1545–51.Google Scholar
Johnson, K A, Moran, E K, Becker, J A, Blacker, D, Fischman, A J and Albert, M S. 2007a. Single photon emission computed tomography perfusion differences in mild cognitive impairment. J Neurol Neurosurg Psychiatry 78, 240–7.Google Scholar
Johnson, S C, Baxter, L C, Susskind-Wilder, L, Connor, D J, Sabbagh, M N and Caselli, R J. 2004. Hippocampal adaptation to face repetition in healthy elderly and mild cognitive impairment. Neuropsychologia 42, 980–99.Google Scholar
Johnson, S C, Ries, M L, Hess, T M, et al. 2007b. Effect of Alzheimer disease risk on brain function during self-appraisal in healthy middle-aged adults. Arch Gen Psychiatry 64, 1163–71.Google Scholar
Johnson, S C, Saykin, A J, Baxter, L C, et al. 2000. The relationship between fMRI activation and cerebral atrophy: Comparison of normal aging and Alzheimer disease. Neuroimage 11, 179–87.Google Scholar
Johnson, S C, Schmitz, T W, Asthana, S, Gluck, M A and Myers, C. 2008. Associative learning over trials activates the hippocampus in healthy elderly but not mild cognitive impairment. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 15, 129–45.Google Scholar
Johnson, S C, Schmitz, T W, Moritz, C H, et al. 2006a. Activation of brain regions vulnerable to Alzheimer's disease: The effect of mild cognitive impairment. Neurobiol Aging 27, 1604–12.Google Scholar
Johnson, S C, Schmitz, T W, Trivedi, M A, et al. 2006b. The influence of Alzheimer disease family history and apolipoprotein E epsilon4 on mesial temporal lobe activation. J Neurosci 26, 6069–76.Google Scholar
Julin, P, Almkvist, O, Basun, H, et al. 1998. Brain volumes and regional cerebral blood flow in carriers of the Swedish Alzheimer amyloid protein mutation. Alzheimer Dis Assoc Disord 12, 49–53.Google Scholar
Julin, P, Lindqvist, J, Svensson, L, Slomka, P and Wahlund, L O. 1997. MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's disease. J Nucl Med 38, 914–9.Google Scholar
Kato, T, Knopman, D S and Liu, H. 2001. Dissociation of regional activation in mild AD during visual encoding: A functional MRI study. Neurology 57, 812–6.Google Scholar
Kemppainen, N M, Aalto, S, Wilson, I A, et al. 2007. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology 68, 1603–06.Google Scholar
Kessler, J, Herholz, K, Grond, M and Heiss, W D. 1991. Impaired metabolic activation in Alzheimer's disease: A PET study during continuous visual recognition. Neuropsychologia 29, 229–43.Google Scholar
Kircher, T T, Erb, M, Grodd, W and Leube, D T. 2005. Cortical activation during cholinesterase-inhibitor treatment in Alzheimer disease: Preliminary findings from a pharmaco-fMRI study. Am J Geriatr Psychiatry 13, 1006–13.Google Scholar
Klunk, W E, Engler, H, Nordberg, A, et al. 2004. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol 55, 306–19.Google Scholar
Klunk, W E and Mathis, C A. 2008. The future of amyloid-beta imaging: A tale of radionuclides and tracer proliferation. Curr Opin Neurol 21, 683–7.Google Scholar
Kogure, D, Matsuda, H, Ohnishi, T, et al. 2000. Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT. J Nucl Med 41, 1155–62.Google Scholar
Koivunen, J, Pirttilä, T, Kemppainen, N, et al. 2008. PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment. Dementia Geriatr Cogn Disord 26, 378–83.Google Scholar
Langbaum, J B, Chen, K, Lee, W, et al. 2009. Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Neuroimage 45, 1107–16.Google Scholar
Lee, K U, Lee, J S, Kim, K W, et al. 2003. Influence of the apolipoprotein E type 4 allele on cerebral glucose metabolism in Alzheimer's disease patients. J Neuropsychiatry Clin Neurosci 15, 78–83.Google Scholar
Lehtovirta, M, Kuikka, J, Helisalmi, S, et al. 1998. Longitudinal SPECT study in Alzheimer's disease: Relation to apolipoprotein E polymorphism. J Neurol Neurosurg Psychiatry 64, 742–6.Google Scholar
Lehtovirta, M, Soininen, H, Laakso, M P, et al. 1996. SPECT and MRI analysis in Alzheimer's disease: Relation to apolipoprotein E epsilon 4 allele. J Neurol Neurosurg Psychiatry 60, 644–9.Google Scholar
Lekeu, F, Linden, M, Chicherio, C, et al. 2003. Brain correlates of performance in a free/cued recall task with semantic encoding in Alzheimer disease. Alzheimer Dis Assoc Disord 17, 35–45.Google Scholar
Levy, R. 1994. Aging-associated cognitive decline. Int Psychogeriatr 6, 63–8.Google Scholar
Li, S J, Li, Z, Wu, G, Zhang, M J, Franczak, M and Antuono, P G. 2002. Alzheimer Disease: Evaluation of a functional MR imaging index as a marker. Radiology 225, 253–9.Google Scholar
Lind, J, Ingvar, M, Persson, J, et al. 2006a. Parietal cortex activation predicts memory decline in apolipoprotein E-epsilon4 carriers. Neuroreport 17, 1683–6.Google Scholar
Lind, J, Persson, J, Ingvar, M, et al. 2006b. Reduced functional brain activity response in cognitively intact apolipoprotein E epsilon4 carriers. Brain 129, 1240–8.Google Scholar
Lipton, A M, McColl, R, Cullum, C M, et al. 2003. Differential activation on fMRI of monozygotic twins discordant for AD. Neurology 60, 1713–6.Google Scholar
Machulda, M M, Ward, H A, Borowski, B, et al. 2003. Comparison of memory fMRI response among normal, MCI, and Alzheimer's patients. Neurology 61, 500–6.Google Scholar
Masdeu, J C, Zubieta, J L and Arbizu, J. 2005. Neuroimaging as a marker of the onset and progression of Alzheimer's disease. J Neurol Sci 236, 55–64.Google Scholar
Matsuda, H. 2001. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease. Ann Nucl Med 15, 85–92.Google Scholar
Matsuda, H, Kitayama, N, Ohnishi, T, et al. 2002. Longitudinal evaluation of both morphologic and functional changes in the same individuals with Alzheimer's disease. J Nucl Med 43, 304–11.Google Scholar
Maxim, V, Sendur, L, Fadili, J, et al. 2005. Fractional Gaussian noise, functional MRI and Alzheimer's disease. Neuroimage 25, 141–58.Google Scholar
Mielke, R, Zerres, K, Uhlhaas, S, Kessler, J and Heiss, W D. 1998. Apolipoprotein E polymorphism influences the cerebral metabolic pattern in Alzheimer's disease. Neurosci Lett 254, 49–52.Google Scholar
Minoshima, S, Giordani, B, Berent, S, Frey, K A, Foster, N L and Kuhl, D E. 1997. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol 42, 85–94.Google Scholar
Mintun, M A, Larossa, G N, Sheline, Y I, et al. 2006. [11C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease. Neurology 67, 446–52.Google Scholar
Mondadori, C R, Quervain, D J, Buchmann, A, et al. 2007. Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers. Cerebral Cortex 17, 1934–47.Google Scholar
Mormino, E C, Kluth, J T, Madison, C M, et al. 2009. Episodic memory loss is related to hippocampal-mediated {beta}-amyloid deposition in elderly subjects. Brain 132, 1310–23.Google Scholar
Morris, J C. 2006. Mild cognitive impairment is early-stage Alzheimer disease: Time to revise diagnostic criteria. Arch Neurol 63, 15–6.Google Scholar
Mosconi, L, Brys, M, Switalski, R, et al. 2007. Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism. Proc Natl Acad Sci U S A 104, 19 067–72.Google Scholar
Mosconi, L, Santi, S, Brys, M, et al. 2008. Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. Biol Psychiatry 63, 609–18.Google Scholar
Mosconi, L, Herholz, K, Prohovnik, I, et al. 2005. Metabolic interaction between ApoE genotype and onset age in Alzheimer's disease: Implications for brain reserve. J Neurol Neurosurg Psychiatry 76, 15–23.Google Scholar
Mosconi, L, Nacmias, B, Sorbi, S, et al. 2004a. Brain metabolic decreases related to the dose of the ApoE e4 allele in Alzheimer's disease. J Neurol Neurosurg Psychiatry 75, 370–6.Google Scholar
Mosconi, L, Perani, D, Sorbi, S, et al. 2004b. MCI conversion to dementia and the APOE genotype: A prediction study with FDG-PET. Neurology 63, 2332–40.Google Scholar
Mosconi, L, Sorbi, S, Leon, M J, et al. 2006. Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer's disease. J Nucl Med 47, 1778–86.Google Scholar
Mosconi, L, Sorbi, S, Nacmias, B, et al. 2004c. Age and ApoE genotype interaction in Alzheimer's disease: An FDG-PET study. Psychiatry Res 130, 141–51.Google Scholar
Moulin, C J, Laine, M, Rinne, J O, Kaasinen, V S, Hiltunen, J and Kangasmäki, A. 2007. Brain function during multi-trial learning in mild cognitive impairment: A PET activation study. Brain Res 1136, 132–41.Google Scholar
Nestor, P G, Fryer, T D, Smielewski, P and Hodges, J R. 2003a. Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment. Ann Neurol 54, 343–51.Google Scholar
Nestor, P G, Fryer, T D, Ikeda, M and Hodges, J R. 2003b. Retrosplenial cortex (BA 29/30) hypometabolism in mild cognitive impairment (prodromal Alzheimer's disease). Eur J Neurosci 18, 2663–7.Google Scholar
Nishi, H, Sawamoto, N, Namiki, C, et al. 2010. Correlation between cognitive deficits and glucose hypometabolism in mild cognitive impairment. J Neuroimaging 20, 29–36.Google Scholar
Nobili, F, Salmaso, D, Morbelli, S, et al. 2008. Principal component analysis of FDG PET in amnestic MCI. Eur J Nucl Med Mol Imaging 35, 2191–202.Google Scholar
Ohnishi, T, Hoshi, H, Nagamachi, S, et al. 1995. High-resolution SPECT to assess hippocampal perfusion in neuropsychiatric diseases. J Nucl Med 36, 1163–9.Google Scholar
Ott, B R, Heindel, W C, Tan, Z and Noto, R B. 2000. Lateralized cortical perfusion in women with Alzheimer's disease. J Gender-Spec Med 3, 29–35.Google Scholar
Pariente, J, Cole, S, Henson, R, et al. 2005. Alzheimer's patients engage an alternative network during a memory task. Ann Neurol 58, 870–9.Google Scholar
Perneczky, R, Hartmann, J, Grimmer, T, Drzezga, A and Kurz, A. 2007. Cerebral metabolic correlates of the clinical dementia rating scale in mild cognitive impairment. J Geriatr Psychiatry Neurol 20, 84–8.Google Scholar
Persson, J, Lind, J, Larsson, A, et al. 2008. Altered deactivation in individuals with genetic risk for Alzheimer's disease. Neuropsychologia 46, 1679–87.Google Scholar
Petersen, R C. 2007. Mild cognitive impairment: Current research and clinical implications. Semin Neurol 27, 22–31.Google Scholar
Petersen, R C, Smith, G E, Waring, S C, Ivnik, R J, Tangalos, E G and Kokmen, E. 1999. Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol 56, 303–08.Google Scholar
Petrella, J R, Lustig, C, Bucher, L A, Jha, A P and Doraiswamy, P M. 2002. Prefrontal activation patterns in subjects at risk for Alzheimer disease. Am J Geriatr Psychiatry 10, 112–3.Google Scholar
Petrella, J R, Prince, S E, Krishnan, S, Husn, H, Kelley, L and Doraiswamy, P M. 2009. Effects of donepezil on cortical activation in mild cognitive impairment: A pilot double-blind placebo-controlled trial using functional MR imaging. Am J Neuroradiol 30, 411–6.Google Scholar
Petrella, J R, Wang, L, Krishnan, S, et al. 2007. Cortical deactivation in mild cognitive impairment: High-field-strength functional MR imaging. Radiology 245, 224–35.Google Scholar
Pike, K E, Savage, G, Villemagne, V L, et al. 2007. Beta-amyloid imaging and memory in non-demented individuals: Evidence for preclinical Alzheimer's disease. Brain 130, 2837–44.Google Scholar
Rapoport, S I. 1997. Discriminant analysis of brain imaging data identifies subjects with early Alzheimer's disease. Int Psychogeriatr 9 (Suppl. 1), 229–35.Google Scholar
Reiman, E M, Caselli, R J, Chen, K, Alexander, G E, Bandy, D and Frost, J. 2001. Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proc Natl Acad Sci U S A 98, 3334–9.Google Scholar
Reiman, E M, Caselli, R J, Yun, L S, et al. 1996. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 334, 752–8.Google Scholar
Reiman, E M, Chen, K, Alexander, G E, et al. 2004. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci U S A 101, 284–9.Google Scholar
Reiman, E M, Chen, K, Alexander, G E, et al. 2005. Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism. Proc Natl Acad Sci U S A 102, 8299–302.Google Scholar
Rimajova, M, Lenzo, N P, Wu, J S, et al. 2008. Fluoro-2-deoxy-D-glucose (FDG)-PET in APOEepsilon4 carriers in the Australian population. J Alzheimer's Dis 13, 137–46.Google Scholar
Risacher, S L, Saykin, A J, West, J D, et al. 2009. Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort. Curr Alzheimer Res 6, 347–61.Google Scholar
Rombouts, S A, Barkhof, F, Veltman, D J, et al. 2000. Functional MR imaging in Alzheimer's disease during memory encoding. Am J Neuroradiol 21, 1869–75.Google Scholar
Rombouts, S A and Scheltens, P. 2005. Functional connectivity in elderly controls and AD patients using resting-state fMRI: A pilot study. Curr Alzheimer Res 2, 115–6.Google Scholar
Rossor, M, Kennedy, A M and Frackowiak, R S. 1996. Clinical and neuroimaging features of familial Alzheimer's disease. Ann N Y Acad Sci 777, 49–56.Google Scholar
Rossor, M, Newman, S, Frackowiak, R S, Lantos, P and Kennedy, A M. 1993. Alzheimer's disease families with amyloid precursor protein mutations. Ann N Y Acad Sci 695, 198–202.Google Scholar
Sakamoto, S, Ishii, K, Sasaki, M, et al. 2002. Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease. J Neurol Sci 200, 27–32.Google Scholar
Sakamoto, S, Matsuda, H, Asada, T, et al. 2003. Apolipoprotein E genotype and early Alzheimer's disease: A longitudinal SPECT study. J Neuroimag 13, 113–23.Google Scholar
Saykin, A J, Wishart, H A, Rabin, L A, et al. 2004. Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. Brain 127, 1574–83.Google Scholar
Saykin, A J, Wishart, H A, Rabin, L A, et al. 2006. Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology 67, 834–42.Google Scholar
Scarmeas, N, Anderson, K E, Hilton, J, et al. 2004a. APOE-dependent PET patterns of brain activation in Alzheimer disease. Neurology 63, 913–5.Google Scholar
Scarmeas, N, Habeck, C, Anderson, K E, et al. 2004b. Altered PET functional brain responses in cognitively intact elderly persons at risk for Alzheimer disease (carriers of the E4 allele). Am J Geriatr Psychiatry 12, 596–605.Google Scholar
Scarmeas, N, Habeck, C, Hilton, J, et al. 2005. APOE related alterations in cerebral activation even at college age. J Neurol Neurosurg Psychiatry 76, 1440–4.Google Scholar
Scarmeas, N and Stern, Y. 2006. Imaging studies and APOE genotype in persons at risk for Alzheimer's disease. Curr Psychiatry Rep 8, 11–7.Google Scholar
Scheltens, P, Launer, L J, Barkhof, F, Weinstein, H C and Jonker, C. 1997. The diagnostic value of magnetic resonance imaging and technetium 99m-HMPAO single-photon-emission computed tomography for the diagnosis of Alzheimer disease in a community-dwelling elderly population. Alzheimer Dis Assoc Disord 11, 63–70.Google Scholar
Schröder, J, Buchsbaum, M S, Shihabuddin, L, et al. 2001. Patterns of cortical activity and memory performance in Alzheimer's disease. Biol Psychiatry 49, 426–36.Google Scholar
Seo, S W, Cho, S S, Park, A, Chin, J and Na, D L. 2009. Subcortical vascular versus amnestic mild cognitive impairment: Comparison of cerebral glucose metabolism. J Neuroimag 19, 213–9.Google Scholar
Shulman, G L, Fiez, J A, Corbetta, M, et al. 1997. Common blood flow changes across visual tasks: II. Decreases in cerebral cortex. J Cogn Neurosci 9, 648–63.Google Scholar
Silverman, D H. 2004. Brain 18F-FDG PET in the diagnosis of neurodegenerative dementias: Comparison with perfusion SPECT and with clinical evaluations lacking nuclear imaging. J Nucl Med 45, 594–607.Google Scholar
Small, B J, Mazziotta, J C, Collins, M T, et al. 1995. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. J Am Med Assoc 273, 942–7.Google Scholar
Small, G W, Komo, S, Rue, A, et al. 1996. Early detection of Alzheimer's disease by combining apolipoprotein E and neuroimaging. Ann N Y Acad Sci 802, 70–8.Google Scholar
Small, G W, Okonek, A, Mandelkern, M A, et al. 1994. Age-associated memory loss: Initial neuropsychological and cerebral metabolic findings of a longitudinal study. Int Psychogeriatr 6, 23–44.Google Scholar
Small, S A, Perera, G M, Delapaz, R, Mayeux, R and Stern, Y. 1999. Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease. Ann Neurol 45, 466–72.Google Scholar
Small, S A, Tsai, W Y, Paz, R, Mayeux, R and Stern, C E. 2002. Imaging hippocampal function across the human life span: Is memory decline normal or not? Ann Neurol 51, 290–5.Google Scholar
Small, S A, Wu, E X, Bartsch, D, et al. 2000. Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice. Neuron 28, 653–4.Google Scholar
Smith, C D, Andersen, A H, Kryscio, R J, et al. 1999. Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease. Neurology 53, 1391–6.Google Scholar
Smith, C D, Andersen, A H, Kryscio, R J, et al. 2002. Women at risk for AD show increased parietal activation during a fluency task. Neurology 58, 1197–202.Google Scholar
Smith, C D, Kryscio, R J, Schmitt, F A, et al. 2005. Longitudinal functional alterations in asymptomatic women at risk for Alzheimer's disease. J Neuroimag 15, 271–7.Google Scholar
Sorg, C, Riedl, V, Mühlau, M, et al. 2007. Selective changes of resting-state networks in individuals at risk for Alzheimer's disease. Proc Natl Acad Sci U S A 104, 18 760–5.Google Scholar
Sperling, R A, Bates, J F, Chua, E F, et al. 2003. fMRI studies of associative encoding in young and elderly controls and mild Alzheimer's disease. J Neurol Neurosurg Psychiatry 74, 44–50.Google Scholar
Supekar, K, Menon, V, Rubin, D, Musen, M and Greicius, M D. 2008. Network analysis of intrinsic functional brain connectivity in Alzheimer's disease. PLoS Comput Biol 4, e1000100.Google Scholar
Thompson, P M, Hayashi, K M, Zubicaray, G, et al. 2003. Dynamics of gray matter loss in Alzheimer's disease. J Neurosci 23, 994–1005.Google Scholar
Trivedi, M A, Murphy, C M, Goetz, C, et al. 2008a. fMRI activation changes during successful episodic memory encoding and recognition in amnestic mild cognitive impairment relative to cognitively healthy older adults. Dementia Geriatr Cogn Disord 26, 123–37.Google Scholar
Trivedi, M A, Schmitz, T W, Ries, M L, et al. 2006. Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's disease: A cross-sectional study. BMC Med 4, 1.Google Scholar
Trivedi, M A, Schmitz, T W, Ries, M L, et al. 2008b. fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: Risk factors for Alzheimer's disease. Neuropsychologia 46, 1667–78.Google Scholar
Dyck, C H, Gelernter, J, Macavoy, M G, et al. 1998. Absence of an apolipoprotein E epsilon4 allele is associated with increased parietal regional cerebral blood flow asymmetry in Alzheimer disease. Arch Neurol 55, 1460–6.Google Scholar
Visser, P J, Scheltens, P, Verhey, F R, et al. 1999. Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment. J Neurol 246, 477–85.Google Scholar
Wahlund, L, Basun, H, Almkvist, O, et al. 1999. A follow-up study of the family with the Swedish APP 670/671 Alzheimer's disease mutation. Dementia Geriatr Cogn Disord 10, 526–33.Google Scholar
Wang, K, Jiang, T, Liang, M, et al. 2006a. Discriminative analysis of early Alzheimer's disease based on two intrinsically anti-correlated networks with resting-state fMRI. Med Image Comput ComputAssist Interv 9, 340–7.Google Scholar
Wang, K, Liang, M, Wang, L, et al. 2007. Altered functional connectivity in early Alzheimer's disease: A resting-state fMRI study. Hum Brain Mapp 28, 967–78.Google Scholar
Wang, L, Zang, Y, He, Y, et al. 2006b. Changes in hippocampal connectivity in the early stages of Alzheimer's disease: Evidence from resting state fMRI. Neuroimage 31, 496–504.Google Scholar
Wang, P J, Saykin, A J, Flashman, L A, et al. 2006c. Regionally specific atrophy of the corpus callosum in AD, MCI and cognitive complaints. Neurobiol Aging 27, 1613–7.Google Scholar
Waragai, M, Mizumura, S, Yamada, T and Matsuda, H. 2008. Differentiation of early-stage Alzheimer's disease from other types of dementia using brain perfusion single photon emission computed tomography with easy z-score imaging system analysis. Dementia Geriatr Cogn Disord 26, 547–55.Google Scholar
Weiner, M W. 2009. Imaging and biomarkers will be used for detection and monitoring progression of early Alzheimer's disease. J Nutr Health Aging 13, 332.Google Scholar
Wierenga, C E and Bondi, M W. 2007. Use of functional magnetic resonance imaging in the early identification of Alzheimer's disease. Neuropsychol Rev 17, 127–43.Google Scholar
Winblad, B, Palmer, K, Kivipelto, M, et al. 2004. Mild cognitive impairment – Beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. J Int Med 256, 240–6.Google Scholar
Wishart, H A, Saykin, A J, Rabin, L A, et al. 2006. Increased brain activation during working memory in cognitively intact adults with the APOE epsilon4 allele. Am J Psychiatry 163, 1603–10.Google Scholar
Wolf, H, Jelic, V, Gertz, H J, Nordberg, A, Julin, P and Wahlund, L O. 2003. A critical discussion of the role of neuroimaging in mild cognitive impairment. Acta Neurol Scand Suppl 179, 52–76.Google Scholar
Wolk, D A, Price, J C, Saxton, J A, et al. 2009. Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol 65, 557–68.Google Scholar
Woodard, J L, Grafton, S T, Votaw, J R, Green, R C, Dobraski, M E and Hoffman, J M. 1998. Compensatory recruitment of neural resources during overt rehearsal of word lists in Alzheimer's disease. Neuropsychology 12, 491–504.Google Scholar
Xu, G, Mclaren, D G, Ries, M L, et al. 2008. The influence of parental history of Alzheimer's disease and apolipoprotein E {varepsilon}4 on the BOLD signal during recognition memory. Brain 132, 383–91.Google Scholar
Yassa, M A, Verduzco, G, Cristinzio, C and Bassett, S S. 2008. Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease. Neurology 70, 1898–904.Google Scholar
Zhou, Y, Dougherty, J H J, Hubner, K F, Bai, B, Cannon, R L and Hutson, R K. 2008. Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment Alzheimer's Dementia 4, 265–70.Google Scholar

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