Age at onset of dementia and age of menopause in women with Down's syndrome M. P. Cosgrave, 1,2 J. Tyrrell, 1 M. McCarron, 1 M. Gill 1,3 & B. A. Lawlor 1,2 1 Department of Psychiatry, Trinity College, Dublin, Ireland 2 Department of Old Age Psychiatry, St Patrick's and St James's Hospitals, Dublin, Ireland 3 Department of Genetics, Trinity College, Dublin, Ireland Abstract Menstrual status and the age of menopause were investigated in 143 Irish females with Down's syndrome (DS). The average age of menopause in 42 subjects (44.7 years) was younger than in the general population. The age at onset of dementia correlated with the age of menopause. This finding may be a manifestation of accelerated ageing in DS or point to oestrogen deficiency being an independent risk factor for the development of Alzheimer's dementia in DS. The implications of this finding for possible treatments are discussed. Keywords Alzheimer's disease, correlation, dementia, Down's syndrome, menopause Introduction The association of Down's syndrome (DS) with Alzheimer's disease (AD) has been the subject of study for many years, and clinical descriptions of dementia in DS date back over 100 years (Fraser & Mitchell 1876). The possession of extra chromosomal material from the triplicated chromosome 21 which codes for amyloid precursor protein is believed to be the main risk factor for AD in DS (Armstrong et al. 1996). In recent times, attention has turned to other possible susceptibility factors in the general population which may be acting independently, such as the Apolipoprotein E genotype: the e2 allele appears to be protective (Talbot et al. 1994) and the e4 allele deleterious (Saunders et al. 1993). Other potential risk factors have included oestrogen deficiency: one case control study showed that hormone replacement therapy reduced the risk of dying with dementia by 35% (Paganini-Hill & Henderson 1996). Two other prospective community based studies demonstrated a reduction of 50% in the risk of developing AD in those who had taken hormone replacement therapy (Tang et al. 1996; Kawas et al. 1997). Oestrogen is known to promote the growth of cholinergic neurones (Tang et al. 1996), it acts as an antioxidant (Niki & Nakano 1990) and suppresses levels of Apolipoprotein E (Paganini-Hill & Henderson 1996). Apolipoprotein E has been studied in the population with DS and the e2 allele has been found to be protective against the development of dementia (Tyrrell et al. 1998). There have been no studies on the relationship between hormone replacement therapy and the development of dementia in the DS population. However, two studies on the menopause Correspondence: Dr Mary P. Cosgrave, Martha Whiteway Day Hospital, St Patrick's Hospital, James's Street, Dublin 8, Ireland. # 1999 Blackwell Science Ltd Journal of Intellectual Disability Research VOLUME 43 PART 6 pp 461±465 DECEMBER 1999 461