REMEMBER WHEN

BY ALLAN L. BERNSTEIN, M.D.

We’ve forgotten birthdays, misspelled names, and gotten turned around while driving. Some of us will laugh o these instances; others will claim “Senior moment!” and move on. But when should you worry that such occurrences are a sign of something bigger? Memory is based on a series of actions within the brain that include input, sorting, storage and retrieval. Input is an essential component in creating memories, since if information is never received, it e ectively doesn’t exist in the brain’s memory system. Di culty hearing may create gaps in memory: A conversation can’t have been forgotten if it was never entered into the memory system due to a hearing loss. Similarly, decreased vision, loss of taste or smell, and loss of touch may limit the information getting into the memory system. Not paying attention also impairs input, regardless of how well the other sensory modalities are functioning. We’ve all had a teacher go on about a topic we weren’t interested in: If asked about it later, it’s a blank in our memory.

THE MEMORY BANK

Sorting the information in our memory bank is a skill that improves with age. Young people retain large amounts of extraneous material, possibly because they have more “storage” space. As we get older, we get more selective in what is important to keep in the system.

Storage of memory has both short-term and long-term components. A critical part of creating long-term memory is sleep. Poor sleep, such as occurs with sleep apnea or insomnia, can prevent new memory material from being properly stored. We may have pulled “all-nighters” during our school years to get through an exam the next day, successfully passing the test. However, a large amount of that material may be missing when we try to recall it a week later, having not “slept on it.” Another essential aspect of storage is having intact connections in the brain. Damage from trauma and strokes may limit both storage space and the ability to connect the various parts of the brain where information is retained.

Retrieval — or, more accurately, the slowing of retrieval — is what we notice with aging. Information used frequently is rapidly available, while less used material may take a little longer. A “noun delay” is common, with the right word arriving too late to fit in the conversation. This is normal. CAUSES OF DEMENTIA

Dementia is the gradual loss of the ability to create new memories and to retrieve old ones. It is accompanied by di culty in speech, judgement, orientation to time and location, loss of previously acquired skills, loss of the ability to perform chores that were normally routine, and di culty recognizing common objects and people. There are multiple causes of dementia, some preventable, some treatable, as well as some that still need more study. The key to meaningful intervention is to recognize that dementia is present in an individual, and start to look for causes.

In the past, getting old equaled becoming “senile” i.e., demented. Since we all know cognitively intact people in their 0s, 90s and 100s, it’s time to reconsider that concept. Dementia has decreased overall due to actively treating high blood pressure and smoking cessation, thereby minimizing stroke-related dementia. We have also become better at recognizing the effect of toxins in the environment that can cause dementia, limiting exposure to lead and mercury, for example.

Today, we actively monitor people for abnormalities in their thyroid function and vitamin 12 status, potentially reversing memory loss associated with these conditions. reating a sleep disorder may significantly improve memory in many people. Depression, if unrecognized, may produce a dementia-like condition, since it is associated with lack of interest in current activities and therefore not paying attention to new material inputs.

Medications, both prescription and over the counter (OTC), may contribute significantly to memory problems. ommon OTC medications to aid in sleep often contain diphenhydramine (Benadryl), which, when taken for long periods of time, may impair memory. Even medications prescribed for anxiety or sleep, if taken for a prolonged period, start to interfere with memory. Most of these offenders should be prescribed for a few weeks or months, but end up being used for years, which is when the problems start to surface.

Repeated head trauma, known as chronic traumatic encephalopathy (CTE) has become more recently recognized in football players, boxers, wrestlers and soccer players (among others) as a potential cause of dementia. In the United States, the age of starting to play tackle football seems to be a marker for developing CTE, with boys who start playing before puberty being at the highest risk. Starting later, such as high school or college, seems less risky — though it’s still not safe.

A previously unrecognized risk factor for dementia is related to gum and tooth disease. Fragments of mouth bacteria can often be found in the brains of people with dementia. This suggests some level of infection or

in ammation, starting in the mouth, may be triggering the cascade of events leading to dementia or even Alzheimer’s disease.

ALZHEIMER’S DISEASE

he first symptom of lzheimer’s disease is often forgetting recent events, though lapses in judgement, getting lost in familiar places, or inability to do common (though more complex) tasks, such as cooking, may be the first presentation. In many cases, it is the diagnosis that remains when all of the other possible causes are eliminated. It is a specific type of dementia, first described by psychiatrist and neuropathologist lois lzheimer in 1906. His patient was a young woman whose ailment was associated with a specific set of findings in her brain: deposits of a protein known as beta amyloid and associated protein strands from broken nerve fibers called neurofibrillary tangles, or tau.

Recent advances in diagnostic testing let us determine the level of amyloid and tau in the brain using a radioactive tracer. We can also monitor these same chemicals in spinal uid, using a lumbar puncture procedure. Given the lack of an effective treatment of this progressively degenerative condition, these tests are rarely used outside of research settings. What these tests are showing, however, is that amyloid may start to build up in the brain 10 to 20 years before any symptoms of lzheimer’s disease appear. au may appear two to five years before symptoms occur. The condition is highly prevalent in countries with aging populations, it is more common in women, and the incidence increases with age.

There is also a genetic risk, which can be evaluated by a test for the APOE marker. Apolipoprotein E, or APOE, is a protein involved in the metabolism of fats in the body of mammals. The three most common, though slightly different versions (alleles) of the PO gene are e2, e and e . ccording to the U.S. National Library of Medicine (medlineplus.gov), people who inherit one copy of the APOE e4 allele have an increased chance of developing Alzheimer’s; those who inherit two copies of the allele are at even greater risk. The APOE e4 allele may also be associated with an earlier onset of memory loss and other symptoms, when compared to individuals with Alzheimer’s disease who do not have this allele.

It is not known how the APOE e4 allele is related to the risk of Alzheimer’s disease. However, researchers have found that this allele is associated with an increased number of protein clumps, called amyloid plaques, in the brain tissue of affected people. buildup of amyloid plaques may lead to the death of nerve cells (neurons) and the progressive signs and symptoms of this disorder.

It is important to note that people with the APOE e4 allele inherit an increased risk of developing Alzheimer’s disease, not the disease itself. Not all people with Alzheimer’s have the APOE e4 allele, and not all people who have this allele will develop the disease. hose with an PO 2 allele have a lower risk of Alzheimer’s disease.

ONGOING RESEARCH

Research is being pursued worldwide to both prevent Alzheimer’s and to stop the disease’s progression once it appears. There is currently no way to repair damaged brains, so prevention is the ideal goal. The most recent drugs in the news are monoclonal antibodies designed to remove amyloid from the brain in the hope this will prevent further damage related to the disease. However, in spite of a huge amount of publicity, they have not reversed any damage and have not stopped progression — only slowed it slightly — in limited studies.

These medications are given intravenously, monthly, without a clear stopping point. There are associated risks, including brain swelling and bleeding into the brain, that commonly occur. Other areas of research include diabetes-related medications that change how glucose is used in the brain, antiin ammatory medications that can get into the brain, magnetic stimulation to activate injured parts of the brain to stop further damage, and pills that may prevent the formation of amyloid before it reaches the brain.

A major drawback to all of these studies is that they are starting with brains that are already injured. The degree of injury may be mild to moderate, but they’re nevertheless damaged beyond repair. Since we have the ability to identify risk factors, such as a positive genetic marker and amyloid and tau deposits in the brain, before any symptoms appear, that would seem to be an ideal time to start a prevention study. The problem, of course, is that this type of study would take many years and would be extremely expensive. No single organization, government or industry, has proposed taking on this type of project.

PLAN FOR THE FUTURE

The current best plan for improving memory, preventing mental decline and treating early symptoms still rests with behavior modification, making it a life-long project. Physical activity, social engagement, diets low in saturated fats, not smoking, minimizing alcohol intake and continuing education have all been shown to delay onset of dementia. Being aware of toxins in the environment and reducing exposure as much as possible should also be a goal. General health maintenance such as blood pressure control, diabetes control and dental care are further contributors to preserving memory.

Go over your medication list, including OTC medications that are often not on your medical record, with your health care provider annually. You may be able to reduce medications that are no longer needed. Medical breakthroughs are still on the horizon, so be leery of “magic cures” for failing memory.

And, admitting to a strong bias: No one should take up boxing — at any age.

About the author: A native of Brooklyn, Allan Bernstein attended college and medical school in upstate New York, trained in Internal Medicine in Los Angeles and Neurology in Boston. He was Professor of Clinical Neurology at UC Davis College of Medicine and Chief of Neurology at Kaiser in Santa Rosa. An author of more than 40 publications in medical journals and textbook chapters, Bernstein is currently Professor of Clinical Medicine at UCSF and actively involved in research in the field of memory loss and Alzheimer’s disease.