Alzheimer’s within men and woman

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Introduction

Alzheimer’s disease (AD) is the most prevalent type of dementia accounting for 60%–70% of total dementia cases (Mielke et al., 2014), although it affects men and women differently. There is a clear evidence that AD is more prevalent in women than it is in men such that about two-thirds of people who have been diagnosed with AD are women (Mielke et al., 2014).  Besides, converging lines of evidence taken from post-mortem analysis, brain imaging, genetics and hormone therapy indicates that AD affects women differently from the way in which it affects men (Lin et al., 2015). Some of the gender-based risk factors for development of AD include; women having reduced estrogen after menopause and bilateral oophorectomy; reduction of the Allopregnanolone during pregnancy; depression; men having a bigger cognitive reserve; the role of apolipoprotein E ε4 allele.

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Sex Difference in Development and Prevalence of AD

One of the major cause for AD prevalence in women is the APoE4 gene which is attributed to AD being different in women.  The risk factor of ApoE4 allele in development of AD is, however, higher in females than it is in men.  The initial research on the ApoE4 gene indicated that the effects of the allele were present only among the women and not men.  Various study that was specific to understanding the role of the allele in development of AD found that it carried more risks among the females than it did among males (Ungar et al., 2014).

According to Laws et al. (2016), the ApoE4 allele is found in more than 50% of all patients diagnosed with AD and is present in only 15% among healthy people in the old age. Most people inherit two copies of the APoE3 gene from each of the parents. However, some people inherit at least a single copy of the ApoE4 while a few people have two copies of the ApoE4. Research confirms that the ApoE4 gene is a carrier for AD that confers a relatively higher risk for development of the disease in men compared to women. Even among healthy elderly women, ApoE4 has been linked to hippocampal atrophy. The ApoE4 risk factors interact with the aging process and sex to cause common abnormalities in AD such as senile plaques and the neurofibrillary tangles.

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Research also indicates that estrogen has significant effect on the development of AD since women above the age of 60 years are more likely to have Alzheimer’s compared to younger females. These females have reduced levels of estrogen due to menopause. In an attempt to understand the effect of reduced estrogen levels on the brain research was done among the pregnant women. The findings of the research revealed that in the last trimester and postpartum period the verbal records deteriorated significantly in pregnant women. Also, a longitudinal study on pregnant women indicated that they had poor performance on tasks that tested the verbal memory, speed processing and visuospatial task (Rocca et al., 2014). These findings provide evidence that the reproductive changes that occur in women have a direct effect on their cognitive function.

There are findings that have even proved that verbal sex difference in AD can be precipitated by the deficiency of estrogen in women. A research study indicated that when estrogen therapy is administered immediately after the removal of ovaries in perimenopause women with risk of developing AD then the risk was considerably lowered. Besides, when estrogen therapy is given to women who have already been diagnosed with AD the women perform better in naming and other verbal memory task compared to men or women who are not receiving the estrogen therapy.  The effect of reduced estrogen levels on AD is primarily noted in verbal functioning requiring memory.

More females compared to males have developed AD- more than two-thirds of AD cases occur in females. A meta-analysis that involved 13 population study from Europe, United States, and Asia showed that women have a much greater risk of developing AD compared to their male counterparts (Laws et al., 2016). The sex difference with regards to the prevalence of dementia has been shown to reduce as the age advances. However, diagnosis in the onset of late adulthood shows that more women compared to men are diagnosed with AD across the globe. Women aged sixty and above have a double risk of developing AD.

The Allopregnanolone (Allo) is a neurosteroid that promotes endogenous regeneration of the brain. The Allow is responsible for activating the signaling pathways that is necessary for regeneration and differentiation of the neuro stem cell. Besides, Allo is responsible for the regulation of the cholesterol homeostasis.  In an experimental study of the mouse with disease that resembled AD, it was established that Allopregnanolone caused generation of the oligodendrogenesis, neurogenesis, white matter and cholesterol homeostasis while at the same time reducing neuro-inflammatory burden and β-amyloid (Irwin et al., 2014). During development of the fetus after conception, the Allopregnanolone is used for developing the brain of the fetus. This implies that the woman remains with lesser Allo yet is responsible for the regulation of cholesterol homeostasis. This exposes the woman to develop AD since there are many studies that have proven cholesterol homeostasis is linked to AD.

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Depression also makes women to be more vulnerable to developing AD as compared to men. Many women are often diagnosed with depression through there lifetime. Some causes of depression in women can be hysterectomy, childbirth and other sociocultural norms that suppress women. Such episodes of depression have a contributing role in the development of AD. Some studies have suggested that depression results in high production of the cortisol hormone which adversely affects the hippocampus. The hippocampus is the part of brain that is responsible for new learning and memory. Episodes of depression or having depression in late adulthood can, therefore, act as a precipitating factor for dementia. Since women are more likely to develop recurring depression the effect in the hippocampus is more intense hence increased exposure to AD.

Conclusion

Female genotype risk factors including reduced estrogen after menopause and bilateral oophorectomy; reduction of the Allopregnanolone during pregnancy; the role of apolipoprotein E ε4 allele, prevalence of depression due to biological and non-biological factors all causes risk of AD. Women with APoE4 have a higher risk of developing AD compared to men with the same gene. The reduced estrogen levels in females is also reduced after menopause resulting in verbal and short memory loss that characterize AD. In addition, women lose the Allopregnanolone which is used in development of fetus during pregnancy and as a result, they lose cholesterol balance and are exposed to AD. Having more depression instances also precipitates AD among females. In overall it is evident that females have a higher risk of AD compared to males not only due to genetic and sex differences but also some biological and sociocultural factors.

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  1. Irwin, R. W., Solinsky, C. M., & Brinton, R. D. (2014). Frontiers in therapeutic development of allopregnanolone for Alzheimer’s disease and other neurological disorders. Frontiers in cellular neuroscience8.
  2. Laws, K. R., Irvine, K., & Gale, T. M. (2016). Sex differences in cognitive impairment in Alzheimer’s disease. World journal of psychiatry6(1), 54.
  3. Lin, K. A., Choudhury, K. R., Rathakrishnan, B. G., Marks, D. M., Petrella, J. R., Doraiswamy, P. M., & Alzheimer’s Disease Neuroimaging Initiative. (2015). Marked gender differences in progression of mild cognitive impairment over 8 years. Alzheimer’s & dementia: translational research & clinical interventions1(2), 103-110.
  4. Mielke, M. M., Vemuri, P., & Rocca, W. A. (2014). Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences. Clinical epidemiology6, 37.
  5. Rocca, W. A., Mielke, M. M., Vemuri, P., & Miller, V. M. (2014). Sex and gender differences in the causes of dementia: a narrative review. Maturitas79(2), 196-201.
  6. Ungar, L., Altmann, A., & Greicius, M. D. (2014). Apolipoprotein E, Gender, and Alzheimer’s Disease: An Overlooked, but Potent and Promising Interaction. Brain Imaging and   Behavior8(2), 262–273. http://doi.org/10.1007/s11682-013-9272-x
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