Is There a Higher Risk of Alzheimer's Disease During Menopause Transition?

No evidence of a coincidental effect of Alzheimer’s disease (AD) susceptibility on genetically determined age at menarche or age at menopause, or vice versa, finds a bidirectional MR study.

Is there a link between the age at menarche or menopause, which is determined by genetics, and the risk of Alzheimer's disease?

Aging-US published "The role of age at menarche and age at menopause in Alzheimer’s disease: evidence from a bidirectional Mendelian randomization study" which reports that the Previous observational studies on the relationship between endogenous estrogen exposure and Alzheimer's disease have been inconclusive, and few Mendelian randomization studies have focused on their causality thus far.

‘The study provided no evidence for a causal effect of the genetically determined age at menarche or age at menopause on Alzheimer’s disease (AD) susceptibility or vice versa.’

The MR analyses revealed no link between the genetically determined age at menarche or age at menopause and the risk of developing Alzheimer's disease. The age at menarche and body mass index, on the other hand, showed an inverse relationship.

Dr. Zengnan Mo said, "As the population ages, almost 115.4 million people worldwide will have dementia by 2050, with the main cause being Alzheimer’s disease."

To note, women had 55% greater Alzheimer's disease risks in their lifetime, especially around age 65 than their male counterparts, and constitute more than two-thirds of the Alzheimer's diseases in old age. Lately, the female sex hormones, lured in the masses, because of the popular belief that exogenous hormone replacement therapy plays a protective role in cognitive loss and dementia progression in case of the postmenopausal women.

For instance, a large, diversified cohort study demonstrated that delay in menarche may increase the dementia risk, however, that association disappears after adjusting for some of the baseline risk factors related to dementia as proposed by other studies.

On the same note, the inconsistency in the estimates were ranging from a mildly elevated dementia or Alzheimer's disease risk, with the earlier onset of natural menopause to no statistical evidence or an inverse association.

As the genetic variants are delegated at random during conception and are unchanged besides environmental and lifestyle factors, the typical confounding variables or reverse causation found in observational studies could be whittled down. MR analysis, on the other hand, can provide indirect evidence for a causal relationship if the following three core assumptions are satisfied.

The IVs should have had a strong relationship with exposure. The IVs should be free of any confounding variables in the exposure-outcome relationship because they only affect the risk of outcome through exposure and not through any other pathways.

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The Mo Research Team concluded in their Aging-US Research Output, "our bidirectional MR study provided no evidence for a causal effect of the genetically determined age at menarche or age at menopause on AD susceptibility or vice versa. In contrast, earlier menarche might be associated with higher adult BMI. Further studies combining individual epidemiological and genetic data are warranted to validate and replicate these findings."

Source-Medindia