Alzheimer Disease (AD)

 

This post is about Alzheimer disease. Please read a separate post on Dementia, which provides the larger perspective on this subject.

 Alzheimer disease is a brain disorder. It is named after Dr. Alois Alzheimer who first reported this condition. He discovered certain abnormalities in autopsy specimen of the brain of a patient with this disease.

 

What exactly is the problem in AD?

AD is a degenerative brain disorder. Brain neurons of patients with AD have abnormalities called neurofibrillary tangles and plaques. It is not completely known how this disease starts, what exactly leads to build-up of these abnormalities, and why brain is unable to stop this process. The result is degeneration or destruction of neurons.

 

How common is AD?

AD is the most common cause of dementia, affecting about 6 million people in USA. This number is rapidly increasing and is expected to triple by 2050. Generally speaking, it is a disease of old age; almost 80% of patients are 75 and up. Women are about twice more affected than men.

 

What is the typical life expectancy with AD?

It is about 15-20 year.

 

Is AD a genetic disorder?

Genetic abnormalities are significantly involved or understood in a small percentage of patients. Risk of AD increases if a first-degree relative is affected, but in most cases exact mode of inheritance is not well defined. It can still happen without any family history. In my practice, I do not recommend genetic analysis due to multiple reasons. First, there is no available specific treatment to alter its course, and so no incentive for exploration. Second, a negative test does not preclude having the disease. Third, in most cases diagnosis of Alzheimer is not difficult to make without genetic analysis. Genetic analysis results, even if inconclusive, may still expose individuals to discrimination in health care, employment, or insurance.  

 

What are the risk factors for AD?

Following are identifiable risk factors, some are specific for AD, and others are for dementia in general:

            . Genetic factors (AD)

            . Hypertension

            . Diabetes mellitus

            . Stroke

            . Down Syndrome (AD)

            . Traumatic brain injury

            . Obstructive sleep apnea

            . Low baseline education

            . Sedentary lifestyle

            . Social isolation

            . Chronic depression

            . Alcohol and drug abuse, including marijuana

 

Can AD affect younger people?

Most patients with AD are 75 plus, but it can affect patients younger than 65. In patients with Down syndrome, it may start in their 30s.  

 

How is AD diagnosed?

Dementia is mostly diagnosed by taking relevant history from the patient and the people around the patient (family members, friends, etc.). Neurological examination with special emphasis to mental functioning is also helpful.  Most patients can be diagnosed with this much information. Further testing may be required to figure the type of dementia.

 

If Alzheimer disease is suspected, further testing may be needed to make a more definitive diagnosis. This is done with help of a blood test, analysis of cerebrospinal fluid, or a special brain scan called PET. Any or all these tests only provide statistical probability of Alzheimer. Its definitive diagnosis, if needed, is made by a brain biopsy (almost never done) or at autopsy (if ever done.)

 

 

What is imaging (CT and MRI) finding in AD?

 CT or MRI may reveal atrophy (shrinking) of brain. This is noted more so in parietal and temporal lobes, and is more prominent in younger patients with AD. In addition, imaging helps to rule out alternate causes.

 

What is the role of PET scan in AD?

Unlike CT or MRI scans, which reveal a picture of brain, PET scan reveals functional capacity of brain. Two types of PET imaging is available: the so-called, FDG PET and amyloid PET. The FDG PET provides information about general functional capacity of different areas of brain. It may help to differentiate between different types of degenerative dementias. This is usually performed only for atypical dementias, like frontal or occipital lobe dementia. More commonly, for Alzheimer, amyloid PET is performed, which provides information about amyloid load in the brain.

 

What is amyloid hypothesis of Alzheimer disease?

According to this theory, in a patient with AD, the brain accumulates abnormal protein fragments called amyloid-β (Aβ). These fragments are produced when a normal brain protein, amyloid precursor protein (APP), is cut in a particular way by enzymes (β- and γ-secretases). Instead of being cleared away, these Aβ fragments clump together and form amyloid plaques in the spaces between nerve cells. The plaques (and smaller soluble Aβ oligomers) are thought to disrupt communication between neurons, trigger inflammation, and set off a toxic chain of events. This cascade ultimately leads to:

• Tau protein abnormalitiesinside neurons (forming neurofibrillary tangles),
• Neuron dysfunction and death, and
• Progressive memory loss and cognitive decline.

 

Is there a blood test for AD?

There is a blood test to assess level of amyloid and tau protein deposition in brain, which helps to decide if any further tests for Alzheimer are needed or not. Otherwise, currently there is no specific blood test for AD.

 

 

What are different stages of AD?

Usually patients are given diagnosis of mild, moderate, and severe dementia, and also in-between such as mild to moderate and moderate to severe. All these designations are determined based upon history and patient’s clinical examination. There is no particular blood or imaging test to determine these stages.

 

What is mild cognitive impairment?

The diagnosis of mild cognitive impairment is given to a patient who might have mild symptoms suggestive of dementia, but formal examination and testing do not reveal any significant issues. Some but not all of these patients progress to develop dementia.

 

How is AD treated?

There are a few available drugs that may help to lower amyloid deposition in brain, which may lead to improvement in cognitive functions. It is not clear if they slow down the disease process or stop its trigger. These are biological drugs. Currently available drugs are approved for early-stage Alzheimer. As there could be significant side effects, patients are carefully chosen to minimize risk. These drugs may cause brain swelling, a stroke or bleeding in brain, which in rare case can be fatal. Besides this type, many other drugs are used to treat dementia symptoms.  

Symptoms of Alzheimer may be divided in three categories:

1. Cognitive
2. Behavioral
3. Functional.

This type of division is helpful, especially in clinical trials when medicines are tested for dementia. Cognitive symptoms may include problems with memory, language, calculation, space orientation, or drawing. Behavioral problems may include anxiety, depression, paranoia, delusions, hallucinations, anger and agitation. In Functional category are activities a person undertakes to maintain normal healthy life, e.g., personal care and hygiene, space management, day-to-day work, driving, etc.

Different types of scales are used for each category to assess severity of symptoms, from mild, moderate to severe. Forgetfulness may be the initial symptom of Alzheimer, in later stages patients usually have problems in all these categories.

Before one consider a medicine for dementia, it is important to mitigate any ongoing factors or conditions that may negatively be impacting the patient. This include alcohol or drug use, including marijuana; sleep disorders, including obstructive sleep apnea; medicines that patient is already taking, including over-the-counter medicines, and psycho-social factors, including underlying mood disorder(s). Also, starting from early stage of the disease, the patient and the family are counseled to decide for appropriate proxy documents for health care needs, and Power of Attorney for any legal or fiscal matters.

Formal counseling or therapy may provide some help in early stages of dementia, especially in making appropriate decisions about employment, family, and financial matters. It is important to include at least one other person in this process, spouse, or any other person the patient may trust or feels comfortable with. In later stages of dementia, therapy or formal counseling has limited value, if any at all. Frequently, family member(s) needs counseling to help deal with the situation, avoid any conflict between the patient and the family member(s), and sometimes between the family member(s) and the treating physician. I routinely advise families to avoid any conflict-provoking situation within the family, which may have tremendous negative impact on patient’s wellbeing.

If needed, a larger group of family members may also meet the treating physician. Depending upon severity of dementia, this meeting can be with or without patient’s presence, but with consent of patient’s Healthcare Proxy, if it applies. This type of meeting may help mitigate any potential conflicts within the family, which may impact the patient. It also helps different family members to get first-hand information from the physician and directly ask questions. It may not be practical to have this type of meeting on regular basis. I advise families to refer all further inquiries to the patient’s proxy. Finally, physicians do not act as attorneys, but they do have ethical and legal responsibilities to safeguard patient’s interests. In a rare situation, if family is unable to provide appropriate supervision and care, or if no family member or friend is in the picture, the physician may invoke the legal process of an alternate guardianship for the patient. 

Unfortunately, in most places, there is no organized manner of care for elderly or patients with dementia. This creates another layer of challenge both for the treating physician(s) and the patient’s caretaker(s). Physicians do not have much control over providing needed ancillary services, and the caretaker(s) is left arranging them privately, which a lot of them cannot afford. Some social service groups like Elder Care Services, local support group, or any similar organizations are helpful to fill some of these gaps.

 

What other drugs are available to improve cognitive functioning in AD?

Two classes of drugs are approved for this purpose: Cholinesterase inhibitors (donepezil [Aricept], galantamine [Razadyne], and rivastigmine [Excelon]). They are available in different strengths and different formulations, mostly in generic forms. The other drug is memantine [Namenda].

 

Is there a cure for AD?

Currently, not. 

 

Where can I get more information on AD? 

American Academy of Neurology

American Alzheimer Association