Treatment of Dementia with Vasoactive Drugs

  • Richard C. Mohs

Abstract

Both atherosclerosis and dementia are common in the elderly, and the incidence of both conditions increases throughout the sixth, seventh, and eighth decades of life (Keys, 1970; Mortimer et al, 1981). Brain cells, like those in other organs, require an adequate blood supply for survival and normal functioning. These facts, along with a lack of more precise knowledge about the causes of dementia in old age, led to the view, widely held for many years, that vascular disease was a primary cause of most age-related dementias. More specific formulations of this hypothesis often held that the loss of functioning brain cells in dementias of old age resulted from a lack of sufficient oxygen due to reduced blood flow (Jacobs et al., 1969). A variety of treatments designed to rectify these deficits by increasing either blood flow or oxygen availability were subsequently developed and tested. As our knowledge of the pathophysiology of dementia has increased, it has become clear that this view of the relationship of vascular disease to dementia is almost entirely wrong. Nevertheless, it is also clear that there are cerebrovascular changes associated with most age-related dementias. In addition, a variety of drugs that have been proposed as possible treatments for dementia have effects on the cerebral vascular system, although in many instances these may be only secondary effects.

Keywords

Neurol Oxalate Alkaloid Cardiol Verapamil 

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References

  1. Ball, J. A. C, and Taylor, A. R., 1967, Effect of cyclandelate on mental function and cerebral blood flow in elderly patients, Br. Med. J. 3: 525–528.PubMedCrossRefGoogle Scholar
  2. British Medical Bulletin (Editorial), 1979, Vasodilators in senile dementia, Br. Med, Bull. 2:511–512.Google Scholar
  3. Coyle, J. T., Price, D. R., and DeLong, M. R., 1983, Alzheimer’s disease: A disorder of cortical cholinergic innervation, Science 219: 1184–1190.PubMedCrossRefGoogle Scholar
  4. Crook, T., Ferris, S., and Bartus. R., 1983, Assessment in Geriatric Psychopharmacology, Mark Powley, New Canaan, CT.Google Scholar
  5. DeFeudis, F. V. 1983, “Calcium antagonists” and atherosclerosis—Basic studies and therapeutic implications, Life Sci. 32:557–563.PubMedCrossRefGoogle Scholar
  6. DeLeon, M. J., Ferris, S. H., George, A. E., Reisber G, B., Christman, D. R., Krichefe, I., and Wolf, A. P., 1983, Computed tomography and positron emission transaxial tomography evaluations in normal aging and Alzheimer’s disease, J. Cereb. Blood Flow Metab. 3: 391–394.CrossRefGoogle Scholar
  7. Dowson, J. H., 1982, Pharmacological treatment of chronic cognitive deficit: A review, Comp. Psychiatry 23: 85–89.CrossRefGoogle Scholar
  8. Dravid, A. R., 1983, Deficits in cholinergic enzymes and muscarinic receptors in the hippocampus and striatum of senescent rats: Effect of chronic hydergine treatment, Arch. Int. Pharmacodyn. Ther. 264: 195–202.PubMedGoogle Scholar
  9. Fonnum, B., 1984, Glutamate: a neurotransmitter in mammalian brain, J. Neurochem. 42: 1–11.PubMedCrossRefGoogle Scholar
  10. Frackowiak, R. S. J., Puzzilli, C, Legg, N.J., DuBoulay, G. H., Marshall, J., Lenzi, G. L., and Jones, T., 1981, Regional cerebral oxygen supply and utilization in dementia, Brain 104: 753–778.PubMedCrossRefGoogle Scholar
  11. Freyhan, F. A., Woodford, R. B., and Kety, S. S., 1951, Cerebral flow and metabolism in psychoses of senility, J. Nerv. Ment. Dis. 113: 449–456.PubMedGoogle Scholar
  12. Hachinski, V. C, Lassen, N. A., and Marshall, J., 1974, Multi-infarct dementia: A cause of mental deterioration in the elderly, Lancet 2: 207–210.PubMedCrossRefGoogle Scholar
  13. Hachinski, V. C, Iliee, L. D., Zilhka, E., DuBoulay, G. H., McAllister, V. L., Marshall, J., Russell, R. W. R., and Symon, L., 1975, Cerebral blood flow in dementia, Arch. Neurol. 32: 632–637.PubMedGoogle Scholar
  14. Hafkenschiel, J. H., Crumpton, C. W., Moyer, J. H., and Jeffers, W. A., 1950, The effects of dihydroergocornine on the cerebral circulation of patients with essential hypertension, J. Clin. Invest. 29: 408–411.PubMedCrossRefGoogle Scholar
  15. Hagberg, B., and Ingvar, D. H., 1976, Cognitive reduction in presenile dementia related to regional abnormalities of the cerebral blood flow, Br. J. Psychiatry 128: 209–222.PubMedCrossRefGoogle Scholar
  16. Henry, P. D., 1980, Comparative pharmacology of calcium antagonists: Nifedipine, verapamil, and difiazem, Am. J. Cardiol. 46: 1047–1058.CrossRefGoogle Scholar
  17. Hollister, L. E., 1981, An overview of strategies for the development of an effective treatment for senile dementia, in: Strategies for the Development of an Effective Treatment for Senile Dementia (T. Crook and S. Gershon, eds.), Mark Powley Assoc., New Caanan, CT, pp. 7– 16.Google Scholar
  18. Hughes, J. R., Williams, J. G., and Currier, R. D., 1976, An ergot alkaloid preparation (Hydergine) in the treatment of dementia: Critical review of the clinical literature, J. Am. Geriatr. Soc. 24: 490–497.PubMedGoogle Scholar
  19. Ingvar, D. H., and Risberg, J., 1967, Increase of regional cerebral blood flow during mental effort in normals and in patients with focal brain disorders, Exp. Brain Res. 3: 195–211.PubMedCrossRefGoogle Scholar
  20. Ingvar, D. H., Risberg, J., and Schwartz, M. S., 1975, Evidence of subnormal function of association cortex in presenile dementia, Neurology 25: 964–974PubMedGoogle Scholar
  21. Jacobs, E. A., Winter, P. M., Alvin. H. J., and Small, S. M., 1969, Hyperoxygenation effect on cognitive functioning in the aged, N. Engl. J. Med. 281: 753–758.PubMedCrossRefGoogle Scholar
  22. Jayne, H. W., Scheinberg, P., Rich, M., and Belle, M. S., 1952, The effect of intravenousGoogle Scholar
  23. papaverine hydrochloride on the cerebral circulation, J. Clin. Invest. 31:111–114.Google Scholar
  24. Kase, C, 1986, “Multiinfarct” dementia: A real entity? J. Am. Geriatr. Soc. 34:482–484.PubMedGoogle Scholar
  25. Keys, A., 1970, Coronary heart disease in seven countries, Circulation 41: 1–211.Google Scholar
  26. Loew, D. M., Vigouret, J. M., and Jaton, A. L., 1976, C.N.S. effects of ergot akaloids, Postgrad. Med. J. 52: 40–46.PubMedGoogle Scholar
  27. Meldrum, B., 1985, Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters, Clin. Sci. 68: 113–122.PubMedGoogle Scholar
  28. Meyer, J. S., 1985, Calcium channel blockers in the prophylactic treatment of vascular headache, Ann. Intern. Med. 102: 395–396.PubMedGoogle Scholar
  29. Middlemiss, D. N., and Spedding, M., 1985, A functional correlate for the dihydropyridine binding site in rat brain, Nature 314: 94–96.PubMedCrossRefGoogle Scholar
  30. Mortimer, J. A., Schuman, L. M., and French, L. R., 1981, Epidemiology of dementing illness, in: The Epidemiology of Dementia (J. A. Mortimer and L. M. Schuman, eds.), Oxford University Press, New York, pp. 3–23.Google Scholar
  31. Obrien, M. D., and Mallett, B. L., 1970, Cerebral cortex perfusion rates in dementia, J. Neurol. Neurosurg. Psychiatry 33: 497–500.CrossRefGoogle Scholar
  32. Obrist, W. D., Chivian, E., Cronqvist, S., and Ingvar, D., 1970, Regional cerebral blood flow in senile and presenile dementia, Neurology 20: 315–322.PubMedGoogle Scholar
  33. Rosen, W. G., Terry, R. D., Fuld, P. A., Katzman, R., and Peck, A., 1980, Pathological verification of ischemic score in differentiation of dementias, Ann. Neurol. 7: 486–488.PubMedCrossRefGoogle Scholar
  34. Rosen, W. G., Mohs, R. C, and Davis, K. L., 1984, A new rating scale for Alzheimer’s disease, Am. J. Psychiatry 141:1356–1364.PubMedGoogle Scholar
  35. Rosenblum, I. Y., Flora, L., and Eisenstein, R., 1975, The effect of disodium ethane-1- hydroxy-1, 1-diphosphonate (EHDP) on a rabbit model of atheroarteriosclerosis, Atherosclerosis 22: 411–424.PubMedCrossRefGoogle Scholar
  36. Rothman, S. M., and Olney, J. W., 1986, Glutamate and the pathophysiology of hypoxicischemic brain damage, Ann. Neurol. 19: 105–111.PubMedCrossRefGoogle Scholar
  37. Schramm, M., and Towart, R., 1985, Modulation of calcium channel function by drugs, Life Sci. 37: 1843–1860.PubMedCrossRefGoogle Scholar
  38. Simard, D., Olesen, J., Paulson, O. B., Lassen, N. A., and Skinhoj, E., 1971, Regional cerebral blood flow and its regulation in dementia, Brain 94: 273–288.PubMedCrossRefGoogle Scholar
  39. Sulkava, R., Haltia, M., Paetau, A., Wikstrom, J., and Palo, J., 1983, Accuracy of clinical diagnosis in primary degenerative dementia: correlation with clinical diagnosis, J. Neurol. Neurosurg. Psychiatry 46: 9–13.PubMedCrossRefGoogle Scholar
  40. Terry, R. D., and Katzman, R., 1983, Senile dementia of the Alzheimer type, Ann. Neurol. 14: 497–506.PubMedCrossRefGoogle Scholar
  41. Tomlinson, B. E., Blessed, G., and Roth, M., 1970, Observations of the brains of demented old people. J. Neurol. Sci. 11: 205–242.PubMedCrossRefGoogle Scholar
  42. Worm-Petersen, J., and Pakkenberg, H., 1968, Atherosclerosis of cerebral arteries, pathological and clinical correlations, J. Gerontol 23: 445–449.PubMedGoogle Scholar
  43. Yamaguchi, F., Meyer, J. S., Yamamoto, M., Sarai, F., and Shaw, T., 1980, Noninvasive regional cerebral blood flow measurements in dementia, Arch. Neurol. 37: 410–418.PubMedGoogle Scholar
  44. Yesavage, J. A., Tinklenberg, J. A., Hollister, L. E., and Berger, P. A., 1979, Vasolidators in senile dementia, Arch. Gen. Psychiatry 36: 220–223.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Richard C. Mohs
    • 1
    • 2
  1. 1.Psychiatry ServiceVeterans Administration Medical CenterBronxUSA
  2. 2.Department of PsychiatryMount Sinai School of MedicineNew YorkUSA

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