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Vital Signs: B12 and Dementia

Why was my patient suddenly falling apart after decades of healthy living?

By Lesley Evans Ogden
Feb 1, 2000 6:00 AMMay 9, 2023 4:19 PM


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Although I had known Pop Katz and his family for a long time, I had not seen him in years. Now I scarcely recognized him. He was standing in my office-just barely. If his grandson hadn't been holding him up, he'd have pitched straight forward onto his face. Saliva dribbled from the corners of his mouth. His eyes were vacant.

The two had just flown in from Miami to see me. Pop's wife said she couldn't take care of him anymore, but she didn't want him to end up in a nursing home. So she asked their grandson, a psychologist, to bring the octogenarian to me for an evaluation.

Together we reviewed the history. A month ago, the grandson had visited his grandparents and as usual, Pop took him on a three-mile run, joking all the while about how his strict vegetarian habits helped him outperform his juniors. A week or so later, Pop's wife was troubled. "He cries so easily," she told her grandson. The grandson had advised a visit to their doctor, even though he knew Pop liked doctors about as much as rare steak. His wife managed to get him there anyway, and after a cursory exam and blood count, he went away with a clean bill of health.

Then, about two weeks ago, Pop disappeared. Eight hours later, the police brought him home. They had found his car parked on the shoulder of a highway. Pop sat inside, confused. He had been there for hours.

A second visit to the doctor and Pop's condition was diagnosed as "senile dementia." He had lost control of his bladder, was wandering around at night, refusing to eat, leaving the house partially clothed.

Pop was still well nourished and tanned, but he couldn't run three yards, to say nothing of three miles. Something physical had to be wrong. This had come on too quickly, and it didn't fit the scenario of pseudo-dementia some depressed patients develop.

Doctor On Call In medical school, Leslie Bernstein was undecided about whether to become an internist or a surgeon. He settled on gastroenterology because it allowed him to work with his hands and stay within internal medicine. "I get to use all kinds of instruments and endoscopes to see inside the body," he says. Bernstein is a professor of medicine at the Albert Einstein College of Medicine in New York City and the former head of gastroenterology at Montefiore Medical Center. In 1998, he won the clinical achievement award from the American College of Gastroenterology. This is his first piece for Vital Signs.

"How are you, Pop?" I asked. He looked up from his seat, broke into a broad grin, then burst into tears. I admitted him and ordered a workup.

Within a few hours, we got some test results. A cat scan showed no evidence of cerebral atrophy, a shrinkage of the brain that can accompany Alzheimer's. There was no sign of stroke or tumor, nor was fluid accumulating inside the brain, which could create pressure. A spinal tap revealed clear, normal fluid. The blood work was normal, although the red cells were slightly larger than they should have been. There were no signs of infection or cancer.

After a consultation with a neurologist, Pop's problems were given an obvious diagnosis: "rapidly progressive dementia of unknown origin, with severe changes in coordination, emotional lability, and signs of frontal lobe dysfunction involving higher centers of reasoning and memory."

A psychiatrist concluded that Pop suffered from "toxic/organic disease without significant depression." Yet there was no trace in his blood of surreptitious or accidental ingestion of sedatives, narcotics, or tranquilizers, or exposure to poisonous metals, such as lead, thallium, or mercury. A test for exposure to pesticides was negative.

On the second day of hospitalization, more results came back. Pop's thyroid was normal. That ruled out problems with mental function from low levels of thyroid hormone. The results of another brain-imaging test, which traced the path of spinal fluid over the surface of his brain, showed normal results. Still, Pop was getting worse. He could barely stand, even with assistance, and he had lost control of his bowel movements.

I was worried. The longer the cause remained a mystery, the slimmer the chances of a full recovery. "The diagnosis is in the history 90 percent of the time," I thought. "What are we missing?"

The history was simple: In a matter of weeks, a man who hadn't been sick for 80 years suddenly became demented. Yet none of his lab work was abnormal-except for that slight increase in the size of his red blood cells. Liver tests were normal; nothing suggested exposure to a toxin.

What about a deficiency? Iodine deficiency in mothers has been associated with cretinism in the newborn and hypothyroidism in adults, but Pop's tests were negative and his thyroid was normal. What about a vitamin deficiency? The three D's of pellagra include dementia, diarrhea, and dermatitis, but Pop was missing the last two signs. Besides, who ever heard of niacin or any other vitamin deficiency in a vegetarian?

"Holy smoke!" I thought. "I'm an idiot! The man's been a vegetarian for 38 years. No meat. No fish. No eggs. No milk. He hasn't had any animal protein in four decades. He has to be B12 deficient!"

Within minutes a new blood sample was drawn. Then we gave Pop an injection of 1,000 micrograms of vitamin B12. Five hours later, the blood work was back: The level of B12 had been too low to measure.

By the following morning, Pop could sit without help, and within 48 hours, his bladder and bowel control had returned. By the end of the week he could play simple card games, read his get-well cards, and talk on the phone. Unfortunately, some personality changes still remained. He still cried easily, and his attention span was so short that he couldn't go back to work.

Four decades of strict vegetarianism had been Pop's undoing. Delay in diagnosis and treatment had been disastrous. His body had slowly run out of a vitamin that humans get only from animal products. Vitamin B12 is so necessary to the nervous system that without it the cerebral cortex, the spinal cord, and even the peripheral nerves will fail. And it is so integral to cell reproduction that without it the blood-producing bone marrow goes into low gear and, finally, complete arrest. The condition, called pernicious anemia, was first described in 1821, but it wasn't until 1926 that investigators figured out that patients could be treated by adding lots of liver to their diets. After B12 was isolated in 1948, doctors administered the vitamin itself.

What is this substance that evolution has decreed necessary for all animals but none can manufacture? B12 is a substance called a cobalamin, a series of joined rings linked to an atom of cobalt. Of all organisms, only bacteria can make cobalamins, and of the many variations they produce, nature has appointed only one to act as a crucial catalyst in higher organisms. B12 is used in a series of reactions essential for cell division and for the maintenance of the nervous system.

Bacteria make cobalamins in the rumens of animals. We ingest this substance when we eat the meat of an animal or drink its milk. Other nonruminant animals have different ways of obtaining their cobalamins from bacterial sources, but humans are dependent upon animal sources. Inside our digestive tract, the vitamin is freed from the animal protein and combined with intrinsic factor, a substance the body produces to facilitate the absorption of B12. Then the molecule is split; the body absorbs the vitamin and the intrinsic factor is recycled in the gut. The usual reason for B12 deficiency is the gradual loss of intrinsic factor, but in some rare cases, like Pop's, the problem is due to a lack of animal protein in the diet.

My friend's experience teaches a number of lessons: First, age is not a cause of dementia and a diagnosis of senile dementia is unacceptable. Also, not all causes of dementia are irreversible. No one should be committed to a nursing facility without a thorough workup. Second, a diet free of animal protein can be healthful and safe, but it should be supplemented periodically with vitamin B12, by mouth or by injection. And, last of all, despite the proliferation of modern medical tests, there is no substitute for a careful history, a physical exam, and a thoughtful look at both.

The case described in Vital Signs is based on a true story. Some details have been changed to protect the patient's privacy.

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