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Sex, Gender and Risk Factors

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The cause of dementia is unknown but certain risk factors have been shown to be linked in its development. Women have two times a higher risk of developing dementia, specifically AD, than men. The main risk factors for dementia are age, family history and APOE status and the presence of traditional vascular risk factors such as hypertension, diabetes mellitus (DM) and hypercholesterolemia. New risk factors that are emerging and currently being researched include increased homocysteine levels, obesity,  estrogen use and metabolic syndrome [10].

Age

  • age is the strongest risk factor for dementia as the prevalence of AD doubles every 5 years beyond the age of 65 [1]

  • the rates of dementia are higher among women as women tend to live longer and compromise a greater proportion of those in the "oldest old" age group

Family History

  • first degree relatives with dementia have a 10-30% risk of developing AD [10]

  • in familial autosomal dominant AD, a genetic connection has been shown as in certain families, it is passed directly from one generation to another through a dominant inheritance pattern

  • follow this link to find out more about heredity:  Alzheimer Society Information on AD and heredity

Estrogen

  • cognitive decline is often accelerated in women after menopause as studies show that there are sex-based differences in the ageing of the brain

  • it is possible that estrogen may function as a mild vasodilator and increase the blood flow in the brain, hence having a protective effect in pre-menopausal women [2]

  • results of various longitudinal stuides suggested a beneficial effect of estrogen therapy on cognitive function in symptomatic post-menopausal women; however, the results of a large recent clinical trial, the Women’s Health Initiative Study (WHIMS) does not support this in women over 65 years [3]

  • this trial demonstrated an increased occurrence of dementia in postmenopausal women who received combined estrogen-progestin therapy [3]

  • hence, the routine therapeutic use of estrogen in women over age 65 is not justified based on the existing evidence [3]

APOE (Apolipoprotein E epsilon) Gene

  • the APOE gene is carried on chromosome 19 and has 3 alleles: APOE e2, APOE e3 and APOE e4 and is the most significant known genetic risk factor for dementia [5,6]

  • APOE e4 is associated  increasing the likelihood of late onset AD, raising  total cholesterol levels and shifting the age onset an average of 5-20 years earlier depending on the number of alleles present [5,6]

  • this genotype seems to have greater effects on women with respect to hippocampal pathology and memory performance

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1. Hanon O, Forette F. Treatment of hypertension and prevention of dementia. Alzheimer's and Dementia 2005; 1:30-7.

2. Sheppard JE. Effects of cognition, mood and degenerative brain diseases. J Am Pharm Assoc 2001; 41(2):221-8.

3. Espeland MA, Rapp SR, Shumaker SA Brunner R, Manson JE, Sherwin, BB et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2959-68.

10. van Duijin CM, Clayton D et al. Familial aggression of Alzheimer's disease and related disorders: a collaborative re-analysis of case-control studies. International Journal of Epidemilogy. 1991; 20(2):S13.

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