NEUROLOGY 1998;50:996-1002
© 1998 American Academy of Neurology
Estrogen-replacement therapy and Alzheimer's disease in the Italian Longitudinal Study on Aging
M. Baldereschi, MD,
A. Di Carlo, MD,
V. Lepore, MD,
L. Bracco, MD,
S. Maggi, MD,
F. Grigoletto, ScD,
G. Scarlato, MD,
L. Amaducci, MD and
ILSA Working Group*
From the Progetto Finalizzato Invecchiamento (Drs. Baldereschi, Di Carlo, Maggi, and Amaducci), Italian National Research Council, Rome; Institute of Hygiene (Dr. Grigoletto), University of Padova; Department of Neurology(Dr. Lepore), University of Bari; Department of Neurology (Dr. Bracco), University of Firenze; and the Institute of Clinical Neurology (Dr. Scarlato), University of Milan, Italy.
Address correspondence and reprint requests to Dr. Marzia Baldereschi, CNR PF Invecchiamento, Via Pancaldo 21, 50127, Firenze, Italy.
Objective: To study the association of estrogen-replacement therapy and other estrogen-related variables with Alzheimer's disease in postmenopausal women.
Background: Postmenopausal estrogen use has been reported to lower the risk of Alzheimer's disease.
Design: A population-based, multicenter survey was carried out in eight Italian municipalities. The sample of 2,816 women, aged 65 to 84 years, was randomly selected from the population register of each municipality and stratified in 5-year age groups. All women were screened using the Mini-Mental State Examination and interviewed concerning risk factors. Those who screened positive underwent a clinical assessment. Dementia syndrome was diagnosed according to DSM-III-R criteria, and Alzheimer's disease was diagnosed according to NINCDS-ADRDA criteria for possible and probable Alzheimer's disease.
Results: The estimated prevalence of postmenopausal estrogen use adjusted to the 1991 Italian female population was 12.3%. The frequency of estrogen use was higher among nonpatients compared with Alzheimer's disease patients (odds ratio, 0.24; 95% confidence interval, 0.07 to 0.77). The inverse association between estrogen therapy and Alzheimer's disease remained significant after adjustment for age, education, age at menarche, age at menopause, smoking and alcohol habits, body weight at the age of 50 years, and number of children(odds ratio, 0.28; 95% confidence interval, 0.08 to 0.98).
Conclusions: Our data from a population-based study support the hypothesis that estrogen-replacement therapy is associated with a reduced prevalence of Alzheimer's disease in postmenopausal women. Prospective clinical trials are required to enable women and their physicians to weigh risks and benefits of estrogen-replacement therapy for the prevention of dementia.
As part of the Progetto Finalizzato Invecchiamento, the ILSA has been supported by the Italian National Research Council by means of annual grants to each research unit from 1991 through 1995.
Received July 7, 1997. Accepted in final form November 7, 1997.
*Members of the ILSA Working Group are listed in the Appendix on page 1001.
 Deceased.
This article has been cited by other articles:
|
|
|
|
 
A. M. Barron, M. Cake, G. Verdile, and R. N. Martins
Ovariectomy and 17{beta}-Estradiol Replacement Do Not Alter {beta}-Amyloid Levels in Sheep Brain
Endocrinology,
July 1, 2009;
150(7):
3228 - 3236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. Petitti, V. C. Crooks, V. Chiu, J. G. Buckwalter, and H. C. Chui
Incidence of Dementia in Long-term Hormone Users
Am. J. Epidemiol.,
March 15, 2008;
167(6):
692 - 700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Genazzani, N. Pluchino, S. Luisi, and M. Luisi
Estrogen, cognition and female ageing
Hum. Reprod. Update,
March 1, 2007;
13(2):
175 - 187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. H. Lu, D. A. Masterman, R. Mulnard, C. Cotman, B. Miller, K. Yaffe, E. Reback, V. Porter, R. Swerdloff, and J. L. Cummings
Effects of Testosterone on Cognition and Mood in Male Patients With Mild Alzheimer Disease and Healthy Elderly Men
Arch Neurol,
February 1, 2006;
63(2):
177 - 185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A. Rippon, M. X. Tang, J. H. Lee, R. Lantigua, M. Medrano, and R. Mayeux
Familial Alzheimer disease in Latinos: Interaction between APOE, stroke, and estrogen replacement
Neurology,
January 10, 2006;
66(1):
35 - 40.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. Petitti and D. A. Freedman
Invited Commentary: How Far Can Epidemiologists Get with Statistical Adjustment?
Am. J. Epidemiol.,
September 1, 2005;
162(5):
415 - 418.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. W. Baum
Sex, Hormones, and Alzheimer's Disease
J Gerontol A Biol Sci Med Sci,
June 1, 2005;
60(6):
736 - 743.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J-C Lambert, N Coyle, and C Lendon
The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for Alzheimer's disease
J. Med. Genet.,
February 1, 2004;
41(2):
104 - 112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Shumaker, C. Legault, S. R. Rapp, L. Thal, R. B. Wallace, J. K. Ockene, S. L. Hendrix, B. N. Jones III, A. R. Assaf, R. D. Jackson, et al.
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
JAMA,
May 28, 2003;
289(20):
2651 - 2662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. N. McLay, P. M. Maki, and C. G. Lyketsos
Nulliparity and Late Menopause Are Associated With Decreased Cognitive Decline
J Neuropsychiatry Clin Neurosci,
May 1, 2003;
15(2):
161 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. B. Sherwin
Estrogen and Cognitive Functioning in Women
Endocr. Rev.,
April 1, 2003;
24(2):
133 - 151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Clark and J. H.T. Karlawish
Alzheimer Disease: Current Concepts and Emerging Diagnostic and Therapeutic Strategies
Ann Intern Med,
March 4, 2003;
138(5):
400 - 410.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. in 't Veld, L. J. Launer, M. M. B. Breteler, A. Hofman, and B. H. Ch. Stricker
Pharmacologic Agents Associated with a Preventive Effect on Alzheimer's Disease: A Review of the Epidemiologic Evidence
Epidemiol. Rev.,
December 1, 2002;
24(2):
248 - 268.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Zandi, M. C. Carlson, B. L. Plassman, K. A. Welsh-Bohmer, L. S. Mayer, D. C. Steffens, J. C. S. Breitner, and for the Cache County Memory Study Investigators
Hormone Replacement Therapy and Incidence of Alzheimer Disease in Older Women: The Cache County Study
JAMA,
November 6, 2002;
288(17):
2123 - 2129.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Fillit
The Role of Hormone Replacement Therapy in the Prevention of Alzheimer Disease
Arch Intern Med,
September 23, 2002;
162(17):
1934 - 1942.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. R. Ott, D. Belazi, and K. L. Lapane
Cognitive Decline Among Female Estrogen Users in Nursing Homes
J Gerontol A Biol Sci Med Sci,
September 1, 2002;
57(9):
M594 - M598.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. Petitti, J. G. Buckwalter, V. C. Crooks, and V. Chiu
Prevalence of Dementia in Users of Hormone Replacement Therapy as Defined by Prescription Data
J Gerontol A Biol Sci Med Sci,
August 1, 2002;
57(8):
M532 - M538.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Chappell and H. Cohen
Frontiers in Neuropharmacotherapy Part I: Alzheimer's Disease and Epilepsy
Journal of Pharmacy Practice,
June 1, 2002;
15(3):
195 - 220.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. P. Greenfield, L. W. Leung, D. Cai, K. Kaasik, R. S. Gross, E. Rodriguez-Boulan, P. Greengard, and H. Xu
Estrogen Lowers Alzheimer beta -Amyloid Generation by Stimulating trans-Golgi Network Vesicle Biogenesis
J. Biol. Chem.,
March 29, 2002;
277(14):
12128 - 12136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Asthana, L. D. Baker, S. Craft, F. Z. Stanczyk, R. C. Veith, M. A. Raskind, and S. R. Plymate
High-dose estradiol improves cognition for women with AD: Results of a randomized study
Neurology,
August 28, 2001;
57(4):
605 - 612.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. I. Geerlings, A. Ruitenberg, J. C. M. Witteman, J. C. van Swieten, A. Hofman, C. M. van Duijn, M. M. B. Breteler, and L. J. Launer
Reproductive Period and Risk of Dementia in Postmenopausal Women
JAMA,
March 21, 2001;
285(11):
1475 - 1481.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Seshadri, G. L. Zornberg, L. E. Derby, M. W. Myers, H. Jick, and D. A. Drachman
Postmenopausal Estrogen Replacement Therapy and the Risk of Alzheimer Disease
Arch Neurol,
March 1, 2001;
58(3):
435 - 440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Turner
Alzheimer's Disease in Man and Transgenic Mice : Females at Higher Risk
Am. J. Pathol.,
March 1, 2001;
158(3):
797 - 801.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. R. Smith, S. Minoshima, D. E. Kuhl, and J.-K. Zubieta
Effects of Long-Term Hormone Therapy on Cholinergic Synaptic Concentrations in Healthy Postmenopausal Women
J. Clin. Endocrinol. Metab.,
February 1, 2001;
86(2):
679 - 684.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Marder and M. Sano
Estrogen to treat Alzheimer's disease: Too little, too late?: So what's a woman to do?
Neurology,
June 13, 2000;
54(11):
2035 - 2037.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Rice, A. B. Graves, S. M. McCurry, L. E. Gibbons, J. D. Bowen, W. C. McCormick, and E. B. Larson
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,
June 12, 2000;
160(11):
1641 - 1649.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Maruyama, H. Toji, C. R. Harrington, K. Sasaki, Y. Izumi, T. Ohnuma, H. Arai, M. Yasuda, C. Tanaka, P. C. Emson, et al.
Lack of an Association of Estrogen Receptor {alpha} Gene Polymorphisms and Transcriptional Activity With Alzheimer Disease
Arch Neurol,
February 1, 2000;
57(2):
236 - 240.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. W. Henderson, A. Paganini-Hill, B. L. Miller, R. J. Elble, P. F. Reyes, D. Shoupe, C. A. McCleary, R. A. Klein, A. M. Hake, and M. R. Farlow
Estrogen for Alzheimer's disease in women: Randomized, double-blind, placebo-controlled trial
Neurology,
January 25, 2000;
54(2):
295 - 295.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Mayeux and M. Sano
Treatment of Alzheimer's Disease
N. Engl. J. Med.,
November 25, 1999;
341(22):
1670 - 1679.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. N. Epperson, K. L. Wisner, and B. Yamamoto
Gonadal Steroids in the Treatment of Mood Disorders
Psychosom Med,
September 1, 1999;
61(5):
676 - 697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
