Patterns of Brain Activation in People at Risk for Alzheimer's Disease
Open accessAbstract
BACKGROUND: The epsilon4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease, we performed APOE genotyping and functional magnetic resonance imaging (MRI) of the brain in older persons with intact cognition. METHODS: We studied 30 subjects (age, 47 to 82 years) who were neurologically normal, of whom 16 were carriers of the APOE epsilon4 allele and 14 were homozygous for the APOE epsilon3 allele. The mean age and level of education were similar in the two groups. Patterns of brain activation during functional MRI scanning were determined while subjects memorized and recalled unrelated pairs of words and while subjects rested between such periods. Memory was reassessed in 14 subjects two years later. RESULTS: Both the magnitude and the extent of brain activation during memory-activation tasks in regions affected by Alzheimer's disease, including the left hippocampal, parietal, and prefrontal regions, were greater among the carriers of the APOE epsilon4 allele than among the carriers of the APOE epsilon3 allele. During periods of recall, the carriers of the APOE epsilon4 allele had a greater average increase in signal intensity in the hippocampal region (1.03 percent vs. 0.62 percent, P<0.001) and a greater mean (+/-SD) number of activated regions throughout the brain (15.9+/-6.2 vs. 9.4+/-5.5, P=0.005) than did carriers of the APOE epsilon3 allele. Longitudinal assessment after two years indicated that the degree of base-line brain activation correlated with degree of decline in memory. CONCLUSIONS: Patterns of brain activation during tasks requiring memory differ depending on the genetic risk of Alzheimer's disease and may predict a subsequent decline in memory.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous studies have already linked APOE4 to increased (hyper-)metabolism in young individuals.
“However, previous studies have already linked APOE4 to increased (hyper-)metabolism in young individuals.”
From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [46]
The introduction (p. 451) says PET studies found deficits, not increases, in resting glucose metabolism among middle-aged APOE4 carriers. The Results report greater task-related fMRI activation in participants aged 47–82, which is not evidence of hypermetabolism in young individuals. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredStudies in young adults, before the onset of a pathology, showed that APOE4 carriers display hypermetabolism and hyperactivity in distinct brain regions, such as the hippocampus, entorhinal cortex, and cortical regions.
“Studies in young adults, before the onset of a pathology, showed that APOE4 carriers display hypermetabolism and hyperactivity in distinct brain regions, such as the hippocampus, entorhinal cortex, and cortical regions [44,45,46].”
From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [46]
The Results and Discussion report greater memory-task activation in APOE e4 carriers in hippocampal and cortical regions. But the studied participants were 47–82 years old, not young adults; the study measured functional MRI activation, not hypermetabolism, and does not identify increased activation in the entorhinal cortex. The paper's background discussion instead describes glucose-metabolism deficits in middle-aged carriers (p. 451). (LLM, conf=0.89)
Experimental — accuracy not yet measuredHealthy young and middle-aged adult apoE4 carriers show increased hippocampal activation during encoding task performance.
“and increased hippocampal activation during encoding task performance [179–181]”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [180]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Self-citationTalairach, J., Tournoux, P., & Rayport, M. (1988) · Thieme eBooks · Cited by 5,058 · see citing works
Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation.
Kwong, K. K., Belliveau, J. W., Chesler, D. A., Goldberg, I. E., Weisskoff, R. M., Poncelet, B. P., Kennedy, D. N., Hoppel, B. E., Cohen, M. S., & Turner, R. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5675 · Cited by 4,212 · see citing works
Self-citationAssociation of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
Self-citationOgawa, S., Tank, D. W., Menon, R., Ellermann, J. M., Kim, S. G., Merkle, H., & Ugurbil, K. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.13.5951 · Cited by 3,681 · see citing works
A Standardized Memory Scale for Clinical Use
Wechsler, D. (1945) · The Journal of Psychology · doi:10.1080/00223980.1945.9917223 · Cited by 2,960 · see citing works
Fox, P. T., & Raichle, M. E. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.4.1140 · Cited by 2,056 · see citing works
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Self-citationEvaluating storage, retention, and retrieval in disordered memory and learning
Buschke, H., & Fuld, P. (1974) · Neurology · doi:10.1212/wnl.24.11.1019 · Cited by 1,614 · see citing works
Practice-related Changes in Human Brain Functional Anatomy during Nonmotor Learning
Raichle, M. E., Fiez, J. A., Videen, T. O., MacLeod, A.-M. K., Pardo, J. V., Fox, P. T., & Petersen, S. E. (1994) · Cerebral Cortex · doi:10.1093/cercor/4.1.8 · Cited by 1,593 · see citing works
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D. (1996) · New England Journal of Medicine · doi:10.1056/nejm199603213341202 · Cited by 1,366 · see citing works
Brain Activation Modulated by Sentence Comprehension
Just, M. A., Carpenter, P. A., Keller, T. A., Eddy, W. F., & Thulborn, K. R. (1996) · Science · doi:10.1126/science.274.5284.114 · Cited by 1,146 · see citing works
Automated Image Registration: II. Intersubject Validation of Linear and Nonlinear Models
Woods, R. P., Grafton, S. T., Watson, J. D. G., Sicotte, N. L., & Mazziotta, J. C. (1998) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199801000-00028 · Cited by 993 · see citing works
Self-citationDiagnosis and Treatment of Alzheimer Disease and Related Disorders
Small, G. W. (1997) · JAMA · doi:10.1001/jama.1997.03550160083043 · Cited by 984 · see citing works
Self-citationLesion analysis in neuropsychology
Damásio, H., & Damásio, A. R. (1989) · Oxford University Press eBooks · Cited by 881 · see citing works
Parametric Analysis of fMRI Data Using Linear Systems Methods
Cohen, M. S. (1997) · NeuroImage · doi:10.1006/nimg.1997.0278 · Cited by 723 · see citing works
Self-citationAge-related changes in cortical blood flow activation during visual processing of faces and location
Grady, C., Maisog, J. M., Horwitz, B., Ungerleider, L. G., Mentis, M. J., SALERNO, J., Pietrini, P., Wagner, E., & Jv, H. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-03-01450.1994 · Cited by 696 · see citing works
Small, G. W. (1995) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1995.03520360056039 · Cited by 604 · see citing works
Self-citationActivation of the prefrontal cortex in a nonspatial working memory task with functional MRI
Cohen, J. D., Forman, S. D., Braver, T. S., Casey, B. J., Servan‐Schreiber, D., & Noll, D. C. (1994) · Human Brain Mapping · doi:10.1002/hbm.460010407 · Cited by 576 · see citing works
Separate Neural Bases of Two Fundamental Memory Processes in the Human Medial Temporal Lobe
Gabrieli, J. D. E., Brewer, J. B., Desmond, J. E., & Glover, G. H. (1997) · Science · doi:10.1126/science.276.5310.264 · Cited by 569 · see citing works
Localization of brain function using magnetic resonance imaging
Cohen, M. S., & Bookheimer, S. Y. (1994) · Trends in Neurosciences · doi:10.1016/0166-2236(94)90055-8 · Cited by 256 · see citing works
Self-citationApolipoprotein E genotyping in Alzheimer's disease
Relkin, N. R. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90284-6 · Cited by 241 · see citing works
Hippocampal Neuron Loss and Memory Scores Before and After Temporal Lobe Surgery for Epilepsy
Rausch, R., & Babb, T. L. (1993) · Archives of Neurology · doi:10.1001/archneur.1993.00540080023008 · Cited by 211 · see citing works
Brain regions associated with episodic retrieval in normal aging and Alzheimer’s disease
Bäckman, L., Andersson, J. L. R., Nyberg, L. H., Winblad, B. G., Nordberg, A. K., & Almkvist, O. (1999) · Neurology · doi:10.1212/wnl.52.9.1861 · Cited by 210 · see citing works
Diffusion weighted fMRI at 1.5 T
Song, A. W., Wong, E. C., Tan, S. G., & Hyde, J. S. (1996) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910350204 · Cited by 208 · see citing works
Small, G. W. (1997) · JAMA · doi:10.1001/jama.278.16.1363 · Cited by 203 · see citing works
Self-citationHippocampal formation size predicts declining memory performance in normal aging
Golomb, J. B., Kluger, A., de Leon, M. J., Ferris, S. H., Mittelman, M. S., Cohen, J., & GEORGE, A. E. (1996) · Neurology · doi:10.1212/wnl.47.3.810 · Cited by 150 · see citing works
O'Hara, R. M., Yesavage, J. A., KRAEMER, H. C., Mauricio, M., Friedman, L., & Murphy, G. M. (1998) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1998.tb01532.x · Cited by 130 · see citing works
Automatic vessel segmentation using active contours in cine phase contrast flow measurements
Kozerke, S., Botnar, R. M., Oyre, S., Scheidegger, M. B., Pedersen, E. M., & Boesiger, P. (1999) · Journal of Magnetic Resonance Imaging · doi:10.1002/(sici)1522-2586(199907)10:1 · Cited by 98 · see citing works
Mentis, M. J., Horwitz, B., Grady, C. L., Alexander, G., VanMeter, J. W., Maisog, J. M., Pietrini, P., Schapiro, M. B., & Рапопорт, С. И. (1996) · American Journal of Psychiatry · doi:10.1176/ajp.153.1.32 · Cited by 98 · see citing works
Grady, C. L., Haxby, J. V., Horwitz, B., Gillette, J., Salerno, J. A., Gonzalez-Aviles, A., Carson, R. E., Herscovitch, P., Schapiro, M. B., & Rapoport, S. I. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90018-7 · Cited by 90 · see citing works
Sulcal variability in the Alzheimer's brain
Mega, M. S., Thompson, P. M., Cummings, J. L., Back, C., Xu, M., Zohoori, S., Goldkorn, A., Moussai, J., Fairbanks, L. A., Small, G. W., et al. (1998) · Neurology · doi:10.1212/wnl.50.1.145 · Cited by 49 · see citing works
Self-citationPrice (1999) · doi:10.1002/1531-8249(199903)45:3
Flagged first, then by citations
Research works printed but not linked: 2
- Benton AL, Hamsher K. Multilingual aphasia examination. Rev. ed. Iowa City: University of Iowa Press, 1978.
- Cohen MS, DuBois RM. Stability, repeatability, and the expression of signal magnitude in functional magnetic resonance imaging. J Magn Reson Imaging 1999;10:33-40.
Cited by
Sorted by citations
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420 · see citing works
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888 · see citing works
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459 · see citing works
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280 · see citing works
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969 · see citing works
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · see citing works
RetractedNeurovascular regulation in the normal brain and in Alzheimer's disease
Iadecola, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1387 · Cited by 2,213 · see citing works
Hansson, O., Zetterberg, H., Buchhave, P., Londos, E., Blennow, K., & Minthon, L. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70355-6 · Cited by 1,700 · see citing works
Lautenschlager, N. T., Cox, K. L., Flicker, L., Foster, J. K., van Bockxmeer, F. M., Xiao, J., Greenop, K. R., & Almeida, O. P. (2008) · JAMA · doi:10.1001/jama.300.9.1027 · Cited by 1,637 · see citing works
The cognitive neuroscience of ageing
Grady, C. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3256 · Cited by 1,286 · see citing works
Maintenance, reserve and compensation: the cognitive neuroscience of healthy ageing
Cabeza, R., Albert, M., Belleville, S., Craik, F. I. M., Duarte, A., Grady, C. L., Lindenberger, U., Nyberg, L., Park, D. C., Reuter-Lorenz, P. A., et al. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0068-2 · Cited by 1,289 · see citing works
Mueller, S. G., Weiner, M. W., Thal, L. J., Petersen, R. C., Jack, C. R., Jagust, W., Trojanowski, J. Q., Toga, A. W., & Beckett, L. (2005) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2005.06.003 · Cited by 1,233 · see citing works
Sperling, R. A., LaViolette, P. S., O'Keefe, K., O'Brien, J., Rentz, D. M., Pihlajamaki, M., Marshall, G., Hyman, B. T., Selkoe, D. J., Hedden, T., et al. (2009) · Neuron · doi:10.1016/j.neuron.2009.07.003 · Cited by 1,027 · see citing works
Hariri, A. R., Goldberg, T. E., Mattay, V. S., Kolachana, B. S., Callicott, J. H., Egan, M. F., & Weinberger, D. R. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06690.2003 · Cited by 1,045 · see citing works
Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior
Selkoe, D. J. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.02.016 · Cited by 1,038 · see citing works
Network abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022 · see citing works
Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD
Dickerson, B. C., Salat, D. H., Greve, D. N., Chua, E. F., Rand-Giovannetti, E., Rentz, D. M., Bertram, L., Mullin, K., Tanzi, R. E., Blacker, D., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000171450.97464.49 · Cited by 910 · see citing works
Brain Imaging in Alzheimer Disease
Johnson, K. A., Fox, N. C., Sperling, R. A., & Klunk, W. E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006213 · Cited by 875 · see citing works
Apolipoprotein E in Alzheimer’s disease and other neurological disorders
Verghese, P. B., Castellano, J. M., & Holtzman, D. M. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70325-2 · Cited by 857 · see citing works
Georganopoulou, D. G., Chang, L., Nam, J.-M., Thaxton, C. S., Mufson, E. J., Klein, W. L., & Mirkin, C. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409336102 · Cited by 835 · see citing works
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723 · see citing works
Age, APOE and sex: triad of risk of Alzheimer’s disease.
Riedel, B. C., Thompson, P. M., & Brinton, R. D. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.03.012 · Cited by 627 · see citing works
Baker, L. D., Cross, D. J., Minoshima, S., Belongia, D., Watson, G. S., & Craft, S. (2011) · Archives of Neurology · doi:10.1001/archneurol.2010.225 · Cited by 639 · see citing works
Neuron Number in the Entorhinal Cortex and CA1 in Preclinical Alzheimer Disease
Price, J. L., Ko, A. I., Wade, M. J., Tsou, S. K., McKeel, D. W., & Morris, J. C. (2001) · Archives of Neurology · doi:10.1001/archneur.58.9.1395 · Cited by 596 · see citing works
Yassa, M. A., Lacy, J. W., Stark, S. M., Albert, M. S., Gallagher, M., & Stark, C. E. L. (2011) · Hippocampus · doi:10.1002/hipo.20808 · Cited by 595 · see citing works
Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease
D'Amelio, M., Cavallucci, V., Middei, S., Marchetti, C., Pacioni, S., Ferri, A., Diamantini, A., De Zio, D., Carrara, P., Battistini, L., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2709 · Cited by 572 · see citing works
Sengillo, J. D., Winkler, E. A., Walker, C. T., Sullivan, J. S., Johnson, M., & Zlokovic, B. V. (2013) · Brain Pathology · doi:10.1111/bpa.12004 · Cited by 553 · see citing works
Structure–function correlates of cognitive decline in aging
Persson, J., Nyberg, L., Lind, J., Larsson, A., Nilsson, L.-G., Ingvar, M., & Buckner, R. L. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhj036 · Cited by 473 · see citing works
Fox, N. C., Crum, W. R., Scahill, R. I., Stevens, J. M., Janssen, J. C., & Rossor, M. N. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05408-3 · Cited by 455 · see citing works
Stuttered and fluent speech production: An ALE meta‐analysis of functional neuroimaging studies
Brown, S., Ingham, R. J., Ingham, J. C., Laird, A. R., & Fox, P. T. (2005) · Human Brain Mapping · doi:10.1002/hbm.20140 · Cited by 449 · see citing works
Apolipoprotein E and Cognitive Performance: A Meta-Analysis.
Small, B. J., Rosnick, C. B., Fratiglioni, L., & Bäckman, L. (2004) · Psychology and Aging · doi:10.1037/0882-7974.19.4.592 · Cited by 447 · see citing works
Neuroimaging and Early Diagnosis of Alzheimer Disease: A Look to the Future
Petrella, J. R., Coleman, R. E., & Doraiswamy, P. M. (2003) · Radiology · doi:10.1148/radiol.2262011600 · Cited by 427 · see citing works
Episodic memory in normal aging and Alzheimer disease: Insights from imaging and behavioral studies
Tromp, D., Dufour, A., Lithfous, S., Pebayle, T., & Després, O. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.08.006 · Cited by 390 · see citing works
Genetic and neurochemical modulation of prefrontal cognitive functions in children
Diamond, A., Briand, L., Fossella, J., & Gehlbach, L. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.1.125 · Cited by 381 · see citing works
Impairments of neural circuit function in Alzheimer's disease
Busche, M. A., & Konnerth, A. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0429 · Cited by 360 · see citing works
fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease
Bondi, M. W., Houston, W. S., Eyler, L. T., & Brown, G. G. (2005) · Neurology · doi:10.1212/01.wnl.0000150885.00929.7e · Cited by 372 · see citing works
Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors
Jann, M. W., Shirley, K. L., & Small, G. W. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241100-00003 · Cited by 365 · see citing works
Self-citationIndependent predictors of cognitive decline in healthy elderly persons
Marquis, S., Moore, M. M., Howieson, D. B., Sexton, G., Payami, H., Kaye, J. A., & Camicioli, R. (2002) · Archives of Neurology · doi:10.1001/archneur.59.4.601 · Cited by 344 · see citing works
Your Brain on Google: Patterns of Cerebral Activation during Internet Searching
Small, G. W., Moody, T. D., Siddarth, P., & Bookheimer, S. Y. (2009) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181953a02 · Cited by 306 · see citing works
Self-citationTechnical aspects and utility of fMRI using BOLD and ASL
Detre, J. A., & Wang, J. (2002) · Clinical Neurophysiology · doi:10.1016/s1388-2457(02)00038-x · Cited by 291 · see citing works
Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment
Scheef, L., Spottke, A., Daerr, M., Joe, A., Striepens, N., Kölsch, H., Popp, J., Daamen, M., Gorris, D., Heneka, M. T., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e31826c1a8d · Cited by 277 · see citing works
Dean, D. C., Jerskey, B. A., Chen, K., Protas, H., Thiyyagura, P., Roontiva, A., O'Muircheartaigh, J., Dirks, H., Waskiewicz, N., Lehman, K., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2013.4544 · Cited by 263 · see citing works
Bi, D., Wen, L., Wu, Z., & Shen, Y. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12088 · Cited by 232 · see citing works
Neurovascular Dysfunction and Faulty Amyloid -Peptide Clearance in Alzheimer Disease
Sagare, A. P., Bell, R. D., & Zlokovic, B. V. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011452 · Cited by 251 · see citing works
Ungar, L., Altmann, A., & Greicius, M. D. (2014) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9272-x · Cited by 246 · see citing works
Understanding Genetic Risk for Aggression: Clues From the Brain’s Response to Social Exclusion
Eisenberger, N. I., Way, B. M., Taylor, S. E., Welch, W. T., & Lieberman, M. D. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.08.007 · Cited by 229 · see citing works
Fleisher, A. S., Sherzai, A., Taylor, C., Langbaum, J. B. S., Chen, K., & Buxton, R. B. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.06.021 · Cited by 217 · see citing works
Exercise improves cognition and hippocampal plasticity in <i>APOE</i> ɛ4 mice
Nichol, K., Deeny, S. P., Seif, J., Camaclang, K., & Cotman, C. W. (2009) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2009.02.006 · Cited by 213 · see citing works
Schott, B. H., Seidenbecher, C. I., Fenker, D. B., Lauer, C. J., Bunzeck, N., Bernstein, H.-G., Tischmeyer, W., Gundelfinger, E. D., Heinze, H.-J., & Düzel, E. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3463-05.2006 · Cited by 214 · see citing works
The Utility of Cerebral Blood Flow as a Biomarker of Preclinical Alzheimer’s Disease
Hays, C. C., Zlatar, Z. Z., & Wierenga, C. E. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-015-0261-z · Cited by 213 · see citing works
Chow, N., Bell, R. D., Deane, R., Streb, J. W., Chen, J., Brooks, A., Van Nostrand, W., Miano, J. M., & Zlokovic, B. V. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608251104 · Cited by 209 · see citing works
Temporal lobe functional activity and connectivity in young adult <i>APOE</i> ɛ4 carriers
Dennis, N. A., Browndyke, J. N., Stokes, J., Need, A., Burke, J. R., Welsh‐Bohmer, K. A., & Cabeza, R. (2010) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2009.07.003 · Cited by 201 · see citing works
Reduced cerebral blood flow response and compensation among patients with untreated hypertension
Jennings, J. R., Muldoon, M. F., Ryan, C., Price, J. C., Greer, P., Sutton-Tyrrell, K., van der Veen, F. M., & Meltzer, C. C. (2005) · Neurology · doi:10.1212/01.wnl.0000158283.28251.3c · Cited by 198 · see citing works
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease
Najm, R., Jones, E. A., & Huang, Y. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0324-6 · Cited by 183 · see citing works
Buttini, M., Yu, G.-Q., Shockley, K., Huang, Y., Jones, B., Masliah, E., Mallory, M., Yeo, T., Longo, F. M., & Mucke, L. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-24-10539.2002 · Cited by 183 · see citing works
“…to have relatively little impact on the severity and progression of neuronal deficits in old age and during later stages of AD (Farrer et al., 1997; Bookheimer et al., 2000; Greenwood et al., 2000; Small et al., 2000; Yaffe et al., 2000; Caselli et al., 2001; Chapman et al., 2001; Reiman et al.,…”
BackgroundInfluentialNuriel, T., Angulo, S. L., Khan, U., Ashok, A., Chen, Q., Figueroa, H. Y., Emrani, S., Liu, L., Herman, M., Barrett, G., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01444-0 · Cited by 181 · see citing works
Effects of a 14-Day Healthy Longevity Lifestyle Program on Cognition and Brain Function
Small, G. W., Silverman, D. H. S., Siddarth, P., Ercoli, L. M., Miller, K. J., Lavretsky, H., Wright, B. C., Bookheimer, S. Y., Barrio, J. R., & Phelps, M. E. (2006) · The American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000219279.72210.ca · Cited by 176 · see citing works
Self-citationThe potential of functional MRI as a biomarker in early Alzheimer's disease
Sperling, R. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.09.009 · Cited by 187 · see citing works
Alzheimer’s disease: Targeting the glutamatergic system
Conway, M. E. (2020) · Biogerontology · doi:10.1007/s10522-020-09860-4 · Cited by 180 · see citing works
Sleep Interacts with Aβ to Modulate Intrinsic Neuronal Excitability
Tabuchi, M., Lone, S. R., Liu, S., Liu, Q., Zhang, J., Spira, A. P., & Wu, M. N. (2015) · Current Biology · doi:10.1016/j.cub.2015.01.016 · Cited by 165 · see citing works
Harris, S. S., Wolf, F., De Strooper, B., & Busche, M. A. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.005 · Cited by 161 · see citing works
The APOE ɛ4 allele modulates brain white matter integrity in healthy adults
Heise, V, Filippini, N., Ebmeier, K. P., & Mackay, C. E. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.90 · Cited by 152 · see citing works
Evidence of Neuronal Compensation During Episodic Memory in Subjective Memory Impairment
Erk, S. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.80 · Cited by 147 · see citing works
Bosma, I., Douw, L., Bartolomei, F., Heimans, J. J., van Dijk, B. W., Postma, T. J., Stam, C. J., Reijneveld, J. C., & Klein, M. (2008) · Neuro-Oncology · doi:10.1215/15228517-2008-034 · Cited by 145 · see citing works
Yew, B., Nation, D. A., & Initiative, F. T. A. D. N. (2017) · Brain · doi:10.1093/brain/awx112 · Cited by 133 · see citing works
LANGE, K. L., BONDI, M. W., SALMON, D. P., GALASKO, D., DELIS, D. C., THOMAS, R. G., & THAL, L. J. (2002) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617702870096 · Cited by 129 · see citing works
Cacciaglia, R., Molinuevo, J. L., Falcón, C., Brugulat‐Serrat, A., Sánchez‐Benavides, G., Gramunt, N., Esteller, M., Morán, S., Minguillón, C., Fauria, K., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.01.016 · Cited by 124 · see citing works
Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline
Leal, S. L., Landau, S. M., Bell, R. K., & Jagust, W. J. (2017) · eLife · doi:10.7554/elife.22978 · Cited by 117 · see citing works
Puzzling Out Synaptic Vesicle 2 Family Members Functions
Bartholome, O., Van den Ackerveken, P., Sánchez Gil, J., de la Brassinne Bonardeaux, O., Leprince, P., Franzen, R., & Rogister, B. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00148 · Cited by 107 · see citing works
Deeny, S. P., Poeppel, D., Zimmerman, J. B., Roth, S. M., Brandauer, J., Witkowski, S., Hearn, J. W., Ludlow, A. T., Contreras-Vidal, J. L., Brandt, J., et al. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2008.02.007 · Cited by 107 · see citing works
Altered deactivation in individuals with genetic risk for Alzheimer's disease
Persson, J., Lind, J., Larsson, A., Ingvar, M., Sleegers, K., Van Broeckhoven, C., Adolfsson, R., Nilsson, L.-G., & Nyberg, L. (2008) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2008.01.026 · Cited by 102 · see citing works
APOE related alterations in cerebral activation even at college age
Scarmeas, N. (2005) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.053645 · Cited by 97 · see citing works
Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial
Lindbergh, C. A., Renzi-Hammond, L. M., Hammond, B. R., Terry, D. P., Mewborn, C. M., Puente, A. N., & Miller, L. S. (2018) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617717000534 · Cited by 94 · see citing works
Cavanagh, C., Tse, Y. C., Nguyen, H.-B., Krantic, S., Breitner, J. C. S., Quirion, R., & Wong, T. P. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.009 · Cited by 79 · see citing works
Cai, W., Li, L., Sang, S., Pan, X., & Zhong, C. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-022-00985-9 · Cited by 83 · see citing works
Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging
Papenberg, G., Salami, A., Persson, J., Lindenberger, U., & Bäckman, L. (2015) · Neuropsychology Review · doi:10.1007/s11065-015-9279-8 · Cited by 39 · see citing works
Dietary supplementation of creatine monohydrate reduces the human fMRI BOLD signal
Hammett, S. T., Wall, M. B., Edwards, T. C., & Smith, A. T. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.05.054 · Cited by 38 · see citing works
O'Dwyer, L., Lamberton, F., Matura, S., Scheibe, M., Miller, J., Rujescu, D., Prvulovic, D., & Hampel, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0036024 · Cited by 34 · see citing works
Apolipoprotein E ε4-related thickening of the cerebral cortex modulates selective attention
Espeseth, T., Westlye, L. T., Walhovd, K. B., Fjell, A. M., Endestad, T., Rootwelt, H., & Reinvang, I. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.12.027 · Cited by 32 · see citing works
Diffusion tensor magnetic resonance imaging of the brain in app transgenic mice: A cohort study.
Müller, H.-P., Kassubek, J., Vernikouskaya, I., Ludolph, A. C., Stiller, D., & Rasche, V. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067630 · Cited by 22 · see citing works
Meijboom, R., Steketee, R. M. E., Ham, L. S., van der Lugt, A., van Swieten, J. C., & Smits, M. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160564 · Cited by 17 · see citing works
APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons
Budny, V., Knöpfli, Y., Meier, D., Zürcher, K., Bodenmann, C., Peter, S. L., Müller, T., Tardy, M., Cortijo, C., & Tackenberg, C. (2024) · Cells · doi:10.3390/cells13141207 · Cited by 15 · see citing works
Harrison, T. M., & Bookheimer, S. Y. (2016) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2015.09.003 · Cited by 12 · see citing works
Self-citation
- Authors
- Bookheimer, S. Y., Strojwas, M. H., Cohen, M. S., Saunders, A. M., Pericak-Vance, M. A., Mazziotta, J. C., & Small, G. W.
- Affiliations
- University of California, Los Angeles (US)
- Neurology, Inc (US)
- Duke Medical Center (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2000-08-17
- Volume
- 343
- Issue
- 7
- Pages
- 450-456
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2831477
- OpenAlex
- W2060629467
- Cited by
- 1,328
- References
- 35
- Citations by year
- 2026: 27 · 2025: 20 · 2024: 33 · 2023: 42 · 2022: 31 · 2021: 40 · 2020: 33 · 2019: 37 · 2018: 42 · 2017: 38 · 2016: 37 · 2015: 59 · 2014: 58 · 2013: 67 · 2012: 53
- FWCI
- 29.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- Ahmanson Foundation
- National Institute on Aging (AG-13308, P50AG005128, R01AG013308, P60AG011268, P30AG010123, U24AG021886)
- National Institute of Mental Health (MH52453, R01MH052453)
- National Institute of Neurological Disorders and Stroke (P01NS026630, R01NS031153)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neurobiology of Language and Bilingualism
- Keywords
- Alzheimer's disease, APOE ε4, apolipoprotein E, genetic risk, brain activation, memory, hippocampus, memory decline, older adults, functional MRI, APOE genotyping, prefrontal cortex, parietal cortex
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Brain Mapping, Female, Heterozygote, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Memory, Middle Aged, Neuropsychological Tests, Apolipoprotein E3, Apolipoprotein E4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
