Cognitive decline in the elderly: A double- blind, placebo- controlled multicenter study on efficacy of phosphatidylserine administration


This double- blind study assesses the therapeutic efficacy and the safety of oral treatment with phosphatidylserine (BC- PS) vs placebo (300 mg/day for 6 months) in a group of geriatric patients with cognitive impairment. A total of 494 elderly patients (age between 65 and 93 years), with moderate to severe cognitive decline, according to the Mini Mental State Examination and Global DeteriorationScale, were recruited in 23 Geriatric or General Medicine Units in Northeastern Italy. Sixty- nine patients dropped out within the 6- month trial period. Patients were examined just before starting therapy, and 3 and 6 months thereafter. The efficacy of treatment compared to placebo was measured on the basis of changes occurring in behavior and cognitive performance using the Plutchik Geriatric Rating Scale and the Buschke Selective Reminding Test. Statistically significant improvements in the phosphatidylserine- treated group compared to placebo were observed both in terms of behavioral and cognitive parameters. In addition, clinical evaluation and laboratory tests demonstrated that BC- PS was well tolerated. These results are clinically important since the patients were representative of the geriatric population commonly met in clinical practice. (Aging Clin. Exp. Res. 5: 123- 133, 1993).

This is a preview of subscription content, access via your institution.


  1. 1.

    Greene J.G., Smith R., Gardiner M., Timbury G.C.: Measuring behavioural disturbance of elderly demented patients in the community and its effects on relatives: a factor analytic study. Age Ageing 11: 121–126, 1982.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Folstein M.F., Anthony J.C., Parhad I., Duffy B., Gruenberg E.M.: The meaning of cognitive impairment in the elderly. J. Am. Geriatr. Soc. 33: 228–235, 1985.

    PubMed  CAS  Google Scholar 

  3. 3.

    Katzman R.: Alzheimer’s disease. N. Engl. J. Med. 314: 964–973, 1986.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Svennerholm L., Bostrom K., Heiander C.G., Jungbjer B.: Membrane lipids in the aging human brain. J. Neurochem. 56: 2051–2059, 1991.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Schroeder F.: Role of membrane lipid asymmetry in aging. Neurobiol. Aging 5: 323–333, 1984.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Rapoport S.I., London E.D.: Brain metabolism during aging of the rat and dog. Implications for brain function in man during aging and dementia. In: Terry R.D., Bolis C.G., Toffano G. (Eds.), Neural Aging and its implications in human neurological pathology. Raven Press, New York, 1982, pp. 79–88.

    Google Scholar 

  7. 7.

    Hirata F., Axelrod J.: Phospholipid methylation and biological signal transmission. Science 209: 1082–1090, 1980.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    DeKosky S.T., Scheff S.W.: Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann. Neurol. 27: 457–464, 1990.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Feinstein A.R.: An additional basic science for clinical medicine: II. The limitations of randomized trials. Ann. Intern. Med. 99: 544–550, 1983.

    Article  CAS  Google Scholar 

  10. 10.

    Toffano G., Bruni A.: Pharmacological properties of phospholipid liposomes. Pharmacol. Res. Commun. 12: 829–845, 1980.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Calderini G., Bellini F., Bonetti A.C., Galbiati E., Guidolin D., Milan F., Nunzi M.G., Rubini R., Zanotti A., Toffano G.: Pharmacological properties of phosphatidylserine in the ageing brain. Clin. Trials J. 24: 9–17, 1987.

    Google Scholar 

  12. 12.

    Toffano G., Leon A., Mazzari S., Savoini G., Teolato S., Orlando P.: Modification of noradrenergic hypothalamic system in rat injected with phosphatidylserine liposomes. Life Sci. 23: 1093–1102, 1987.

    Article  Google Scholar 

  13. 13.

    Mazzari S., Battistella A.: Phosphatidylserine effects on dopamine release from striatum synaptosomes. In: Di Benedetta C., Balazs R., Gombos G., Porcellati G. (Eds.), Multidisciplinary approach to brain development. North-Holland/Elsevier, Amsterdam, 1980, pp. 569–570.

    Google Scholar 

  14. 14.

    Vannucchi M.G., Pepeu G.: Effect of phosphatidylserine on acetylcholine release and content in cortical slices from aging rats. Neurobiol. Aging 8: 403–407, 1987.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Casamenti F., Scali C., Pepeu G.: Phosphatidylserine reverses the age-dependent decrease in cortical acetylcholine release: a microdialysis study. Eur. J. Pharmacol. 194: 11–16, 1991.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Nunzi M.G., Milan F., Guidolin D., Toffano G.: Dendritic spine loss in hippocampus of aged rats. Effect of brain phosphatidylserine administration. Neurobiol. Aging 8: 501–551, 1987.

    Article  CAS  Google Scholar 

  17. 17.

    Guidolin D., Milan F., Polato P., Nunzi M.G., Toffano G.: Phosphatidylserine treatment prevents age-induced structural alterations in the rat septo-hippocampal system. In: Bazan N.G., Horrocks L.A., Toffano G. (Eds.), Phospholipid in the nervous system: biochemical and molecular pathology. Liviana Press, Padova, 1989, pp. 183–193.

    Google Scholar 

  18. 18.

    Corwin J., Dean R.L. III, Bartus R.T., Rotrosen J., Watkins D.L.: Behavioral effects of phosphatidylserine in the aged Fischer 344 rat: amelioration of passive avoidance deficits without changes in psychomotor task performance. Neurobiol. Aging 6: 11–15, 1985.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Drago F., Canonico P.L., Scapagnini U.: Behavioral effects of phosphatidylserine in aged rats. Neurobiol. Aging 2: 209–213, 1981.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Zanotti A., Valzelli L., Toffano G.: Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. Psychopharmacology 99: 316–321, 1989.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Amaducci L., Crook T.H., Lippi A.: Use of phosphatidylserine in Alzheimer’s Disease. Ann. N.Y. Acad. Sci. 640: 245–249, 1991.

    PubMed  CAS  Google Scholar 

  22. 22.

    Monteleone P., Beinat L., Tanzillo C., Maj M., Kemali D.: Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology 52: 243–248, 1990.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Monteleone P., Maj M., Beinat L., Natale M., Kemali D.: Blunting by chronic phosphatidylserine of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur. J. Clin. Pharmacol. 41: 385–388, 1992.

    Google Scholar 

  24. 24.

    Rosadini G., Sannita W.G., Nobili F., Cenacchi T.: Phosphatidylserine: quantitative EEG effects in healthy volunteers. Neuropsychobiology 24: 42–48, 1991.

    Article  CAS  Google Scholar 

  25. 25.

    Klinkhammer P., Szelies B., Heiss W.D.: Effect of phosphatidylserine on cerebral glucose metabolism in Alzheimer’s disease. Dementia 1: 197–201, 1990.

    Google Scholar 

  26. 26.

    Palmieri G., Palmieri R., Inzoli M.R., Lomabardi G., Sottini C., Tavolato B., Giometto B.: Double-blind controlled trial of phosphatidylserine in patients with senile mental deterioration. Clin. Trials J. 24: 73–83, 1987.

    Google Scholar 

  27. 27.

    Villardita C., Grioli S., Salmeri G., Nicoletti F., Pennisi G.: Multicentre clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration. Clin. Trials J. 24: 84–93, 1987.

    Google Scholar 

  28. 28.

    Maggioni M., Picotti G.B., Bondiolotti G.P., Panerai A., Cenacchi T., Nobile P., Brambilla F.: Effects of phosphatidylserine therapy in geriatric patients with depressive disorders. Acta Psychiatr. Scand. 81: 265–270, 1990.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Crook T.H., Tinklenberg J., Yesavage J., Petrie W., Nunzi M.G., Massari C.D.: Effects of phosphatidylserine in age-associated memory impairment. Neurology 41: 644–649, 1991.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Delwaide P.J., Gyselynck-Mambourg A.M., Hurlet A., Ylieff M.: Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta Neurol. Scand. 73: 136–140, 1986.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Amaducci L. and the SMID Group: Phosphatidylserine in the treatment of Alzheimer’s disease: results of a multicenter study. Psychopharmacol. Bull. 24: 130–134, 1988.

    PubMed  CAS  Google Scholar 

  32. 32.

    Folstein M.F., Folstein S.E., McHugh P.R.: “Mini Mental State”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12: 189–198, 1975.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Reisberg B.: The brief cognitive rating scale and Global Deterioration Scale. In: Crook T., Ferris S., Bartus R. (Eds.), Assessment in Geriatric Psychopharmacology. Mark Powley Associates, New Canaan, Connecticut, 1983, pp. 19–28.

    Google Scholar 

  34. 34.

    Reisberg B., Ferris S.H., Crook T.: Guidelines for drug trials in the treatment of age-associated cognitive decline and Alzheimer’s disease. Drug Inf. J. 19: 405–420, 1985.

    Google Scholar 

  35. 35.

    Wells C.E.: Pseudodementia. Am. J. Psychiatry 136: 895–900, 1979.

    PubMed  CAS  Google Scholar 

  36. 36.

    Blessed G., Tomlinson B.E., Roth M.: The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br. J. Psychiatry 114: 797–811, 1968.

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Hamilton M.: A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 23: 56–62, 1960.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Hamilton M.: Rating depressive patients. J. Clin. Psychiatry 41: 21–24, 1980.

    PubMed  CAS  Google Scholar 

  39. 39.

    Plutchik R., Conte H., Lieberman M., Bakur M., Grossman J., Lehrman N.: Reliability and validity of a scale for assessing the functioning of geriatric patients. J. Am. Geriatr. Soc. 18: 491–500, 1970.

    PubMed  CAS  Google Scholar 

  40. 40.

    Buschke H., Fuld P.A.: Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology 24: 1019–1025, 1974.

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Smith J.M., Bright B., McCloskey J.: Factor analytic composition of the Geriatric Rating Scale (GRS). J. Gerontol. 32: 58–62, 1977.

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Muramoto O.: Selective reminding in normal and demented aged people: auditory verbal versus visual spatial task. Cortex 20: 461–478, 1984.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Bartolini V., Tagliavini C., Zampolli A.: Lessico di Frequenza della Lingua Italiana Contemporanea. Garzanti, Milano, 1972.

    Google Scholar 

  44. 44.

    Bertoldin T., Farina C., Crepaldi G.: Memory function, cognitive status and aging: a study employing MMSE and Selective Reminding Technique. The Third Congress of the International Psychogeriatric Association, Chicago, Illinois, U.S.A., 1987, pp. 97–98, (Abstract).

  45. 45.

    Hachinski V., Iliff L., Du Boulay G., Phil M., Zilhka E, McAllister L., Marshall J.: Cerebral blood flow in dementia. Arch. Neurol 32: 632–637, 1975.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Fleiss J.L.: Analysis of data from Multicentric Trials. Controlled Clin. Trials 7: 267–275, 1986.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Larson E.B., Reifler B.V., Sumi S.M., Canfield C.G., Chinn N.M.: Diagnostic evaluation of 200 elderly outpatients with suspected dementia. J. Gerontol. 40: 536–543, 1985.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Parkin A.J., Walter B.M.: Aging, short-term memory, and frontal dysfunction. Psychobiology 19: 175–179, 1991.

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Teresa Cenacchi Ph.D..

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cenacchi, T., Bertoldin, T., Farina, C. et al. Cognitive decline in the elderly: A double- blind, placebo- controlled multicenter study on efficacy of phosphatidylserine administration. Aging Clin Exp Res 5, 123–133 (1993).

Download citation


  • Cognitive decline
  • elderly
  • phosphatidylserine