For decades, the fear of dementia has often been associated with a genetic doom, a fate inscribed in a code that cannot be changed. Today, a new study led by the University of California, San Francisco (UCSF) shakes up this view, offering a concrete course of action for anyone concerned about their cognitive future.
The research, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, highlights one fact: While genes explain about half of the risk of developing dementia, the other half is determined by modifiable factors. We are talking about variables such as social isolation,physical inactivity, and uncorrected hearing loss. In short, our environment and choices matter as much as our DNA.
Four interconnected factors
The most innovative aspect of the study lies in its ability to predict dementia risk by combining an individual’s genetic profile with his or her risk factors for cardiovascular disease, such aselevated Ldl hypercholesterolaemia, obesity, and hypertension.
The team of researchers analyzed data from 3,500 adults, with an average age of 75, over a six-year period. Initially, none had dementia, but one in four participants showed mild cognitive impairment (Mci), a common precursor. By the end, a quarter of the survivors (among those who had normal cognition or Mci) had developed the condition.
The researchers found that risk is influenced by four crucial factors that act in synergy. The first is family history, which is having a parent or sibling with dementia. The second factor isspecific genetic inheritance, which results in having at least one copy of the Apoe4 gene variant significantly associated with Alzheimer’s. The third factor is having a high polygenic risk score, which reflects the cumulative effect of many minor genetic effects. Finally, the fourth factor is the presence of a high cardiovascular risk score, which is closely related to conditions such as hypertension and high cholesterol.
Increased risk
The results suggest that the greater the number of factors present in a person, the greater the likelihood of developing dementia. One factor increases the risk by 27 percent; two factors by 83 percent; three by 100 percent. Four factors, on the other hand, quintuple the risk.
This underscores the close correlation between vascular and brain health. As the author of the study, Shea Andrews, explains, “In Alzheimer’s disease, several vascular diseases, such as hypertension and diabetes, could be involved. If you make lifestyle changes and improve control of diseases like these, you could reduce the overall extent of brain damage, potentially delaying or even preventing symptoms.” His observation confirms that cardiovascular care is, in fact, a neuroprotective strategy.
Precision medicine
Historically, Alzheimer’s did not allow for a “precision medicine” approach focused on reducing modifiable risks, simply because both early diagnosis and effective treatments were lacking. Andrews notes that the landscape has radically changed: “Before, we didn’t have a precision medicine approach to help patients reduce modifiable risks because Alzheimer’s couldn’t be diagnosed or treated.” But now, Andrews continues, “treatments are available that can slow the progression of the disease, especially in its early stages, which can be identified with a blood test or a specific type of brain imaging called a PET scan.”
The goal is to integrate genetic data-which is expected to become more readily available in the coming years-with cardiovascular and lifestyle assessment.
An “optimal scenario for using this data,” Andrews hypothesizes, might involve a patient with a diagnosed relative sharing his or her concerns with the family physician. The latter, after discussing the genetic data, “would work with the patient to find solutions to reduce modifiable risks.” This approach aims to turn fear into informed action.
Power to the patient
The real breakthrough of this research, beyond the numbers, is the psychological impact on high-risk patients. As the study’s lead author, Kristine Yaffe, a pioneer in the study of modifiable factors, points out, “I think focusing on what patients can control gives them decision-making power and a sense of responsibility.”
This approach offers the possibility of “taking proactive measures, rather than waiting for symptoms to emerge.” It is not about eliminating genetic risk, but acting on its expression through lifestyle choices and strict management of cardiovascular health. The environment, habits and therapies for vascular disease thus become the tools of affordable prevention, showing that the dementia equation is less deterministic than previously believed.
