Scientists have discovered a new parental link to increased risk of dementia

People whose mothers had Alzheimer’s disease are more likely to develop dementia, new research suggests. The study shows that whether a person inherits the risk of Alzheimer’s from their mother or father influences the risk of the biological changes in the brain that lead to the disease.

Taking gender-specific parental history into account could be important to help identify adults at increased risk of dementia, scientists say. US researchers looked at levels of amyloid – a protein linked to Alzheimer’s disease – in 4,400 adults aged 65 to 85 without cognitive impairment.

They found an increase in amyloid in those who reported their mothers had Alzheimer’s symptoms. Increased levels of amyloid were also found in those with a history of the disease on both sides of their family and in those whose fathers had an early onset of symptoms.

The study’s lead author, Dr. Hyun-Sik Yang, a neurologist at Mass General Brigham, Boston, said: “Our study found that if participants had a family history on their mother’s side, a higher level of amyloid was seen.”

Dr. Yang, who is also a neurology investigator for the Mass General Research Institute, teamed up with other Mass General Brigham researchers and scientists at Vanderbilt and Stanford University for the study. He said previous smaller studies have investigated the role family history plays in Alzheimer’s disease.

Some of those suggested that maternal history was a higher risk of developing Alzheimer’s. But the research team wanted to revisit the question with cognitively normal participants and gain access to a larger set of data from clinical trials.

Participants were asked about the onset of memory loss symptoms in their parents. The researchers also asked if their parents had ever been formally diagnosed or had autopsy confirmation of Alzheimer’s disease.

Dr Yang said: “Some people choose not to pursue a formal diagnosis and attribute memory loss to age, so we focused on memory loss and the dementia phenotype.”

The team then compared the responses and measured amyloid in the participants. They found that maternal history of memory impairment at all ages and paternal history of early-onset memory impairment was associated with higher levels of amyloid in asymptomatic study participants. The team also found that having only a paternal history of late-onset memory impairment was not associated with higher levels of amyloid.

The study’s first author, postdoctoral researcher Dr Mabel Seto, said: “If your father had early-onset symptoms, this is associated with increased levels in the offspring. However, it doesn’t matter when your mother first developed symptoms—if she did, it’s associated with increased amyloid.

Dr. Seto, who has also worked on other projects related to sex differences in neurology, says the results of the new study are “fascinating” because Alzheimer’s disease tends to be more prevalent in women. She said: “It’s very interesting from a genetic point of view to see that one sex is contributing something that the other sex is not.”

Dr. Seto also noted that the results were not affected by whether the study participants were biologically male or female. Dr. Yang says a limitation of the study is that some of the participants’ parents died young, before they could develop symptoms of cognitive impairment.

He said social factors such as access to resources and education may also have played a role in when someone recognized cognitive impairment and whether they were ever formally diagnosed. Co-author Professor Reisa Sperling, a neurologist at Mass General Brigham, said the findings could soon be used in clinical translation.

She added: “This work indicates that maternal inheritance of Alzheimer’s disease may be an important factor in identifying asymptomatic individuals for ongoing and future prevention trials.”