The metabolic topography of normal aging
Abstract
Normal aging is associated with the degeneration of specific neural systems. We used [18F] fluorodeoxyglucose (FDG)/positron emission tomography (PET) and a statistical model of regional covariation to explore the metabolic topography of this process. We calculated global and regional metabolic rates for glucose (GMR and rCMRglc) in two groups of normal subjects studied independently on different tomographs: Group 1--130 normal subjects (62 men and 68 women; range 21-90 years); Group 2--20 normal subjects (10 men and 10 women; range 24-78 years). In each of the two groups, the Scaled Subprofile Model (SSM) was applied to rCMRglc data to identify specific age-related profiles. The validity of these profiles as aging markers was assessed by correlating the associated subject scores with chronological age in both normal populations. SSM analysis disclosed two significant topographic profiles associated with aging. The first topographic profile, extracted in an analysis of group 1 normals, was characterized by relative frontal hypometabolism associated with covariate metabolic increases in the parietooccipital association areas, basal ganglia, mid-brain, and cerebellum. Subject scores for this profile correlated significantly with age in both normal groups (R2 = 0.48 and 0.33, p < 0.0001 for groups 1 and 2, respectively). Because of clinical similarities between normal motoric aging and parkinsonism, we explored the possibility of shared elements in the metabolic topography of both processes. We performed a combined group SSM analysis of the 20 group 2 normals and 22 age-matched Parkinson's disease patients, and identified another aging-related topographic profile. This profile was characterized by relative basal ganglia hypermetabolism associated with covariate decreases in frontal premotor cortex. Subject scores for this profile also correlated significantly with age in both normal groups (group 1: R2 = 0.30, p < 0.00001; group 2: R2 = 0.59, p < 0.01). Healthy aging is associated with reproducible topographic covariation profiles associated with specific neural systems. FDG/PET may provide a useful metabolic marker of the normal aging process.
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Most previous studies have reported decreased activity in frontal areas and the anterior cingulate gyrus with age.
“Most previous studies have reported decreased activity in frontal areas and the anterior cingulate gyrus with age, using SPECT [44], [ 15 O]H2O-PET [5,12,42,48,54] or 18 FDG-PET [28,32,49,58,86,87,89].”
From Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging (2009) · cites this paper as [49]
Less metabolic decrease was found within the inferior temporal (fusiform cortex) and occipital areas (calcarine area and lingual gyrus), consistent with the literature.
“Consistent with the literature, less metabolic decrease was found within the inferior temporal (fusiform cortex) and occipital areas (calcarine area and lingual gyrus) [32,49,58,86].”
From Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging (2009) · cites this paper as [49]
Cites
The attention system of the human brain
Posner, M. I., & Petersen, S. E. (1990) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.13.030190.000325 · Cited by 8,070 · see citing works
The cholinergic hypothesis of geriatric memory dysfunction
Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982) · Science · doi:10.1126/science.7046051 · Cited by 5,545 · see citing works
AGEING AND PARKINSON'S DISEASE: SUBSTANTIA NIGRA REGIONAL SELECTIVITY
FEARNLEY, J. M., & LEES, A. J. (1991) · Brain · doi:10.1093/brain/114.5.2283 · Cited by 3,529 · see citing works
A cortical network for directed attention and unilateral neglect
Mesulam, M. ‐. (1981) · Annals of Neurology · doi:10.1002/ana.410100402 · Cited by 2,498 · see citing works
Bunney, W. E., Hippius, H., Laakmann, G., & Schmauß, M. (1990) · Springer eBooks · doi:10.1007/978-3-642-74034-3 · Cited by 1,523 · see citing works
CEREBRAL BLOOD FLOW, BLOOD VOLUME AND OXYGEN UTILIZATION
Leenders, K. L., Perani, D., Lammertsma, A. A., Heather, J. D., Buckingham, P. D., Jones, T., Healy, M. J. R., GIBBS, J. M., WISE, R. J. S., Hatazawa, J., et al. (1990) · Brain · doi:10.1093/brain/113.1.27 · Cited by 1,094 · see citing works
Observations on the brains of non-demented old people
Tomlinson, B. E., Blessed, G., & Roth, M. (1968) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(68)90154-8 · Cited by 681 · see citing works
Aging and Extrapyramidal Function
McGeer, P. L., McGeer, E. G., & Suzuki, J. S. (1977) · Archives of Neurology · doi:10.1001/archneur.1977.00500130053010 · Cited by 648 · see citing works
REACTION TIME IN PARKINSON'S DISEASE
Evarts, E. V., Teräväinen, H., & Calne, D. B. (1981) · Brain · doi:10.1093/brain/104.1.167 · Cited by 515 · see citing works
Common Principal Components and Related Multivariate Models.
Boik, R. J., & Flury, B. N. (1990) · Journal of the American Statistical Association · doi:10.2307/2289562 · Cited by 474 · see citing works
The metabolic topography of parkinsonism
Eidelberg, D., Moeller, J. R., Dhawan, V., Spetsieris, P., Takikawa, S., Ishikawa, T., Chaly, T., Robeson, W., Margouleff, D., Przedborski, S., et al. (1994) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1994.99 · Cited by 455 · see citing works
Self-citationDecreases in regional cerebral blood flow with normal aging
Martin, A. J., Friston, K. J., Colebatch, J. G., & Frackowiak, R. S. J. (1991) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1991.121 · Cited by 393 · see citing works
Deecke, L., & Kornhuber, H. H. (1978) · Brain Research · doi:10.1016/0006-8993(78)90561-9 · Cited by 347 · see citing works
Striatal dopamine deficiency in parkinson's disease: Role of aging
Scherman, D., Desnos, C., Darchen, F., Pollak, P., Javoy-Agid, F., & Agid, Y. (1989) · Annals of Neurology · doi:10.1002/ana.410260409 · Cited by 284 · see citing works
Nigrostriatal function in humans studied with positron emission tomography
Martin, W. R. W., Palmer, M. R., Patlak, C. S., & Calne, D. B. (1989) · Annals of Neurology · doi:10.1002/ana.410260407 · Cited by 282 · see citing works
Inferior parietal lobule. Divergent architectonic asymmetries in the human brain.
Eidelberg, D., & Galaburda, A. (1984) · Archives of Neurology · doi:10.1001/archneur.1984.04050190049013 · Cited by 278 · see citing works
Self-citationRegional Cerebral Oxygen Consumption, Blood Flow, and Blood Volume in Healthy Human Aging
Marchal, G., Rioux, P. P., Petit-Taboué, M.-C., Sette, G., Travère, J.-M., Poec, C. L., Courtheoux, P., Derlon, J.-M., & Baron, J. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530340029014 · Cited by 271 · see citing works
Creasey, H. M., & Rapoport, S. I. (1985) · Annals of Neurology · doi:10.1002/ana.410170103 · Cited by 250 · see citing works
Regional Cerebral Blood Flow in Mood Disorders
Sackeïm, H. A. (1990) · Archives of General Psychiatry · doi:10.1001/archpsyc.1990.01810130062009 · Cited by 247 · see citing works
Duara, R., Margolin, R. A., Robertson‐Tchabo, E. A., London, E. D., Schwartz, M. L., Renfrew, J. W., Koziarz, B., Sundaram, M., GRADY, C., Moore, A. M., et al. (1983) · Brain · doi:10.1093/brain/106.3.761 · Cited by 228 · see citing works
Self-citationMoeller, J. R., Strother, S. C., Sidtis, J. J., & Rottenberg, D. A. (1987) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1987.118 · Cited by 214 · see citing works
Self-citationMurphy, D., DeCarli, C. S., Schapiro, M. B., Rapoport, S. I., & Horwitz, B. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530320063013 · Cited by 214 · see citing works
Eidelberg, D., Moeller, J. R., DHAWAN, V. M., Sidtis, J. J., Ginos, J. Z., Strother, S. C., Cedarbaum, J. M., Greene, P., Fahn, S., & Rottenberg, D. A. (1990) · Movement Disorders · doi:10.1002/mds.870050304 · Cited by 204 · see citing works
Self-citationMoeller, J. R., & Strother, S. C. (1991) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1991.47 · Cited by 184 · see citing works
Self-citationIntercorrelations of regional cerebral glucose metabolic rates in Alzheimer's disease
Horwitz, B., Grady, C. L., Schlageter, N. L., Duara, R., & Рапопорт, С. И. (1987) · Brain Research · doi:10.1016/0006-8993(87)91107-3 · Cited by 181 · see citing works
Self-citationYoshii, F., Barker, W. W., Chang, J. Y., Loewenstein, D., Apicella, A., Smith, D. D., Boothe, T. E., Ginsberg, M. D., Pascal, S., & Duara, R. (1988) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1988.112 · Cited by 168 · see citing works
Alexander, G. E., & Moeller, J. R. (1994) · Human Brain Mapping · doi:10.1002/hbm.460020108 · Cited by 159 · see citing works
Self-citationHigh-resolution PET studies in Alzheimer's disease.
Kumar, A. A., Schapiro, M. B., Grady, C., Haxby, J. V., Wagner, E., Salerno, J. A., Friedland, R. P., & Рапопорт, С. И. (1991) · PubMed · Cited by 154 · see citing works
Self-citationCerebral Metabolic Relationships for Selected Brain Regions in Healthy Adults
Metter, E. J., Riege, W. H., Kuhl, D. E., & Phelps, M. E. (1984) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1984.1 · Cited by 136 · see citing works
Assessment of disease severity in parkinsonism with fluorine-18-fluorodeoxyglucose and PET.
Eidelberg, D., Moeller, J. R., Ishikawa, T., DHAWAN, V. M., Spetsieris, P. G., Chaly, T., Robeson, W., Dahl, J., & Margouleff, D. (1995) · PubMed · Cited by 136 · see citing works
Self-citationCrossman, A. R., Mitchell, I. J., & Sambrook, M. A. (1985) · Neuropharmacology · doi:10.1016/0028-3908(85)90070-x · Cited by 121 · see citing works
Palombo, E., Porrino, L. J., Bankiewicz, K. S., Crane, A., Sokoloff, L., & Kopin, I. J. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-03-00860.1990 · Cited by 120 · see citing works
Fishman, L. M. (1990) · Topics in Geriatric Rehabilitation · doi:10.1097/00013614-199004000-00018 · Cited by 114 · see citing works
&NA; (1985) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198501000-00013 · Cited by 107 · see citing works
Age differences in intercorrelations between regional cerebral metabolic rates for glucose
Horwitz, B., Duara, R., & Rapoport, S. I. (1986) · Annals of Neurology · doi:10.1002/ana.410190111 · Cited by 103 · see citing works
Regional Correction of Positron Emission Tomography Data for the Effects of Cerebral Atrophy
Videen, T. O., Perlmutter, J. S., Mintun, M. A., & Raichle, M. E. (1988) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1988.113 · Cited by 98 · see citing works
Positron Emission Tomography and Computed Tomography Assessments of the Aging Human Brain
de Leon, M. J., GEORGE, A. E., Ferris, S. H., Christman, D. R., Fowler, J. S., Gentes, C. I., Brodie, J. D., Reisberg, ., & Wolf, A. P. (1984) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-198402000-00017 · Cited by 97 · see citing works
The effect of normal aging on patterns of local cerebral glucose utilization
Kuhl, D. E., Metter, E. J., Riege, W. H., & Hawkins, R. A. (1984) · Annals of Neurology · doi:10.1002/ana.410150726 · Cited by 87 · see citing works
de Leon, M. J., George, A. E., Tomanelli, J., Christman, D., Kluger, A., Miller, J., Ferris, S. H., Fowler, J., Brodie, J. D., van Gelder, P., et al. (1987) · Neurobiology of Aging · doi:10.1016/0197-4580(87)90070-4 · Cited by 79 · see citing works
Alterations in critical flicker frequency as a function of age and light:dark ratio.
McFarland, R. A., Warren, A. B., & Karis, C. (1958) · Journal of Experimental Psychology · doi:10.1037/h0049128 · Cited by 74 · see citing works
Matsuda, H., MAEDA, T., Yamada, M., et al. (1984) · Stroke · doi:10.1161/01.str.15.2.336 · Cited by 57 · see citing works
Readiness potential of cortical area 6 preceding self paced movement in Parkinson's disease.
Simpson, J. A., & Khuraibet, A. J. (1987) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.50.9.1184 · Cited by 54 · see citing works
Relation of measured brain glucose utilisation and cerebral atrophy in man.
Schlageter, N. L., Horwitz, B., Creasey, H. M., Carson, R. E., Duara, R., BERG, G. W., & Рапопорт, С. И. (1987) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.50.6.779 · Cited by 52 · see citing works
Spetsieris, P. G., DHAWAN, V. M., Takikawa, S., Margouleff, D., & Eidelberg, D. (1993) · IEEE Computer Graphics and Applications · doi:10.1109/38.180113 · Cited by 39 · see citing works
Self-citationAging of the Nigrostriatal Pathway in Humans
Calne, D. B., & Peppard, R. F. (1987) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100037847 · Cited by 30 · see citing works
Superpett 3000 time-of-flight PET tomograph: optimization of factors affecting quantitation
Robeson, W., DHAWAN, V. M., Takikawa, S., Babchyck, B., ZANZI, I., Margouleff, D., & Eidelberg, D. (1993) · IEEE Transactions on Nuclear Science · doi:10.1109/23.212329 · Cited by 26 · see citing works
Self-citationSensory Processes in Man During Maturity and Senescence
Corso, J. F. (1975) · Advances in behavioral biology · doi:10.1007/978-1-4684-0925-3_5 · Cited by 21 · see citing works
Grady, C. L. (1991) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1991.38 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
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Liang, W. S., Reiman, E. M., Valla, J., Dunckley, T., Beach, T. G., Grover, A., Niedzielko, T. L., Schneider, L. E., Mastroeni, D., Caselli, R., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709259105 · Cited by 585 · see citing works
Liu, F., Shi, J., Tanimukai, H., Gu, J., Gu, J., Grundke-Iqbal, I., Iqbal, K., & Gong, C.-X. (2009) · Brain · doi:10.1093/brain/awp099 · Cited by 439 · see citing works
Brain networks associated with cognitive reserve in healthy young and old adults
Stern, Y. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhh142 · Cited by 417 · 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
Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging
Kalpouzos, G., Chételat, G., Baron, J.-C., Landeau, B., Mevel, K., Godeau, C., Barré, L., Constans, J.-M., Viader, F., Eustache, F., et al. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.05.019 · Cited by 392 · see citing works
Liang, W. S., Dunckley, T., Beach, T. G., Grover, A., Mastroeni, D., Ramsey, K., Caselli, R. J., Kukull, W. A., McKeel, D., Morris, J. C., et al. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.00242.2007 · Cited by 309 · see citing works
The role of glucose transporters in brain disease: Diabetes and Alzheimer’s disease
Shah, K., DeSilva, S., & Abbruscato, T. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131012629 · Cited by 288 · see citing works
Petit-Taboué, M. C., Landeau, B., Desson, J. F., Desgranges, B., & Baron, J. C. (1998) · NeuroImage · doi:10.1006/nimg.1997.0318 · Cited by 221 · see citing works
Age-dependent changes in sleep EEG topography
Landolt, H.-P., & Borbély, A. A. (2001) · Clinical Neurophysiology · doi:10.1016/s1388-2457(00)00542-3 · Cited by 200 · see citing works
Berti (2014) · doi:10.1016/j.cpet.2013.10.006 · Cited by 152 · see citing works
Age, sex and laterality effects on cerebral glucose metabolism in healthy adults
Willis, M. W., Ketter, T. A., Kimbrell, T. A., George, M. S., Herscovitch, P., Danielson, A. L., Benson, B. E., & Post, R. M. (2002) · Psychiatry Research Neuroimaging · doi:10.1016/s0925-4927(01)00126-3 · Cited by 150 · see citing works
Brain FDG PET study of normal aging in Japanese: effect of atrophy correction
Yanase, D., Matsunari, I., Yajima, K., Chen, W., Fujikawa, A., Nishimura, S., Matsuda, H., & Yamada, M. (2005) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-005-1767-2 · Cited by 104 · see citing works
Tarantini, S., Tucsek, Z., Valcarcel-Ares, M. N., Toth, P., Gautam, T., Giles, C. B., Ballabh, P., Wei, J. Y., Wren, J. D., Ashpole, N. M., et al. (2016) · AGE · doi:10.1007/s11357-016-9931-0 · Cited by 98 · see citing works
Chételat, G., Landeau, B., Salmon, E., Yakushev, I., Bahri, M. A., Mézenge, F., Perrotin, A., Bastin, C., Manrique, A., Scheurich, A., et al. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.03.009 · Cited by 92 · see citing works
Aging and alexithymia association with reduced right rostral cingulate volume
Paradiso, S., Vaidya, J. G., McCormick, L. M., Jones, A., & Robinson, R. G. (2008) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31817e73b0 · Cited by 80 · see citing works
Reduced brain creatine in gyrate atrophy of the choroid and retina with hyperornithinemia
Näntö–Salonen, K., Komu, M., Lundbom, N., Heinänen, K., Alanen, A., Sipilä, I., & Simell, O. (1999) · Neurology · doi:10.1212/wnl.53.2.303 · Cited by 63 · see citing works
Karbe, H., Herholz, K., Weber-Luxenburger, G., Ghaemi, M., & Heiss, W.-D. (1998) · Brain and Language · doi:10.1006/brln.1997.1937 · Cited by 37 · see citing works
Visualizing the evolution of abnormal metabolic networks in the brain using PET
Spetsieris, P. G., Moeller, J. R., Dhawan, V., Ishikawa, T., & Eidelberg, D. (1995) · Computerized Medical Imaging and Graphics · doi:10.1016/0895-6111(95)00011-e · Cited by 23 · see citing works
Self-citation
- Authors
- Moeller, J. R., Ishikawa, T., Dhawan, V., Spetsieris, P., Mandel, F., Alexander, G. E., Grady, C., Pietrini, P., & Eidelberg, D.
- Affiliations
- New York State Psychiatric Institute (US)
- Departments of Neurology
- Cornell University (US)
- National Institutes of Health (US)
- Corresponding author
- Eidelberg, D.
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 1996-05
- Volume
- 16
- Issue
- 3
- Pages
- 385-398
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W1984294537
- Cited by
- 254
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 9 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 10
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- normal aging, brain glucose metabolism, frontal hypometabolism, premotor cortex, aging markers, Parkinson's disease, motor aging, FDG-PET
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Brain, Brain Mapping, Deoxyglucose, Female, Fluorine Radioisotopes, Humans, Male, Middle Aged, Models, Neurological, Parkinson Disease, Reference Values, Regression Analysis, Tomography, Emission-Computed, Fluorodeoxyglucose F18
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