Age at onset of dementia and age of menopause in women with Down’s syndrome

Cosgrave, Mary; Tyrrell, Janette; McCarron, Mary; Gill, Michael; Lawlor, Brian A.

doi:10.1046/j.1365-2788.1999.00192.x

Cited by 68 publications

(41 citation statements)

References 19 publications

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“…One previous study found a correlation between age at menopause and onset of AD in women with DS, 35 but the number of dementia cases was low and supporting hormonal data were not available. In addition, the presence of the apolipoprotein E (ApoE) ε4 allele is associated with earlier age at onset and increased risk of AD in adults with and without DS.…”

mentioning

confidence: 86%

“…In keeping with convention, we classified age at natural menopause as the age at the last menstrual period preceding cessation of menses for 12 months, in the absence of known causes of amenorrhea (eg, surgery). The median age at menopause was 46.0 years (range, [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]. For analysis of AD risk associated with age at menopause, we split at the median to classify women as experiencing "early" (Յ46 years) or "late" (Ͼ46 years) age at menopause.…”

Section: Classification Of Age At Menopausementioning

confidence: 99%

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

Schupf

Pang

Patel

et al. 2003

Annals of Neurology

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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.

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mentioning

confidence: 86%

Section: Classification Of Age At Menopausementioning

confidence: 99%

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

Schupf

Pang

Patel

et al. 2003

Annals of Neurology

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“…In females with Down's syndrome, the average age of menopause (44.7 yr; n ϭ 42) is younger than in the general population, and onset of dementia correlates with the age of menopause (440). The results of a multicenter clinical trial in women with established AD showed that estrogen treatment for 12 months did not halt the decline in cognitive function (441), but the average age of the women studied was 75 yr; and it remains to be determined whether younger women would benefit.…”

Section: Estradiol and Admentioning

confidence: 98%

Molecular Endocrinology and Physiology of the Aging Central Nervous System

2005

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Aging is associated with a progressive decline in physical and cognitive functions. The impact of age-dependent endocrine changes regulated by the central nervous system on the dynamics of neuronal behavior, neurodegeneration, cognition, biological rhythms, sexual behavior, and metabolism are reviewed. We also briefly review how functional deficits associated with increases in glucocorticoids and cytokines and declining production of sex steroids, GH, and IGF are likely exacerbated by age-dependent molecular misreading and alterations in components of signal transduction pathways and transcription factors. (Endocrine Reviews 26: 203-250, 2005)

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“…Some investigators do not report beneficial effects of estrogen in any memory tasks in women with AD (Mulnard et al, 2000), leaving this important question unresolved to date. Estradiol treatment has not been tested in elderly women with DS, even though they are twice as likely to undergo early menopause than non-DS women (Carr and Hollins, 1995;Schupf et al, 1997;Cosgrave et al, 1999) and show a decline in cognitive function linked to menopause (Patel et al, 2001). Estradiol modifies the function and morphology of hippocampal neurons in situ and in tissue culture.…”

Section: Introductionmentioning

confidence: 99%

Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome

et al. 2003

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ABSTRACT:Individuals with Down syndrome (DS) develop the pathological hallmarks of Alzheimer's disease at an early age, later followed by memory decline and dementia. Women with DS are twice as likely to undergo early menopause, and levels of estradiol correlate with onset of cognitive decline in these women. We have demonstrated that a mouse model of DS, mice with segmental trisomy of chromosome 16 (Ts65Dn), develop a significant deficit in both reference and working memory as young adults (6 -10 months of age), coupled with phenotypic loss of cholinergic neurons in the basal forebrain and altered growth factor levels. In the present study we examined cholinergic and dendritic markers in the hippocampal formation and levels of the amyloid precursor protein (APP) in different brain regions of Ts65Dn mice treated with estradiol for 60 days. The density of the dendritic marker Map2 was significantly decreased in the hippocampal formation of middle-aged trisomic mice (9 -15 months old), and the density of cholinergic neurites (acetylcholinesterase [AChE] histochemistry) was also decreased in specific layers of the hippocampus. Treatment with 17␤-estradiol alleviated the decreases in Map2 and AChE staining, but had no effect on full-length APP levels in the hippocampus. In contrast, a main effect of treatment on APP levels in the striatum was noted, with significant elevations observed in controls and trisomics. These findings demonstrate that estrogen can alleviate deficits in cholinergic and dendritic elements in the hippocampal formation and further strengthens the rationale to explore estrogen replacement therapy in women with DS.

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Age at onset of dementia and age of menopause in women with Down’s syndrome

Cited by 68 publications

References 19 publications

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

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

Molecular Endocrinology and Physiology of the Aging Central Nervous System

Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome

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