When most people think of Alzheimer’s disease, they imagine someone in their seventies or eighties slowly losing memories. Francisco “Pako” Rios was 46 when he heard those words. His diagnosis of early-onset Alzheimer’s, driven by a rare PSEN1 gene mutation, places him in a small group of families living with dominantly inherited Alzheimer’s disease. His story is not only about symptoms and scans, but also about love, advocacy, and discovering how to live with a future that feels like it arrived too early.

For more than a year before his diagnosis, Rios noticed that something was off. He began losing his train of thought mid-sentence and forgetting things that had just happened. His wife, Zahydie Burgos, saw changes in the way he interacted with others. Everyday tasks like making appointments on the phone suddenly became difficult. People seemed aggravated or confused by his communication, which was out of character for him.

The changes went beyond memory. Burgos recalls shifts in judgment, unusual food cravings that did not match his normal habits, and moments when he walked into a room and simply could not remember what he was supposed to do. His attention and concentration were clearly different. He became more withdrawn and apathetic, not necessarily toward her, but toward the world around him. Because apathy is easy to mistake for depression, that was the label attached to his symptoms at first.

Rios also struggled with sleep. Some nights, it was not racing thoughts that kept him awake. Instead, it was as if his body no longer felt the need to sleep. At the same time, he experienced a deep depression that did not respond to medication. Taken together, these signs disrupted his daily life, yet they were initially attributed to mood and anxiety rather than younger-onset dementia.

The turning point came because of an MRI ordered for an unrelated medical concern. The scan revealed brain atrophy, a finding that did not match his age. That prompted a referral to a neurologist, then to a specialized young-onset dementia clinic. There, his diagnostic workup included a PET scan suggesting Alzheimer’s pathology, neuropsychological testing, blood work, and a more comprehensive evaluation. Later, in Baltimore, he underwent a lumbar puncture that confirmed abnormal tau and amyloid in his cerebrospinal fluid. Genetic testing revealed a mutation in the presenilin 1 (PSEN1) gene, a known cause of dominantly inherited Alzheimer’s disease.

This genetic confirmation carried emotional weight. Rios had already lived in the shadow of Alzheimer’s since adolescence. His father, grandfather, and great-grandmother all developed the disease, and other relatives in Puerto Rico were affected as well. Burgos describes how they always suspected a strong hereditary component but did not fully grasp that a single gene could carry a near-certain risk. In genetic counseling, they learned that a PSEN1 mutation can mean an extremely high likelihood of developing Alzheimer’s, often decades before typical late-onset cases.

Looking back, Rios is not sure whether he would have wanted to know his genetic status as a teenager. On one hand, it might have allowed him to change his lifestyle to prioritize brain health through exercise and nutrition. On the other hand, he wonders if such knowledge at a young age might have led to overwhelming depression. His uncertainty reflects a challenge many families face when they learn an Alzheimer’s gene runs in their bloodline: how much do you want to know, and when?

Once diagnosed, Rios and Burgos encountered another obstacle that many people with younger-onset Alzheimer’s face. The support systems around them were not designed for someone in their forties. Burgos describes the landscape in Florida as limited, especially for individuals who are not yet seniors. There are programs for older adults and day centers for social interaction, but very few options tailored to middle-aged people living with early-onset Alzheimer’s and still navigating careers, relationships, and financial responsibilities.

To fill those gaps, they turned to creative solutions. A local support group that meets monthly has become one of their most important lifelines. Beyond that, they have built their own network of complementary supports, including music, language therapy, and structured physical activity. Many of these interventions rely on self-payment, which underscores how uneven access to resources can be for families dealing with a rare, genetically driven condition at a younger age.

Their journey also led them into the world of Alzheimer’s clinical trials. Through the Dominantly Inherited Alzheimer Network, known as DIAN, Rios was offered an opportunity to participate in a study combining the anti-amyloid antibody lecanemab, marketed as Leqembi, with an experimental anti-tau therapy labeled E2814. Lecanemab targets amyloid plaques while the second drug aims at tau, another key protein involved in Alzheimer’s pathology. For individuals who were already symptomatic like Rios, the trial protocol began with lecanemab infusions, followed by the addition of the tau-directed therapy after six months.

These are intravenous treatments that require a structured schedule. Every two weeks, Rios receives an infusion of Leqembi. Once a month, he receives both drugs on the same day. The researchers use a randomized design, yet based on his side effects, he and Burgos believe he is receiving active medication. After infusions, especially when both drugs are given together, he experiences a strong sense of malaise, redness, itchiness, chest pressure, and significant increases in heart rate and blood pressure. On those days, he spends up to 72 hours mostly in bed, recovering.

At one point, the side effects were severe enough to land him in the hospital. Local doctors who did not know his trial history initially suspected infection or a heart problem because his vital signs were so alarming. Once the episode was linked to the medications, his clinical team adjusted his regimen with premedications and post-infusion care to help him tolerate the treatments more safely.

Despite the physical toll, both Rios and Burgos remain fiercely committed to his participation in the clinical trial. Burgos notes that they have openly discussed whether to stop when the side effects feel overwhelming. His response, however, is consistent. When he asked, “What’s my option?” and realized there were no equivalent alternatives, he chose to continue. Their lives now revolve around the infusion schedule. Friends and family know that health and trial participation come first. Over time, the hospital nurses and study team have become part of their extended community.

Although they do not yet have access to detailed personal results, they receive yearly updates about the progress of DIAN research and broader findings related to dominantly inherited Alzheimer’s disease. Burgos says what they have heard so far is promising and believes that medications like lecanemab, alone or in combination, can be powerful tools. She is convinced that Rios is functioning better than many peers who were diagnosed around the same time, though that perspective is based on observation rather than formal data shared by the trial.

One detail that stands out in their story is the question of children and genetic risk. Rios and Burgos do not have children, which brings them a measure of relief knowing the PSEN1 mutation will not be passed directly to a next generation. Still, they have relatives who have not undergone genetic testing and whose future risk is unknown. That uncertainty fuels Rios’s motivation to contribute to research. According to Burgos, his main goal is not just to help himself but to benefit those who come after him, whether relatives or strangers affected by familial Alzheimer’s disease.

For people newly diagnosed with Alzheimer’s or just beginning to explore concerning cognitive symptoms, Rios offers one central piece of advice. He encourages them to give themselves time to grieve. Whether that period lasts a day or a year, allowing space for sadness, shock, and fear can become the first step toward accepting the diagnosis and finding the strength to fight for quality of life. Burgos’s reflections add another layer. She emphasizes the importance of listening closely when a loved one says something feels wrong and of seeking second opinions when symptoms do not improve with initial treatments for depression or anxiety.

Their story highlights the importance of vigilant clinicians who look beyond the most common explanations and consider family history when a younger adult experiences memory loss or behavioral change. It also sheds light on the power and burden of genetic knowledge, the gaps in support for people with younger-onset dementia, and the resilience that families can build when they reorganize life around care, community, and research participation. In a landscape that can feel isolating, the journey of Pako and Zahydie offers a deeply human picture of what it means to live with a rare Alzheimer’s gene mutation while still insisting on purpose, agency, and connection.

Read more at https://beingpatient.com/alzheimer-diagnosis-at-46-francisco-rios-psen1-mutation/