Stereological quantification of the cerebellum in patients with Alzheimer's disease

Nonquantitative studies indicate that the cerebellum is neuropathologically affected in Alzheimer's disease; however, no quantitative studies on the subject have yet been conducted. Ten cerebella from elderly female subjects with severe Alzheimer's disease and 10 age- and gender-matched controls were examined. The cerebellum was divided into 5 regions and the Purkinje and granule cell number and density, cortical volume, molecular and granular layer volume and thickness, white matter volume, surface area, and the Purkinje cell gradient were stereologically estimated. There was no significant difference between the groups in Purkinje or granule cell number or density, and no overall difference in Purkinje cell gradient. However, there was a significant 12.7% reduction in total cerebellar volume in the Alzheimer's group and significant localized differences between the groups regarding other parameters. The relative lack of neuropathological changes in the cerebellum of severely demented Alzheimer's patients suggests that neuronal cell bodies on a global scale apparently still are intact.

[1]  J. Bower,et al.  Is the cerebellum sensory for motor's sake, or motor for sensory's sake: the view from the whiskers of a rat? , 1997, Progress in brain research.

[2]  Kinuko Suzuki,et al.  Atypical Alzheimer's disease with spastic paresis and ataxia , 1985, Annals of neurology.

[3]  H. J. G. GUNDERSEN,et al.  Some new, simple and efficient stereological methods and their use in pathological research and diagnosis , 1988, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[4]  G. Šimić,et al.  Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer's disease , 1997, The Journal of comparative neurology.

[5]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[6]  B. Pakkenberg,et al.  Optimizing sampling designs for volume measurements of components of human brain using a stereological method , 1989, Journal of microscopy.

[7]  A. Jackowski,et al.  Cerebellum and psychiatric disorders. , 2008, Revista Brasileira de Psiquiatria.

[8]  W. T. Thach,et al.  Posterior vermal split syndrome , 1998, Annals of neurology.

[9]  Yoshiro Okubo,et al.  Reduced volume of the cerebellar vermis in neuroleptic-naive schizophrenia , 2001, Biological Psychiatry.

[10]  Andrew King,et al.  Staging of Neurofibrillary Pathology in Alzheimer's Disease: A Study of the BrainNet Europe Consortium , 2008, Brain pathology.

[11]  P. Coleman,et al.  Dendritic growth in the aged human brain and failure of growth in senile dementia. , 1979, Science.

[12]  Philip Shaw,et al.  Cerebellar development and clinical outcome in attention deficit hyperactivity disorder. , 2007, The American journal of psychiatry.

[13]  C. Kawas,et al.  The CA1 Region of the Human Hippocampus Is a Hot Spot in Alzheimer's Disease , 2000, Annals of the New York Academy of Sciences.

[14]  Bente Pakkenberg,et al.  Measuring morphological and cellular changes in Alzheimer's dementia: a review emphasizing stereology. , 2005, Current Alzheimer research.

[15]  A. L. Leiner,et al.  The human cerebro-cerebellar system: its computing, cognitive, and language skills , 1991, Behavioural Brain Research.

[16]  K. Davis,et al.  The Alzheimer's disease assessment scale: an instrument for assessing treatment efficacy. , 1983, Psychopharmacology bulletin.

[17]  J. M. Anderson,et al.  A quantitative study of cerebral atrophy in old age and senile dementia , 1981, Journal of the Neurological Sciences.

[18]  H J Gundersen,et al.  Size of neocortical neurons in control subjects and in Alzheimer's disease , 2001, Journal of anatomy.

[19]  A. Hirano,et al.  Hirano bodies in the perikaryon of the Purkinje cell in a case of Alzheimer's disease , 2004, Acta Neuropathologica.

[20]  W. T. Thach Motor Learning and Synaptic Plasticity in the Cerebellum: On the specific role of the cerebellum in motor learning and cognition: Clues from PET activation and lesion studies in man , 1997 .

[21]  J. Schmahmann,et al.  The neuropsychiatry of the cerebellum — insights from the clinic , 2008, The Cerebellum.

[22]  Gloria Dal Forno,et al.  Cognitive decline strongly correlates with cortical atrophy in Alzheimer’s dementia , 1998, Neurobiology of Aging.

[23]  B. Ghetti,et al.  Cerebellar plaques in familial Alzheimer's disease (Gerstmann-Sträussler-Scheinker variant?) , 2004, Acta Neuropathologica.

[24]  Irene Daum,et al.  Cerebellar contributions to cognitive functions: A progress report after two decades of research , 2008, The Cerebellum.

[25]  B. Pakkenberg,et al.  No global neocortical nerve cell loss in brains from patients with senile dementia of Alzheimer's type , 1994, Neurobiology of Aging.

[26]  Alistair Burns,et al.  Observations on the brains of demented old people. B.E. Tomlinson, G. Blessed and M. Roth, Journal of the Neurological Sciences (1970) 11, 205–242; (1968) 7, 331–356 , 1997 .

[27]  C V Howard,et al.  The total number of neurons in the human neocortex unbiasedly estimated using optical disectors , 1990, Journal of microscopy.

[28]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[29]  B. Pakkenberg,et al.  Cerebral atrophy in AIDS: a stereological study , 2004, Acta Neuropathologica.

[30]  H. Gundersen Stereology of arbitrary particles * , 1986, Journal of microscopy.

[31]  J. Schmahmann An emerging concept. The cerebellar contribution to higher function. , 1991, Archives of neurology.

[32]  J. Schmahmann,et al.  The cerebellar cognitive affective syndrome. , 1998, Brain : a journal of neurology.

[33]  D. Marr A theory of cerebellar cortex , 1969, The Journal of physiology.

[34]  J Blumenthal,et al.  Brain Imaging of Attention Deficit/Hyperactivity Disorder , 2001, Annals of the New York Academy of Sciences.

[35]  B. Pakkenberg,et al.  No change in total length of white matter fibers in Alzheimer's disease , 2008, Neuroscience.

[36]  J. Troncoso,et al.  Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease , 1994, The Lancet.

[37]  J. Soares,et al.  The anatomy of mood disorders—review of structural neuroimaging studies , 1997, Biological Psychiatry.

[38]  J. Wegiel,et al.  Cerebellar atrophy in Alzheimer's disease—clinicopathological correlations , 1999, Brain Research.

[39]  P. Hof,et al.  A novel approach to non-biased systematic random sampling: A stereologic estimate of Purkinje cells in the human cerebellum , 2008, Brain Research.

[40]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[41]  S. DeKosky,et al.  Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity , 1990, Annals of neurology.

[42]  R. B. Frick,et al.  Psychiatric symptoms and cerebellar pathology. , 1983, The American journal of psychiatry.

[43]  L. Regeur,et al.  Increasing loss of brain tissue with increasing dementia: a stereological study of post‐mortem brains from elderly females , 2000, European journal of neurology.

[44]  J R Nyengaard,et al.  Tissue shrinkage and unbiased stereological estimation of particle number and size * , 2001, Journal of microscopy.

[45]  Stephan Arndt,et al.  The cerebellum plays a role in conscious episodic memory retrieval , 1999, Human brain mapping.

[46]  Roberto Sassi,et al.  Ressonância magnética estrutural nos transtornos afetivos , 2001 .

[47]  S. M. de la Monte,et al.  Quantitation of cerebral atrophy in preclinical and end‐stage alzheimer's disease , 1989, Annals of neurology.

[48]  H. Nasrallah,et al.  CEREBELLAR ATROPHY IN SCHIZOPHRENIA AND MANIA , 1981, The Lancet.

[49]  Bente Pakkenberg,et al.  Aging of the human cerebellum: A stereological study , 2003, The Journal of comparative neurology.

[50]  D. Salmon,et al.  Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment , 1991, Annals of neurology.

[51]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[52]  Paul D. Coleman,et al.  Neuron numbers and dendritic extent in normal aging and Alzheimer's disease , 1987, Neurobiology of Aging.

[53]  N C Andreasen,et al.  Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[54]  J. Price,et al.  Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. , 1998, Archives of neurology.

[55]  B. Reisberg,et al.  The Global Deterioration Scale for assessment of primary degenerative dementia. , 1982, The American journal of psychiatry.

[56]  H. Gundersen,et al.  Unbiased stereological estimation of the number of neurons in the human hippocampus , 1990, The Journal of comparative neurology.

[57]  B. Pakkenberg,et al.  A quantitative study of the human cerebellum with unbiased stereological techniques , 1992, The Journal of comparative neurology.

[58]  R. Mohs,et al.  Consortium to establish a registry for Alzheimer's disease (CERAD) clinical and neuropsychological assessment of Alzheimer's disease. , 2002, Psychopharmacology bulletin.

[59]  Bente Pakkenberg,et al.  Neocortical Glial Cell Numbers in Alzheimer’s Disease , 2003, Dementia and Geriatric Cognitive Disorders.

[60]  B. B. Andersen Reduction of Purkinje cell volume in cerebellum of alcoholics , 2004, Brain Research.

[61]  J. Albus A Theory of Cerebellar Function , 1971 .

[62]  J A Corsellis,et al.  VARIATION WITH AGE IN THE VOLUMES OF GREY AND WHITE MATTER IN THE CEREBRAL HEMISPHERES OF MAN: MEASUREMENTS WITH AN IMAGE ANALYSER , 1980, Neuropathology and applied neurobiology.

[63]  J E Gardi,et al.  Automatic sampling for unbiased and efficient stereological estimation using the proportionator in biological studies , 2008, Journal of microscopy.

[64]  N. Andreasen,et al.  The Role of the Cerebellum in Schizophrenia , 2008, Biological Psychiatry.

[65]  K. Beyreuther,et al.  Quantitative assessment of the synaptophysin immuno-reactivity of the cortical neuropil in various neurodegenerative disorders with dementia. , 1993, Dementia.

[66]  L M Cruz-Orive,et al.  Estimation of surface area from vertical sections , 1986, Journal of microscopy.

[67]  J. Morris,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease , 1989, Neurology.

[68]  R. Lane,et al.  Neuroanatomical correlates of happiness, sadness, and disgust. , 1997, The American journal of psychiatry.

[69]  Elisabet Englund,et al.  Alzheimer’s Disease and the Cerebellum: A Morphologic Study on Neuronal and Glial Changes , 2001, Dementia and Geriatric Cognitive Disorders.

[70]  D. Flood Region-specific stability of dendritic extent in normal human aging and regression in Alzheimer's disease. II. Subiculum , 1991, Brain Research.

[71]  J. Schmahmann Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. , 2004, The Journal of neuropsychiatry and clinical neurosciences.

[72]  Sidney H Kennedy,et al.  Is the cerebellum relevant in the circuitry of neuropsychiatric disorders? , 2005, Journal of psychiatry & neuroscience : JPN.

[73]  P. Bugalho,et al.  [Role of the cerebellum in cognitive and behavioural control: scientific basis and investigation models]. , 2006, Acta medica portuguesa.