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Published on: March 4, 2020
by Women’s Brain Health Initiative:
Advanced age is the most significant risk factor for late-onset Alzheimer’s disease, and having a parent with the disease is the second. It is estimated that individuals with a first-degree relative with Alzheimer’s disease (AD) have a four- to ten-fold higher risk of developing AD than individuals who have no family history. However, research suggests that the level of AD risk might vary depending on whether a person’s mother or father (or both) has the disease.
AD Risk: Children of AD-affected Mothers are at Higher Risk
Although it increases a person’s risk of developing AD to have at least one parent with the disease, it appears that when that parent is the mother, the risk is even higher.
Among individuals with AD who have one affected parent, the ratio of mother-to-father being the one affected is approximately 3:1.
It is important to note, though, that even though there is an increased risk for children of mothers with AD, many of these individuals do not go on to develop the disease.
Brain Physiology: AD-like Changes in the Brain More Common in Individuals with Maternal History of AD
Numerous studies have examined the biological markers of AD (i.e. physical signs in the brain associated with the disease) to determine whether these markers vary in cognitively-normal individuals who have either a maternal or paternal history of AD versus individuals with no family history. Maternal history has been linked with alterations in the Alzheimer’s biomarkers, while paternal history and no family history have not
Hypometabolism in the Brain
In an academic review published in February 2010 in Human Genomics, Dr. Lisa Mosconi and colleagues described how brain imaging studies using a particular kind of positron emission tomography (PET) scan revealed that cognitively-normal individuals with a mother with AD had reduced metabolic rate of glucose in regions of the brain associated with AD, compared to the rate in those with a father with AD or no family history. There was no difference found between the children of fathers with AD and children of parents with no AD.
“Over a two-year follow-up interval, the reduction in glucose metabolism in participants with an AD mother got progressively worse,” explained Dr. Mosconi, Director of the Women’s Brain Initiative and Associate Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College/NewYork-Presbyterian Hospital. “This suggests that children of AD-affected mothers who have progressive reductions in glucose metabolism in AD-regions of the brain may be in the preclinical stages of Alzheimer’s disease, although further studies are needed to confirm this.”
Reduced Gray Matter Volume
In another 2010 academic study (published in the January 2010 issue of Neurology), Dr. Robyn Honea and colleagues used magnetic resonance imaging (MRI) scans to compare gray matter volume in cognitively-normal adults with either a family history of AD on the mother’s side or the father’s side, or without any family history. Having less gray matter volume is associated with late-onset AD. The researchers found that a maternal family history of AD was associated with reduced gray matter volume in areas of the brain that are known to be AD-vulnerable.
Dr. Mosconi was also involved with research that used a type of PET scan to look for amyloid-beta in the brains of 42 individuals with healthy brain function. Amyloid-beta plaques are a hallmark of AD. While not everyone who has these plaques develops AD, their presence does increase the risk of the disease. Participants were divided into three equal groups: 14 with mothers who had AD, 14 with fathers who had AD, and 14 with cognitively-healthy parents.
“The PET scans revealed that cognitively-normal individuals with a parental history of late-onset Alzheimer’s disease – either mothers or fathers – had a higher amount of amyloid-beta plaques in AD-affected brain regions, as compared to people with no family history,” explained Dr. Mosconi. “But, it was those with maternal history who were affected the most. They had a higher amount of amyloid-beta that was more widespread in their brains.” These findings were published in March 2010 in PNAS.
What if Both Parents Have AD?
Although having one parent with AD is a major risk factor, research suggests that a person with two AD-affected parents is at even greater risk of developing the disease (as compared to those with one affected parent, or none). Dr. Mosconi and colleagues conducted research – published in March 2014 in Neurology – that looked at common AD biomarkers in the brains of 52 participants who were split evenly into four groups: maternal AD history only, paternal AD history only, maternal and paternal AD history, and no AD history.
The participants, aged 32 to 72 and dementia-free, underwent MRI and PET scans to compare their gray matter volume, amyloid-beta accumulation, and brain glucose metabolism. The findings revealed that those with a maternal history of AD had higher levels of amyloid-beta and hypometabolism than those with a paternal history, while both of these groups had similar (i.e. intermediate) reductions in gray matter volume. “The biggest changes we found in all three of the AD biomarkers, though, was in the group where both parents had AD,” said Dr. Mosconi. “These findings suggest that those with two AD-affected parents are at the highest risk of all.”
Identifying Groups at High-risk of AD Helps in Development of Treatments
“Detection of these types of AD biomarkers in cognitively-normal individuals with parental history of AD represents a unique opportunity to research therapies and, in particular, preventive interventions, potentially decades before onset of any symptoms,” explained Dr. Mosconi. “That’s important because treatments have the potential to work better at that early stage of disease, well before significant neuronal loss has occurred.”
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