Sex and Alzheimer’s Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by deterioration of multiple cognitive functions like learning, concentration, and memory.

The disease begins with mild loss of memory and ultimately leads to a decline in the ability to work independently and perform daily tasks.

Alzheimers Disease

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According to the World Health Organization (WHO), over 50 million people have Alzheimer's disease or related dementia, and these numbers are expected to double in the next 20 years. Recent studies have determined a gender predilection with the disease; as per the latest research, women have a higher risk of being affected by Alzheimer's disease compared with men.

The chances of women developing Alzheimer's disease at the age of 65 are 1 in 5 as compared to 1 in 11 for men of the same age. Researchers are investigating the various biological, genetic variations which lead to a higher risk of Alzheimer's disease in women of any given age

Age - A significant risk factor for developing Alzheimer's disease

Age is a significant risk factor for developing Alzheimer's disease. On average, women live four to five years longer than men.

However, longevity alone may not be able to explain increased Alzheimer's disease risk in women; factors like educational and occupational opportunities are equally responsible.

Less education in women is associated with increased risk of dementia, whereas increased cognitive activity in mid- or late-life is associated with delayed onset of cognitive impairment.

Women are twice as likely as men to be diagnosed with depression. Depression in women is associated with a smaller hippocampus or shrinkage of the hippocampus. The hippocampus is mainly responsible for memory.

Regular exercise decreases the chances of developing AD and associated dementia. As per an observational study, women with high fitness levels had an 88% reduced chance of developing AD in comparison to those with medium fitness level.

Role of estrogen in Alzheimer disease

Estrogen levels play an important role in preventing AD and are postulated as mitochondrial protectors against the damaging effects of AD. Jose et al. demonstrated that estrogen prevents increases in interleukin 1β, TNFα, and COX2 expression induced by β-amyloid peptide (Aβ) in young female rats more than in male rats.

But all these advantages are lost in mitochondria from old females. Thus, as per this hypothesis, elderly females are at higher risk of developing AD.

The role of Apolipoprotein E

Polymorphic apolipoprotein E gene is a major determinant of genetic risk associated with the late onset of AD. Apolipoprotein E (ApoE) is a major cholesterol carrier that assists in lipid transportation and injury repair in the brain.

Of the three different ApoE types (ApoE2, ApoE3, and ApoE4), ApoE4 is associated with an increased risk of AD. ApoE regulates Aβ aggregation and clearance in the brain; ApoE is also associated with an increase in age-related cognitive impairment and cerebral amyloid angiopathy.

Researchers from Stanford University found that women carrying ApoE4 variant were twice as likely to develop Alzheimer's compared with women without the gene. In an ApoE4-positive man, only a slight increase in the risk of developing AD was found. Women with ApoE ε4 mutation are also more susceptible to tau accumulation.

Role of stress in parthenogenesis of Alzheimer's

Women predominantly play the role of a caregiver. Emotions associated with adjusting to the role of care-recipient from a caregiver are different for women than it is for men. Women who receive care go through a conflict of emotions; they describe this negative feeling as one of "grateful guilt."

According to some researchers, this negative feeling needs to be addressed as it plays a vital role in the pathogenesis of AD.

A diagnosis of mild cognitive impairment and AD may be delayed in women; by the time a woman is diagnosed, the disease takes a severe form, which ultimately results in severe consequences. Early detection of AD with sex-specific cutoff scores or memory tests will probably result in a better prognosis.

To conclude, there are specific gender-specific risk factors associated with AD. Understanding these sex and gender differences will help in defining individualized treatment and preventive interventions for AD.

Sources

  • Liu, M., et al. (2019). Sex modulates the ApoE ε4 effect on brain tau deposition measured by 18F-AV-1451 PET in individuals with mild cognitive impairment. Theranostics, 9(17), 4959–4970. https://doi.org/10.7150/thno.35366
  • Ungar, L., et al. (2014). Apolipoprotein E, gender, and Alzheimer's disease: an overlooked, but potent and promising interaction. Brain imaging and behavior, 8(2), 262–273. https://doi.org/10.1007/s11682-013-9272-x
  • Viña J1., et al. (2010). Why women have more Alzheimer's disease than men: gender and mitochondrial toxicity of amyloid-beta peptide. J Alzheimers Dis.;20 Suppl 2:S527-33. doi: 10.3233/JAD-2010-100501.

Further Reading

Last Updated: Apr 14, 2020

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