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Artificial neural networks and artificial organisms can predict alzheimer pathology in individual patients only on the basis of cognitive and functional status

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Abstract

Data from several studies have pointed out the existence of a strong correlation between Alzheimer’s disease (AD) neuropathology and cognitive state. However, because of their highly complex and nonlinear relationship, it has been difficult to develop a predictive model for individual patient classification through traditional statistical approaches. When exposed to complex data sets, artificial neural networks (ANNs) can recognize patterns, learn the relationship of different variables, and address classification tasks. To predict the results of postmortem brain examinations, we applied ANNs to the Nun Study data set, a longitudinal epidemiological study, which includes annual cognitive and functional evaluation. One hundred seventeen subjects from the study participated in this analysis. We determined how demographic data and the cognitive and functional variables of each subject during the last year of her life could predict the presence of brain pathology expressed as Braak stages, neurofibrillary tangles (NFTs) and neuritic plaques (NPs) count in the neocortex and hippocampus, and brain atrophy. The result of this analysis was then compared with traditional statistical models. ANNs proved to be better predictors than Linear Discriminant Analysis in all experimentations (+ ∼10% in overall accuracy), especially when assembled in Artificial Organisms (+ ∼20% in overall accuracy). Demographic, cognitive, and clinical variables were better predictors of tangles count in the neocortex and in the hippocampus when compared to NPs count. These findings strengthen the hypothesis that neurofibrillary pathology may represent the major anatomic substrate of the cognitive impairment found in AD.

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References

  • Arriagada, P., Growdon, J., Hedley-Whyte E., and Hyman, B. (1992a) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology 42, 631–639.

    CAS  Google Scholar 

  • Arriagada, P., Marzloff, K., and Hyman, B. (1992b) Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer’s disease. Neurology 42, 1681–1688.

    CAS  Google Scholar 

  • Braak, H. and Braak, E. (1991) Neuropathological staging of Alzheimer related changes. Acta Neuropathol. 82:239–259.

    Article  CAS  Google Scholar 

  • Bridle, J. S. (1989) Probabilistic Interpretation of Feedforward Classification Network Outputs, with Relationships to Statistical Pattern Recognition. In: Neuro-Computing: Algorithms, Architectures. Fogelman-Soulié, F. and Hérault, J. (eds.) Springer-Verlag, New York.

    Google Scholar 

  • Buscema M. (1998a) Artificial neural networks. (Special Issue Vol. I, Theory) Subst. Use Misuse Vol. 33, No. 1.

  • Buscema M. (1998b) Artificial neural networks. (Special Issue Vol. II, Models) Subst. Use Misuse Vol. 33, No. 1.

  • Buscema, M. (1999) Reti neurali artificiali e sistemi sociali complessi, Vol. 1, Teoria e modelli, Franco Angeli (eds.) Milano.

  • Buscema, M. (1999–2003) Supervised ver. 6.45, Semeion Software, no. 12 Rome.

  • Buscema, M. and Sacco PL. (2000) Feedforward networks in financial predictions: the future that modifies the present, Expet. Syst. Vol. 17, no. 3, 149–170

    Article  Google Scholar 

  • Buscema, M., Breda, M., and Terzi, S. (2000) Sine Net, Rome, Semeion Technical Paper, no. 21.

  • Buscema, M. (2001a) T&T: a new pre-processing tool for non linear dataset. Rome, Semeion Technical Paper, no. 25.

  • Buscema, M. (2001b) I.S. (Input Selection) ver. 1.0, Semeion Software, no. 17 Rome.

  • Buscema, M. (2001–2002) T&T (Training & Testing) ver. 1.0, Semeion Software, no. 16 Rome.

  • Buscema, M. (2002) A brief overview and introduction to artificial neural networks, Subst. Use Misuse (Special Issue on the Middle Eastern Summer Institute on Drug Use, Proceedings: 1997–1999) 37 (8–10), 1093–1148.

    Google Scholar 

  • Buscema, M. (2004) Genetic doping algorithm (GenD). theory and application, Expet Syst. Vol. 21, n. 2, 63–79.

    Article  Google Scholar 

  • Dietterich, T. (1998) Approximate statistical test for comparing supervised classification learning algorithms, Neural Comput. Vol. 10, 1895–1923.

    Article  Google Scholar 

  • Giannakopoulos, P., Herrmann, F. R., Bussiere, T, et al. (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease, Neurol. 60: 1495–1500.

    CAS  Google Scholar 

  • Giannakopoulos, P., Hof, P., Giannakopoulos, A. S., Herrmann, F., Michel, J. P., and Bouras, C. (1995) Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of very old patients, Arch. Neurol. 52: 1150–1160.

    CAS  Google Scholar 

  • Guillozet, A. L., Weintraub, S., Mash, D. C., and Mesulam, M. M. (2003) Neurofibrillary tangles, amyloid, and memory in aging and mild cognitive impairment. Arch. Neurol. 60: 729–736.

    Article  Google Scholar 

  • Mecocci, P., Grossi, E., Buscema, M., et al. (2002) Use of artificial networks in clinic trias: a pilot study to predict responsiveness to Donepezil in Alzheimer’s disease, J. Am. Geriatr. Soc. Vol. 50 no. 11, 1857–1860.

    Article  Google Scholar 

  • Morris, J. C., Heyman, A., Mohs, R. C., et al. (1989) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part I. Clinical ana neuropsychological assessment of Alzheimer’s disease, Neurology 39: 1159–1165.

    CAS  Google Scholar 

  • Petersen, R. C. (2000) Mild cognitive impairment: transition between aging and Alzheimer’s disease, Neurologia, 15(3):93–101.

    CAS  Google Scholar 

  • Price, J., Davis, P., Morris, J., and White, D. (1991) The distribution of tangles, plaques, and related immunohistochemical markers in healthy aging and Alzheimer’s disease, Neurobiol. Aging 12:295–312.

    Article  CAS  Google Scholar 

  • Price, J. and Morris, J. (1999) Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease, Ann. Neurol. 45: 358–368.

    Article  CAS  Google Scholar 

  • Riley, K. P., Snowdon, D. A., and Markesbery, W. R. (2002) Alzheimer’s neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study, Ann. Neurol. 51: 567–577.

    Article  Google Scholar 

  • Snowdon, D. A., Kemper, S. J., Morrimer, J. A., et al. (1996) Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life: findings from the Nun Study, JAMA 275: 528–532.

    Article  CAS  Google Scholar 

  • Vomveg, T. W., Buscema, M, Kauczor, H. U., et al. (2003) Improved artificial neural networks prediction of malignancy of lesions in contrast-enhanced MR-mammography, Med. Phys. Vol. 30 no. 9, 2350–2359.

    Article  Google Scholar 

Suggested Readings

  • Buscema, M. (1995) Self-reflexive networks. theory, topology, applications. Qual. Quant. Int. J. Melhodol. 29(4), 339–403.

    Article  Google Scholar 

  • Davis, D., Schmitt, F., Wekstein, D., and Markesbery, W. (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects, J. Neuropathol. Exp. Neurol. 58: 376–388.

    CAS  Google Scholar 

  • Petersen, R. C., Parisi, J. E., Johonson, K. A., et al. (1997) Neuropathological findings in patients with mild cognitive impairment, Neurology 48: A102.

  • Rumelhart, D. E. and McClelland, J. L. (1986) Parallel Distributed Processing, The MIT Press, Cambridge, MA.

    Google Scholar 

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Buscema, M., Grossi, E., Snowdon, D. et al. Artificial neural networks and artificial organisms can predict alzheimer pathology in individual patients only on the basis of cognitive and functional status. Neuroinform 2, 399–415 (2004). https://doi.org/10.1385/NI:2:4:399

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