It seemed as if everyone who worked at our local hospital knew Jake. A self-proclaimed “recovered hater of doctors,” he became a fixture, volunteering in the emergency room. The wisecracking 86-year-old’s wrinkled face, slumped shoulders, and insightful irreverent remarks provided a potent remedy for long, painful ER visits. He had been my patient for less than a year when he came to my office and repeated the same story I had heard in each of his past several visits because he could not remember telling me.

“Doc, I always feel as if I’m removed from my surroundings,” he complained. “I feel, as the kids today say, ‘out of it.’ ” As always, he exaggerated the enunciation of “out of it” as though he were speaking to someone with limited proficiency in English. He had made two visits to the emergency room as a patient after transient episodes of confusion accompanied by diffuse weakness and unsteadiness that made him unable to stay on his feet. During these episodes, he felt even more dissociated from the world around him. The second episode caused him to fall and strike his head against the closet door in his bedroom, but he did not lose consciousness.

Our bodies go to great lengths to preserve blood flow to our most vital organs. To make sure the brain gets enough blood, baroreceptors in the carotid arteries in the neck monitor blood pressure. When we stand up or lose blood volume through bleeding, sweating, or not taking in enough liquids, the pressure drops and the receptors send signals through our autonomic (involuntary) nervous system to increase the heart rate and the smooth muscle tone in our arteries, which brings up the blood pressure and forces more blood to the brain. We call this series of events the baroreceptor reflex, which, as with most of our reflexes, slows with age. Jake habitually maintained a nice low-normal blood pressure, a desirable feature in a human body because low-pressure circulation preserves organ function, most notably in the heart, brain, and kidneys. The price those with healthy low blood pressure pay is that they are more prone to not being able to get enough blood up to the brain when they become hot, drunk, or dehydrated, which leads to spells of lightheadedness or fainting.

Jake’s low blood pressure and slow baroreceptor reflex did not give us an adequate explanation for his troubles. His episodes did not seem to be associated with position change or factors that would lower his blood volume, and his symptoms did not dissipate quickly, although they did resolve in less than 24 hours without leaving any permanent deficits in his function. The next logical potential culprit was his heart. Temporary heart-rhythm disturbances can cause the heart to beat too fast or too slowly for brief periods. When it beats too fast, the heart’s left ventricle does not have enough time between beats to fill with blood, so it pumps out too low an output of blood through the aorta to provide adequate pressure. If it beats too slow or not at all, the cardiac output is again too low to maintain sufficient pressure. Jake had never had any heart problems, but he did smoke a daily pack of cigarettes for about 40 years before quitting in the early 1980s, and smoking does cause damage that predisposes smokers to heart-rhythm problems.

We monitored Jake’s heart rhythm in the hospital overnight after his second emergency-room visit, and his rhythm was as perfect as the timing of his punch lines. All this left us with was a working diagnosis of transient ischemic attacks (TIAs), which are events in which a part of the brain, most likely the cerebellum in Jake’s case, temporarily loses its blood supply and then regains it. Clots breaking loose from the heart and the carotid arteries can cause these events, so we treated him with a capsule containing two drugs, aspirin and dipyridamole, that prevent platelets, the blood cells that start blood-clot formation, from aggregating as they do to start a clot; the manufacturer of the capsule cleverly named it Aggrenox. Jake did not have any more of these episodes after starting the medication, but he still felt a bit as though he were not part of this world.

Jake was also losing his short-term memory, his balance, and his ability to control his urine. Six months earlier, after hearing these complaints for the first time, I had recalled the mnemonic MAI (memory loss, ataxia, incontinence) I had memorized during my medical school neurology clerkship so that I would recognize patients with normal pressure hydrocephalus (NPH). MAI was easy to remember because it was also the name of a group of two bacteria in the tuberculosis family (mycobacterium avian intracellulare) that infect victims of AIDS and other diseases that destroy the immune system. People with NPH have enlarged cerebral ventricles, the spaces within the brain that contain cerebrospinal fluid (CSF). The enlargement results from the brain’s adaptation to diminished CSF resorption through the arachnoid villi, which lines the ventricles. Because there is a corresponding decrease in brain mass, the fluid pressure remains normal, which is why people with NPH do not complain of increasing headaches. I had ordered a CT scan of Jake’s brain, hoping to find NPH, because many patients with it benefit from surgical placement of a catheter (shunt) that conducts the extra fluid from the brain to the heart or to the peritoneum, the cavity where the intestines reside in the abdomen.

Unfortunately, Jake’s scan showed minimally enlarged ventricles consistent with a normal 86-year-old brain, and the diffuse brain atrophy typical of advancing Alzheimer’s disease, so I treated him with donepezil (Aricept), a drug that slows memory loss in people with Alzheimer’s dementia. Donepezil inhibits the enzyme that breaks down acetylcholine, an important neurotransmitter affecting many organs, including the bladder, but it did not help Jake’s overactive bladder, so I later prescribed oxybutinin, which prevents bladder spasm and incontinence.

The purpose of today’s visit was to see how he was doing. One of the challenges of evaluating people with dementia is figuring out whether treatments are working. We can administer tests in the office to assess their mental status, but other intermittent or vague symptoms are tricky. Because they don’t make new memories, they can’t remember what their condition was before the treatment started, so subjective comparison between then and now is difficult. Many elderly people with mild to moderate memory loss live alone, so there is not a reliable source to give us this information, forcing us to rely on pharmacies and visitors to tell us whether they are taking their medicines and how their condition is changing over time. As the memory worsens, demented people can’t remember what medicines or treatments they are using, let alone whether they are working.

Eleanor, Jake’s wife of 62 years, was our best source. Slow afoot due to Parkinson’s disease, she did not have any problems with her memory, as many Parkinson’s victims do. She never would come with him to his appointments, so I phoned her every time he came in to get a progress report and check his medications. Soon after the first of these checkup calls, she came in for an appointment for her hypertension and Parkinson’s. At the conclusion of our visit, she stood up with the grace that she battled to maintain, looked me in the eye, and advised me in her soft, gravelly voice, “Find out what’s wrong with Jake. Because if he goes, I go too.”

At that moment, I was looking at my grandmother. My grandfather died of lung cancer in 1980 after 50 years of marriage to my grandmother, a female executive in an era when she had few peers. Tall, proud, elegant, and stubborn, she never again wanted to be alive after he died, much to the chagrin of my mother, who was her only child, and the rest of our family. She survived another 13 years before succumbing to complications of a hip fracture.

I knew Eleanor meant what she said. Feeling the eyes of an entire hospital watching me, and remembering Eleanor’s grave warning sounding against my eardrums, I enlisted the help of a local neurologist. He spent two visits interviewing and examining Jake and sorted through the results of the head CT scan, the blood tests I had ordered to check Jake for thyroid dysfunction, vitamin B12 deficiency, and syphilis, all of which were negative, and the hospital records. To be thorough, the neurologist ordered a 24-hour Holter (heart) monitor to be more certain that we had not missed an important heart dysrhythmia during his short hospitalization. We were never able to overcome the obstacles of Jake’s forgetfulness and transportation difficulties to get him into the cardiology office at the appropriate time to get the Holter done.

Eleanor and Jake confirmed at this visit that his condition had not worsened and that he had still not followed through with getting the Holter, which I now wanted for a different reason: I was hearing extra heartbeats when I listened to his heart, so I wanted to be sure that these extra beats were not potentially dangerous. He was not having any chest pain, and his energy level was quite good. I gave him and Eleanor detailed written instructions, in the hope that he would be able to follow through and get his Holter monitor and an ultrasound of his heart done before his next visit.

None of us expected that Jake would die a few weeks later; he was too cheerful for that. Pneumonia remains in the top five causes of death every year, and those who die often succumb to problems in vital organs other than the lungs. One year before Jake’s illness, I got a call from one of my mother’s best friends. She had just taken my mother to a local Kaiser emergency room because my mother was having severe chest pains. She had pneumonia, which stressed her heart enough to cause it to convert out of its normal sinus rhythm into atrial fibrillation, a chaotic rhythm that causes the heart to beat rapidly and pump blood inefficiently. My mother was 15 years younger than Jake, which is perhaps the main reason she is still with us. Shortly after the bacteria invading his lungs proliferated into pneumonia, Jake’s heart had also converted to atrial fibrillation, but his was unable to pump all the blood his vena cava was returning to it, and therefore the extra fluid backed up into his lungs. The combination of congestive heart failure and pneumonia made it impossible for the hospital team of doctors, nurses, and respiratory therapists to deliver enough oxygen through his lungs to sustain his vital organs, even with a ventilator, intravenous antibiotics, and our strongest medications for the heart. None of this had anything to do with what had been wrong with his brain.

Medicine in the 21st Century has created hospitalists to take care of every patient in the hospital, excluding those of us in primary care, so I had not been involved in Jake’s care at the hospital. I called Eleanor when I learned of Jake’s death. “All of those doctors in the hospital, and not one of them could do anything to save my husband,” she began, perhaps implying that I, too, had failed her in that regard. She then gave me the details. I listened, knowing that now wasn’t the time to explain that the death rate for all of us is still 100 percent, and recognizing that I could not repair the defect her partner of 62 years created when he left. She moved to an independent assisted-living facility, where I went to see her once in her apartment after a bad fall, and then I never heard from her again. I assume she followed through on her warning.