A Maternal History of Alzheimer Disease Increases the Risk of Developing It

A new study shows that people who inherit a history of Alzheimer disease (AD) from their mother’s side or from both parents have a greater risk of developing AD. The results were published in JAMA Neurology.

“Our study found if participants had a family history on their mother’s side, a higher amyloid level was observed,” said senior corresponding author Hyun-Sik Yang, MD, a neurologist at Mass General Brigham and behavioral neurologist in the Division of Cognitive and Behavioral Neurology at Brigham and Women’s Hospital, via a press release.

In this cross-sectional study, researchers assessed data from 4413 individuals who were screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study, a randomized clinical trial conducted across 67 sites in the United States, Australia, Canada, and Japan aimed at AD prevention. Patients in the population of interest were all cognitively unimpaired adults between the ages of 65 and 85 years who underwent positron emission tomography (PET) imaging to assess cortical Aβ levels.

The results showed that the average Aβ-PET level was notably higher in individuals with a history of memory impairment in both parents (n=455; mean [SD] standardized uptake value ratio [SUVR], 1.12 [0.19]; Wilcoxon P=1.1 × 10⁻⁵) and in those with only maternal history (n=1772; mean [SD] SUVR, 1.10 [0.19]; Wilcoxon P=2.70 × 10⁻⁵) compared with those with only paternal history (n=632; mean [SD] SUVR, 1.08 [0.18]; Wilcoxon P=1.1 × 10⁻⁵) or no family history (n=1554; mean [SD] SUVR=1.08 [0.19]; Wilcoxon P=1.1 × 10⁻⁵), indicating a higher risk of AD.

“If your father had early onset symptoms, that is associated with elevated levels in the offspring,” said Mabel Seto, PhD, first author and a postdoctoral research fellow in the Department of Neurology at Brigham. “However, it doesn’t matter when your mother started developing symptoms—if she did at all, it’s associated with elevated amyloid.”