Study: Association Between Maternal History of Severe Memory Impairment and Alzheimer Disease

Cognitively unimpaired older adults whose mothers had a history of severe memory impairment were more likely to have a higher β-amyloid (Aβ) burden compared with those with only paternal history or no family history of memory impairment, according to the results of a recent study.

“Family history in one or more first-degree relatives can estimate Aβ burden in older cognitively unimpaired individuals, suggesting that family history may capture the genetic liability of Alzheimer disease (AD) in preclinical stages,” the authors wrote.

In their cross-sectional study, researchers used data from individuals who were screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer study, which was a randomized clinical trial conducted across 67 sites in the United States, Australia, Canada, and Japan between April 2014 and December 2017. A total of 4492 cognitively unimpaired adults between 65 and 85 years of age underwent positron emission tomography (PET) imaging to assess cortical Aβ levels (Aβ-PET). Of the 4492, 79 were excluded due to missing data. The mean age of the 4413 eligible study participants was 71 years, 59% of which were women.

The results showed that the mean Aβ-PET was elevated in individuals with a history of memory impairment in both parents and in those with only maternal history compared with those with only paternal history or no family history.

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“Further, we examined the maternal and paternal age at symptom onset in terms of brain Aβ burden,” the authors wrote. “Paternal history of late-onset memory impairment did not affect offspring Aβ-PET, whereas early-onset paternal history and maternal history at any age were associated with elevated Aβ-PET compared with individuals with no parental history.”

This study had several limitations. For example, the data included self-reported family history, which could lead to a participation bias. Additionally, the definition of parental history of dementia and significant memory impairment, may have included causes of cognitive decline that do not involve AD.

Still, the key findings suggest that familial history of memory impairment, particularly from the maternal side, was associated with β-amyloid burden among asymptomatic older adults, which has the potential to inform clinicians on the likelihood of Aβ burden among offspring as well as identify those who may be high-risk for AD.

“This study found that in asymptomatic older adults, maternal history of memory impairment at all ages and paternal history of early-onset memory impairment were associated with higher Aβ-PET, while paternal history of late-onset memory impairment was not,” the authors concluded. “Our results suggest preferential maternal inheritance of AD starting from the preclinical stage, a finding which has broad clinical and scientific implications.”

Reference:

Seto M, Hohman TJ, Mormino EC, et al. Parental history of memory impairment and β-amyloid in cognitively unimpaired older adults. JAMA Neurol. Published June 17, 2024. Accessed June 19, 2024. doi:10.1001/jamaneurol.2024.1763