Age-associated memory impairment

  • William J. McEntee
  • Glenn J. Larrabee

Opinion statement

At present, there is no formally approved or generally accepted treatment for ageassociated memory impairment (AAMI). Since 1991, when regulatory agencies took a cautious stance on pharmacologic treatments for AAMI, there have been no clinical drug treatment trials for this condition. Regulators are concerned about the safety of a memory-enhancing drug that may entail lifelong intake by otherwise healthy elders and about the abuse potential of a “smart” drug. Such concerns, although valid, should be addressed, not evaded; they should not be a reason to suspend research into drugs to treat AAMI. Moreover, in the opinion of some investigators, AAMI is part of “normal” aging and not a disease and therefore need not be treated. Too little is known about the neurobiology of AAMI to make such a judgment. Even if AAMI is part of so-called normal aging, however, it should not be excluded as a subject for research. As stated by Ferris and Kluger [1], Class IIIc], although “...we think nothing of trying to alleviate or delay the clinical consequences of aging on other organ systems, we seem reluctant to show the same consideration for the brain.” An effective and safe treatment for AAMI would significantly improve the quality of life for many elderly people.


Mild Cognitive Impairment Main Side Effect Main Drug Interaction Pergolide Guanfacine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Recommended Reading

  1. 1.
    Ferris SH, Kluger A: Commentary on age-associated memory impairment, age-related cognitive decline, and mild cognitive impairment. Aging Neuropsychol Cognition 1996, 3:148–153.Google Scholar
  2. 2.
    Crook T, Bartus RT, Ferris SH, et al.: Age-associated memory impairment: proposed diagnostic criteria and measures of clinical change. Report of a National Institute of Mental Health work group. Dev Neuropsychol 1986, 2:261–276.Google Scholar
  3. 3.
    Kral VA: Senescent forgetfulness: benign and malignant. J Can Med Assoc 1962, 86:257–260.Google Scholar
  4. 4.
    Larrabee GJ, Levin HS, High WM: Senescent forgetfulness: a quantitative study. Dev Neuropsychol 1986, 2:373–385.CrossRefGoogle Scholar
  5. 5.
    Larrabee GJ: Age-associated memory impairment: definition and psychometric characteristics. Aging Neuropsychol Cognition 1996, 3:118–131. This article provides a detailed review of the original definition of age-associated memory impairment and suggested modifications to its diagnostic criteria. The paper also contrasts objective memory test and complaint data in age-associated memory impairment with similar data for Alzheimer’s disease and the normal elderly.Google Scholar
  6. 6.
    Larrabee GJ, McEntee WJ: Age-associated memory impairment: sorting out the controversies. Neurology 1995, 45:611–614.PubMedGoogle Scholar
  7. 7.
    Koivisto K, Reinikainen KJ, Hanninen T, et al.: Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland. Neurology 1995, 45:741–747.PubMedGoogle Scholar
  8. 8.
    Lane F, Snowdon J: Memory and dementia: a longitudinal survey of suburban elderly. In Clinical and Abnormal Psychology. Edited by Lovibond P, Wilson P. Amsterdam: Elsevier; 1989:365–376.Google Scholar
  9. 9.
    Smith G, Ivnik RJ, Petersen RC, et al.: Age-associated memory impairment diagnoses: problems of reliability and concerns for terminology. Psychol Aging 1991, 6:551–558.PubMedCrossRefGoogle Scholar
  10. 10.
    Brayne C, Calloway P: Normal aging, impaired cognitive function, and senile dementia of the Alzheimer’s type: a continuum? Lancet 1988, 1:1265–1267.PubMedCrossRefGoogle Scholar
  11. 11.
    Laakso MP, Soininen H, Partanen K, et al.: MRI of the hippocampus in Alzheimer’s disease: sensitivity, specificity, and analysis of the incorrectly classified subjects. Neurobiol Aging 1998, 19:23–31.PubMedCrossRefGoogle Scholar
  12. 12.
    Youngjohn JR, Larrabee GJ, Crook TH: Discriminating age-associated memory impairment and Alzheimer’s disease. Psychol Assess 1992, 4:54–59.CrossRefGoogle Scholar
  13. 13.
    Youngjohn JR, Crook TH: Stability of everyday memory in age-associated memory impairment: a longitudinal study. Neuropsychology 1993, 7:406–416.CrossRefGoogle Scholar
  14. 14.
    Bartus RT: Effects of aging on visual memory, sensory processing and discrimination learning in a nonhuman primate. In Aging. Sensory Systems and Communication in the Elderly. Edited by Ordy JM, Brizzee K. New York: Raven Press; 1979:85–113.Google Scholar
  15. 15.
    Davis HP, Cohen A, Gandy M, et al.: Lexical priming deficits as a function of age. Behav Neurosci 1990, 104:286–295.CrossRefGoogle Scholar
  16. 16.
    Hanninen T, Hallikainen N, Koivisto K, et al.: Decline of frontal lobe function in subjects with age-associated memory impairment. Neurology 1997, 48:148–153. Data in this paper correlate with data from studies of aged monkeys that implicate frontal lobe dysfunction as an anatomic substrate for the cognitive loss associated with aging and support the rationale for studying frontal lobe processes to find therapies for age-related cognitive impairments.PubMedGoogle Scholar
  17. 17.
    Golomb J, Kluger A, deLeon MJ, et al.: Hippocampal formation size in normal human aging: a correlate of delayed secondary memory performance. Learning Memory 1994, 1:45–54.PubMedGoogle Scholar
  18. 18.
    Soininen HS, Partanen K, Pitkanen A, et al.: Volumetric MRI analysis of the amygdala and the hippocampus in subjects with age-associated memory impairment: correlation to visual and verbal memory. Neurology 1994, 44:1660–1668.PubMedGoogle Scholar
  19. 19.
    Weindruch RL, Walford S, Fligiel S, Guthrie D: The retardation of aging by dietary restriction; longevity, immunity, and lifetime energy intake. J Nutr 1986, 116:641–654.PubMedGoogle Scholar
  20. 20.
    Finch CE, Morgan TE: Food restriction and brain aging. In The Aging Brain. Edited by Mattson MP, Geddes JW. Greenwich, CT: JAI Press; 1997:279–297.Google Scholar
  21. 21.
    Pitsikas N, Algeri S: Deterioration of spatial and nonspatial reference and working memory in aged rats: protective effect of life-long caloric restriction. Neurobiol Aging 1992, 13:369–373.PubMedCrossRefGoogle Scholar
  22. 22.
    Stewart J, Mitchell J, Kalant N: The effects of life-long food restriction on spatial memory in young and aged Fischer 344 rats measured in the eight-arm radial and the Morris water mazes. Neurobiol Aging 1989, 10:669–675.PubMedCrossRefGoogle Scholar
  23. 23.
    Bruce-Keller AJ, Umberger G, McFall BS, Mattson MP: Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Ann Neurol 1999, 45:8–15. This is the latest of many reports of data from animal experiments that demonstrate the neuroprotective effects of restricted food intake. In this report, food restriction in rats resulted in resistance to damage to hippocampal and striatal neurons and to impairments of learning and memory induced by neurotoxins. The paper also discusses previous animal studies, which show that food restriction retards age-related changes in brain structure and function.PubMedCrossRefGoogle Scholar
  24. 24.
    Drachman DA, Leavitt J: Human memory and the cholinergic system: a relationship to aging. Arch Neurol 1974, 30:113–121.PubMedGoogle Scholar
  25. 25.
    Bartus RT: Effects of cholinergic agents on learning and memory in animal models of aging. In Alzheimer’s Disease: A Report of Progress in Research, Aging. Edited by Corkin S, Growdon JH, Davis KL, et al. New York: Raven Press; 1982:271–280.Google Scholar
  26. 26.
    Bartus RT, Dean RL, Beer B, Lippa AS: The cholinergic hypothesis of geriatric memory dysfunction. Science 1982, 217:408–417.PubMedCrossRefGoogle Scholar
  27. 27.
    Arnsten AFT: Catecholamine modulation of prefrontal cortical cognitive function. Trends Cogn Sci 1998, 2:436–447. This is an extensive review of behavioral, anatomic, chemical, and pharmacologic aspects of the prefrontal cortex and the role of catecholamines in normal and abnormal function of this area.CrossRefGoogle Scholar
  28. 28.
    McEntee WJ, Crook TH, Jenkyn LR, et al.: Treatment of age-associated memory impairment with guanfacine. Psychopharmacol Bull 1991, 27:41–46.PubMedGoogle Scholar
  29. 29.
    Muller U, von Cramon DY, Pollmann S: D1-versus D2-receptor modulation of visuospatial working memory in humans. J Neurosci 1998, 18:2720–2728.PubMedGoogle Scholar
  30. 30.
    McEntee WJ, Crook TH: Serotonin, memory, and the aging brain. Psychopharmacology (Berl) 1991, 103:143–149.CrossRefGoogle Scholar
  31. 31.
    McEntee W, Oxman T, Ko G, Richter E: Antidepressants and cognition in depressed geriatric patients [abstract]. J Psychopharmacol 1996, 10(suppl):A31.CrossRefGoogle Scholar
  32. 32.
    Crook T, Tinklenberg J, Yesavage J, et al.: Effects of phosphatidylserine in age-associated memory impairment. Neurology 1991, 41:644–649.PubMedGoogle Scholar
  33. 33.
    McEntee WJ, Crook TH: Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology (Berl) 1993, 111:391–401.CrossRefGoogle Scholar
  34. 34.
    West RL, Crook TH: Video training of imagery for mature adults. Appl Cogn Psychol 1992, 6:307–320.CrossRefGoogle Scholar

Copyright information

© Current Science Inc 2000

Authors and Affiliations

  • William J. McEntee
    • 1
  • Glenn J. Larrabee
    • 2
  1. 1.ICSL-Clinical StudiesSarasotaUSA
  2. 2.SarasotaUSA

Personalised recommendations