Onset of dementia is associated with age at menopause in women with Down's syndrome

Nicole Schupf, Deborah Pang, Bindu N. Patel, Wayne P Silverman, Romaine Schubert, Florence Lai, Jennie K. Kline, Yaakov Stern, Michel Ferin, Benjamin Tycko, Richard Mayeux

Research output: Contribution to journalArticle

Abstract

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.

Original languageEnglish (US)
Pages (from-to)433-438
Number of pages6
JournalAnnals of Neurology
Volume54
Issue number4
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

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Menopause
Down Syndrome
Dementia
Alzheimer Disease
Estradiol
Age of Onset
Estrogens
Serum Globulins
Developmental Disabilities
Sex Hormone-Binding Globulin
Pathologic Processes
Hypothyroidism
Intellectual Disability
Caregivers
Medical Records
Body Mass Index
Multivariate Analysis
Regression Analysis
Confidence Intervals
Interviews

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Schupf, N., Pang, D., Patel, B. N., Silverman, W. P., Schubert, R., Lai, F., ... Mayeux, R. (2003). Onset of dementia is associated with age at menopause in women with Down's syndrome. Annals of Neurology, 54(4), 433-438. https://doi.org/10.1002/ana.10677

Onset of dementia is associated with age at menopause in women with Down's syndrome. / Schupf, Nicole; Pang, Deborah; Patel, Bindu N.; Silverman, Wayne P; Schubert, Romaine; Lai, Florence; Kline, Jennie K.; Stern, Yaakov; Ferin, Michel; Tycko, Benjamin; Mayeux, Richard.

In: Annals of Neurology, Vol. 54, No. 4, 01.10.2003, p. 433-438.

Research output: Contribution to journalArticle

Schupf, N, Pang, D, Patel, BN, Silverman, WP, Schubert, R, Lai, F, Kline, JK, Stern, Y, Ferin, M, Tycko, B & Mayeux, R 2003, 'Onset of dementia is associated with age at menopause in women with Down's syndrome', Annals of Neurology, vol. 54, no. 4, pp. 433-438. https://doi.org/10.1002/ana.10677
Schupf N, Pang D, Patel BN, Silverman WP, Schubert R, Lai F et al. Onset of dementia is associated with age at menopause in women with Down's syndrome. Annals of Neurology. 2003 Oct 1;54(4):433-438. https://doi.org/10.1002/ana.10677
Schupf, Nicole ; Pang, Deborah ; Patel, Bindu N. ; Silverman, Wayne P ; Schubert, Romaine ; Lai, Florence ; Kline, Jennie K. ; Stern, Yaakov ; Ferin, Michel ; Tycko, Benjamin ; Mayeux, Richard. / Onset of dementia is associated with age at menopause in women with Down's syndrome. In: Annals of Neurology. 2003 ; Vol. 54, No. 4. pp. 433-438.
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