Mothers with memory problems increase risk of Alzheimer's

Cross-sectional data from the A4 study found that cognitively normal individuals with a maternal history of dementia or severe memory loss were more likely to have a higher brain amyloid beta burden, which is associated with Alzheimer's disease.

The mean amyloid PET burden, as measured by the mean standardized uptake value ratio (SUVR), was significantly higher in those with both parents with memory impairment (1.12) or only a maternal history (1.10) compared with those with only a paternal history or no family history (1.08 for both).

A maternal history of memory loss was associated with increased PET amyloid in asymptomatic older adults, regardless of whether the mother's onset was early or late, Yang Hyun-sik, MD, of Brigham and Women's Hospital in Boston, and his co-authors reported. JAMA Neurology.

Paternal memory impairment before age 65 was associated with higher amyloid concentrations in offspring, but not later onset.

“If fathers have early symptoms, that's associated with higher amyloid levels in their offspring,” co-author Dr. Mabel Seto, also of Brigham and Women's Hospital, said in a statement. “But it doesn't matter when the mother started to have symptoms — if she does, that's associated with higher amyloid levels.”

As research progresses, Matrilineal history, not patrilineal history There's a link to Alzheimer's disease, say Dena Duvall, MD, of the University of California, San Francisco, and Holly Elser, MD, of the University of Pennsylvania, Philadelphia. Accompanying editorial.

“Maternal-to-child transmission of Alzheimer's disease may have biological origins in the transmission of maternal X chromosome, mitochondria, and specific genomic imprinting (gene silencing) to offspring,” the researchers wrote. “A deeper understanding of maternal-to-child transmission risk of Alzheimer's disease is important as it may elucidate mechanisms at the intersection of women's unique biology, risk, and health and disease resilience.”

The editorialists pointed out that the prevalence of Alzheimer's in mothers in families may be due to gender disparities and secular trends: Generations of women with Alzheimer's may have less formal education than their male counterparts, leading to reduced brain reserve.

“Thus, it may seem justified, if not fair, to attribute part of the risk of Alzheimer's disease to mothers,” Duvall and Elser write.

Yang et al. A4 TrialAlzheimer's Disease Prevention Research Investigational solanezumab In asymptomatic adults (anti-amyloid drugs failed to slow cognitive decline).

Participants in A4 were asked about the onset of memory loss in their parents, whether their parents had ever been formally diagnosed, and whether they had autopsy-confirmed Alzheimer's disease.

Data were collected from April 2014 to December 2017. All participants had normal cognitive function at baseline, and cortical amyloid was assessed by PET and compared with previously published cortical composite normalized SUVR. Cerebellar whole reference region.

A total of 4,413 people were included in the analysis. The mean age was about 71 years, and 59.3% were women. Overall, 1,554 people said that neither parent had memory loss, 632 people said that only their father was affected, 1,772 people said that only their mother was affected, and 455 people said that both parents were affected.

People who reported that both parents had memory problems were younger (70 vs. 73 years) and more likely to have at least one memory disorder. Apoe 4 allele (44% vs. 26%).

In sensitivity analyses, the association between amyloid and maternal clinical or autopsy-confirmed Alzheimer's disease was significant. The association between amyloid and paternal clinical or autopsy-confirmed Alzheimer's disease was not significant.

Yang and colleagues acknowledged that their study has several limitations: Parental medical history was self-reported, and basic definitions of parental medical history may have captured non-Alzheimer's causes of cognitive decline. The A4 study did not collect information on etiologies of parental dementia other than Alzheimer's disease.

Moreover, this analysis was cross-sectional and no conclusions could be drawn regarding the trajectory of Alzheimer's disease progression over time.