Correspondence amongst the PENO Test Battery Cognitive Results and Hippocampal Lesions in Alzheimer’s Disease
Author(s)
Rojas Karla,
Díaz Alfonso,
Espinosa Blanca,
Montaño Luis Felipe,
Dilhuydy Hugo,
Geraux Francine,
Joanette Yves,
Robitaille Yves,
Guevara Jorge*
Affiliation(s)
Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía “M.V.S.”, México DF, México. Departamento de Farmacia, Facultad de Ciencias Químicas, BUAP, Puebla, México. Departamento Bioquímica, INER, México DF, México. Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, México DF, México. Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, Montréal, Canadá. Départament de Pathologie, H?pital Ste-Justine, Montreal, Canadá . Departamento de Bioquímica, Facultad de Medicina, UNAM, México DF, México.
Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía “M.V.S.”, México DF, México. Departamento de Farmacia, Facultad de Ciencias Químicas, BUAP, Puebla, México. Departamento Bioquímica, INER, México DF, México. Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, México DF, México. Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, Montréal, Canadá. Départament de Pathologie, H?pital Ste-Justine, Montreal, Canadá . Departamento de Bioquímica, Facultad de Medicina, UNAM, México DF, México.
ABSTRACT
Alzheimer’s disease (AD) is characterized by a decline of cognitive functions. Distinctive histopathological hallmarks are neuritic plaques, neurofibrillary tangles, and synaptic alterations. Abnormally enlarged synaptic structures called “Meganeurite clusters” have been linked to plasticity changes. The aims of this study were to determine if cognitive impairment was related to specific neuritic and synaptic degeneration processes in patients with AD, and if the results of a cognitive test could be correlated with the histopathological damage. The neuropsychological evaluation obtained by the Protocole d’evaluation neuropsychologique optimal (PENO) test battery was used in live AD and control individuals. The histopathological evaluation of their brain after their death was carried out with specific polyclonal and monoclonal antibodies to Aβ, pTau protein, synaptophysin, and GAP-43. Images were obtained by confocal microscopy. The results showed a significant difference between healthy controls and Alzheimer’s patients in neuropsychological evaluation and histopathological hallmarks expression. The most significant positive correlation in AD patients was between memory and language results with the PENO test and the presence of Aβ +pTau+ plaques in the hippocampus. An interesting negative correlation was between cognitive impairment and the presence of Meganeuritic clusters, considered as “plasticity” markers. These results strongly supported the use of the PENO battery test to evaluate the progression of cognitive impairment in AD prone individuals and patients due to the strong correlation of the test results with histopathological brain lesions characteristic of Alzheimer’s disease.
KEYWORDS
Cognitive Decline, Neuropsychological Evaluation, Synapsis, Plasticity, Alzheimer’s Disease
Cognitive Decline, Neuropsychological Evaluation, Synapsis, Plasticity, Alzheimer’s Disease
Cite this paper
Karla, R. , Alfonso, D. , Blanca, E. , Felipe, M. , Hugo, D. , Francine, G. , Yves, J. , Yves, R. and Jorge, G. (2014) Correspondence amongst the PENO Test Battery Cognitive Results and Hippocampal Lesions in Alzheimer’s Disease. Advances in Aging Research, 3, 239-251. doi: 10.4236/aar.2014.33033.
Karla, R. , Alfonso, D. , Blanca, E. , Felipe, M. , Hugo, D. , Francine, G. , Yves, J. , Yves, R. and Jorge, G. (2014) Correspondence amongst the PENO Test Battery Cognitive Results and Hippocampal Lesions in Alzheimer’s Disease. Advances in Aging Research, 3, 239-251. doi: 10.4236/aar.2014.33033.
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[1] Kotze, M.J. and Van Rensburg, S.J. (2012) Pathology Supported Genetic Testing and Treatment of Cardiovascular Disease in Middle Age for Prevention of Alzheimer’s Disease. Metabolic Brain Disease, 27, 255-266.
http://dx.doi.org/10.1007/s11011-012-9296-8 [2] Slavin, M.J., Mattingley, J.B., Bradshaw, J.L. and Storey, E. (2002) Local-Global Processing in Alzheimer’s Disease: An Examination of Interference, Inhibition and Priming. Neuropsychologia, 40, 1173-1186.
http://dx.doi.org/10.1016/S0028-3932(01)00225-1 [3] Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975) “Mini-Mental State”. A Practical Method for Grading the Cognitive State of Patients for the Clinician. Journal of Psychiatric Research, 12, 189-198.
http://dx.doi.org/10.1016/0022-3956(75)90026-6 [4] 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. Archives of Neurology, 56, 303-308.
http://dx.doi.org/10.1001/archneur.56.3.303 [5] Joanette, Y., Ska, B., Poissant, A., Belleville, S., Lecours, A.R. and Peretz, I. (1995) Evaluation neuropsychologique dans la demence de type alzheimers: Un Compromise Optimal. Lánné gérontogique, 9, 175-189. [6] Terry, R.D., Masliah, E., Salmon, D.P., Butters, N., De Teresa, R., Hill, R., Hansen, L.A. and Katzman, R. (1991) Physical Basis of Cognitive Alterations in Alzheimer’s Disease: Synapse Loss Is the Major Correlate of Cognitive Impairment. Annals of Neurology, 30, 572-580.
http://dx.doi.org/10.1002/ana.410300410 [7] Mark, R.J., Fuson, K.S. and May, P.C. (1999). Characterization of 8-Epiprostaglandin F2alpha as a Marker of Amyloid Beta-Peptide-Induced Oxidative Damage. Journal of Neurochemistry, 72, 1146-1153.
http://dx.doi.org/10.1046/j.1471-4159.1999.0721146.x [8] Maccioni, R.B., Farias, G., Morales, I. and Navarrete, L. (2010) The Revitalized Tau Hypothesis on Alzheimer’s Disease. Archives of Medical Research, 41, 226-231.
http://dx.doi.org/10.1016/j.arcmed.2010.03.007 [9] Arriagada, P.V., Growdon, H.J., Hedley-Whyte, T. and Hyman, B.T. (1992) Neurofibrillary Tangles but Not Senile Plaques Parallel Duration and Severity of Alzheimer’s Disease. Neurology, 42, 631-639.
http://dx.doi.org/10.1212/WNL.42.3.631 [10] Carter, M.D., Simms, G.A. and Weaver, D.F. (2010) The Development of News Therapeutics for Alzheimer’s Disease. Clinical Pharmacology & Therapeutics, 88, 475-486.
http://dx.doi.org/10.1038/clpt.2010.165 [11] Espinosa, B., Zenteno, R., Mena, R., Robitaille, Y., Zenteno, E. and Guevara, J. (2001) O-Glycosylation in Sprouting Neurons in Alzheimer Disease, Indicating Reactive Plasticity. Journal of Neuropathology Experimental Neurology, 60, 441-448. [12] Guevara, J., Dilhuydy, H., Espinosa, B., Delacourte, A., Quirion, R., Mena, R., Joanette, Y., Zenteno, E. and Robitaille, Y. (2004) Coexistence of Reactive Plasticity and Neurodegeneration in Alzheimer Diseased Brains. Histology and Histopathology, 19, 1075-1084. [13] Johnson, D.K., Storandt, M., Morris, J.C. and Galvin, J.E. (2009) Longuitudinal Study of the Transition from Healthy Aging to Alzheimer Disease. Archives of Neurology, 66, 1254-1259.
http://dx.doi.org/10.1001/archneurol.2009.158 [14] Joanette, Y., Poissant, A., Ska, B. and Fontaine, F. (1990) Protocole D’Evaluation Neuropsychologique Optimal (PENO). Montreal: Laboratoire Theophile-Alajouanine, Centre de recherché du Centre hospitalier Cótes-des-Neiges. [15] Frances, A., Mack, A.H., First, M.B., Widiger, T.A., Ross, R., Forman, L. and Davis, W.W. (1994) DMS-IV Meets Philosophy. Journal of Medicine and Philosophy, 19, 207-218.
http://dx.doi.org/10.1093/jmp/19.3.207 [16] Khachaturian, Z.S. (1985). Diagnosis of Alzheimer’s Disease. Archives of Neurology, 42, 1097-1105.
http://dx.doi.org/10.1001/archneur.1985.04060100083029 [17] Mirra, S.S., Heyman, A., McKeel, D., Sumi, S.M., Crain, B.J., Brownlee, L.M., Vogel, F.S., Hughes, J.P., van Belle, G. and Berg, L. (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standarization of the Neuropathologic Assessment of Alzheimer’s Disease. Neurology, 41, 479-486.
http://dx.doi.org/10.1212/WNL.41.4.479 [18] Guevara, J., Espinosa, B., Zenteno, E., Vazquez, L., Luna, J., Perry, G. and Mena, R. (1998) Altered Glycosylation Pattern of Proteins in Alzheimer Disease. Journal of Neuropathology & Experimental Neurology, 57, 905-914.
http://dx.doi.org/10.1097/00005072-199810000-00003 [19] D’Amelio, M. and Rossini, P.M. (2012) Brain Excitability and Connectivity of Neuronal Assemblies in Alzheimer’s Disease: From Animal Models to Human Findings. Progress in Neurobiology, 99, 42-60.
http://dx.doi.org/10.1016/j.pneurobio.2012.07.001 [20] Petersen, R.C., Doody, R., Kurz, A., Mohs, R.C., Morris, J.C., Rabins, P.V., Ritchie, K., Rossor, M., Thal L. and Winblad, B. (2001) Current Concepts in Mild Cognitive Impairment. Archives of Neurology, 58, 1985-1992.
http://dx.doi.org/10.1001/archneur.58.12.1985 [21] Zeineh, M.M., Holdsworth, S., Skare, S., Atlas, S.W. and Bammer, R. (2012) Ultra-High Resolution Diffusion Tensor Imaging of the Microscopic Pathways of the Medial Temporal Lobe. Neuroimage, 62, 2065-2082.
http://dx.doi.org/10.1016/j.neuroimage.2012.05.065 [22] Anoop, A., Singh, P.K., Jacob, R.S. and Maji, S.K. (2010) CSF Biomarkers for Alzheimer’s Disease Diagnosis. International Journal of Alzheimer’s Disease, 2010, 1-12.
http://dx.doi.org/10.4061/2010/606802 [23] Levy, S., McConville, M., Lazaro, G.A. and Averback, P. (2007) Competitive ELISA Studies of Neural Thread Protein in Urine in Alzheimer’s disease. Journal of Clinical Laboratory Analysis, 21, 24-33.
http://dx.doi.org/10.1002/jcla.20159 [24] Thongboonkerd, V. (2007) Practical Points in Urinary Proteomics. Journal of Proteome Research, 6, 3881-3890.
http://dx.doi.org/10.1021/pr070328s [25] Gómez-Ravetti, M., Rosso, O.A., Berretta, R. and Moscato, P. (2010). Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus Gene Expression Profiles in Alzheimer’s Disease. PLoS One, e10153.
http://dx.doi.org/10.1371/journal.pone.0010153 [26] Iqbal, K. and Grundke-Iqbal, I. (2008) Alzheimer Neurofibrillary Degeneration: Significance, Etiopathogenesis, Therapeutics and Prevention. Journal of Cellular and Molecular Medicine, 12, 38-55.
http://dx.doi.org/10.1111/j.1582-4934.2008.00225.x [27] Matenia, D. and Mandelkow, E.M. (2009) The Tau of MARK: A Polarized View of the Cytoskeleton. Trends in Biochemical Sciences, 34, 332-342.
http://dx.doi.org/10.1016/j.tibs.2009.03.008 [28] Kosik, K.S. (1993) The Molecular and Cellular Biology of Tau. Brain Pathology, 3, 39-43.
http://dx.doi.org/10.1111/j.1750-3639.1993.tb00724.x [29] Vana, L., Kanaan, N.M., Uqwu, I.C., Wuu, J., Mufson, E.J. and Binder, L.I. (2011) Progression of Tau Pathology in Cholinergic Basal Forebrain Neurons in Mild Cognitive Impairment and Alzheimer’s Disease. American Journal of Pathology, 179, 2533-2550.
http://dx.doi.org/10.1016/j.ajpath.2011.07.044 [30] Price, J.L., McKeel Jr., D.W., Buckles, V.D., Roe, C.M., Xiong, C., Grundman, M., Hansen, L.A., Petersen, R.C., Parisi, J.E., Dickson, D.W., Smith, C.D., Davis, D.G., Schmitt, F.A., Markesbery, W.R., Kaye, J., Kurlan, R., Hulette, C., Kurland, B.F., Higdon, R., Kukull, W. and Morris, J.C. (2009) Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease. Neurobiology of Aging, 30, 1026-1036.
http://dx.doi.org/10.1016/j.neurobiolaging.2009.04.002 [31] Janocko, N.J., Brodersen, K.A., Soto-Ortolaza, A.I., Ross, O.A., Liesinger, A.M., Duara, R., Graff-Radford, N.R., Dickson, D.W. and Murray, M.E. (2012) Neuropathologically Defined Subtypes of Alzheimer’s Disease Differ Significantly from Neurofibrillary Tangle-Predominant Dementia. Acta Neuropathologica, 124, 681-692.
http://dx.doi.org/10.1007/s00401-012-1044-y [32] Serrano-Pozo, A., Frosch, M.P., Masliah, E. and Hyman, B.T. (2011) Neuropathological Alterations in Alzheimer Disease. Cold Spring Harbor Perspectives in Medicine, 1, 1-23.
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