Alzheimer’s disease genetic risk: Education offers protective buffer

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Education offers a protective buffer against Alzheimer’s, even in those genetically predisposed to it. Image credit: Goroden Koff/Getty Images.
  • New research from Mass General Brigham challenges the notion that genetics is the sole determinant in Alzheimer’s risk, particularly for those predisposed to early-onset forms of the disease.
  • The study analyzed data from 675 people carrying the PSEN1 E280A genetic mutation, which often leads to Alzheimer’s symptoms appearing around the age of 49 years.
  • While those with an additional high-risk mutation experienced faster cognitive decline, the researchers found that higher educational attainment could act as a protective factor, slowing down cognitive impairment even in the presence of strong genetic risks.

In a new study, published in Nature Communications, and led by researchers from the Massachusetts General Hospital at Harvard Medical School, the authors explain how genetics is only a single factor in the risk equation for Alzheimer’s disease, even for forms of the disease that have a major genetic component.

Scientists examined the role of genetics and educational level in cognitive deterioration by analyzing data from 675 individuals with a genetic mutation known as PSEN1 E280A, which makes them susceptible to early-onset Alzheimer’s disease.

Those with this mutation typically begin showing dementia symptoms around the age of 49.

The researchers discovered that individuals with this mutation who also had a second risk-increasing mutation — APOE e4 — experienced a faster onset of cognitive decline.

Conversely, those with a protective APOE e2 mutation saw a delayed onset of cognitive symptoms.

The study team also evaluated how educational level influenced cognitive abilities in individuals carrying the PSEN1 E280A mutation, including those with various APOE genetic variants.

Their findings suggested that greater educational achievement, or more years of schooling, was linked to better cognitive function, especially among those with the highest genetic risk for the disease.

Study first author Dr. Stephanie Langella, postdoctoral research fellow in the Department of Psychiatry at Massachusetts General Hospital, spoke to Medical News Today, saying that “in individuals with a genetically determined form of Alzheimer’s disease, the onset of clinical and cognitive impairment is influenced both by other genetic factors and years of educational attainment.”

“Higher educational attainment (years of education) was protective against the strongest genetic risk factors for Alzheimer’s disease and may be an important mechanism of cognitive reserve in those with genetic risk.”

– Dr. Stephanie Langella

Dr. Yakeel T. Quiroz, associate professor at Harvard Medical School, the study’s corresponding author, and a clinical neuropsychologist and neuroimaging researcher at Massachusetts General Hospital, highlighted that having more years of education could serve as a safeguard against cognitive decline, even when strong genetic predispositions are present.

“Our results suggest that increasing educational attainment may be one way to preserve cognitive function in individuals with risk for Alzheimer’s disease,” Dr. Quiroz explained.

Even with the added risk from APOE e4, which is the most significant genetic risk factor for non-familial Alzheimer’s disease, these findings indicate that educational level could serve as an important factor in cognitive resilience for familial forms of Alzheimer’s disease.

Dr. Sumeet Kumar, geneticist and founder of, not involved in this research, told MNT that this study “has provided pivotal insights into the complex interplay between genetic and environmental factors in Autosomal Dominant Alzheimer’s Disease (ADAD).”

“Although a person may be genetically predisposed to develop ADAD, the trajectory of the disease could be influenced by other genetic variables like APOE and environmental factors such as educational attainment. This is enlightening because it opens up avenues for targeted interventions. Educational programs could be strategically designed as preventive measures, especially for those at genetic risk.”

– Dr. Sumeet Kumar

“However, it’s important to contextualize that there are limitations to this study, including its cross-sectional design and the absence of data for certain variables,” Dr. Kumar pointed out. “Moreover, the extent to which these results can be generalized to other types of Alzheimer’s remains unclear.”

“Despite these caveats, the study holds promise for future research to elucidate the biological mechanisms behind these observed trends and for the development of interventions tailored to individual risk profiles,” he further noted.

“This could lead to more personalized approaches in Alzheimer’s care, aligning with the broader shift toward precision medicine in neurodegenerative diseases,” said Dr. Kumar.

Dr. James Giordano, professor of neurology and biochemistry from the Pellegrino Center at Georgetown University Medical Center, also not involved in the research, agreed, saying that “this is a most interesting, well-performed, and well-articulated study that demonstrates the dynamic relationship between genetics, anatomical and physiological expressions, and environmental factors.”

“In other words, it further defines the interaction of “nature via nurture,“ that is, that genetic foundations serve as something akin to blueprints, which are dependent, at least in part upon environmental variables throughout the lifespan, for the physical expression of anatomical, and physiological characteristics in both health and disease.”

– Dr. James Giordano

Dr. Giordano noted that “the major implications of this study are that genetic bases of physical expression of various traits are modifiable, to some extent, upon aspects of lifestyle.”

“Specifically, it suggests that ongoing cognitive and behavioral challenges (such as those inherent to education, and learning and engaging new information, and skills) can afford [the] beneficial opportunity to sustain cognitive capability.”

The study was a collaborative effort involving researchers from Massachusetts General Hospital, Brigham and Women’s Hospital, Mass Eye and Ear, as well as national and international partners.

The findings of their research support those of a previous study completed by researchers at Tohoku University in Senda, Japan, showing that people who took adult education classes in middle-to-old age were less likely to develop dementia or experience cognitive decline.

Both studies show the dynamic relationship between multiple factors. However, it is important to note that not everyone has the same access to higher education, meaning that developing appropriate interventions may be challenging.

Addressing health and educational equity is a complex task that requires concerted efforts from various stakeholders; including government agencies, educational institutions, non-profits, and communities.

Yet the benefits appear to be clear not only from an educational perspective but from a health and wealth perspective, too.

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