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Genetics, Ageing and Dementia

Published online by Cambridge University Press:  29 January 2018

A. F. Wright  and
L. J. Whalley
A. F. Wright*
Affiliation:
M.R.C. Clinical and Population Cytogenetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU
L. J. Whalley
Affiliation:
M.R.C. Brain Metabolism Unit, University Department of Psychiatry, Royal Edinburgh Hospital, Morningside Terrace, Edinburgh EH10 5LG
*
∗Correspondence
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Summary

The contribution of genetic differences to variation in ageing and the relationship of ageing to certain types of dementia are discussed. Neuropathological changes commonly found in the ageing brain are present in more severe form in Alzheimer-type dementia, Down's syndrome, multi-infarct dementia, and a substantial number of patients with Parkinson's disease. An increased frequency of ageing-associated changes outside the brain have been reported in Alzheimer-type dementia, Down's syndrome, and multi-infarct dementia, although the evidence is generally meagre and in many cases requires further corroboration. Genetic studies of Alzheimer-type dementia support the existence of heterogeneity on the basis of family history and age of onset; early onset is associated with greater genetic risk and severity of abnormality. The increasing evidence of an association between DNA damage, premature ageing, and neuronal cell loss may provide insights into the aetiology of these and other forms of dementia.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 145 , Issue 1 , July 1984 , pp. 20 - 38
Copyright
Copyright © 1984 The Royal College of Psychiatrists 

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References

Adolfsson, R., Gottfries, C. G., Roos, B. E. & Winblad, B. (1979) Changes in the brain catecholamines in patients with dementia of Alzheimer type. British Journal of Psychiatry, 135, 216–23.Google Scholar
Akesson, H. O. (1969) A population study of senile and arteriosclerotic psychoses. Human Heredity, 19, 546–66.Google Scholar
Andrews, A. D., Barrett, S. F. & Robbins, J. H. (1976) Relation of DNA repair processes to pathological aging of the nervous system in Xeroderma Pigmentosum. Lancet, i, 1318–20.Google Scholar
Andrews, A. D., Barrett, S. F. & Robbins, J. H. (1978) Xeroderma pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet radiation. Proceedings of the National Academy of Sciences, 75, 1984–8.CrossRefGoogle ScholarPubMed
Arlett, C. F. & Lehmann, A. R. (1978) Human disorders sharing increased sensitivity to the induction of genetic damage. Annual Review of Genetics, 12, 95–115.CrossRefGoogle Scholar
Arlett, C. F. & Muriel, W. J. (1979) Radiosensitivity in Huntington's chorea cell strains; a possible pre-clinical diagnosis. Heredity, 42, 276.Google Scholar
Ball, M. J. & Nuttall, K. (1981) Topography of neurofibrillary tangles and granulovacuoles in hippocampi of patients with Down's syndrome: quantitative comparison with normal ageing and Alzheimer's disease. Neuropathology and Applied Neurobiology, 7, 13–20.Google Scholar
Bank, L. & Jarvik, L. F. (1977) A Longitudinal study of Ageing Human twins. In The Genetics of Aging (ed. Schneider, E. L.). New York: Plenum Press.Google Scholar
Bartus, R. T., Dean, R. L., Beer, B. & Lippa, A. S. (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science, 217, 408–17.Google Scholar
Berg, K. (1983) The genetics of coronary artery disease. Progress in Medical Genetics, 5, (New Series), 35–90.Google Scholar
Bergener, M. & Jungklaas, F. K. (1970) Genetisch befrde bei morbus Alzheimer und seniler demenz. Gerontology Clinics, 12, 71–5.Google Scholar
Bettner, L. G., Jarvik, L. F. & Blum, J. E. (1971) Stroop color-word test, non-psychotic organic brain syndrome, and chromosome losses in aged twins. Journal of Gerontology, 26, 458–69.CrossRefGoogle Scholar
Boller, F., Mizutani, R., Roessmann, U. & Gambetti, P. (1980) Parkinson's disease, dementia and Alzheimer's disease: clinicopathological correlations, Annals of Neurology, 7, 329–35.CrossRefGoogle ScholarPubMed
Bond, D. J. & Chandley, A. C. (1983) Aneuploidy. London: Oxford University Press.Google Scholar
Bondareff, W., Mountjoy, C. Q. & Roth, M. (1981) Selective loss of neurones of origin of adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Lancet, i, 783–84.Google Scholar
Bowen, D. M., Spillane, J., Curzon, G., Meier-Ruge, W., White, P., Goodhardt, M. J., Iwangoff, P. & Davison, A.N. (1979) Accelerated ageing or selective neuronal loss as an important cause of dementia? Lancet, i, 11–14.Google Scholar
Bowen, D. M., Sims, N. R. & Davison, A. N. (1982) Neurochemistry of Alzheimer's disease: an update. In The Ageing Brain. (ed. Hoyer, S.). Berlin: Springer-Verlag.Google Scholar
Brissee, K. R. (1975) Ageing changes in relation to diseases of the nervous system. In Neurobiology of Ageing, (eds. Ordy, J. M. and Brizzee, K. R.). New York and London: Plenum Press.Google Scholar
Brody, H. (1973) Ageing of the vertebrate Brain. Development of Ageing in the Nervous System, (ed. Rockstein, M.). New York: Academic Press.Google Scholar
Brody, H. & Vijayashankar, N. (1977a) Cell loss with ageing. In The Ageing Brain and Senile Dementia. (eds. Nandy, K. and Sherwin, I.). New York: Plenum Press.Google Scholar
Brody, H. & Vijayashankar, N. (1977b) Anatomical changes in the nervous system. Handbook of the Biology of Ageing. (eds. Finch, C. E. and Hayflick, L.). New York: Van Nostrand Reinhold.Google Scholar
Buckton, K. E., Whalley, L. J., Lee, M. & Christie, J. E. (1982) Chromosome aneuploidy in Alzheimer's disease. Experimental Brain Research, Berlin: Springer-Verlag. Supplement 5, 58–63.Google Scholar
Burch, P. R. J. (1968) An enquiry concerning growth, disease and ageing. Edinburgh: Oliver & Boyd.Google Scholar
Burnett, F. M. (1974) Intrinsic Mutagenesis: A Genetic Approach to Ageing. Lancaster, MTP Press.Google Scholar
Callner, D. A., Dustman, R. E., Madsen, J., Schenkenberg, T. & Beck, E. C. (1978) Life span changes in the average evoked responses of Down's syndrome and non-retarded persons. American Journal of Mental Deficiency. 82, 398–405.Google Scholar
Cantu, J. M., Hernandez, A., Plascencia, L., Vaca, G., Moller, M. & Rivera, H. (1980) Partial trisomy and monosomy 21 in an infant with an unusual de novo 21/21 translocation. Annales de Genetique, 23, 183–86.Google Scholar
Carter, C. O. (1969) Genetics of common disorders. British Medical Bulletin, 25, 52–7.Google Scholar
Cervenka, J., Gorlin, R. J. & Djavadi, G. R. (1977) Down's syndrome due to partial trisomy 21q. Clinical Genetics, 11, 119–21.Google Scholar
Chen, H., Tyrkus, M. & Woolley, P. V. Jr. (1976) Partial trisomy 21 due to maternal t(12;21) translocation: further evidence that the Down phenotype is related to trisomy of the distal segment of chromosome 21. Proceedings of the Vth International Congress of Human Genetics, Mexico, Excerpta Medica, Amsterdam, 397, 116.Google Scholar
Chetsanga, C. J., Tuttle, M., Jacobini, A. & Johnson, C. (1979) Age-associated structural alterations in senescent mouse brain DNA. Biochimica et Biophysica Acta, 474, 180–7.Google Scholar
Cohen, D. (1976) A behavioral-chromosome relationship in the elderly: a critical review of biobehavioural hypothesis. Experimental Aging Research, 2, 271–87.Google Scholar
Constantinidis, J., Garrone, G., & De Ajuriaguerra, J. (1962) L'Heredite des demences de l'age avance. Ecephale, 51, 301–44.Google Scholar
Clarke, A. J. & Ganesan, A. (1975) Lists of genes affecting DNA metabolism in Eschericia coli. Molecular Mechanisms for Repair of DNA, Part B. (eds. Hanawalt, P. C. and Setlow, R. B.). New York: Plenum Press.Google Scholar
Countryman, P. I., Heddle, J. A. & Crawford, E. (1977) The repair of X-ray-induced chromosomal damage in trisomy 21 and normal diploid lymphocytes. Cancer Research, 37, 52–8.Google Scholar
Corsellis, J. A. N. (1962) Mental illness and the Ageing Brain. London: Oxford University Press.Google Scholar
Corsellis, J. A. N. (1976) Ageing and the dementias. In Greenfield's Neuropathology, (eds. Blackwood, W. and Corsellis, J. A. N.). London: Edward Arnold.Google Scholar
Couturier, J. Dutrillaux, B., Garber, P., Raoul, O., Croquette, M. F., Fourlinnie, J. C. & Maillard, E. (1979) Evidence for a correlation between late replication and autosomal gene inactivation in a familial translocation t(X;21). Human Genetics, 49, 319–26.Google Scholar
Crapper, D. R., Dalton, A. J., Skopitz, M., Scott, J. W. & Hachinski, V. C. (1975) Alzheimer degeneration in Down Syndrome: electrophysiologic alterations and histopathologic findings. Archives of Neurology, 33, 618–23.Google Scholar
Crome, L. & Kanjilal, G. C. (1971) Cockayne's syndrome: case report. Journal of Neurology, Neurosurgery and Psychiatry, 34, 171–8.Google Scholar
Crome, L. & Stern, J. (1976) Inborn lysosomal enzyme deficiencies. In Greenfield's Neuropathology, (eds. Blackwood, W. and Corsellis, J.A.N.). London, Edward Arnold.Google Scholar
Cross, A. J., Crow, T. J., Perry, E. K., Perry, R. H., Blessed, G. & Tomlinson, B. E. (1981) Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease. British Medical Journal, 282, 93–4.CrossRefGoogle ScholarPubMed
Curtis, H. J. (1966) Biological Mechanisms of Aging. Springfield, Illinois: C. C. Thomas.Google Scholar
Dalton, A. J., Crapper, D. R. & Schlotterer, G. R. (1974) Alzheimer's disease in Down's syndrome: visual retention deficits. Cortex, 10, 366–77.Google Scholar
Dayan, A. D. (1971) Comparative neuropathology of ageing. Studies on the brains of 47 species of Vertebrates. Brain, 94, 31–42.Google Scholar
Dickinson, C. J. & Thomson, A. D. (1961) A post mortem study of the main cerebral arteries with special reference to the cause of strokes. Clinical Sciences, 20, 131–42.Google Scholar
Dowson, J. H. (1982) Neuronal lipofuscin accumulation in ageing and Alzheimer Dementia: a pathogenic mechanism? British Journal of Psychiatry, 140, 142–8.Google Scholar
Ellis, W. G., McCulloch, J. R. & Corley, C. L. (1974) Presenile dementia in Down's syndrome: ultrastructural identity with Alzheimer's disease. Neurology, 24, 101–6.Google Scholar
Evans, H. J., Vijayalaxmi, , & Newton, M. S. (1982) The response of cells from patients with Huntington's Chorea to mutagen-induced chromosome damage. Annals of Human Genetics, 46, 177–85.Google Scholar
Evans, H. J., Vijayalaxmi, , Pentland, B. & Newton, M. S. (1983) Mutagen hypersensitivity in Friedreich's ataxia. Annals of Human Genetics, (in press).Google Scholar
Falconer, D. S. (1965) The inheritance of liability to certain diseases, estimated from the incidence among relatives. Annals of Human Genetics, 29, 51–76.Google Scholar
Finch, C. E. & Hayflick, L. (1977) Handbook of the Biology of Ageing, (eds. Finch, C. E. and Hayflick, L.). New York: Van Nostrand.Google Scholar
Fine, P. E. M. (1977) Analysis of family history data for evidence of non-Mendelian inheritance from vertical transmission. Journal of Medica Genetics, 14, 399–407.Google Scholar
Franks, L. M. (1974) Ageing in differentiated cells. Gerontologia, 20, 51–62.Google Scholar
Goidl, E., Michelis, M., Siskind, G. & Weksler, M. (1981) Effect of age on the induction of autoantibodies. Clinical and Experimental Immunology, 44, 24–30.Google Scholar
Goldstein, S. (1978) Human genetic disorders that feature premature onset and accelerated progression of biological aging. The Genetics of Aging, (ed. Schneider, E. L.). New York: Plenum Press, 171–224.Google Scholar
Goudsmit, J., Morrow, C. H., Asher, D. M., Yanagihara, R. T., Masters, C. L., Gibbs, C. J. Jr. & Gajdusek, C. (1980) Evidence for and against the transmissibility of Alzheimer's disease. Neurology, 30, 945–50.CrossRefGoogle Scholar
Gruenberg, E. M. (1978) Epidemiology of senile dementia. In Neurological Epidemiology: Principles and Clinical applications (ed. Schoenberg, B. S.). New York: Raven Press.Google Scholar
Habedank, M. & Rodewald, A. (1982) Moderate Down's syndrome in three siblings having partial trisomy 21q22.2→qter and therefore on SOD–1 excess. Human Genetics, 60, 74–7.Google Scholar
Hachinski, V. C., Lassen, N. A. & Marshall, J. (1974) Multi-infarct dementia: a cause of mental deterioration in the elderly. Lancet, ii, 207–10.Google Scholar
Hagemeijer, A. & Smit, E. M. E. (1977) Partial trisomy 21. Human Genetics, 38, 15–23.Google Scholar
Hakim, A. M. & Mathieson, G. (1978) Basis of dementia in Parkinson's disease. Lancet, ii, 729.Google Scholar
Harper, P. S. (1977) Mendelian inheritance or transmissible agent? — the lesson of Kuru and the Australia antigen. Journal of Medical Genetics, 14, 389–98.Google Scholar
Helgason, L. (1977) Psychiatric services and mental illness in Iceland. Incidence study (1966–1967) with 6–7 year follow-up. Acta Psychiatrica Scandinavic (Supplement), 268, 1–140.Google Scholar
Heston, L. L. (1981) Genetic studies of dementia with emphasis on Parkinson's Disease and Alzheimer's neurophathology. In The Epidemiology of Dementia. (eds. Mortimer, J. A. and Schuman, L. M.). New York: Oxford University Press.Google Scholar
Heston, L. L. & Mastri, A. R. (1977) The genetics of Alzheimer's disease. Associations with hematologic malignancy and Down's syndrome. Archives of General Psychiatry, 34, 976–81.Google Scholar
Heston, L. L., Mastri, A. R., Anderson, E. & White, J. (1981) Dementia of the Alzheimer type: clinical genetics, natural history, and associated conditions. Archives of General Psychiatry, 38, 1085–90.Google Scholar
Hirsch, G. P. (1978) Somatic mutations and aging. The Genetics of Aging, (ed. Schneider, E. L.). New York: Plenum Press.Google Scholar
Jacob, H. (1970) Muscular twitchings in Alzheimer's disease. In Alzheimer's Disease and Related Conditions, (eds. Wolstenholme, G. E. W. and O'Connor, M.). London: Churchill.Google Scholar
Jacobs, P. A., Brunton, M., Court-Brown, W. M., Doll, R. & Goldstein, H. (1963) Change in human chromosome count distributions with age: evidence for a sex difference. Nature, 197, 1080–1.Google Scholar
Jacobs, P. A., Court-Brown, W. M. & Doll, R. (1961) Distribution of human chromosome counts in relation to age. Nature, 191, 1178–80.Google Scholar
Jarvik, L. F. & Kato, T. (1969) Chromosome and mental changes in octogenarians. Preliminary findings. British Journal of Psychology, 115, 1193–4.Google Scholar
Jarvik, L. F. & Kato, T. (1970) Chromosome examinations in aged twins. American Journal of Human Genetics, 22, 562–73.Google Scholar
Jarvik, L. F., Altshulen, K. Z., Kato, T. & Blumner, B. (1971) Organic brain syndrome and chromosome loss in aged twins. Diseases of the Nervous System, 32, 159–70.Google Scholar
Jarvik, L. F., Blum, J. E. & Varma, A. D. (1972) Genetic components and intellectual functioning during senescence: a 20-year study of ageing twins. Behavioural Genetics, 2, 159–71.Google Scholar
Jarvik, L. F., Yen, F. & Goldstein, F. (1974) Chromosomes and mental status. Archives of General Psychiatry, 30, 186–90.Google Scholar
Jarvik, L. F., Ruth, V. & Matsuyama, S. S. (1980) Organic brain syndrome and ageing. Archives of General Psychiatry, 37, 280–6.Google Scholar
Jellinger, K. & Grisold, W. (1982) Cerebral atrophy in Parkinson Syndrome. The Ageing Brain, (ed. Hoyer, S.). Berlin: Springer-Verlag.Google Scholar
Jervis, G. A. (1970) Premature senility in Down's Syndrome. Annals of the New York Academy of Sciences, 171, 559–61.Google Scholar
Katzman, R. (1976) The prevalence and malignancy of Alzheimer disease. A major killer. Archives of Neurology, 33, 217–8.Google Scholar
Katzman, R. & Karasu, T. B. (1975) Differential diagnosis of dementia. In Neurological and Sensory Disorders in the elderly, (ed. Fields, W.). New York: Stratton Intercontinental.Google Scholar
Kay, D. W. K., Beamish, P. & Roth, M. (1964) Old age mental disorders in Newcastle upon Tyne, I. A study of prevalence. British Journal of Psychiatry, 110, 146–58.Google Scholar
Kay, D. W. K., Bergmann, K., Foster, E. M., McKechnie, A. A. & Roth, M. (1970) Mental illness and hospital usage in the elderly: a random sample followed-up. Comprehensive Psychiatry, 11, 26–35.Google Scholar
Kay, D. W. K. (1972) Epidemiological aspects of organic brain disease in the aged. Ageing and the brain, (ed. Gaitz, C. M.). New York: Plenum Press.Google Scholar
Kohn, R. R. (1977) Heart and cardiovascular system. In Handbook of the Biology of Ageing, (eds. Finch, C. E. and Hayflick, L.). New York: Van Nostrand Reinhold.Google Scholar
Ladurner, G., Iliff, L. D., Sager, W. D. & Lechner, H. (1982) A clinical approach to vascular (multi-infarct) dementia. The Ageing Brain, (ed. Hoyer, S.). Berlin: Springer-Verlag.Google Scholar
Landy, P. J. & Bain, B. J. (1970) Alzheimer's disease in siblings. The Medical Journal of Australia, 2, 832–4.Google Scholar
Larsson, T., Sjogren, T. & Jacobson, G. (1963) Senile dementia: a clinical, sociomedical and genetic study. Acta Psychiatrica Scandinavica, Supplement 167, 39, 1–259.Google Scholar
Larsson, T., Sjogren, T. (1960) Essential tremor. A clinical and genetic population study. Acta Psychiatrica Scandinavica, (Supplement), 36, 1–176.Google Scholar
Lauter, H. & Meyer, J. E. (1968) Clinical and nosological concepts of senile dementia. In Senile Dementias (eds. Muller, C. H. and Ciompi, L.). Bern: Hans Huber.Google Scholar
Lewis, P. D., Corr, J. P., Arlett, C. F. & Harcourt, S. A. (1979) Increased sensitivity to gamma irradiation of skin fibroblasts in Friedreich's ataxia. Lancet, ii, 474–5.Google Scholar
Ling, R. S. M. (1963) The genetic factor in Dupuytren's disease. Journal of Bone and Joint Surgery, 45, 709–18.Google Scholar
Lishman, W. A. (1978) Organic Psychiatry. Oxford: Blackwell.Google Scholar
Lott, I. T. (1982) Down's syndrome, ageing and Alzheimer's disease: a clinical review. Annals of the New York Academy of Sciences, 396, 15–27.Google Scholar
McCombe, P., Lewin, M. & Kidson, C. (1976) Control of DNA repair linked to neuroblastoma differentiation, International Journal of Radiation Biology, 29, 523–31.Google Scholar
McDonald, C. (1969) Clinical heterogeneity in senile dementia. British Journal of Psychiatry, 15, 267–71.Google Scholar
MacKay, I. R. (1972) Ageing and immunological function in man. Gerontologia, 18, 285–304.Google Scholar
McKusick, V. A. (1975) Mendelian Inheritance in Man-Catalogs of Autosomal Dominant, Autosomal Recessive and X-linked Phenotypes. Baltimore: Johns Hopkins University Press.Google Scholar
McGeer, P. L., McGeer, E. G. & Suzuki, J. S. (1976) Ageing and extrapyramidal function. Archives of Neurology, 34, 33–5.Google Scholar
Malamud, N. (1972) Neuropathology of organic brain syndromes associated with ageing. In Ageing and the Brain (ed. Gaits, C. M.). New York: Plenum Press.Google Scholar
Mann, D. M. A. & Sinclair, K. G. A. (1978) The quantitative assessment of lipofuscin pigment, cytoplasmic RNA and nucleolar volume in senile dementia. Neuropathology and Applied Neurobiology, 4, 129–35.Google Scholar
Mark, J. & Brun, A. (1973) Chromosomal deviations in Alzheimer's disease compared to those in senescence and senile dementia. Gerontology Clinics, 15, 253–8.Google Scholar
Martin, G. M. (1977) Genetic syndromes in man with potential relevance to the pathobiology of ageing. In Genetic Effects on Ageing. Birth Defects: Original Article Series (eds. Bergsma, D., Harrison, D. E. and Paul, N. W.). The National Foundation — March of Dimes. New York: A. R. Liss.Google Scholar
Martin, J. M., Kellett, J. M. & Kahn, J. (1981) Aneuploidy in cultured human lymphocytes II. A comparison between senescence and dementia. Age and Ageing, 10, 24–8.Google Scholar
Martin, W., Young, W. I. & Anderson, V. E. (1973) Parkinson's disease: a genetic study. Brain, 96, 495–506.Google Scholar
Matsuyama, A. & Nakumara, S. (1978) Senile change in the brain in the Japanese In Alzheimer's disease: Senile Dementia and Related Disorders, (eds. Terry, R. D., Katzman, R. and Bick, K. L.). New York: Raven Press.Google Scholar
Miller, E. (1977) Abnormal Aging: the Psychology of Senile and Presentile Dementia. Chichester: Wiley.Google Scholar
Miller, E. (1974) Dementia as an accelerated ageing of the nervous system: some psychological and methodological considerations. Age and Ageing, 3, 197–202.Google Scholar
Modak, S. P. & Price, G. B. (1971) Exogenous DNA polymerase-catalysed incorporation of deoxyribonucleotide monophosphates in nuclei of fixed mouse-brain cells. Experimental Cell Research, 65, 289–96.Google Scholar
Mortimer, J. A., Schuman, L. M. & French, L. R. (1981) The epidemiology of dementing illness. In The Epidemiology of Dementia (eds. Mortimer, J. A. and Schuman, L. M.) New York: Oxford University Press.Google Scholar
Murphy, E. A. (1977) Genetics of longevity in man. In The Genetics of Ageing, (ed. Schneider, E. L.). New York: Plenum Press.Google Scholar
Nandy, K. (1977) Immune reactions in ageing brain and senile dementia. The Ageing Brain and Senile Dementia (eds. Nandy, K. and Sherwin, ). New York: Plenum Press.Google Scholar
Nandy, K. (1978) Brain-reactive antibodies in ageing and senile dementia. In Alzheimer's Disease: Senile Dementia and Related Disorders (eds. Terry, R. D., Katzman, R. and Bick, K. L.). New York: Raven Press.Google Scholar
Nandy, K. (1982) Neuroimmunology and the ageing brain. In The Ageing Brain (ed. Hoyer, S.). Berlin: Springer-Verlag.Google Scholar
Niebuhe, E. (1974) Down syndrome: the possibility of a pathogenetic segment on chromosome 21, Humangenetik, 21, 99–101.Google Scholar
Nielsen, J. (1963) Geronto-psychiatric period-prevalence investigation in a geographically delimited population. Acta Psychiatrica Scandinavica, 38, 307–30.Google Scholar
Nielsen, J. (1968) Chromosomes in senile dementia. British Journal of Psychiatry, 114, 303–9.Google Scholar
Nielsen, J. (1970) Chromosomes in senile, presenile and arteriosclerotic dementia. Journal of Gerontology, 25, 312–15.Google Scholar
Nishioka, N., Takahata, N. & Iizuka, R. (1968) Histochemical studies on the lipopigments in the nerve cells. A comparison with lipofuscin and ceroid pigment. Acta Neuropathologica, 11, 174–81.Google Scholar
Nordenson, I., Adolfsson, R., Beckman, G., Bucht, G. & Winblad, B. (1980) Chromosomal abnormality in dementia of the Alzheimer type. Lancet, I, 481–2.Google Scholar
O'Hara, P. T. (1972) Electron microscopical study of the brain in Down's syndrome. Brain, 95, 681–4.Google Scholar
Oppenheimer, D. R. (1976) Diseases of the basal ganglia, cerebellum and motor neurons. In Greenfield's Neuropathology (eds. Blackwood, W. and Corsellis, J. A. N.). London: Edward Arnold.Google Scholar
Paterson, M. C. & Smith, P. J. (1979) Ataxia telangiectasia: an inherited human disorder involving hypersensitivity to ionising radiation and related DNA-damaging chemicals. Annual Review of Genetics, 13, 291–18.Google Scholar
Pearce, J. M. S. (1978) Aetiology and natural history of Parkinson's disease. British Medical Journal, 2, 1664–6.Google Scholar
Pearce, J. M. S. (1974) The extrapyramidal disorder of Alzheimer's disease. European Journal of Neurology, 12, 94–103.Google Scholar
Peck, A., Wolloch, L. & Rodstein, M. (1978) Mortality of the aged with chronic brain syndrome. In Alzheimer's Disease: Senile Dementia and Related Disorders, (eds. Katzman, R., Terry, R. D. and Bick, K. L.). New York: Raven Press.Google Scholar
Perry, E. K. & Perry, R. H. (1982) Neurotransmitter and neuropeptide systems in Alzheimer-type dementia. In The Ageing Brain, (ed. Hoyer, S.). Berlin: Springer-Verlag.Google Scholar
Pfeiffer, R. A., Kessel, E. K. & Soer, K. H. (1977) Partial trisomies of chromosome 21 in man. Two new observations due to translocations 19;21 and 4;21. Clinical Genetics, 11, 207–13.Google Scholar
Ponten, J. (1977) Abnormal cell growth (neoplasma) and aging. Handbook of the Biology of Aging (eds. Finch, C. E. and Hayflick, L.). New York: Van Nostrand Reinhold.Google Scholar
Preston, R. J. (1981) X-ray-induced chromosome aberrations in Down lymphocytes: and explanation of their increased sensitivity. Environmental Mutagenesis, 3, 85–9.Google Scholar
Pueschel, S. M., Padre-Mendoza, T. & Ellenbogen, R. (1980) Partial trisomy 21. Clinical Genetics, 18, 392–5.Google Scholar
Reid, A. H. & Maloney, A. F. J. (1974) Giant cell artertis and arteriolitis associated with amyloid angiopathy in an elderly mongol. Acta Neuropathologica, 27, 131–7.Google Scholar
Reye, C. & Mossman, N. S. W. (1960) Ataxiatelangiectasia. American Journal of Diseases of Children, 99, 238–47.Google Scholar
Robbins, J. H., Kraemer, K. H., Lutzner, M. A., Festoff, B. W. & Coon, H. G. (1974) Xeroderma pigmentosum. Annals of Internal Medicine, 80, 221–48.Google Scholar
Robbins, J. H. (1978) Significance of repair of human DNA: evidence from studies of Xeroderma Pigmentosum. Journal of the National Cancer Institute, 61, 645–56.Google Scholar
Robbins, J. H., Otsuka, F., Tarone, R. E., Polinsky, R. J., Brumback, R. A., Moshell, A. N., Nee, L. E., Ganges, M. B. & Cayeux, S. J. (1983) Radiosensitvity in Alzheimer's disease and Parkinson's disease. Lancet, i, 468–9.Google Scholar
Ropper, A. H. & Williams, R. S. (1980) Relationship between plaques, tangles, and dementia in Down Syndrome. Neurology, 30, 639–44.Google Scholar
Rossor, M. N., Emson, P. C., Mountjoy, C. Q., Roth, M. & Iversen, L. L. (1982a) Neurotransmitters of the cerebral cortex in senile dementia of Alzheimer type. The Ageing Brain (ed. Hoyer, S.). Berlin: Springer-Verlag.Google Scholar
Rossor, M. N. (1982b) Dementia. Lancet, ii, 1200–4.Google Scholar
Rossor, M. N. (1981) Parkinson's disease and Alzheimer's disease as disorders of the isodendritic core. British Medical Journal, 238, 1588–90.Google Scholar
Roth, M. (1972) Recent progress in the psychiatry of old age and its bearing on certain problems of psychiatry in earlier life. Biological Psychiatry, 5, 103–25.Google Scholar
Rossor, M. N. (1978) Diagnosis of senile and related forms of dementia. In Alzheimer's disease: Senile Dementia and Related Disorders (eds. Katzman, R., Terry, R. D. & Bick, K. L.). New York: Raven Press.Google Scholar
Ruberg, M., Ploska, A., Javoy-Agid, F. & Agid, Y. (1982) Muscarinic binding and choline acetyltransferase activity in Parkinsonian subjects with reference to dementia. Brain Research, 232, 129–39.Google Scholar
Sanchez, O., Mamunes, P. & Yunis, J. J. (1977) Partial trisomy 20 (20q13) and partial trisomy 21 (21 pter→21q21.3) Journal of Medical Genetics, 14, 459–60.Google Scholar
Scheibel, M. E. & Scheibel, A. B. (1977) Differential changes with ageing in old and new cortices. In The Ageing Brain and Senile Dementia, (eds. Nandy, K. and Sherwin, I.). New York: Plenum Press.Google Scholar
Schmechel, D., Heyman, A. Wilkinson, W., Hurwitz, B. & Rothman, S. (1981) Excess frequency of Down syndrome in relatives of patients with Alzheimer disease. Archives of Neurology, 31, 90.Google Scholar
Schmidt, R. Mundel, G., Rosenblatt, M. & Katznelson, B. M. (1972) Apparent G-monosomy, G-deletion, and incomplete Down's Syndrome in a single family. Journal of Medical Genetics, 9, 457–61.Google Scholar
Schneider, E. L. (1978) Cytogenetics of Ageing. The Genetics of Aging (ed. Schneider, E. L.). New York: Plenum Press.Google Scholar
Schulz, B. (1932) Zur erbpathologie der schizophrenic Zeitschriftges . Neurologie und Psychiatrie, 143, 175–293.Google Scholar
Scudiero, D. A., Meyer, S. A., Clatterbuck, B. E., Tarone, R. E. & Robbins, J. H. (1981) Hypersensitivity to N-methyl-N'-nitro-N-nitrosoguanidine in fibroblasts from patients with Huntington disease, familial dysautonomia, and other primary neuronal degenerations. Proceedings of the National Academy of Sciences, USA, 78, 6451–5.Google Scholar
Scudiero, D. A., Tarone, R. E., Polinsky, R. J., Brumback, R. A., Nee, L., Clatterbuck, B. E. & Robbins, J. H. (1982) Parkinson's disease and Alzheimer's disease fibroblasts are hypersensitive to killing by N-mthyl-N'-nitro-N-nitrosoguanidine. Clinical Research, 30, 857a (abstract).Google Scholar
Shapiro, B. L. (1983) Down syndrome — a disruption of homeostasis. American Journal of Medical Genetics, 14, 241–69.Google Scholar
St Clair, D. & Whalley, L. J. (1983) Hypertension, multi-infarct dementia and Alzheimer's disease. British Journal of Psychiatry (in press).Google Scholar
Sinet, P. M. (1982) Metabolism of oxygen derivatives in Down's syndrome Annals of New York Academy of Sciences, 396, 83–94.Google Scholar
Sinet, P. M., Couturier, J., Dutrillaux, B., Poissonier, M., Raoul, O., Rethore, M. O., Allard, D. Lejeune, J. & Jerome, H. (1976) Trisomie 21 et superoxyde dismutase-1 (IPO-A). Experimental Cell Research, 97, 47–55.Google Scholar
Sjogren, T., Sjogren, H. & Lindgren, A. G. H. (1952) Morbus Alzheimer and Morbus Pick. A genetic, clinical and patho-anatomical study. Acta Psychiatrica Scandinavica, Supplement 82.Google Scholar
Slater, E. & Cowie, V. A. (1971) The Genetics of Mental Disorders. London: Oxford University Press.Google Scholar
Smith, C., Falconer, D. S. & Duncan, L. J. P. (1972) A statistical and genetical study of diabetes. Annals of Human Genetics, 35, 281–99.Google Scholar
Smith, G. F. & Berg, J. M. (1976) Down's Anomaly. Edinburgh: Churchill Livingstone.Google Scholar
Sourander, P. & Sjogren, M. (1970) The concept of Alzheimer's disease and its clinical implications. In Alzheimer's Disease and Related Conditions (eds. Wolstenholme, G. E. W. and O'Connor, M. E.) London: Churchill.Google Scholar
Sorka, H., Elizan, T. S., Yahr, M. D., Burger, A. & Mendoza, M. R. (1981) Organic mental syndrome and confusional states in Parkinson's disease: relationship to computerized tomographic signs of cerebral atrophy. Archives of Neurology, 38, 339–42.Google Scholar
Strehler, B. L. & Barrows, C. H. (1970) Senescence. Cell biological aspects of aging. In Cell Differentiation, (eds. Schjeide, O. A. and de Vallis, J.). New York: Van Nostrand Reinhold.Google Scholar
Struwe, F. (1929) Histopathologische untersuchungen uber entstehung und wessen der senilen plaques. Zeitschrift ges. Neurologie und Psychiatrie, 122, 291–307.Google Scholar
Tangye, S. R. (1979) The EEG and incidence of epilepsy in Down's syndrome. Journal of Mental Deficiency Research, 23, 17–24.Google Scholar
Taysi, K., Sparkes, R. S., O'Brien, T. J. & Dengler, D. R. (1982) Down's syndrome phenotype and autosomal gene inactivation in a child with presumed (X;21) de novo translocation. Journal of Medical Genetics, 19, 144–8.Google Scholar
Tellez-Nagel, I., Johnson, A. B. & Terry, R. D. (1974) Studies on brain biopsies of patients with Huntington's chorea. Journal of Neuropathology and Experimental Neurology, 33, 308–332.Google Scholar
Tolksdorf, M. & Wiedemann, H. R. (1981) Clinical aspects of Down's syndrome from infancy to adult life. In Trisomy 21. (eds. Burgio, G. R., Fraccaro, M., Tiepolo, L., Wolf, U.). Berlin: Springer-Verlag.Google Scholar
Tomlinson, B. E., Blessed, G. & Roth, M. (1968) Observations on the brains of non-demented old people. Journal of Neurological Science, 7, 331–56.Google Scholar
Tomlinson, B. E., Blessed, G. & Roth, M. (1970) Observations on the brains of demented old people. Journal of Neurological Science, 11, 205–242.Google Scholar
Tomlinson, B. E., Irving, D., & Blessed, G. (1981) Cell loss in the locus coeruleus in senile dementia of Alzheimer type. Journal of Neurological Sciences, 49, 419–28.Google Scholar
Torack, R. M. (1978) The Pathologic Physiology of Dementia. Berlin: Springer-Verlag.Google Scholar
Ulrich, J. (1982) Senile plaques and neurofibrillary tangles of the Alzheimer type in nondemented individuals at presenile age. Gerontology, 28, 86–90.Google Scholar
Vijayalaxmi, & Evans, H. J. (1982) Bleomycin-induced chromosomal aberrations in Down's Syndrome lymphocytes. Mutation Research, 105, 107–13.Google Scholar
Wahrman, J., Goitein, R. Richler, C., Akstein, E. & Chaki, R. (1976) The mongoloid phenotype in man is due to trisomy of the distal pale G-band of Chromosome 21. Chromosome Today, 5, 241–8.Google Scholar
Walford, R. L. (1982) Immunological studies of Down's Syndrome and Alzheimer Disease. Annals of the New York Academy of Sciences, 396, 95–106.Google Scholar
Wang, H. A. & Whanger, A. (1971) Brain impairment and longevity. In Prediction of Life Span (eds. Palmore, E. and Jeffers, F. C.). Lexington, Massachussetts: D. C. Heath.Google Scholar
Wang, H. S. (1978) Prognosis in dementia and related disorders in the aged. In Alzheimer's Disease: Senile Dementia and Related Disorders (eds. Katzman, R., Terry, R. D. and Bick, K. L.). New York: Raven Press.Google Scholar
Ward, B. E., Cook, R. H., Robinson, A. & Austin, J. H. (1979) Increased aneuploidy in Alzheimer disease. American Journal of Medical Genetics, 3, 137–44.Google Scholar
Whalley, L. J. (1982) The dementia of Down's Syndrome and its relevance to aetiological studies of Alzheimer's Disease. Annals of New York Academy of Science, 396, 39–55.Google Scholar
Whalley, L. J., Carothers, A. D., Collyer, S., De Mey, R. & Frackiewicz, A. (1982) A study of familial factors in Alzheimer's disease. British Journal of Psychiatry, 140, 249–56.Google Scholar
White, B. J., Crandell, C., Goudsmit, J., Morrow, C. H., Alling, D. W., Gajdusek, D. C. & Tuio, J. H. (1981) Cytogenetic studies of familial and sporadic Alzheimer Disease. American Journal of Medical Genetics, 10, 77–89.Google Scholar
Whitehouse, P. J., Struble, R. G., Clark, A. W. & Price, D. L. (1982) Alzheimer disease: plaques, tangles, and the basal forebrain. Annals of Neurology, 12, 494.Google Scholar
Williams, J. D., Summitt, R. L., Martens, P. R. & Kimbrell, R. A. (1975) Familial Down Syndrome due to t(10;21) translocation: evidence that the Down phenotype is related to trisomy of a specific segment of chromosome 21. American Journal of Human Genetics, 27, 478–85.Google Scholar
Winblad, B., Adolfsson, R., Carlsson, A. & Gotfries, C. G. (1981) Biogenic amines in brains of patients with dementia of Alzheimer type. Alzheimer's Disease — A Review of Progress. New York: Raven Press.Google Scholar
Wisniewski, K., Howe, J., Williams, D. G. & Wisniewski, H. M. (1978) Precocious aging and dementia in patients with Down's syndrome. Biological Psychiatry, 13, 619–27.Google Scholar
Wisniewski, H. M., Vorbrodt, A. W. Moretz, R. C., Lossinsky, A. S. & Grundke-Iqbal, I. (1982) Pathogenesis of neuritic (senile) and amyloid plaque formation. In The Ageing Brain (ed. Hoyer, S.). Berlin: Springer-Verlag.Google Scholar
Wright, J. R., Calkins, E., Breen, W. J., Stolke, G. & Schultz, R. T. (1969) Relationship of amyloid to ageing. Medicine, 48, 39–60.Google Scholar
Yamada, M. (1978) On the distribution of senile changes in the spinal cord. Folia Psychiatrica et Neurologica Japonica, 32, 249–51.Google Scholar
Yates, C. M., Simpson, J., Maloney, A. J. F., Gordon, A. & Reid, A. H. (1980) Alzheimer-like cholinergic deficiency in Down Syndrome. Lancet, ii, 979.Google Scholar
Yates, C. M., Ritchie, I. M., Simpson, J., Maloney, A. J. F. & Gordon, A. (1981) Noradrenaline in Alzheimer-type dementia and Down's syndrome. Lancet, ii, 39–40.Google Scholar
Zeman, W. (1971) The neuronal ceroid-lipofuscinoses-Batten-Vogt Syndrome: a model for human ageing? Advances in Gerontology Research, 3, 147–70.Google Scholar
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