Musing from his sickbed, Marcel Proust in his 1913 semi-autographical novel Remembrances of Things Past (A` la recherche du temps perdu) famously described the vivid retrieval of a long-lost memory evoked by the smell and taste of a tea-soaked madeleine cake. His childhood memory of cherished Sunday mornings in the country, his aunt Le´onie, and now the rush of memory itself was an exquisite pleasure, he wrote. “And all from my cup of tea.” The Proust effect, as it has come to be called, refers to the phenomenon most of us have experienced, in which sensory cues instantly take us back to a long-ago memory.1

Modern science has since established that taste and smell cues are perhaps the strongest stimuli for retrieving old memories.

Lois pushed ‘pause’ on her audiobook and slipped off her earbuds so she could answer the phone. Flavia de Luce could wait. The name on caller ID announced it was a longtime acquaintance we see occasionally when we cross paths on day hikes in the backwoods Oregon region where she lives. It was mid-March and we hadn’t been out that way for some months, waiting for a break in the rainy season. She and Lois exchanged a few cheerful words. Then she asked after the family and Jack – it turned out she’d happened to be watching the local TV news and the image of an English Cocker Spaniel like Jack flashed on the screen and caught her attention. (He is a very handsome dog.) Then she had noticed my face on the screen and realized it was Jack. Then she saw the screen caption on the story – RETIRED NEUROLOGIST BATTLES ALZHEIMER’S [1].

What makes us what we are? The old nature versus nurture debate isn’t one anymore. We know that our genetic inheritance is only a part of what shapes us. We are, of course, shaped by our experiences throughout our lives, but perhaps most so when we are children. What we learn from our parents depends not only on their genes, but perhaps most strongly on cultural inheritance, the ideas, philosophies, literary preferences, religious beliefs, likes, dislikes and prejudices passed down from our ancestors and blended together into an ethical, artistic and intellectual amalgam.

So often in the Alzheimer’s conversation, or that of any disease with genetic links, as the search for clarity around a diagnosis is paramount, discussion of family history brings parents and extended family into sharp view for that purpose alone – their DNA trail.

Lois could hear the familiar Bach prelude wafting upstairs from the piano and she was pleased that I was playing, since I usually wait until she’s out with Jack to do so. Jack has a tendency to howl or try to climb in my lap, though whether that is a complaint or a desire to perform a duet, we don’t know. Our daughter Susannah was in for a visit, and Jack wasn’t howling, probably distracted. But, as Lois listened, she noticed the prelude sounded a bit halting, with a few mistakes. She paused, worried in that moment, for the first time, that Alzheimer’s might be showing itself this way, and came downstairs to look in on me. She was relieved to discover it wasn’t me at all – it was Susannah, the flutist in the family.

Headlines make scientific breakthroughs seem sudden, but, in truth, the real advancement of science is more like the construction of a pyramid. Each block of the pyramid represents a hypothesis that attempts to explain an observation in nature that has been tested experimentally. Depending on the results of the experiment, the hypothesis is either confirmed, revised and tested again, or rejected. Each block adds to a new layer of the pyramid, each layer built on those below. No single study is likely to crack the code for an immediate Alzheimer’s cure, but each one contributes to our understanding in ways that I am confident will eventually lead to more effective treatment and prevention. Even if it’s not in time for me.

Clinical trials are the bricks and mortar of medical science, and if having Alzheimer’s means I’ve had to step away from any professional involvement with them, it also opened up a new opportunity to stay involved.

The grilled chicken chunks on Lois’s plate glisten with the olive oil, herbs and spices we always use to marinate them before we set the skewers on the grill. Juicy chunks of red pepper, green pepper and onion punctuate the spaces between the tastefully charred chicken bites. Nestled in a bed of brown rice, the whole thing looks like she just lifted her plate from the cover of Bon Appe´tit magazine. Mine, not so much. We are on Day Two of the two-day pre-test elimination diet for an Alzheimer-related clinical trial. More accurately, I am. Researchers are testing an ancient medicinal herb to see how long a specific dose of this extract lasts in my system. In animal studies, a very concentrated tea they’ve made from this plant produces cognitive improvement in a mouse model of Alzheimer’s disease. They hope it will have that effect in humans.

I spend much of my day reading science – updates on clinical studies, current journals, and deep dives into the growing scientific literature on the many facets of neurodegenerative disease, dementia, Alzheimer’s disease and, specifically, early-stage Alzheimer’s. I also read spy novels and work crosswords throughout the day as if my life depended on it. In a way, it does.

The Holy Grail of Alzheimer’s research is the search for a treatment that can halt the underlying disease process. A drug, a procedure, some sophisticated treatment regimen that, in medicine, we call a disease-modifying intervention. While nothing has proved reliably effective in clinical trials so far, a lot has been learned about what goes on in the brain during the disease process. The role of cognitive reserve and resiliency is something of a wild card – it’s not fully understood – but it is emerging as a promising factor in the brain’s capacity to forestall the effects of Alzheimer’s for a longer period without significant symptoms.

A towering stump of basalt second only to the Rock of Gibraltar, Beacon Rock rises 848 feet from the Washington shore of the Columbia River, about 40 miles east of my home on the Oregon side, up a dead-end street in a woodsy hilltop neighborhood in Portland. The river feels like my second home, carrying years of memories and the promise of more good times spent on the water, first with my kids when they were kids, and now with my grandchildren. This is where they learned some lessons in resourcefulness and practical skills for life and where I learned some of the ropes myself.

Those days are numbered now, though the timeline is imprecise. Ordinarily, this would be maddening for me as a former research scientist and neurologist for whom precision is second nature.

A leak in your roof can travel a circuitous route through rafters and joints before it surfaces three rooms away as a creeping stain on the ceiling over your sofa. Symptoms of illness or injury are like the stain, the observable thing that gets your attention and prompts you to investigate further.

Working backward from a symptom to find the cause is the perpetual puzzle of science and medicine. It is particularly so in neurology, with the interconnected complexities of the brain itself, the vast domain of the nervous system, and the mix of hormones and other fluctuating neurochemistry. In any case, the sooner you can track an observable symptom successfully to the source, the sooner you can identify the most effective treatment options

When Auguste D. was about 52, her husband noticed she was acting oddly, misplacing things around the house and suspecting him of having an affair with the next-door neighbor. Her memory rapidly declined over the next year and her paranoia and delusions worsened. The year was 1901, and she was admitted to the Asylum for the Insane and Epileptic in Frankfurt, where she came under the care of Dr. Alois Alzheimer, a young German psychiatrist with an interest in trying to link neuropathological changes in the brain with psychiatric and neurological illnesses. At the time Auguste D. died in 1906, Dr. Alzheimer had moved to another position in Munich, but he was able to obtain her brain for pathological examination. Under the microscope, he saw dark particles between the nerve cells in the outer layers of the brain. He also saw a different type of smaller dark particles within the nerve cells, which were twisted in appearance.

Very early in my career, long before the advent of donepezil (Aricept) and other medications for treating the cognitive symptoms of Alzheimer’s, a middle-aged woman came to see me for a second opinion.She had mild but troubling symptoms of cognitive impairment and had seen another neurologist who made a diagnosis of Alzheimer’s disease. She had already had all the appropriate testing to exclude treatable mimics of dementia, and those tests were normal. Cognitive testing had shown some very subtle impairment of verbal memory and visual–spatial processing.I told her that she might indeed have very early Alzheimer’s disease, but it was impossible for me to make that diagnosis with certainty. There were no tests to make a firm diagnosis of Alzheimer’s at that time, other than a post-mortem examination of brain tissue. A few months later, I learned that she had taken her own life.

Early in my career, when I chose to step away from research and devote my career to clinical neurology, one of the most compelling reasons was how much I loved working directly with patients, able to bring cutting-edge medical approaches to them and see the difference these made in their lives. When I was in medical school, somebody once told me that his father had been a neurologist but had left to go into research because patients were disheartening – there was so little to be done for so many. That was true up to about the 1980s. But by the time I went into practice, that had changed. It was an especially exciting time to be a neurologist because advances in research were producing medications that could dramatically improve a number of these conditions. The advances in medical treatment of migraine and MS had been life-changing for so many of my patients. Unfortunately, dementia was not one of those scientific success stories – at least, not then.

Dead reckoning, one of the oldest and most basic methods of navigation, was for centuries an essential piece of the mariner’s skill set, and it was still required to captain a charter sailing boat in the late 1990s, when the idea of a late summer week on the water off the San Juan Islands first captured my imagination. The islands, hundreds of them, some inhabited and others no bigger than a pickup truck, form an archipelago off the northernmost coast of Washington and British Columbia. On the water, you share the Salish Sea living room with the likes of baleen whales and orcas, sea lions and otters. The sky is just as lively by day, with the sea birds monitoring the waters for their next meal, and at night – the silent, spectacular sea of twinkling stars.

I learned to sail when I was a kid, growing up near the water in Southern California, where skiffs were common. My great-uncle Fred taught me the ropes, but not the dead reckoning system using compass, landmarks, and coordinates of time and speed to chart your course.

Lois had retired professionally from her career as a librarian when we moved to Portland, but her tenacious appetite for digging and discovery found fertile soil in family life. She became an ardent genealogist – she loves puzzles and loves that genealogy is all about solving puzzles and mysteries. She is as happy digging online as she is digging in the garden – which is to say, very happy. This always led to interesting choices for our rare downtime, and I was a grateful beneficiary of her book and TV viewing recommendations. In 2012, we had become fans of the PBS series Finding Your Roots with Henry Louis Gates, Jr., a show that used a combination of traditional genealogical research and DNA testing to trace the family histories of famous people. Around this time, she had been stumped in her efforts to clarify some of the obscure branches of our respective family trees.