Cognitive decline strongly correlates with cortical atrophy in Alzheimer’s dementia

Alzheimer's disease (AD) is characterized by progressive dementia and distinct neuropathology at autopsy. In order to test the relationship between dementia severity and loss of brain volumes, we prospectively documented the neurological/medical health of 26 male and 26 female controls and AD cases, and evaluated a subset of controls and AD cases using the Mini Mental State Examination (MMSE). At autopsy, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria confirmed diagnoses in 33 AD cases and 19 controls, and using unbiased stereology we quantified total volumes of cortical gray matter, subcortical grey matter including white matter, and forebrain. For ages of death between 50 to 100 years, controls showed minor cortical atrophy in the absence of cognitive decline. Cortical atrophy in AD cases was 20 to 25% greater than that in controls; AD patients dying at older ages showed less severe cortical atrophy than those dying at younger ages. Across all AD cases there was a strong correlation between cognitive performance on the Mini Mental State Examination and cortical volume loss. These findings confirm fundamental differences in the temporal patterns of cortical volume loss in aging and AD, and support cortical degeneration as the primary basis for cognitive decline in AD.

[1]  Peter R Mouton,et al.  Empirical assessment of synapse numbers in primate neocortex , 1997, Journal of Neuroscience Methods.

[2]  D. Price,et al.  Loss of the Presynaptic Vesicle Protein Synaptophysin in Hippocampus Correlates with Cognitive Decline in Alzheimer Disease , 1997, Journal of neuropathology and experimental neurology.

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

[4]  J. Tigges,et al.  Mild age-related changes in the dentate gyrus of adult rhesus monkeys. , 1995, Acta anatomica.

[5]  S. Mirra,et al.  Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists. , 1993, Archives of pathology & laboratory medicine.

[6]  Hans Jørgen G. Gundersen,et al.  Absolute number and size of pigmented locus coeruleus neurons in young and aged individuals , 1994, Journal of Chemical Neuroanatomy.

[7]  A. Dekaban,et al.  Changes in brain weights during the span of human life: Relation of brain weights to body heights and body weights , 1978, Annals of neurology.

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

[9]  Peter R. Mouton,et al.  Comparative evaluation of synaptophysin-based methods for quantification of synapses , 1996, Journal of neurocytology.

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

[11]  B. Pakkenberg,et al.  Neocortical neuron number in humans: Effect of sex and age , 1997, The Journal of comparative neurology.

[12]  J. Glass,et al.  Stereological analysis of cerebral atrophy in human immunodeficiency virus-associated dementia. , 1996, Journal of neuropathology and experimental neurology.

[13]  J. Morrison,et al.  Life and death of neurons in the aging brain. , 1997, Science.

[14]  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.

[15]  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.

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

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

[18]  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.

[19]  D. Salmon,et al.  Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type. , 1996, Archives of neurology.

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

[21]  D. Flood,et al.  Region-specific stability of dendritic extent in normal human aging and regression in Alzheimer's disease. I. CA1 of hippocampus , 1991, Brain Research.

[22]  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.

[23]  J Bohl,et al.  Spatial, Temporal and Numeric Analysis of Alzheimer Changes in the Nucleus Coeruleus , 1997, Neurobiology of Aging.

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

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

[26]  A. Burns.  Clinical diagnosis of Alzheimer's disease , 1991 .

[27]  J. Tigges,et al.  Preservation into old age of synaptic number and size in the supragranular layer of the dentate gyrus in rhesus monkeys. , 1996, Acta anatomica.

[28]  A. Smith,et al.  Rapidly progressing atrophy of medial temporal lobe in Alzheimer's disease , 1994, The Lancet.

[29]  H. Braak,et al.  Frequency of Stages of Alzheimer-Related Lesions in Different Age Categories , 1997, Neurobiology of Aging.

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

[31]  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.

[32]  J. Hatazawa,et al.  Sex Difference in Brain Atrophy During Aging: A Quantitative Study with Computed Tomography , 1982, Journal of the American Geriatrics Society.

[33]  John X. Morris,et al.  The diagnosis of Alzheimer's disease. , 1999, Journal of Alzheimer's disease : JAD.

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

[35]  A. Alzheimer.  Uber eine eigenartige Erkrankung der Hirnrinde , 1907 .

[36]  M. Roth,et al.  The Association Between Quantitative Measures of Dementia and of Senile Change in the Cerebral Grey Matter of Elderly Subjects , 1968, British Journal of Psychiatry.