Dr. Alan Zacharias on Memory Loss: What's Normal? What's Not?

Some memory loss is a normal part of aging. But sometimes, forgetfulness is an early sign of serious conditions such as Alzheimer’s disease.

During a free online health lecture, board-certified neurologist Alan Zacharias, MD, of Associated Neurologists explained the difference between normal and abnormal memory lapses. He emphasized, “The word for tonight is hope.” Adding, “Finally, there is some hope as the first medication in 18 years, known as aducanumab, has been approved by the U.S. Food and Drug Administration for the treatment of Alzheimer’s disease.”

Topics Dr. Zacharias’ presentation addressed:

• Normal Memory Loss With Aging
• Worried Well
• Mild Cognitive Impairment
• Alzheimer’s Disease
• Risk Factors
• Symptoms of Alzheimer’s Disease
• Prevention and Treatment

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Watch "Memory Loss: What’s Normal, What’s Not?"

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Normal Memory Loss With Aging

One of the most common concerns of patients is wanting to understand what is normal as we age. Dr. Zacharias shared, “Changes as we age are incredibly variable for physical and cognitive function. It depends a lot on genetics, environment and lifestyle. Sadly, by the age of 20, we start to lose brain cells and many of the important chemicals for our brain function.”

So, what is normal? Dr. Zacharias explained that short-term and remote memories—memories of events that happened days, weeks or a few months ago—are usually unaffected by aging. However, it’s common to have an issue with coming up with a word temporarily or the name of someone whom you’ve recently met. While Dr. Zacharias says this can be “peculiar, frustrating or something you may laugh about with your friends or family, it should not have an impact on your ability to function.”

Many terms have been applied to normal aging-related memory loss:

• Late-life forgetfulness
• Benign senescent forgetfulness
• Age-associated memory impairment
• Aging associated cognitive decline

Dr. Zacharias added, “When you are more aware of your memory issues than others are, that is often a good sign of the benign nature of your concerns."

Dr. Zacharias explained the difference between normal and abnormal memory loss is the degree that it impairs one’s daily life.

As an example, he described a 55-year-old businesswoman who is concerned about her memory. “She is under a great deal of stress at work and has difficulty coming up with the names of recent clients. She occasionally misplaces objects at home. Her mother had Alzheimer’s at age 80, and consequently she is concerned that she may be developing symptoms.”

“In a case like this,” he explained, “the neurologic exam is almost always normal. This represents what is termed the 'Worried Well.' We reassure the patient that this is not dementia. However, we add that we have no idea if it will become dementia. We might suggest that she modify her work schedule and slow down if possible.”

Mild Cognitive Impairment

Mild cognitive impairment (MCI) is the stage between the normal cognitive decline of aging and the early stages of some type of dementing condition that affects memory, thinking and social abilities to a degree that interferes with daily life.

“MCI memory problems are more severe than normal aging-related concerns, but not serious enough to affect daily life. The distinction, however, is not cut and dry,” said Dr. Zacharias. There is no definitive test or single symptom that results in a diagnosis of MCI. Dr. Zacharias further explained, “It’s a judgement that we have to make to the best of our ability.”

Dr. Zacharias describes a 68-year-old retired schoolteacher as an example. “He has become increasingly forgetful even as the demands on this man have been reduced in retirement. He's having difficulty recalling details of events, trying to recall important information such as a doctor's appointment, luncheon engagements and golf tee times. His family has been noticing that he’s forgetting information that he formerly would not have forgotten.”

“This is a red flag,” Dr. Zacharias warned. “In testing for an individual like this in the office, he (the patient) might start missing a few words when asked to recall them from a list. The remainder of the exam might be essentially normal. There may be some issues with remembering new information, but it doesn’t rise to the level of dementia.” These changes aren't enough to significantly interfere with daily life and usual activities.

“MCI will progress to dementia, usually Alzheimer’s, at a rate of about 10 to 15 percent per year,” Dr. Zacharias stated. This would compare to the general population incidence of a one-to-two percent risk per year in the same age group of 65 years and older.

It’s important to note that not all of those with MCI will develop Alzheimer’s disease. A small percentage of people with MCI improve. Some remain stable for many years. Dr. Zacharias noted that while we are getting better, we are not yet at a point where we can predict how a patient will progress.

Alzheimer’s Disease

Alzheimer’s disease is the most common form of dementia with 4.5 million cases worldwide. It is also the sixth leading cause of death for Americans ages 65 years and older.

The disease is an irreversible, progressive brain disorder that slowly destroys memory and, eventually, a person’s ability to perform even the simplest tasks such as bathing, feeding and dressing.

Dr. Zacharias said, “This condition causes atrophy or loss of tissue volume that begins in the brain’s hippocampus, the area involved in the formation of new memories. It then spreads to affect other parts of the brain.” One of the hallmarks of Alzheimer’s disease are deposits of amyloid-beta (Aβ) protein in amyloid plaques in the brain. 

The major risk factor for Alzheimer’s is age, with about one to two percent of those age 65 having the disease. According to Dr. Zacharias, the numbers roughly increase by another 10 percent per decade, and by the time you're 85, there's a 40% risk of having Alzheimer’s disease.

Twenty percent of patients will have one or more siblings, or a parent affected with the disease. Alzheimer’s is also a little more common in women.

Dr. Zacharias added that increased education and exercise are associated with a lower risk of the disease, and those who are more religious and spiritual seem to have a lower risk as well. Diabetes, high cholesterol, high blood pressure and being overweight increase the risk for Alzheimer’s. Anti-inflammatory medicines, like Advil once thought to be protective, probably are not.

According to Dr. Zacharias, “We’re starting to say that Alzheimer’s starts 10, 15, maybe 20 years before it’s diagnosed.” He added, “In the next 10 years, we’re probably going to have data that will reliably indicate our risk for this disease, and hopefully there will be more that we can do about it.”

Symptoms of Alzheimer’s Disease

Alzheimer’s disease, as well as dementia of any form, doesn’t begin abruptly. This is a key indicator when distinguishing dementia from other changes in cognition.

It is diagnosed when there's a significant change in one’s ability to function, in addition to memory loss and other areas of impairment. Some key indicators of Alzheimer’s disease include:

• Repeating conversations
• Significant trouble expressing one’s self
• Getting lost while driving or in a parking lot
• Trouble with a checkbook or finances
• Writing bad checks
• Not paying the mortgage (receiving an overdue notice)
• Trouble following a recipe or planning a trip
• Apathy such as not wanting to go out
• Loss of motivation
• Signs of depression (occurs in 30% of patients during early stages)
• Anxiety when alone or forced to interact in large groups
• Paranoia and delusions as the disease progresses (“You’re cheating on me, who’s stealing my things, the kids want all of our money, etc.”)
• Agitation and aggression
• Strange or inappropriate jokes or behavior

Prevention and Treatment

Dr. Zacharias said, “It’s important to stay physically active, intellectually engaged, eat well and keep your eyes open for new therapies.”

Until June of this year (2021), there were no drugs or treatments approved by the U.S. Food and Drug Administration (FDA) for mild cognitive impairment (MCI)—a precursor to Alzheimer's disease. “But now,” said Dr. Zacharias, “the FDA has approved aducanumab - brand name: Aduhelm^TM - and it may be appropriate to consider for some patients: patients who have biomarkers that suggest they’re at high risk for developing Alzheimer’s.”

Aducanumab is an intravenous drug. It takes one to three hours to administer. Dr. Zacharias noted, “It may be appropriate to test those with MCI to see if they might fall into the category of those for whom the clinical trial documented borderline improvements to no improvements.” He explained further, “A small number of patients in the aducanumab clinical trials experienced a slowdown of about four months in their overall decline.”

Other therapies are primarily focused on treating cognitive symptoms. Approved drugs for symptom management include Aricept, Razadyne, Exelon, Namenda and now aducanumab. Most of the benefits of these current therapies are mild but are appropriate to consider.

"Donepezil (Aricept) may slow down the development of Alzheimer’s a bit for about two years, but after 36 months there is no difference when compared to a placebo,” said Dr. Zacharias. “All of the current therapies are primarily for treating symptoms; none have been proven to delay the progression of the disease, until aducanumab. Aducanumab does irrefutably and significantly decrease the volume of amyloid in the brain. The hope is that this will slow down Alzheimer’s progression,” Dr. Zacharias stated.

There are also no FDA-approved drugs for treating behavioral symptoms associated with dementia. “However, we can treat depression, anxiety, obsessive behavior and insomnia for patients with dementia,” he said.

“Vitamin E we thought might work. It has not however had much of an effect at this point," said Dr. Zacharias. “We are all still learning. If a strategy is not yet proven, but seems reasonable to you, you might consider trying it. Breakthroughs have just begun and they’re going to continue. This is very encouraging progress."

Contact your primary care physician, psychiatrist or neurologist for more help with and understanding of memory loss.

Click here to view/download a PDF of slides shown during this lecture.

To make an appointment with Dr. Zacharias, call (303) 415-8800.