Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women - The Women's Health Initiative Memory Study: A Randomized Controlled Trial

Journal of the American Medical Association

Volumn 289, Issue 20, 2003, Pages 2651-2662

  Shumaker, Sally A ^a   Legault, Claudine ^a   Rapp, Stephen R ^a   Thal, Leon ^b   Wallace, Robert B ^c   Ockene, Judith K ^d   Hendrix, Susan L ^e   Jones III, Beverly N ^a   Assaf, Annlouise R ^f   Jackson, Rebecca D ^g   Kotchen, Jane Morley ^h   Wassertheil Smoller, Sylvia ⁱ   Wactawski Wende, Jean ^j  

^a WAKE FOREST UNIVERSITY HEALTH SCIENCES   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF IOWA   (United States)

^d UNIVERSITY OF MASSACHUSETTS   (United States)

^e WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f BROWN UNIVERSITY   (United States)

^g OHIO STATE UNIVERSITY   (United States)

^h MEDICAL COLLEGE OF WISCONSIN   (United States)

ⁱ ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^j UNIVERSITY AT BUFFALO   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CONJUGATED ESTROGEN; GESTAGEN; MEDROXYPROGESTERONE ACETATE; PLACEBO; PROGESTERONE DERIVATIVE;

ALZHEIMER DISEASE; ARTICLE; CLINICAL TRIAL; COGNITIVE DEFECT; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEMENTIA; DISEASE CLASSIFICATION; DOUBLE BLIND PROCEDURE; DRUG EFFECT; ESTROGEN THERAPY; HEALTH HAZARD; HUMAN; INCIDENCE; MAJOR CLINICAL STUDY; MEMORY; POSTMENOPAUSE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RISK BENEFIT ANALYSIS; AGED; CHEMICALLY INDUCED DISORDER; COGNITION; FEMALE; MULTICENTER STUDY; NEUROPSYCHOLOGICAL TEST; PROPORTIONAL HAZARDS MODEL; RISK;

AGED; COGNITION; COGNITION DISORDERS; DEMENTIA; DOUBLE-BLIND METHOD; ESTROGEN REPLACEMENT THERAPY; ESTROGENS, CONJUGATED (USP); FEMALE; HUMANS; MEDROXYPROGESTERONE 17-ACETATE; NEUROPSYCHOLOGICAL TESTS; POSTMENOPAUSE; PROGESTERONE CONGENERS; PROPORTIONAL HAZARDS MODELS; RISK;

EID: 0038386058     PISSN: 00987484     EISSN: None     Source Type: Journal    
DOI: 10.1001/jama.289.20.2651     Document Type: Article

References (82)

1. Evans DA. Estimated prevalence of Alzheimer disease in the United States. Milbank Q. 1990;68:297-289.
2. Ernst RL, Hay JW. The US economic and social costs of Alzheimer disease revisited. Am J Public Health. 1994;84:1261-1264.
3. Birge SJ. The role of estrogen in the treatment and prevention of dementia: introduction. Am J Med. 1997;103(suppl):1S-2S.
4. Paganini-Hill A, Henderson VW. Estrogen deficiency and risk of Alzheimer disease in women. Am J Epidemiol. 1994;140:256-261
5. Judd HL, Judd GE, Lucas WE, Yen SS. Endocrine function of the postmenopausal ovary: concentration of androgens in ovarian and peripheral vein blood. J Clin Endocrinol Metab. 1974;39:1020-1024.
6. Brinton RD, Chen S, Montoya M, et al. The Women's Health Initiative estrogen replacement therapy is neurotrophic and neuroprotective. Neurobiol Aging. 2000;21:475-496.
7. Chen JG, Edwards CL, Vidyarthi S, et al. Learning and recall in subjects at genetic risk for Alzheimer disease. J Neuropsychiatry Clin Neurosci. 2002;14;58-63.
8. Phillips S, Sherwin BB. Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology. 1992;17:485-495.
9. Sherwin BB. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology. 1998;13:345-357.
10. Kampen DL, Sherwin BB. Estrogen use and verbal memory in healthy postmenopausal women. Obstet Gynecol. 1994;83:979-983.
11. Kawas C, Resnick SM, Morrison A, et al. A prospective study of estrogen replacement therapy and the risk of developing Alzheimer disease: the Baltimore Longitudinal Study on Aging. Neurology. 1997;48:1517-1521.
12. Resnick SM, Maki PM, Golski S, Kraut MA, Zonderman AB. Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance. Horm Behav. 1998;34:171-182.
13. Maki PM, Resnick SM. Longitudinal effects of estrogen replacement therapy on PET cerebral blood flow and cognition. Neurobiol Aging. 2000;21:373-383.
14. Maki PM, Rich JB, Rosenbaum RS. Implicit memory varies across the menstrual cycle: estrogen effects in young women. Neuropsychologia. 2002;40:518-529.
15. Henderson VW, Paganini-Hill A, Emanuel CK, et al. Estrogen replacement therapy in older women: comparison between Alzheimer disease cases and nondemented control groups. Arch Neurol. 1994;51:896-900.
16. Waring SC, Rocca WA, Petersen RC, O'Brien PC, Tangalos EG, Kokmen E. Postmenopausal estrogen replacement therapy and risk of AD: a population-based study. Neurology. 1999;52:965-970.
17. Steffens DC, Norton MC, Plassman BL, et al. Enhanced cognitive performance with estrogen use in nondemented community-dwelling older women. J Am Geriatr Soc. 1999;47:1171-1175.
18. Baldereschi M, DiCado A, Lepore V, et al. Estrogen-replacement therapy and Alzheimer disease in the Italian Longitudinal Study on Aging. Neurology. 1998;50:996-1002.
19. Tang MX, Jacobs D, Stern Y, et al. Effect of estrogen during menopause on risk and age at onset of Alzheimer disease. Lancet. 1996;348:429-432.
20. Jacobs DM, Tang MX, Stern Y, et al. Cognitive function in nondemented older women who took estrogen after menopause. Neurology. 1998;50:368-373.
21. Matthews K, Cauley J, Yaffe K, Zmuda JM. Estrogen replacement therapy and cognitive decline in older community women. J Am Geriatr Soc. 1999;47:518-523.
22. Cauley JA, Cummings SR, Black DM, Mascioli SR, Seeley DG. Prevalence and determinants of estrogen replacement therapy in elderly women. Am J Obstet Gynecol. 1990;163:1438-1444.
23. Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA. 1998;279:688-695.
24. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement: scientific review. JAMA. 2002;288:872-881.
25. Barrett-Connor E, Kritz-Silverstein D. Estrogen replacement therapy and cognitive function in older women. JAMA. 1993;269:2637-2641.
26. Brenner DE, Kukull WA, Stergachis A, et al. Postmenopausal estrogen replacement therapy and the risk of Alzheimer disease: a population-based case-control study. Am J Epidemiol. 1994;140:262-267.
27. Henderson VW, Paganini-Hill A, Miller BL, et al. Estrogen for Alzheimer disease in women: randomized, double-blind, placebo-controlled trial. Neurology. 2000;54:295-301.
28. Mulnard RA, Cotman CW, Kawas C, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease. JAMA. 2000;283:1007-1015.
29. Wang PN, Liao SQ, Liu RS, et al. Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study. Neurology. 2000;54:2061-2066.
30. Hogervorst E, Williams J, Budge M, Riedel W, Jolles J. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis. Neuroscience. 2000;101:485-512.
31. LeBlanc ES, Janowsky J, Chan BK, Nelson HD. Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA. 2001;285:1489-1499.
32. Shumaker SA, Reboussin BA, Espeland MA, et al. The Women's Health Initiative Memory Study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Control Clin Trials. 1998;19:604-621.
33. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.
34. Women's Health Initiative Study Group. Design of the Women's Health Initiative clinical trial and observational study. Control Clin Trials. 1998;19:61-109.
35. Rapp S, Espeland MA, Shumaker SA, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289:2663-2672.
36. Teng EL, Chui H. The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry. 1987;48:314-318.
37. Tombaugh TN, Hubley Am, McDowell I, Kristjansson B. Mini-mental state examination (MMSE) and the modified MMSE (3MS): a psychometric comparison and normative data. Psychol Assess. 1996;8:48-59.
38. Graham JE, Rockwood K, Beattie BL, et al. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet. 1997;349:1793-1796.
39. Teng EL, Chui H, Gong A. Comparisons between the Mini-Mental State Exam (MMSE) and its modified version - the 3MS test. In: Psychogeriatrics: Biomedical and Social Advances. Tokyo, Japan: Excerpta Medica; 1990:189-192.
40. Morris JC, Heyman A, Mohs RC, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD), I: clinical and neuropsychological assessment of Alzheimer disease. Neurology. 1989;39:1159-1165.
41. Isaacs B, Kennie AT. The Set test as an aid to the detection of dementia in old people. Br J Psychiatry. 1973;123:467-470.
42. Goodglass H, Weintraub S. The Boston Naming Test. Philadelphia, Pa: Lea & Febiger; 1983.
43. Atkinson RC, Shiffrin RM. The control of short-term memory. Sci Am. 1971;225:82-90.
44. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer disease. Am J Psychiatry. 1984;141:1356-1364.
45. Reitan RM, Wolfson D. Conventional intelligence measurements and neuropsychological concepts of adaptive abilities. J Clin Psychol. 1992;48:521-529.
46. Spitzer RL, Williams JB, Kroenke K, et al. Utility of a new procedure for diagnosing mental disorders in primary care: the PRIME-MD 1000 study. JAMA. 1994;272:1749-1756.
47. Burke WJ, Roccaforte WH, Wengel SP. The short form of the Geriatric Depression Scale: a comparison with the 30-item form. J Geriatr Psychiatry Neurol. 1991;4:173-178.
48. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association; 1994.
49. Petersen RC, Doody R, Kurz A, et al. Current concepts in mild cognitive impairment. Arch Neurol. 2001;58:1985-1992.
50. Cox DR. Regression models and life tables. J R Stat Soc B. 1972;34:187-220.
51. Freedman LS, Anderson GL, Kipnis V, et al. Approaches to monitoring the results of long-term disease prevention trials: examples from the Women's Health Initiative. Control Clin Trials. 1996;17:509-525.
52. Rice MM, Graves AB, McCurry SM, et al. Postmenopausal estrogen and estrogen-progestin use and 2-year rate of cognitive change in a cohort of older Japanese American women: the KAME Project. Arch Intern Med. 2000;160:1641-1649.
53. Kalaria RN, Harshbarger-Kelly M, Cohen DL, Premkumar DR. Molecular aspects of inflammatory and immune responses in Alzheimer disease. Neurobiol Aging. 1996;17:687-693.
54. Jellinger KA, Seppi K, Wenning GK, Poewe W. Impact of coexistent Alzheimer pathology on the natural history of Parkinson's disease. J Neural Transm. 2002;109:329-339.
55. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MMB. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003;348:1215-1222.
56. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. JAMA. 1997;277:813-817.
57. Kuller LH, Lopez OL, Newman A, et al. Risk factors for dementia in the Cardiovascular Health cognitive study. Neuroepidemiology. 2003;22:13-22.
58. Gibbs RB. Effects of gonadal hormone replacement on measures of basal forebrain cholinergic function. Neuroscience. 2000;101:931-938.
59. Marriott LK, Hauss-Wegrzyniak B, Benton RS, Vrniak PD, Wenk GL. Long-term estrogen therapy worsens the behavioral and neuropathological consequences of chronic brain inflammation. Behav Neurosci. 2002;116:902-911.
60. Behl C, Skutella T, Lezoualc'h F, et al. Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Mol Pharmacol. 1997;51:535-541.
61. Goodman Y, Bruce AJ, Cheng B, Mattson MP. Estrogens attenuate and corticosteroid exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J Neurochem. 1996;66:1836-1844.
62. Wise PM, Dubal DB, Wilson ME, Eau SW. Estradiol is a neuroprotective factor in in vivo and in vitro models of brain injury. J Neurocytol. 2000;29:401-410.
63. Xu H, Gouras GK, Greenfield JP, et al. Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides. Nature Med. 1998;4:447-451.
64. Gibbs RB, Aggarwal P. Estrogen and basal forebrain cholinergic neurons: implications for brain aging and Alzheimer disease-related cognitive decline. Horm Behav. 1998;34:98-111.
65. Gibbs RB. Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition. Horm Behav. 1999;36:222-233.
66. Warren SG, Juraska JM. Spatial and nonspatial learning across the rat estrous cycle. Behav Neurosci. 1997;111:259-266.
67. Nilson J, Brinton RD. Impact of progestins on estradiol potentiation of the glutamate calcium response. Neuroreport. 2002;13:825-830.
68. Chesler EJ, Juraska JM. Acute administration of estrogen and progesterone impairs the acquisition of the spatial Morris water maze in ovariectomized rats. Horm Behav. 2000;38:234-242.
69. Herbison AE, Horvath TL, Naftolin F, Leranth C. Distribution of estrogen receptor-immunoreactive cells in monkey hypothalamus: relationship to neurons containing luteinizing hormone-releasing hormone and tyrosine hydroxylase. Neuroendocrinology. 1995;61:1-10.
70. Ott A, Stolk RP, Hofman A, van Harskamp F, Grobbee DE, Breteler MMB. Association of diabetes mellitus and dementia: the Rotterdam study. Diabetologia. 1996;39:1392-1397.
71. Leibson CL, Rocca WA, Hanson VA, et al. Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol. 1997;145:301-308.
72. Yoshitake T, Kiyohara Y, Kato I, et al. Incidence and risk factors of vascular dementia and Alzheimer disease in a defined elderly Japanese population: the Hisayama Study. Neurology. 1995;45:1161-1168.
73. Coker LH, Shumaker SA. Type 2 diabetes mellitus and cognition: an understudied issue in women's health. J Psychosom Res. 2003;54:129-139.
74. Rodriguez EG, Dodge HH, Birzescu MA, Stoehr GP, Ganguli M. Use of lipid-lowering drugs in older adults with and without dementia: a community-based epidemiological study. J Am Geriatr Soc. 2002;50:1852-1856.
75. Hajjar I, Schumpert J, Hirth V, Wieland D, Eleazer GP. The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment. J Gerontol A Biol Sci Med Sci. 2002;57: M414-M418.
76. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet. 2000;356:1627-1631.
77. Hogervorst E, Yaffe K, Richards M, Huppert F. Hormone replacement therapy to maintain cognitive function in women with dementia. Cochrane Database Syst Rev. 2002;(3):CD003799.
78. Resnick SM, Henderson VW. Hormone therapy and risk of Alzheimer disease: a critical time. JAMA. 2002;288:2170-2172.
79. Grodstein F, Clarkson TB, Manson JE. Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med. 2003;348:645-650.
80. Zandi PP, Carlson MC, Plassman BL, et al. Hormone replacement therapy and the incidence of Alzheimer disease in older women: the Cache County Study. JAMA. 2002;288:2123-2129.
81. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303-308.
82. Kawas CH, Corrada MM, Brookmeyer R, et al. Visual memory predicts Alzheimer's disease more than a decade before diagnosis. Neurology. 2003;60:1089-1093.