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Diagnostic and Pharmacological Approaches in Alzheimer’s Disease

  • Clinical Pharmacology
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Summary

Alzheimer’s disease is a chronic progressive disease affecting higher intellectual functioning. The clinical diagnosis is made when the onset of illness is insidious, the course slowly progressive and all the treatable causes of dementia have been ruled out. The use of more stringent criteria has improved clinical diagnosis, but at best only 80% of patients are accurately diagnosed. Ultimately the diagnosis depends upon pathological confirmation. The neuritic plaques and neurofibrillary tangles described by Alzheimer, although not pathognomonic for the disease, continue to be the basis for pathological diagnosis.

The aetiology and pathophysiology of Alzheimer’s disease are presently unknown. Epidemiological studies have suggested a genetic basis for the disorder, and many biochemical studies have linked it to degeneration of central cholinergic neurons, and possibly to abnormalities of other neurotransmitter systems. A marker which would permit accurate diagnosis early in the course of disease would be of major importance to researchers and clinicians alike. No marker has been found to date, although recent research results are promising.

Various pharmacological strategies have been employed in the treatment of Alzheimer’s disease. More recently attempts have focused on enhancing central cholinergic transmission. Despite the well-founded rationale for these studies, results have been modest.

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References

  • Alzheimer A. Ueber eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiat 64: 146–148, 1907

    Google Scholar 

  • Arai H, Kobayashi K, Ikeda K, et al. A computed tomography study of Alzheimer’s disease. Journal of Neurology 229: 69–77, 1983

    PubMed  CAS  Google Scholar 

  • Arnsten AFT, Cai JX, Goldsman-Rakic PS. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. Journal of Neuroscience 8: 4287–4296, 1988

    PubMed  CAS  Google Scholar 

  • Bagne CA, Pomara N, Crook T, Gershon S. Alzheimer’s disease: strategies for treatment and research. In Crook et al. (Eds) Treatment development strategies for Alzheimer’s disease, pp. 584–638, Mark Powley Associates, Connecticut, 1986

    Google Scholar 

  • Balldin J, Gottfries CG, Karlsson L, et al. Dexamethasone suppression test and serum prolactin in dementia disorders. British Journal of Psychiatry 143: 277–281, 1983

    PubMed  CAS  Google Scholar 

  • Barclay L, Zemcov A, Blass JP, McDowell F. Rates of decrease of cerebral blood flow in progressive dementias. Neurology 341: 1555–1560, 1984

    Google Scholar 

  • Barnes JM, Barnes NM, Costall B, Naylor RJ, Tyers MB. 5-HT3 receptors mediate inhibition of acetylcholine release in cortical tissue. Nature 338: 762–763, 1989

    PubMed  CAS  Google Scholar 

  • Bartus RT, Dean III RL, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–417, 1982

    PubMed  CAS  Google Scholar 

  • Bartus RT, Dean RL, Flicker C. Cholinergic psychopharmacology: an integration of human and animal research on memory. In Meltzer (Ed.) Psychopharmacology: the third generation of progress, pp. 219–232, Raven Press, NY, 1987

    Google Scholar 

  • Bartus RT, Dean RL, Pontecorvo MJ, Flicker C. The cholinergic hypothesis: a historical overview, current perspective and future directions. Annals of the New York Academy of Sciences 444: 332–358, 1985

    PubMed  CAS  Google Scholar 

  • Bartus RT, Dean RL, Sherman KA, Friedman E. Baer B. Profound effects of combining choline and piracetam on memory. Neurobiology of Aging 2: 105–111, 1981

    PubMed  CAS  Google Scholar 

  • Becker R, Giacobini E, Elble R, Mcllhani M, Sherman K. Potential pharmacotherapy of Alzheimer’s disease: a comparison of various routes of administration. Acta Neurologica Scandinavica 116(Suppl.): 19–32, 1988

    PubMed  CAS  Google Scholar 

  • Beller SA, Overall JE, Rhoades HM, Swann AC. Long term outpatient treatment of senile dementia with oral physostigmine. Journal of Clinical Psychiatry 49: 400–404, 1988

    PubMed  CAS  Google Scholar 

  • Bergmann I, et al. Alaproclate: a pharmacokinetics and biochemical study in patients with dementia of Alzheimer type. Psychopharmacology 80: 279–283, 1983

    Google Scholar 

  • Bird TD, Lampe TH, Nemens EJ, Miner GW, Sumi S, et al. Diagnosis of dementia: clinicopathological correlations. Neurology 29: 76–79, 1989

    Google Scholar 

  • Blessed G, Tomlinson BE, Roth M. The association between quantitative measurements of dementia and of senile changes in the cerebral gray matter of elderly subjects. British Journal of Psychiatry 114: 797–811, 1968

    PubMed  CAS  Google Scholar 

  • Boller F, Lopez OL, Mossy J. Diagnosis of dementia: clinicopathological correlations. Neurology 29: 76–79, 1989

    Google Scholar 

  • Bondareff W, Mountjoy CQ, Roth M. Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Neurology 32: 164–168, 1982

    PubMed  CAS  Google Scholar 

  • Bondareff W, Raval J, Colletti PM, Hauser DD. Quantitative magnetic resonance imaging and the severity of dementia in Alzheimer disease. American Journal of Psychiatry 145: 853–856, 1988

    PubMed  CAS  Google Scholar 

  • Bowen DM, Allen SJ, Benton JS, et al. Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer’s disease. Journal of Neurochemistry 41: 266–272, 1983

    PubMed  CAS  Google Scholar 

  • Bowen DM, Sims NR, Benton JS, et al. Treatment of Alzheimer’s disease: a cautionary note. New England Journal of Medicine 305: 1016, 1987

    Google Scholar 

  • Branconnier RJ. The efficacy of the cerebral metabolic enhances in the treatment of senile dementia. Psychopharmacology Bulletin 19: 212–219, 1983a

    PubMed  CAS  Google Scholar 

  • Branconnier RJ, Cole JO, Dessain EC, Spera KF, Ghazvinian S, et al. The therapeutic efficacy of piracetam in Alzheimer’s disease: preliminary observations. Psychopharmacology Bulletin 19: 726–730, 1983b

    Google Scholar 

  • Brufani M, Marta M, Pomponi M. Anticholinesterase activity of a new carbamate, heptylphysostigmine, in view of its use in patients with Alzheimer-type dementia. European Journal of Biochemistry 157: 115–120, 1986

    PubMed  CAS  Google Scholar 

  • Bruno G, Mohr E, Gillespie M, et al. RS-86 therapy of Alzheimer’s disease. Archives of Neurology 43: 659–661, 1985

    Google Scholar 

  • Chatellier G, Lacomblez L. Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. British Medical Journal 300: 495–499, 1990

    PubMed  CAS  Google Scholar 

  • Chiarello RJ, Cole JO. The use of psychostimulants in general psychiatry. Archives of General Psychiatry 44: 286–295, 1987

    PubMed  CAS  Google Scholar 

  • Christie JE, Kean DM, Douglas RH, Engleman HM, St Clair D, et al. Magnetic resonance imaging in pre-senile dementia of the Alzheimer-type, multi-infarct dementia and Korsakoffs syndrome. Psychology Medicine 18: 319–329, 1988

    CAS  Google Scholar 

  • Christie JE, Shering A, Ferguson J, Glen AIM. Physostigmine and arecoline: effects of intravenous infusions in Alzheimer’s presenile dementia. British Journal of Psychiatry 138: 46–50, 1981

    PubMed  CAS  Google Scholar 

  • Christie JE, Whalley LJ, Bennie J, et al. Characteristic plasma hormone changes in Alzheimer’s disease. British Journal of Psychiatry 150: 674–681, 1987

    PubMed  CAS  Google Scholar 

  • Cohen M, Satlin A, Zubenko GS. S-Adenosyl-L-methionine in the treatment of Alzheimer’s disease. Journal of Clinical Psychopharmacology 8: 43–47, 1988

    PubMed  CAS  Google Scholar 

  • Cook P, James I. Cerebral vasodilators. New England Journal of Medicine 305: 1508–1513, 1560-1564, 1981

    PubMed  CAS  Google Scholar 

  • Coper H, Herrmann WM. Psychostimulants, analeptics, nootropics: an attempt to differentiate and assess drugs designed for the treatment of impaired brain functions. Pharmacopsychiatry 21: 211–217, 1988

    PubMed  CAS  Google Scholar 

  • Crook T. Clinical drug trials in Alzheimer’s disease. Annals of New York Academy of Science 444: 428–436, 1985

    CAS  Google Scholar 

  • Crook T, Ferris S, Sathananthan G, et al. The effect of methylphenidate on test performance in the cognitively impaired aged. Psychopharmacology 52: 251–255, 1977

    PubMed  CAS  Google Scholar 

  • Cross AJ, Crow TJ, Ferrier IN, Johnson JA. The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia. Neurobiology of Aging 7: 3–7, 1986

    PubMed  CAS  Google Scholar 

  • Cuello AC: Towards trophic factor pharmacology. Neurobiology of Aging 10: 539–540, 1989

    PubMed  CAS  Google Scholar 

  • Cutler NR, Haxby J, Narang PK, May C, Burg C, et al. Evaluation of an analog of somatostatin (L363, 586) in Alzheimer’s disease. New England Journal of Medicine 312: 725, 1985

    PubMed  CAS  Google Scholar 

  • Davidson M, Bastaens L, Davis BM, Shah MB, Davis KL. Endocrine changes in Alzheimer’s disease. Neurologic Clinics 6: 149–157, 1988

    PubMed  CAS  Google Scholar 

  • Davidson M, Bierer LM, Kaminsky R, Ryan TM, Davis KL. Combined administration of physostigmine and clonidine to patients with dementia of the Alzheimer type: a pilot safety study. Alzheimer Disease and Associated Disorders 1: 1–4, 1989

    CAS  Google Scholar 

  • Davison M, Mohs RC, Hollander E, Zeminshlany Z, Powchik P, et al. Lecithin and piracetam in patients with Alzheimer’s disease. Biological Psychiatry 22: 112–114, 1987

    Google Scholar 

  • Davidson M, Zemishlany Z, Mohs RC, Horvath TB, Powchik P, et al. 4-Aminopyridine in the treatment of Alzheimer’s disease. Biological Psychiatry 23: 485–490, 1988

    PubMed  CAS  Google Scholar 

  • Davies P. Genetics of Alzheimer’s disease: a review and a discussion of the implications. Neurobiology of Aging 7: 456–459, 1986

    Google Scholar 

  • Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2: 1403–1405, 1976

    PubMed  CAS  Google Scholar 

  • Davis BM, Brown GM, Miller M, et al. Effects of cholinergic stimulation of pituitary hormone release. Psychoneuroendocrinology 7: 347, 1982

    PubMed  CAS  Google Scholar 

  • Davis BM, Mathe AA, Mohs RC, et al. Effects of propantheline bromide on basal growth hormone, Cortisol and prolactin levels. Psychoneuroendocrinology 18: 103–107, 1983

    Google Scholar 

  • Davis KL, Hollander E, Davidson M, Davis B, Mohs RC, et al. Induction of depression with oxotremorine in Alzheimer’s disease patients. American Journal of Psychiatry 144: 468–471, 1987

    PubMed  CAS  Google Scholar 

  • Dehlin O, Hedenrud B, Jansson P, Nörgåard J. A double-blind comparison of alaproclate and placebo in the treatment of patients with senile dementia. Acta Psychiatrica Scandinavica 71: 190–196, 1985

    PubMed  CAS  Google Scholar 

  • de Leon MJ, George AE, Reisberg B, Ferris SH, Kluger A, et al. Alzheimer’s disease: longitudinal CT studies of ventricular change. American Journal of Roentgenology 152: 1257–1262, 1989

    PubMed  Google Scholar 

  • De Wied D. The importance of vasopressin in memory. Trends in Neuroscience 7: 62–63, 1984

    Google Scholar 

  • Drachman DA, Leavitt J. Human memory and the cholinergic system. Archives of Neurology 30: 113–121, 1974

    PubMed  CAS  Google Scholar 

  • Drukarch B, Kits S, Van Der Meer EG, Lodder JC, Stoof JC. 9-amino-1,2,3,4-tetrahydroacridine (THA), an alleged drug for the treatment of Alzheimer’s disease, inhibits acetylcholinesterase activity and slow outward K+ current. European Journal of Pharmacology 141: 153–157, 1987

    PubMed  CAS  Google Scholar 

  • Drukarch B, Leysen JE, Stoof JC. Further analysis of the neuropharmacological profile of 9-amino-1,2,3,4-tetrahydroacridine (THA), an alleged drug for the treatment of Alzheimer’s disease. Life Sciences 42: 1011–1017, 1988

    PubMed  CAS  Google Scholar 

  • Duara R, Grady C, Haxby J, Sundaram M, Cutler NR, et al. Positron emission tomography in Alzheimer’s disease. Neurology 36: 879–887, 1986

    PubMed  CAS  Google Scholar 

  • Ferris SH. Empirical studies in senile dementia with central nervous system stimulants and metabolic enhances. In Crook & Gershon (Eds) Strategies for the development of an effective treatment for senile dementia, pp. 173–187, Mark Powley Associates Inc, 1981

    Google Scholar 

  • Ferris SH, Reisberg B, Crook T, Friedman E, Schneck MK, et al. Pharmacologic treatment of senile dementia: choline, L-DOPA, piracetam and choline plus piracetam. In Corkin et al. (Eds) Alzheimer’s disease: a report of progress, pp. 475–481, Raven Press, NY, 1982

    Google Scholar 

  • Ferris SH, Sathananthan G, Gershon S, et al. Senile dementia treatment with deanol. Journal of the American Geriatric Society 25: 241–244, 1977

    CAS  Google Scholar 

  • Fields RB, Van Kamman DP, Peters JL, Rosen J, Van Kammen WB, et al. Clonidine improves memory function in schizophrenia independently from changes in psychosis. Schizophrenia Research 1: 417–423, 1988

    PubMed  CAS  Google Scholar 

  • Fitch N, Becker R, Heller A. The inheritance of Alzheimer’s disease: a new interpretation. Annals of Neurology 23: 14–19, 1988

    PubMed  CAS  Google Scholar 

  • Fitten LJ, Perryman KM, Gross PL, Fine H, Cummins J, et al. Treatment of Alzheimer’s disease with short and long term oral THA and lecithin: a double-blind study. American Journal of Psychiatry 147: 2239–2244, 1990

    Google Scholar 

  • Folstein M. Heterogeneity in Alzheimer’s disease. Neurology of Aging 10: 434–435, 1989

    CAS  Google Scholar 

  • Freedman SB, Harley EA, Patel S, Saunders J, MacLeod A, et al. British Journal of Pharmacology, in press, 1990

    Google Scholar 

  • Friedman E, Sherman KA, Ferris SH, Reisberg B, Bartus RT, et al. Clinical response to choline pulls piracetam in senile dementia; relation to red-cell choline levels. New England Journal of Medicine 304: 1490–1491, 1981

    PubMed  CAS  Google Scholar 

  • Funk KF, Schmidt J. Cholinergic effects of nootropics. Biomedica Biochimica Acta 47: 417–421, 1988

    PubMed  CAS  Google Scholar 

  • Gauthier S, Leblanc R, Quirion R, et al. Transmitter-replacement therapy in Alzheimer’s disease using intracerebroventricular infusions of receptor agonists, Canadian Journal of Neurological Science 13: 394–402, 1986

    CAS  Google Scholar 

  • Gauthier S, Masson H, Gauthier L, et al. Tetrahydroamino acridine and lecithin in Alzheimer’s disease. In Giacobini E (Ed.) Current research in Alzheimer therapy, Taylor and Francis, New York, 1988

    Google Scholar 

  • Gemmell HG, Sharp PF, Besson JA, Ebmeier KP, Smith FW. A comparison of Tc-99m HM-PAO and 1-123 IMP cerebral SPECT images in Alzheimer’s disease and multi-infarct dementia. European Journal of Nuclear Medicine 14: 463–466, 1988

    PubMed  CAS  Google Scholar 

  • George AE, de Leon MJ, Ferris SH, Kricheff II. Parenchymal CT correlates of senile dementia (Alzheimer’s disease): loss of grey-white discriminality. American Journal of Neurology Research 2: 205–213, 1981

    CAS  Google Scholar 

  • Ghanbari HA, Miller BE, Haigler HJ, Arato M, Bisette G, et al. Biochemical assay of Alzheimer’s disease-associated protein(s) in human brain tissue. Journal of the American Medical Association 263: 2907–2910, 1990

    PubMed  CAS  Google Scholar 

  • Giurgea CE. Vers une pharmacologic de L’activite integrative du cerveaux: tentative du concept nootrope en psychopharmacologie. Actual Pharmacol (Paris) 25: 115–157, 1972

    CAS  Google Scholar 

  • Golbe LI, Langston JW, Shoulson I. Selegiline and Parkinson’s disease: protective and symptomatic considerations:. Drugs 39: 646–651, 1990

    PubMed  CAS  Google Scholar 

  • Gottfries CG, Adolfsson R, Aquilonius SM, et al. Biochemical changes in dementia disorders of the alzheimer type (AD/SDAT). Neurobiology of Aging 4: 261, 1983

    PubMed  CAS  Google Scholar 

  • Gottfries CG, Bartfai T, Carlsson A, Eckernas S, Svennerholm L. Multiple deficits in both grey and white matter in Alzheimer’s brains. Progress in Neuro-Psychopharmacology and Biological Psychiatry 10: 405–415, 1986

    PubMed  CAS  Google Scholar 

  • Grady C. Longitudinal changes in brain metabolism. In Friedland (Moderator) Alzheimer’s disease: clinical and metabolic heterogeneity, pp. 302–304. Annals of Internal Medicine 109: 298–311, 1988

    Google Scholar 

  • Greenwald BS, Mathe AA, Mohs RC, et al. Cortison and Alzheimer’s disease, II: dexamethasone suppression, dementia severity and affective symptoms. American Journal of Psychiatry 143: 442–446, 1986

    PubMed  CAS  Google Scholar 

  • Growdon JH, Corkin S, Huff FJ, Rosen TJ. Piracetam combined with lecithin in the treatment of Alzheimer’s disease. Neurobiology of Aging 7: 269–276, 1986

    PubMed  CAS  Google Scholar 

  • Harbaugh RE. Intracerebroventricular bethanechloride administration in Alzheimer’s disease: preliminary results of a double blind study. Journal of Neurotransmission 24(Suppl.): 271–277, 1987

    CAS  Google Scholar 

  • Haroutunian V, Kanof PD, Davis KL. Pharmacological alleviation of cholinergic lesion induced memory deficits in rats. Life Science 37: 945–952, 1985

    CAS  Google Scholar 

  • Haroutunian V, Kanof PD, Tsuboyama G, Davis KL. Restoration of cholinomimetic activity by clonidine in cholinergic plus adrenergic lesioned rats. Brain Research, in press, 1990

    Google Scholar 

  • Haxby JF, Duara R, Grady CL, Cutler NR, Rapoport SI. Relations between a neuropsychological and cerebral metabolic asymmetries in early Alzheimer’s disease. Journal of Cerebral Blood Flow Metabolism 5: 193–200, 1985

    PubMed  CAS  Google Scholar 

  • Haxby JV, Grady CL, Duara R, Schlageter NL, Berg G, et al. Neocortical metabolic abnormalities precede non-memory cognitive defects in Alzheimer’s-type dementia. Archives of Neurology 43: 882–885, 1986

    PubMed  CAS  Google Scholar 

  • Hefti F, Hartikka J, Knusel B. Function of neurotropic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases. Neurobiology of Aging 10: 513–533, 1989

    Google Scholar 

  • Heiss WD, Heboid I, Klinkhammer P, Ziffling P, Szelies B, et al. Effect of piracetam on cerebral glucose metabolism in Alzheimer’s disease as measured by positron emission tomography. Journal of Cerebral Blood Flow Metabolism 8: 613–617, 1988

    PubMed  CAS  Google Scholar 

  • Hellman RS, Tikofsky RS, Collier BD, Hoffmann RG, Palmer DW, et al. Alzheimer disease: quantitative analysis of I-123-iodoamphetamine SPECT brain imaging. Radiology 1172: 183–188, 1989

    Google Scholar 

  • Henderson VW, Roberts E, Wimer C, et al. Multicenter trial of naloxone in Alzheimer’s disease. Annals of Neurology 25: 404–406, 1989

    PubMed  CAS  Google Scholar 

  • Heston LL. Alzheimer’s dementia and Down’s genetic evidence suggesting an association. Annals of the New York Academy of Sciences 396: 29–37, 1982

    PubMed  CAS  Google Scholar 

  • Heston LL, Mastri AR, Anderson VE, White J. Dementia of the Alzheimer type: clinical genetics, natural history and associated conditions. Archives of General Psychiatry 38(10): 1085–1090, 1981

    PubMed  CAS  Google Scholar 

  • Heyman A, Wilkinson WE, Hurwitz BJ, Schmechel D. Alzheimer’s disease: genetic aspects and associated clinical disorders. Annals of Neurology 14: 507–515, 1983

    PubMed  CAS  Google Scholar 

  • Hollander E, Davidson M, Mohs RC, Horvath TB, Davis BM, et al. RS 86 in the treatment of Alzheimer’s disease: cognitive and biological effects. Biological Psychiatry 22: 1067–1078, 1987

    PubMed  CAS  Google Scholar 

  • Hollister LE, Yesavage J. Ergoloid mesylates for senile dementias; unanswered questions. Annals of Internal Medicine 100: 894–898, 1984

    PubMed  CAS  Google Scholar 

  • Itil TM, Gopi N, Menon GN. The effects of oxiracetam (ISF 2522) in patients with organic brain syndrome (a double-blind controlled study with piracetam). Drug Development Research 2: 447–461, 1982

    Google Scholar 

  • Itil TM, Menon GN, Songar A, Itil KZ. CNS pharmacology and clinical therapeutical effects of oxiracetam. Clinical Neuropharmacology 9(Suppl. 3): 670–672, 1986

    Google Scholar 

  • Jellinger K, Flament H, Riedere P, Schmid H, Riedere P, et al. Levodopa in the treatment of (pre) senile dementia. Mechanisms of Aging and Development 14: 253–264, 1980

    CAS  Google Scholar 

  • Joachim CL, Hiroshi M, Selkoe DJ. Amyloid β-protein deposition in tissue other than brain in Alzheimer’s disease. Nature 341: 226–230, 1989

    PubMed  CAS  Google Scholar 

  • Jolles J. Neuropeptides and the treatment of cognitive deficits in aging and dementia. Progress in Brain Research 70: 429–441, 1986

    PubMed  CAS  Google Scholar 

  • Jorm AF. Effects of cholinergic enhancement therapies on memory function in Alzheimer’s disease: a meta-analysis of the literature. Australian and New Zealand Journal of Psychiatry 20: 237–240, 1986

    PubMed  CAS  Google Scholar 

  • Kaye WH. Modest facilitation of memory in dementia with combined lecithin and anticholinesterase treatment. Biological Psychiatry 17: 275–280, 1982

    PubMed  CAS  Google Scholar 

  • Kido KD, Caine ED, LeMay M, et al. Temporal lobe atrophy in patients with Alzheimer’s disease: a CT study. American Journal of Neurology Research 10: 551–555, 1989

    CAS  Google Scholar 

  • Komatani A, Yamaguchi K, Sugai Y, Takanashi T, Kera M, et al. Assessment of demented patients by dynamic SPECT of inhaled xenon-133. Journal of Nuclear Medicine 29: 1621–1626, 1988

    PubMed  CAS  Google Scholar 

  • Kopeland MD, Lishman WA. Pharmacological treatments of dementia (non-cholinergic). British Medical Bulletin 42: 101–105, 1986

    Google Scholar 

  • Kragh-Sorensen P, Lolk A. Neuropeptides and dementia. Progress in Brain Research 72: 269–277, 1987

    PubMed  CAS  Google Scholar 

  • Krieger DT, Krieger HP. Orcadian pattern of plasm 17-hydroxycorticosteroid: alteration by anticholinergic agents. Science 155: 1421, 1967

    PubMed  CAS  Google Scholar 

  • Kristensen V, Olsen M, Theilgard A. Levodopa treatment of presenile dementia. Acta Psychiatrica Scandinavica 55: 41–51, 1977

    PubMed  CAS  Google Scholar 

  • Lavy S, Melamed E, Bentin S, et al. Bihemispheric decrease of regional cerebral blood flow in dementia: correlation with age-matched normal controls. Annals of Neurology 4: 445–450, 1978

    PubMed  CAS  Google Scholar 

  • Lehman HE, Ban TA. Central nervous stimulants and anabolic substances in geropsychiatric therapy. In Gershon & Raskin (Eds) Aging, Vol. 2, pp. 179–202, Raven Press, NY, 1975

    Google Scholar 

  • LeMay M, Stafford JM, Sandor T, Albert M, Haykal H, et al. Statistical assessment of perceptual CT ratings in patients with Alzheimer type dementia. Journal of Computer Assisted Tomography 10: 802–809, 1986

    PubMed  CAS  Google Scholar 

  • Little A, Levy R, Chuaqui-Kidd P, Hand D. A double blind placebo controlled trial of high-dose lecithin in Alzheimer’s disease. Journal of Neurological and Neurosurgical Psychiatry 48: 736–742, 1985

    CAS  Google Scholar 

  • Levy R, Little A, Chuaqui-Kidd P, Reith M. Early results from double blind, placebo controlled trial of high-dose phosphatidylcholine in Alzheimer’s disease. Lancet 1: s987–988, 1983

    Google Scholar 

  • Lorranger AW, Goodell H, Lee JW, et al. Treatment of Parkinson’s syndrome: improved intellectual functioning. Archives of General Psychiatry 26: 163, 1972

    Google Scholar 

  • Luxenberg J. Imaging studies of brain anatomy. In Friedland (Moderator) Alzheimer’s disease: clinical and metabolic heterogeneity. Annals of Internal Medicine 109: 298–311, 1988

    PubMed  Google Scholar 

  • Marazita ML, Spence A, Heyman A. Tests for genetic heterogeneity among 18 families with Alzheimer’s disease. Neurology 37: 1678–1679, 1987

    PubMed  CAS  Google Scholar 

  • Marsh GR, Linnoila M. The effect of deanol on cognitive performance and electrophysiology in elderly humans. Psychopharmacology 66: 99–104, 1979

    PubMed  CAS  Google Scholar 

  • Marta M, Castellano C, Oliverio A, Pavone F, Pagella PG, et al. New analogs of physostigmine: alternative drugs for Alzheimer’s disease? Life Sciences 43: 1921–1928, 1988

    PubMed  CAS  Google Scholar 

  • Martini E, Pataky I, Szilagyi K, Venter V. Brief information on an early phase-II-study with deprenyl in demented patients. Pharmacopsychiatry 20: 256–257, 1987

    PubMed  CAS  Google Scholar 

  • Marx J. NGF and Alzheimer’s: hopes and fears. Science 24: 408–410, 1990

    Google Scholar 

  • McDonald RJ. Drug treatment of senile dementia. In Wheatley (Ed.) Psychopharmacology of old age, pp. 113–138, Oxford University Press, London, 1983

    Google Scholar 

  • McEntee W, Mair R. Memory enhancement in Korsakoff’s psychosis by clonidine: further evidence of a noradrenergic deficit. Annals of Neurology 27: 466–470, 1980

    Google Scholar 

  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology 34: 939–944, 1984

    PubMed  CAS  Google Scholar 

  • Mendelson WB, Sitaram N, Wyatt RJ, et al. Methylscopalamine inhibition of sleep related growth hormone secretion. Journal of Clinical Investigation 61: 1683–1690, 1978

    PubMed  CAS  Google Scholar 

  • Mizuki Y, Yamada M, Kato I, Takada Y, Tsujimaru S, et al. Effects of aniracetam, a nootropic drug, in senile dementia - a preliminary report. Kurume Medical Journal 31: 135–143, 1984.

    PubMed  CAS  Google Scholar 

  • Mobley WC, Neve RL, Prusiner SB, McKinley MP. Nerve growth factor induces gene expression for prion and Alzheimer’s beta-amyloid proteins. Proceedings of the National Academy of Science, USA 85: 9811–9815, 1988

    CAS  Google Scholar 

  • Moglia A, Sinforiani E, Zandrini C, et al. Activity of oxiracetam in patients with organic brain syndrome: a neuropsychological study. Clinical Neuropharmacology 9(Suppl. 3): 573–578, 1986

    Google Scholar 

  • Mohr E, Schlegel J, Fabbrini G, et al. Clonidine treatment of Alzheimer’s disease. Archives of Neurology 46: 376–378, 1989

    PubMed  CAS  Google Scholar 

  • Mohs RC, Breitner JCS, Silverman JM, et al. Alzheimer’s disease morbid risk among first degree relatives approximates 50% by 90 years. Archives of General Psychiatry 44: 405–408, 1987

    PubMed  CAS  Google Scholar 

  • Mohs RC, Davis KL. The experimental pharmacology of Alzheimer’s disease and related dementias. In Meltzer (Ed.) Psychopharmacology: the third generation of progress, pp. 921–928, Raven Press, NY, 1987

    Google Scholar 

  • Mohs RC, Greenberg DA, Silverman JM. Genetic studies of typical Alzheimer’s disease. Neurobiology of Aging 10: 438–439, 1989

    PubMed  CAS  Google Scholar 

  • Mondadori C, Petschke F. Do piracetam-like compounds act centrally via peripheral mechanisms? Brain Research 435: 310–314, 1987

    PubMed  CAS  Google Scholar 

  • Morris JC, McKeel Jr DW, Fulling K, Torack RM, Berg L. Validation of clinical diagnostic criteria in senile dementia of the Alzheimer type. Annals of Neurology 24: 17–22, 1988

    PubMed  CAS  Google Scholar 

  • Mouradian MM, Mohr E, Williams AJ, Chase TN. No response to high-dose muscarinic agonist therapy in Alzheimer’s disease. Neurology 38: 606–608, 1988

    PubMed  CAS  Google Scholar 

  • Nakahara N, Iga Y, Mizobe F, Kawanishi G. Amelioration of experimental amnesia (passive avoidance failure) in rodents by selective M1 agonist AF102B. Japan Journal of Pharmacology 48: 502–505, 1988

    CAS  Google Scholar 

  • Nee LE, Eldridge R, Sunderland T, et al. Dementia of the Alzheimer type: clinical and family study of 22 twin pairs. Neurology 37: 359–363, 1987

    PubMed  CAS  Google Scholar 

  • Nee LE, Polinsky RJ, Eldridge R. A family with histologically confirmed Alzheimer’s disease. Archives of Neurology 40: 203–208, 1983

    PubMed  CAS  Google Scholar 

  • Newhouse PA, Sunderland T, Tariot PN, Blumhardt CL, Weingartner H, et al. IV nicotine in Alzheimer’s disease, a pilot study. Psychopharmacology 95: 2–11, 1988

    Google Scholar 

  • Ono S, Saito Y, Ohgane N, Kawanishi G, Mizobe F. Heterogeneity of muscarinic heteroreceptors in the rat brain: effects of a novel M1 agonist, AF102B. European Journal of Pharmacology 155: 77–84, 1988

    PubMed  CAS  Google Scholar 

  • Ostfeld A, Smith CM, Slotsky BA. The systemic use of procaine in the treatment of the elderly. Journal of the American Geriatric Society 25: 1–19, 1977

    CAS  Google Scholar 

  • Penn RD, Martin EM, Wilson RS, Fox JH, Savoy SM. Intraventricular Bethanechol infusion of Alzheimer’s disease: results of double blind and escalating dose trials. Neurology 38: 219–222, 1988

    PubMed  CAS  Google Scholar 

  • Perry EK. Cortical neurotransmitter chemistry in Alzheimer’s disease. In Meltzer (Ed.) Pharmacology: the third generation of progress, New York, Raven Press, 1987

    Google Scholar 

  • Perry EK, Tomlinson BE, Blessed G, Bergman K, Igson PH, et al. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. British Medical Journal 2: 1457–1459, 1978

    PubMed  CAS  Google Scholar 

  • Pomara N, Block R, Moore N, Rhiew HP, Berchou R, et al. Combined piracetam and cholinergic precursor treatment for primary degenerative dementia. IRCS Medical Science 12: 388–389, 1984

    Google Scholar 

  • Press GA, Amaral DG, Squire LR. Hippocampal abnormalities in amnesic patients revealed by high-resolution magnetic resonance imaging. Nature 341: 54–57, 1989

    PubMed  CAS  Google Scholar 

  • Prien RF. Psychostimulants in the treatment of senile dementia in Alzheimer’s disease. In Reisberg (Ed.) Alzheimer’s disease, pp, 381–386, Free Press, NY, 1983

    Google Scholar 

  • Procter AW, Bowen DM. Betha-carbolines for Alzheimer’s disease? - more evidence, a test of efficacy and some precautions. Trends in Neuroscience 11: 208–209, 1988

    CAS  Google Scholar 

  • Prohovnik I, Mayeux R, Sackheim HA, Smith G, Stern Y, et al. Cerebral perfusion as a diagnostic marker of early Alzheimer’s disease. Neurology 38: 931–937, 1988

    PubMed  CAS  Google Scholar 

  • Raskind M, Peskind E, Rivard MF, et al. Dexamethasone suppression test and Cortisol and circadian rhythm in primary degenerative dementia. American Journal of Psychiatry 139: 1468–1471, 1982

    PubMed  CAS  Google Scholar 

  • Reifler BV, Larson E, Hanley R. Coexistence of cognitive impairment and depression in geriatric outpatients. American Journal of Psychiatry 139: 623–626, 1982

    Google Scholar 

  • Reisberg B, Ferris SH, Anand R, Mir P, De Leon MJ, et al. Naloxone effects on primary degenerative dementia (PDD). Psychopharmacology Bulletin 19: 45–47, 1983a

    Google Scholar 

  • Reisberg B, Ferris SH, Anand R, Mir P, Geibel V, et al. Effects of naloxone in senile dementia: a double blind trial. New England Journal of Medicine 308: 721–722, 1983b

    PubMed  CAS  Google Scholar 

  • Riederer P, Jellinger K. Morphological and biochemical changes in the aging brain: pathophysiological and possible therapeutic consequences. Experimental Brain Research 5(Suppl.): 158, 1982

    CAS  Google Scholar 

  • Roses AD. A conservative viewpoint on linkage in Alzheimer’s disease. Neurobiology of Aging 10: 427–429, 1989

    Google Scholar 

  • Rossor M, Iversen LL. Non-cholinergic neurotransmitter abnormalities in Alzheimer’s disease. British Medical Bulletin 42: 70–74, 1986

    PubMed  CAS  Google Scholar 

  • Rovner BW, Broadhead J, Spencer M, Carson K, Folstein MF. Depression and Alzheimer’s disease. American Journal of Psychiatry 146: 350–353, 1989

    PubMed  CAS  Google Scholar 

  • Sandor T, Albert M, Stafford J, Harpley S. Use of computerized CT analysis to discriminate between Alzheimer patients and normal control subjects. American Journal of Neurology Research 9: 1181–1187, 1988

    CAS  Google Scholar 

  • Sarter M. Some considerations of different modes of action of nootropic drugs. Neuropsychobiology 15: 192–200, 1986

    PubMed  CAS  Google Scholar 

  • Sarter M, Schneider HH, Stephens DN. Treatment strategies for senile dementia: antagonist betha-carbolines. Trends in Neuroscience 11: 13–16, 1988

    CAS  Google Scholar 

  • Saunders J, Showell GA, Snow J, et al. 2-Methyl-1, 3-dioxaazaspiro [4.5] decanes as novel muscarinic cholinergic agonists. Journal of Medical Chemistry 31: 487–491, 1988

    Google Scholar 

  • Schellenberg GD, Bird TD, Wijsman EM, et al. Absence of linkage of chromosome 21q21 markers to familial Alzheimer’s disease. Science 241: 1507–1510, 1988

    PubMed  CAS  Google Scholar 

  • Schlegel J, Mohr E, Williams J, Mann U, Gering M, et al. Guanfacine treatment of Alzheimer’s disease. Clinical Neuropharmacology 12: 124–128, 1989

    PubMed  CAS  Google Scholar 

  • Schneck MK. Nootropics. In Reisbert (Ed.) Alzheimer’s disease, pp. 362–368, Free Press, NY, 1983

    Google Scholar 

  • Schneck MK, Reisberg B, Ferris SH. Neurotransmitter treatment of senile dementia, Alzheimer’s type. International Drug Therapy Newsletter 2: 5–8, 1981

    Google Scholar 

  • Shutske GM, Pierrat FA, Cornfeldt ML, Szewczak MR, Huger FP, et al. Disease, pp. 362–368, Free Press, NY, 1983

    Google Scholar 

  • Shutske GM, Pierrat FA, Cornfeldt ML, Szewczak MR, Huger FP, et al. (±)-9-Amino-1,2,3,4,-tetrahydroacridin-1-o1: a potential Alzheimer’s disease therapeutic of low toxicity. Journal of Medical Chemistry 31: 1278–1279, 1988

    CAS  Google Scholar 

  • Sitaram N, Weingartner H, Gillin JC. Human serial learning: enhancement with arecoline and impairment with scopolamine correlated with performance on placebo. Science 201: 274–276, 1978

    PubMed  CAS  Google Scholar 

  • Smith RC, Vroulis G, Johnson R, Morgan R. Comparison of therapeutic response to long-term treatment with lecithin versus piracetam plus lecithin in patients with Alzheimer’s disease. Psychopharmacology Bulletin 20: 542–546, 1984

    PubMed  CAS  Google Scholar 

  • Sourander LB, Portin R, Molsa P, et al. Senile dementia of the Alzheimer’s type treated with aniracetam. Psychopharmacology 91: 90–95, 1987

    PubMed  CAS  Google Scholar 

  • Spar JE, Gerner R. Does the dexamethasone suppression test distinguish dementia from depression? American Journal of Psychiatry 139: 238–240, 1982

    PubMed  CAS  Google Scholar 

  • Stern Y, Sano M, Mayeux R. Effects of oral physostigmine in Alzheimer’s disease. Annals of Neurology 22: 306–310, 1987

    PubMed  CAS  Google Scholar 

  • St George-Hyslop PH, Myers RH, Haines JL, et al. Familial Alzheimer’s disease: progress and problems. Neurobiology of Aging 10: 417–425, 1989

    PubMed  CAS  Google Scholar 

  • St George-Hyslop PH, Tanzi RE, Polinsky RJ, et al. The genetic defect causing familial Alzheimer’s disease maps on chromosome 21. Science 235: 885–890, 1987

    Google Scholar 

  • Summers WK, Altmann F. THA: a review of the literature and its use in treatment of five overdose patients. Clinical Toxicology 16: 269–281, 1981

    Google Scholar 

  • Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A. Oral tetrahydroaminoacridine in long term treatment of senile dementia Alzheimer type. New England Journal of Medicine 315: 1241–1245, 1986

    PubMed  CAS  Google Scholar 

  • Summers WK, Viesselman JO, Marsh GM, Candelora K. Use of THA in treatment of Alzheimer-like dementia: pilot study in twelve patients. Biology Psychiatry 16: 145–153, 1981

    CAS  Google Scholar 

  • Tariot PN, Cohen RM, Sunderland T, Newhouse PA, Yount D, et al. L-Deprenyl in Alzheimer’s disease. Archives of General Psychiatry 44: 427–433, 1987a

    PubMed  CAS  Google Scholar 

  • Tariot PN, Cohen RM, Welkowitz JA, Sunderland T, Newhouse PA, et al. Multiple-dose arecoline infusions in Alzheimer’s disease. Archives of General Psychiatry 45: 901–905, 1988b

    PubMed  CAS  Google Scholar 

  • Tariot PN, Sunderland T, Cohen RM, Newhowse PA, Mueller EA, et al. Trancylpromine compared with L-deprenyl in Alzheimer’s disease. Journal of Clinical Psychopharmacology 8: 23–27, 1988a

    PubMed  CAS  Google Scholar 

  • Tariot PN, Sunderland T, Weingartner H, Murphy DL, Welkowitz JA, et al. Cognitive effects of L-deprenyl in Alzheimer’s disease. Psychopharmacology 91: 489–495, 1987b

    PubMed  CAS  Google Scholar 

  • Thal LJ, Salmon DP, Lasker B, Bower RNC, Klauber MR. The safety and lack of efficacy of vinpocetine in Alzheimer’s disease. Journal of the American Geriatric Society 37: 515–520, 1989

    CAS  Google Scholar 

  • Tomlinson BE, Blessed G, Roth M. Observations on the brains of non-demented old people. Journal of the Neurological Sciences 7: 331–356, 1968

    PubMed  CAS  Google Scholar 

  • Tourigny-Rivard MF, Raskind M, Rivard D. The dexamethasone suppression test in an elderly population. Biological Psychiatry 16: 1177–1184, 1981

    PubMed  CAS  Google Scholar 

  • Vernon M, Sorkin EM. Piracetam: an overview of its pharmacological properties and a review of its therapeutic use in senile cognitive disorders. Drugs and Aging 1: 17–35, 1991

    PubMed  CAS  Google Scholar 

  • Vida S, Gauthier L, Gauthier S. Canadian collaborative study of tetrahydroaminoacridine (THA) and lecithin treatment of Alzheimer’s disease: effect on mood. Canadian Journal of Psychiatry 34: 165–170, 1989

    CAS  Google Scholar 

  • Villardita C, Parini J, Grioli S, et al. Clinical and neuropsychological investigations on oxiracetam in patients with mild to moderate dementia. Clinical Neuropharmacology 9(Suppl. 14): 301–303, 1986

    Google Scholar 

  • Waters C. Cognitive enhancing agents: current status in the treatment of Alzheimer’s disease. Canadian Journal of Neurological Science 15: s249–256, 1988

    Google Scholar 

  • Weiner MF, Davis BM, Mohs RC, et al. Influence of age and relative weight on Cortisol suppression in normal subjects. American Journal of Psychiatry 144: 646–649, 1987

    PubMed  CAS  Google Scholar 

  • Wesseling H, Agoston S, Van Dam GBP, Pasma J, De Witt DJ, et al. Effects of 4-aminopyridine in elderly patients with Alzheimer’s disease. New England Journal of Medicine 310: 988–989, 1984

    PubMed  CAS  Google Scholar 

  • Wettstein A, Spiegel R. Clinical studies with the cholinergic drug RS-86 in Alzheimer’s disease (AD) and senile dementia of Alzheimer type (SDAT). Psychopharmacology 84: 572–573, 1984

    PubMed  CAS  Google Scholar 

  • Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, et al. Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science 215: 1237–1239, 1982

    PubMed  CAS  Google Scholar 

  • Wilson RS, Martin EM. New intrathecal drugs in Alzheimer’s disease and psychometric testing. Annals of New York Academy of Sciences 531: 180–186, 1988

    CAS  Google Scholar 

  • Wisniewski KE, Dalton AJ, McLachlan C, et al. Alzheimer’s disease in Downs syndrome: clinicopathologic studies, Neurology 35: 957–961, 1985

    PubMed  CAS  Google Scholar 

  • Wittenborn JR. Pharmacotherapy for aged related behavioral deficiencies. Journal of Nervous Mental Disorders 169: 139–156, 1981

    CAS  Google Scholar 

  • Wolozin BL, Pruchniki A, Dickson DW, Davies P. A neuronal antigen in the brains of patients with Alzheimer’s disease. Science 232: 648, 1986

    PubMed  CAS  Google Scholar 

  • Wurtman RJ, Magill SG, Reinstein DK. Piracetam diminishes hippocampal ACh levels in rats. Life Sciences 28: 1091–1093, 1981

    PubMed  CAS  Google Scholar 

  • Yamamoto T, Hirano A. Nucleus raphe dorsalis in Alzheimer’s disease: neurofibrillary tangles and loss of large neurons. Annals of Neurology 17: 573–577, 1985

    PubMed  CAS  Google Scholar 

  • Yesavage JA, Tinklenberg JR, Hollister LE, Berger PA. Vasodilators in senile dementia: a review of the literature. Archives of General Psychiatry 36: 220–223, 1979

    PubMed  CAS  Google Scholar 

  • Zubenko GS, Cohen BM, Boiler F, et al. Platelet membrane abnormality in Alzheimer’s disease. Annals of Neurology 22: 224–234, 1987

    Google Scholar 

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  1. Department of Psychiatry, Mount Sinai School of Medicine, Box 1230, 1 Gustave L, Levy Place, New York, New York, 10128, USA

    Carol Hermann, Robert G. Stern, Miklos F. Losonzcy, Stacey Jaff & Michael Davidson

  2. The Bronx Veterans Administration Medical Center, Bronx, New York, USA

    Carol Hermann, Robert G. Stern, Miklos F. Losonzcy, Stacey Jaff & Michael Davidson

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Hermann, C., Stern, R.G., Losonzcy, M.F. et al. Diagnostic and Pharmacological Approaches in Alzheimer’s Disease. Drugs & Aging 1, 144–162 (1991). https://doi.org/10.2165/00002512-199101020-00006

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