What’s my Alzheimer’s risk, and can I really do anything to change it?

Some years back, my father received a diagnosis of Alzheimer’s disease, mirroring the experiences of his older brother and mother. Gradually, I have noticed a decline in his personality. Now, at 75, his cognitive decline is becoming more pronounced; he struggles to recognize his granddaughters and lives in a near-constant state of confusion, leading to a loss of independence.

As I grapple with this emotional loss and strive to support my family, my curiosity about my own familial predisposition to this disease has grown. At 43, the age when misfolded proteins associated with Alzheimer’s might begin accumulating in the brain, I wanted to understand my personal risk and explore whether there was anything I could do about it. Would undergoing a DNA test to assess my hereditary vulnerability to Alzheimer’s be beneficial? How could I interpret the increasingly prominent advice that we can potentially “prevent” Alzheimer’s through lifestyle modifications like diet and exercise? Given my family’s history with the disease, I approached this subject with skepticism.

What I uncovered was often perplexing and exasperating due to the intricate nature of Alzheimer’s disease, necessitating careful analysis of almost everything. Yet, surprisingly, I also found the information to be empowering. As Rudolph Tanzi, a neurologist at Massachusetts General Hospital, aptly puts it: “Genetics deals you a hand, which may not be favorable, but how you play it truly matters.”

The situation my family faces is, unfortunately, common. Approximately 55 million individuals globally live with dementia, with Alzheimer’s being the most prevalent form; this number is projected to reach 78 million by 2030. Despite significant advances, the exact causes of Alzheimer’s remain frustratingly vague, largely attributed to age-related changes in the brain along with genetic, health, and lifestyle influences.

Neuroinflammation

The leading theory is known as the amyloid hypothesis, proposing that the aggregation of a misfolded protein termed amyloid-beta between neurons triggers the erroneous formation of another protein called tau within the cells, leading to tangles. This progression subsequently causes neuroinflammation, disrupts synaptic connections, and results in cell death. “Amyloids serve as the match, while tangles act as the brush fires,” Tanzi explains. “You can’t develop Alzheimer’s from that alone, as it must induce neuroinflammation — a wildfire that destroys sufficient neurons and synapses to result in the disease.”

However, there are indications that the amyloid hypothesis may not encompass the entire scenario. For an extended time, the novel treatments inspired by this theory — antibodies formulated to eliminate misfolded proteins from the brain — have not succeeded in alleviating symptoms. Recently, however, some of these medications, such as Lecanemab, received approval from the US Food and Drug Administration, as they demonstrated modest effectiveness in decelerating cognitive decline in patients with early-stage Alzheimer’s.

Many specialists still regard the advantages as inadequate in light of the risk of brain swelling and bleeding associated with this treatment. Nevertheless, as the first “disease-modifying” therapy, these medications mark progress and indicate that more effective alternatives may be forthcoming. Earlier this year, for example, pharmaceutical company Roche announced promising early findings from a small trial for a drug called Trontinemab, which seems to minimize amyloid deposits while reducing the likelihood of brain bleeds.

This all comes too late for my father, of course. However, it serves as inspiration for me to probe my risk further: since the optimal outcome involves “early prediction, early detection, and early intervention,” as Tanzi suggests, I want to ascertain when and if I should take action.

Genetic Vulnerability

When considering early detection, my genetic makeup is the first area to investigate. It’s established that genetics significantly impact Alzheimer’s risk, predominantly via the gene responsible for the apolipoprotein E (APOE) protein, which plays a role in the transportation of fats and cholesterol throughout the body and brain.

Every individual possesses two copies of the APOE gene, one from each parent, and there are three variants. The most prevalent variant, APOE3, does not seem to influence Alzheimer’s risk. In contrast, APOE2, which is relatively uncommon, might offer some level of protection against the disease. Meanwhile, APOE4 is clearly linked with an increased risk. Research indicates that possessing one copy of this variant raises the likelihood of developing Alzheimer’s three to fourfold compared to those with none, while having two copies can amplify the risk up to 15 times.

Considering my family’s background, I assume I belong to the 25 percent of the global population who have at least one copy of the APOE4 variant — and possibly even within the 2 percent who carry two.

Nowadays, it’s fairly straightforward to discover this, courtesy of direct-to-consumer genetic testing services. The most well-known option is the “health and ancestry kit” provided by 23andMe, which can generate reports relating to the APOE gene. A quick search in the UK also reveals several other products promoted solely as APOE tests. Initially, I was eager. However, upon receiving the kit, I found myself hesitating.

All Alzheimer’s organizations in the UK and the US generally advise against such testing. Their primary argument is that APOE does not determine destiny since numerous other risk factors also play a role. “Yes, having two copies of APOE4 significantly heightens your risk, but it doesn’t guarantee that you will develop Alzheimer’s,” states Charles Marshall, who specializes in dementia research at Queen Mary University of London.

Additionally, as dementia is so prevalent, most individuals have some family history, according to Marshall. “Therefore, unless someone in your family had notably early onset dementia, the fact that a parent had it later in life doesn’t greatly affect an individual’s risk.”

The broad caution against APOE testing is also related to the potential psychological distress it can create, as noted by Ashvini Keshavan at University College London’s Dementia Research Centre. “The benefits [of genetic testing] are minimal, while the drawbacks are significant regarding anxiety generation, thus such tests should not be pursued,” she asserts.

As someone prone to ruminating, this gave me considerable pause. Eventually, however, I opted to go ahead with the test. For better or worse, I had convinced myself that I likely had at least one copy of APOE4, and anything less would feel like a relief.

As I awaited my results, I began thinking about detection — specifically about the misfolded proteins believed to incite Alzheimer’s, which can start gathering in the brain two decades before even mild cognitive impairment occurs. “If you possess APOE4, you might want to know whether amass of amyloid has begun in your brain and if tau tangles are forming, as that’s how it works,” reveals Tanzi. The concept is that you would then have a chance to take proactive steps at an early stage of the disease’s progression.

What’s the Situation with Biomarker Tests?

Recently, researchers have illustrated that tests measuring blood biomarkers can detect amyloid-beta and tau in the brain with greater ease than current methods used for diagnosing early-stage Alzheimer’s. One particularly promising blood test identifies a specific protein called p-tau217, a key indicator of disease pathology, often well before symptoms manifest. A 2024 study analyzing the p-tau217 test demonstrated that it was equally accurate as cerebrospinal fluid analysis and superior to PET scans.

Currently, efforts are focused on determining the best ways to implement these blood tests in clinical practice. However, it is anticipated they might ultimately be used for screening everyone over 50, similarly to how assessments for high cholesterol are currently conducted. “That’s the objective,” says Tanzi. “We won’t be able to eradicate Alzheimer’s by only acting after the brain deteriorates enough for symptoms to arise.”

Nonetheless, there is currently insufficient evidence to confirm that blood tests can reliably forecast an individual’s risk of developing Alzheimer’s or when that might occur, according to Keshavan. “These blood tests indicate changes in asymptomatic individuals, but their presence doesn’t necessarily imply that you’ll develop symptoms at any point in your life.” Some individuals may harbor amyloid and tau in their brains for decades without manifesting Alzheimer’s symptoms — a phenomenon researchers term “resilience.”

Understandably, these blood biomarker tests are already emerging in the consumer market. However, Tanzi advocates caution: “If finding out you carry APOE4 evokes anxiety, consider the emotional toll of discovering that amyloid is accumulating in your brain.”

Keshavan is even more resolute in her stance. She fears we may find ourselves in a situation akin to that faced by medical professionals dealing with current at-home APOE tests, where “patients arrive with their results and we must manage the resulting anxiety and distress,” she explains. “This is why we are vocal in advising against such tests!”

I heed this guidance. It is likely still premature for me. However, I wouldn’t entirely dismiss the idea of pursuing a blood biomarker test in the coming years, particularly if new amyloid-targeting treatments become available by that time.

Exploring the Potential of Alzheimer’s Vaccines

On this front, vaccines aimed at targeting amyloid-beta and tau present the most thrilling prospect. The principle is straightforward: with the aid of vaccine additives known as adjuvants, the body’s immune response is intensified to eliminate the misfolded proteins. Numerous candidates are currently undergoing clinical trials, with aims not only to slow or halt disease progression but also to aid in preventing it. However, it’s essential to recognize that there’s no guarantee these Alzheimer’s vaccines will ever receive medical approval, let alone in time to assist me or others in similar situations.

This leads to the critical question: what, if anything, can we do in the meantime? Following current developments in the field, you might believe we already possess the solutions. A constant flow of news asserts that we can “prevent” dementia through healthier lifestyle choices. Yet, I instinctively felt doubtful, perhaps because reporting often oversimplifies the details of these studies, their robustness, and their implications for individuals like me with a family history of the disease.

A recent wave of coverage was triggered by a Lancet Commission report from 2024, in which 27 experts evaluated the best existing evidence and concluded that 45 percent of dementia cases could potentially be prevented by addressing 14 critical lifestyle factors. These include lower education levels, sensory impairments, high blood pressure, elevated cholesterol, obesity, diabetes, smoking, excessive drinking, environmental pollution, social isolation, depression, traumatic brain injuries, and lack of physical activity.

The key takeaway is that “there’s a lot that we can do to either prevent or postpone dementia onset,” emphasizes Gill Livingston, a neurologist at University College London and the report’s lead author. “While some individuals will still develop dementia, if they manage these lifestyle factors, they generally will experience a delayed onset and shorter duration of the disease. That’s significant because delaying onset by 10 or 15 years might mean you never have to confront it in your lifetime.”

Nevertheless, critics of the Lancet report pointed out that the analysis relied primarily on observational studies, establishing correlations but not direct causation. “We lack definitive evidence that addressing any of these risk factors can prevent dementia,” Marshall remarked at the time.

Livingston, however, counters that some matters simply cannot be resolved through randomized controlled trials (RCTs), which are deemed the standard for research, for a variety of ethical and practical reasons. She notes that the observational studies considered in the Lancet report were generally large, high-quality studies that produced effects of a similar magnitude in the same direction. “While correlation does not imply causation, it often does,” says Livingston. “For instance, there are no RCTs demonstrating a link between smoking and lung cancer, as such trials would be unethical. Yet, very few would dispute that a relationship exists based on the accumulated evidence.”

It’s also important to note that the Lancet review did encompass several RCTs — for example, examining the influences of blood pressure and diabetes. Notably, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) stands out as the first extensive RCT to showcase lifestyle interventions as a means of preventing cognitive decline in older adults at risk of dementia.

The initial FINGER study, published in 2015, included over 1200 participants aged 60 to 77 with heightened risk of dementia but no evident memory issues. Half of the subjects engaged in a comprehensive programme of lifestyle interventions encompassing dietary changes, physical activity, cognitive training, and blood pressure management, while the control group received standard health guidance. After two years, cognitive performance showed improvement in both groups; however, the intervention group achieved an overall average enhancement of 25 percent more than the control group.

“Additionally, we found that those in the control group exhibited a 30 percent higher risk for cognitive decline,” states Miia Kivipelto at the Karolinska Institute in Stockholm, Sweden, who leads the FINGER program. The team also demonstrated a reduction in the estimated risk of dementia.

The success of the FINGER trials set the stage for several follow-up studies where interventions have been tailored for different populations across more than 60 countries, yielding further promising results.

While these outcomes appear encouraging, and many researchers commend the rigor of the FINGER studies, we must remember that these trials have not yet conclusively proven a reduction in dementia cases, according to Marshall. “The observed improvements in cognitive test scores over time raise questions about how these translate to real-world dementia prevention,” he states. “Individuals in the intervention group improve a little more than those in the control group, but this doesn’t automatically translate into preventing dementia.”

Strengthening Resilience

What we can assert is that such lifestyle modifications seem to influence how resilient your brain is to dementia, potentially Alzheimer’s pathology specifically, if either condition arises. “It is likely that these changes may delay the onset of symptoms in light of Alzheimer’s pathology, which pragmatically means that some individuals might ultimately pass away from other causes before experiencing symptoms,” Marshall comments.

This does resemble prevention to some extent. “Clear evidence suggests that factors contributing to brain resilience have an impact,” Livingston adds. Tanzi believes that it’s never too soon to adopt habits that can enhance this resilience, irrespective of one’s APOE status. “The message is clear: in 98 percent of cases involving family history or genetic predisposition, lifestyle choices are impactful,” he asserts.

As for which specific lifestyle factors take precedence, each researcher I engaged with had a slightly different perspective. The FINGER studies emphasize two essential elements: adhering to a Mediterranean-style diet rich in vegetables, fruits, nuts, and whole grains while being low in red meat, and maintaining an active lifestyle—physically, mentally, and socially. However, Livingston underscores the importance of managing blood pressure and cholesterol levels, as numerous studies indicate that good vascular health can mitigate dementia risk.

Your age and personal circumstances can also play significant roles. Many individuals in their 40s, like me, juggle work, childcare, and aging parents, making stress a vital factor, according to Kivipelto. “Instead of concentrating solely on cognitive stimulation, someone in your situation might prioritize sleep and stress reduction, possibly through increased physical activity, and checking for high blood pressure,” she advises.

After completing the genetic testing, I learn that I possess one copy of the APOE4 gene variant. To summarize, this implies that I am three to four times more likely to develop Alzheimer’s compared to someone with no copies of that variant. However, this revelation doesn’t induce significant anxiety because, at this point, I have gained enough insights to understand that my APOE status does not determine my destiny — and I have become somewhat confident, however tentative the evidence, that I might be capable of postponing the onset of cognitive decline.

If anything, this result motivates me to follow through on long-standing plans to adopt a health-focused lifestyle, especially since Kivipelto and her colleagues have shown that APOE4 carriers reap greater benefits from the FINGER interventions than non-carriers.

I’m mindful that this is essentially generic health advice — healthier eating, increased physical activity, etc. Nevertheless, it is empowering. As trivial as it may sound, every time I choose a mackerel salad for lunch, go for a run in the woods, or arrange to meet friends, I remind myself that I am bolstering my brain’s long-term resilience against neurodegeneration.

Until more effective treatment options are available, that’s all we can do. “At the individual level, no one can claim to be preventing Alzheimer’s since no such guarantees exist,” Tanzi remarks. “However, maintaining brain health and enhancing resilience is undoubtedly worthwhile, and it likely means living longer without dementia.”