Mohammed T. Abou-Saleh

46 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYpermanent structural brain changes. More information will helpus to be able to separate the changes in normal ageing from thoseof neurodegenerative disorders and thereby understand the ageconditioned functional deficits.REFERENCESFigure 8.1 The number of neocortical neurons in normal Danes as afunction of sex (*, males, *, females) and age (left). The two orthogonalregression lines are indicated. To the right is illustrated the (absence of a)relation between the total number of neurons and the body height (cm) foreach sex separately. The bivariate means for both sexes are shown in eachdiagram. All axes except the age axis are logarithmicreductions occurred in neocortical volume, surface area, whitematter, archicortex volume and brain weight, concomitant with alarge increase in the ventricular system, while no change wasfound in grey matter volume and neocortical thickness. After sexand age were accounted for, neocortical neuron number was adominating factor in determining the size of other brainstructures. Neuronal density was not a function of sex or age.A major problem in the interpretation of these data is evidentlythat one must take secular changes into account. Body height inDanish males has increased by approximately 9–10 cm from 1920to 1980. Precisely how to correct for such changes is not known.In conclusion, age may account for changes in both neocorticalneuron number and neocortical volume without any effect onneuronal density. The reduction in cortical volume is seen withoutconcomitant reduction in neocortical thickness, but only withconsequence for surface area, a condition rather different from,for example, AD and AIDS, where the equally large atrophy onlyaffects the neocortical thickness 17 . The largest changes in brainvolumes are found in the brain white matters, with a reduction of30%. In a recent paper by Tang et al. 18 , the total length of themyelinated fibres in five elderly women of 86 000 km wasstatistically significantly decreased by 27%, compared with118 000 km in five younger females. As expected, the ventricularvolumes increased by 50%, which could at least in part be a whitematter volume reduction.More research is needed to give us knowledge of possiblechanges during development, ageing and disease. Serious developmentdefects and diseases, such as mental retardation, AD,schizophrenia and AIDS, have all been shown to involve1. Blinkov SM, Glezer II. The Human Brain in Figures and Tables: AQuantitative Handbook. New York: Plenum, 1968, 201–13.2. Brody H. Organization of the cerebral cortex. J Comp Neurol 1955;102: 511–56.3. Haug H. Brain sizes, surfaces, and neuronal sizes of the cortex cerebri:a stereological investigation of man and his variability and acomparison with some mammals (primates, whales, marsupials,insectivores, and one elephant). 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The new stereologicaltools: dissector, fractionator, nucleator, and point-sampled interceptsand their use in pathological research and diagnosis. Acta PathMicrobiol Immunol Scand 1988; 96: 857–81.10. Pakkenberg B, Gundersen HJG. Total number of neurons and glialcells in human brain nuclei estimated by the dissector and thefractionator. J Microsc 1988; 150: 1–20.11. West MJ, Gundersen HJG. Unbiased stereological estimation of thenumber of neurons in the human hippocampus. J Comp Neurol 1990;296: 1–22.12. Williams RW, Rakic P. Three-dimensional counting: an accurate anddirect method to estimate numbers of cells in sectioned material. JComp Neurol 1988; 278: 344–52.13. Williams RW, Rakic P. Erratum and Addendum. Three-dimensionalcounting: an accurate and direct method to estimate numbers of cellsin sectioned material. J Comp Neurol 1989; 281: 335.14. Gundersen HJG. Stereologi—Eller Hvordan Tal for Rumlig Form ogIndhold Opna˚s ved Iagttagelse af Strukturer pa˚ Snitplaner.Copenhagen: Lægeforeningens Forlag, 1981, 1–25 (in Danish).15. Howard V, Reid S, Baddeley A, Boyde A. Unbiased estimation ofparticle density in the tandem scanning reflected light microscope. JMicrosc 1985; 138: 203–12.16. Gundersen HJG. Stereology of arbitrary particles. A review ofunbiased number and size estimators and the presentation of somenew ones, in memory of William R. Thompson. J Microsc 1986; 143:3–45.17. Pakkenberg B, Gundersen HJG. Neocortical neuron number inhumans: effect of sex and age. J Comp Neurol 1997; 384: 312–20.18. Tang Y, Nyengaard JR, Pakkenberg B, Gundersen HJG. Ageinducedwhite matter changes in the human brain: a stereologicalinvestigation. Neurobiol Aging 1997; 18: 609–15.