What if it is not Alzheimer’s?

Worldwide, around 50 million people have dementia, and there are nearly 10 million new cases every year. Alzheimer’s disease is the most common form of dementia and may contribute to 60–70% of cases. India houses more than 4 million people suffering from some form of dementia. Alzheimer’s affect around 1.6 million. Alarmingly, this number is set to triple by 2050! Among people 65 and older, the rate of Alzheimer’s has gone up tenfold in the past few decades – and 24-fold among those under 65!

 

But here’s an even more disturbing fact.

 

According to a recent study, most people diagnosed with Alzheimer’s don’t even have it! Instead, they have other problems that were missed – and could have been treated if simply looked for. The study autopsied the brains of 426 Japanese-American men who died at an average age of 87. 211 of them had been diagnosed with dementia when they were alive, usually from Alzheimer’s disease. The autopsies revealed that about half of those diagnosed with Alzheimer’s disease didn’t have toxic clumps (amyloid) and tangles of protein (tau) that are the hallmarks of Alzheimer’s disease. This study was reported at the recent annual meeting of the American Academy of Neurology, and it confirms that many (if not most) people diagnosed with Alzheimer’s do not have the disease.

 

The discovery of Alzheimer’s

Around the turn of last century, German doctor, Alois Alzheimer working in Frankfurt sent the brain of an elderly patient who suffered from memory loss and delusions to undergo a process only recently perfected: brain staining using silver dye.

When the results came back, Alois Alzheimer was stunned. They revealed the woman’s brain was filled with small sticky plaques in between the nerve cells, almost like the neurons had been gummed up.  The plaques were made of a protein called beta-amyloid. They block neurons from talking to each other. Another protein called tau also appears to be involved, forming into “tangles” that cut off the transport system that ferries nutrients within brain cells.

Both plaques and tangles form first in the areas of the brain important to memory and learning and then gradually progress to other regions, killing neurons as they go. Patients lose their memory first, and then other functions progressively deteriorate.

Alzheimer’s, which is the leading cause of dementia, can lead to immobility and problems with feeding and swallowing, which can cause pneumonia, heart failure and eventually death.

 

What is neurodegeneration and dementia?

“Neurodegeneration reflects the fact that there are misfolded proteins that are accumulating in our brains. All of our brain cells or neurons depend on functioning of proteins. And under some circumstances these proteins can become misfolded and when they become misfolded, they can no longer perform their essential function. And depending on where in the brain this process is occurring out, we’ll see different kinds of symptoms. So, if there are proteins accumulating in the part of the brain that are important for language it will result in some difficulty with language functioning. If there are proteins that are becoming misfolded and accumulating in the memory part of the brain that will result in some difficulty with memory. So, neurodegeneration is when misfolded proteins accumulate in a particular part of the brain. And as these misfolded proteins accumulate, they cause difficulties with various kinds of symptoms. The symptoms worsen with time as misfolded proteins accumulate. And dementia refers to the progressive cognitive change that occurs as these misfolded proteins accumulate in the brain”, explains Dr. Murray Grossman, Professor of Neurology, Director, Penn FTD Center, University of Pennsylvania.

Dementia is any acquired brain condition that interferes with the ability to think and to carry out routine daily functions. Dementia can have many different causes – and many of them are reversible. Dementia can be caused by a vitamin deficiency, such as low levels of vitamin B12. It can be from a drug side effect. Or a symptom of depression. Hypothyroidism can cause it. So can head trauma from a fall. Even dehydration can cause dementia.

Non-Alzheimer’s Dementia

Conditions that can masquerade as Alzheimer’s include underactive thyroid, vitamin deficiencies, too much calcium in the blood, syphilis that has spread to the brain, severe clinical depression, delirium, certain viral or bacterial infections, lead and mercury poisoning, schizophrenia and NPH (normal pressure hydrocephalus). Many of these are treatable, and some are completely curable.

 

Parkinson’s Disease Dementia

Parkinson’s disease (PD) has long been considered predominantly a motor disorder. However, it is frequently associated with dementia, which contributes significantly to the morbidity and mortality of the condition. Parkinson’s disease dementia is caused when deposits of a compound, known as alpha-synuclein, builds up in the brain. It is estimated that 50 to 80 percent of those with Parkinson’s disease eventually experience Parkinson’s disease dementia. The average time from onset of Parkinson’s to developing dementia is about 10 years.

NPH Dementia

After six years and consultations with numerous physicians, it turned out that Bhavani did not have Alzheimer’s or Parkinson’s after all. She had a rare disorder called normal pressure hydrocephalus (NPH). Amazingly, within two weeks of a surgical procedure, she was walking and thinking clearly again. “It’s a miracle,” says Mr. Mehra, Bhavani’s husband. “All of her symptoms are gone now. We thank God and the doctors every day. She’s a new person.”

Bhavani Mehra was thoroughly confused and sitting in a wheelchair while her husband, helplessly looked on, wondering what on earth had happened to her. This formerly vigorous woman had become wheelchair-bound and incontinent. She also showed clear signs of dementia and was diagnosed with probable Alzheimer’s and Parkinson’s.

Cerebrospinal fluid is produced in our brains and bathes our skulls with nutrients and cushions our gray matter. It trickles down the spine and is absorbed back into the body in a constant flow. Sometimes, the body produces too much fluid or it doesn’t drain the skull adequately, or fails to absorb the fluid properly. The fluid gradually fills up the brain’s ventricles, pushing the brain against the skull and stretching nerve endings. That increased pressure in the ventricles can cause all kinds of mental problems.

There are no statistics available on how often normal pressure hydrocephalus is missed, but doctors agree that 5 percent to 10 percent of dementia diagnosis are actually NPH.

 

Frontotemporal Dementia  

FTD or frontotemporal dementia is much less common than Alzheimer’s disease. Patients have FTD or frontotemporal degeneration when there is just the tau protein alone that is accumulating in the brain.  Half of the folks with FTD have a form of language difficulty that’s called Progressive Aphasia and this is because the language parts of the brain are in the frontal and temporal parts of the brain. There are different forms of Progressive Aphasia. One kind of progressive aphasia can affect difficulty in understanding the meanings of words and difficulty in understanding objects. By comparison, another protein can accumulate in the frontal parts of the brain and cause very effortful and non-fluent speech.

 

Diagnosis Scenario

According to Dr. Grossman, the most important initial test is a clinical examination by an expert in the area. So being seen first by an experienced neurologist who has seen lots of individuals is a great way to begin the diagnostic process.

Once a clinical evaluation has been performed, the next step will be getting an MRI scan to see if there’s a correspondence between the clinical difficulties that are seen and looking to make sure that there are no injuries in the part of the brain that corresponds to the difficulties that the clinician is saying.

What kinds of things can occur? Many things can mimic neurodegeneration. For example, there could be a tumor in the brain, or there could be inflammation that is gradually slowing down functioning of the part of the brain, or there could be an infection that is compromising brain functioning. So, an MRI scan will help rule out all of these various conditions that can mimic a neurodegenerative condition. And there are also some systemic conditions that can mimic dementia. And so there are some blood tests that are important to obtain to make sure that there’s no systemic condition that could be mimicking dementia.

The next step after this involves being seen at a specialty center.  Specialty centers will have the infrastructure, equipment, expertise and support to study and understand the nuances of the difficulties that patients are experiencing and provide targeted therapies for the same.

Tests that are routinely administered can include a lumbar puncture to analyze cerebrospinal fluid (CSF) for accumulated proteins, various blood tests, PET scans. Most of these are disease modifying treatments.

“I think another sort of diagnostic tool we have, particularly as we’re seeing patients who have much more mild symptoms, something that we sometimes refer to as mild cognitive impairment is that we follow patients over time and measure whether or not they’re showing any evidence of progression in their condition. And that also is, I think a useful tool. Sometimes we don’t have a definitive answer the first time we see a patient, but the evolution can help us”, chimes in Dr. David Wolk, Associate Director, Penn Memory Center.

 

What would be the best method or activity to maintain brain health?

Dr. Grossman says, “There is now a very good evidence in the medical literature to suggest that physical exercise and mental exercise or both are very important to being able to maintain brain health. There is a concept that’s called cognitive reserve and the cognitive reserve concept is that we can enhance our healthy living and maintain our brain health by having a high education, high occupational payment and engaging in significant midlife activities. And so, all of these things speak to the fact that being active cognitively is very, very important. There’s also good data to support the claim that a moderate amount of exercise on a weekly basis is really a good way to maintain brain health.”

“Try to keep yourself mentally stimulated and doing things that you enjoy. So, if it’s crossword puzzles, you like, do crossword puzzles, if it’s reading you like, do reading, but keeping it as engaged as possible I think is important. Social engagement also maybe for the same reason is another thing that has been shown to seem to stave off the development of cognitive decline”, adds Dr. Wolk.

 

This article was first published in The Week magazine dated October 26, 2018 under the title, Brain Storm.