Alzheimer’s disease is a chronic, progressive neurodegenerative brain disorder that affects patient’s memory, language, and judgment, decision making, planning and organizing.

Alzheimer’s disease (AD) remains the most common cause of dementia.  There are currently 5.3 million Americans affected by the disease, and as the number of aging population increases without a disease modifying treatment, it is projected to be 15 million by 2050.

AD is a complex disease; hence the treatment can at times be complicated and often challenging to the treating physicians.  Successful treatment of patients with AD requires a thorough understanding of the patient and the family dynamic. AD like any other chronic condition may have other medical and psychiatric co-morbidities that need to be addressed. Treating the AD with anti-dementia drugs is a small part of the comprehensive management of AD. The discussion of medical co-morbidities   are beyond the scope of this article, however, the psychiatric co-morbidities such as depression, anxiety, delusions, hallucinations, agitation and aggression will be discussed.  Some patients may have an undiagnosed personality disorder that resurfaces as the patient’s ability to compensate diminishes.

The physicians who treat patients with AD need to keep in mind that the management of this disease is more than just memory medication. Even among the patients with AD the presentation and the course of the disease varies. Therefore the successful management of A D requires a comprehensive approach not only to the memory, but also the co-morbidities.

Depression

Depression affects 20% to 32% of patients with dementia, though more prevalent in vascular dementia as compared to AD.  The diagnosis and treatment of depression in patients with dementia is quite challenging as it can be an early manifestation of dementia or cause of the dementia called pseudo-dementia. The depression can fluctuate and the presentation may vary, such as difficulty with attention and focusing, apathy, anxiety, and agitation as opposed to feeling of guilt, insomnia, hypersomnia or suicidality. There may also exist an undiagnosed bipolar depression that needs attention as the treatment is somewhat different. There are several scales to assess depression in patients with dementia, such as Geriatric depression scale, Hamilton depression and Cornell scale for depression.  The treatment of depression in dementia include; pharmacotherapy and psychosocial modalities, although ECT has been used for severe cases. The SSRIs remain the mainstay of treatments and have a better safety profile as these patients are prone to medication side effects. In the case of bipolar depression, treatment with mood stabilizers may improve the patient’s mood. This may be one of the reasons that Depakote has been effective in treating some patients with dementia.  The psychosocial stimulation, such as supportive therapy, focusing on positive aspects of life, happy memories, enjoyable experiences, and previous accomplishments are effective non-pharmacological approach to depression.

Anxiety

Anxiety affects 20% of patients with dementia. In the initial stages of the disease is the fear of losing control. Generalized anxiety disorder occurs in 5% of patients with AD. As the disease progresses anxiety level can fluctuate depending on the living situation and the patient’s support structure. Patients may present with restlessness, irritability, fatigue and sleep disturbance. Anxiety like depression can be measured using standard scales such as Worry scale which is a self report in mild dementia, and Rating Anxiety in Dementia relies on all available data to rate the anxiety.  This includes the care giver report and patient observation.  Treatment of anxiety includes social intervention such as milieu therapy, addressing patient’s specific stressors or environmental factors, and pharmacotherapy, although this approach needs to be addressed with extreme caution as patients with dementia are sensitive to tranquilizers. The initial approach should b a trial of SSRI antidepressants, as most drugs in this class also treat anxiety successfully.  In generalized anxiety disorders, Buspirone can also be helpful.

Psychosis

Delusions and hallucinations have been present in 15%-20% of patients with dementia, and increase with the disease progression. Hospital induced psychosis such as delirium, during a hospital stay secondary to urinary tract infection or pneumonia could be the first manifestation of dementia in elderly population. The delusions are usually persecutory and misidentification as part of the triad, the agnosia seen in patients with AD. Paranoid delusion of intruders and missing personal possession are common. Some patients do not recognize family members or their own home, and some report seeing dead relatives, animals and children in the house as part of visual hallucinations.  The psychotic symptoms are often accompanied by agitation and aggressive behavior.  The psychosis is often elicited from the patient or caregiver and by the use of scales such as BEHAVE-AD, dementia psychosis scale or NPI (Neuropsychiatric Interview). The treatment of psychosis in dementia is quite challenging as the new data reports increased risk of cardiovascular related death in elderly patients with dementia. As long as the psychosis is not disruptive to the patient and family, it does not have to be treated. Behavioral and environmental interventions, such as avoiding confrontation, argument, gentle touching, and environmental modifications are the first line therapy, and should be employed in combination with psychopharmalogical therapy.  This requires a tremendous patience on the part of the care giver as it tends to occur quite frequently.

In the cases where some form of antipsychotic treatment must be used for patient and family safety, the newer antipsychotic drugs such as Abilify, Seroquel, Zyprexa, Geodon or Risperdal are recommended. These drugs have a better side effect profile on extra pyramidal symptoms such as Parkinsonism, sedation, anticholinergic side effects,   and orthostatic hypotension and tardive dyskinesia.  Older antipsychotic drugs such as Haldol and Thorazine should be avoided at all costs. The patients and their family should be informed of the black box warnings related antipsychotic drugs.  It is also important to recognize depression induced psychosis which may improve by treating the patients with antidepressants such as SSRIs. The bipolar depression can also present with psychosis during manic episodes.  As mentioned earlier psychosis could be a manifestation of an underlying medical condition that needs a thorough investigation.

Agitation and Aggression

Among patients with dementia, 27% exhibit agitation and/or aggressive behavior. There are two categories of agitation/aggression in dementia. One with psychosis such as delusions and hallucination and the other without psychosis. Agitation/Aggression should be thoroughly investigated as can signal an underlying medical condition or a patient need that cannot be properly communicated, such as hunger, thirst, pain or a need for toileting. It can also be secondary to the underlying dementia, depression or anxiety. These symptoms are particularly important as it can be a concern for patient and/or caregiver safety.  Patients with severe agitation are often angry with others, especially with the care giver. They often resist help such as shower, getting dressed or toileting. Patients with dementia often get agitated in a new environment such as hospital a new facility, new caregivers and drug side effects. For example certain tranquilizers and anticholinergic drugs that are used for bladder control can cause agitation in these patients.  So the cause should be sought, and addressed first. The environmental modification and supportive therapy is the mainstay of the treatment. Physical restraints should be the last resort only in cases where the patient is a danger to himself or others. The medications such as antidepressants, mood stabilizes, and if needed, antipsychotics can be used, again with special attention to the potential side effects.

One important psychiatric co-morbidity that is often overlooked by physicians caring for patients with dementia is undiagnosed personality disorder that can explain many of the behavioral disturbances that accompany a difficult patient. The patients with personality disorder pose a real challenge to the treating physician, as the patients are not aware of their illness. Unfortunately the diagnosis of this co-morbidity is quite difficult and the treatment almost impossible.

Conclusion

The psychiatric co-morbidities in patients with AD could be either part of the dementia or an undiagnosed condition. In either case it is the second most important issue that needs to be addressed and treated. It is important to keep in mind that the treatment of dementia is not just memory treatment that has been the main focus of dementia treatment. The successful management of patients with dementia in general and Alzheimer’s dementia in particular is treating all symptoms of disease.

On the other hand people with MCI may in addition to memory impairment, have difficulty with language, judgment, and problem solving with preserved normal functioning.   According to American College of Physicians 20% of the population over the age of 70 have some form of MCI.  MCI can also present with non-memory symptoms such as depression, anxiety, and personality changes that are clearly a change from previous level of functioning.  Although there are various subtypes of MCI, we will focus on the most common form called the amnesic type of MCI.  MCI has been extensively studied and it appears that it is a pre-dementia state leading to Alzheimer’s disease (AD) in a rate of about 20% per year. In other words majority of patients who have a diagnosis of MCI will develop AD within 5 years.   There is a smaller population who develop dementias other that AD and some will remain as MCI and yet others will revert back to normal. The reason for these variations  are not fully understood, but thought to be the type and location of the brain damage, genetic factors as well as presence or absence of Amyloid plaques that are thought to be the initial step in development of AD.  MCI has been studies using Pittsburgh compound B (PIB) that detects amyloid plaques in the brain of the patients destined to develop AD.  In patients with MCI the amyloid plaques are present in smaller proportion as compared to the patients with AD.

The cause or causes of MCI are unknown; however the risk factors appear to be similar to AD, such as age, education, genetic susceptibility such as APO-E positivity and co-morbid medical conditions such as strokes, hypertension, heart disease, diabetes and high cholesterol. So what should you do if you suspect that you may have MCI? The first step is to recognize the pattern of forgetfulness and determine if this is a recurring issue or just an isolated incident. If you notice a pattern that is also verified by others such as friends or family members, then it is time to ask your doctor and start the process of evaluation. Your doctor will determine if it needs further investigation or just follow up.

There are currently no approved medicines for MCI, however in one study Aricept did slow the progression of MCI to AD by about 6 month, the effect was short lived and lasted only about 18 month.  Although there are genetic susceptibilities that play an important role in the development of MCI, one can lower the risk factors such as physical activity, mental stimulation, healthy diet habits, and attending to medical co-morbidities such as hypertension, heart disease, high cholesterol and diabetes.

M. Reza Bolouri, MD

With increasing life expectancy across the world, the number of elderly people at risk of developing dementia is growing rapidly. The prevalence of dementia rises steeply with age, doubling every 5 years from the age of 60, so that more than one-third of individuals over the age of 80 years of age are likely to develop a dementia.  Alzheimer’s disease remains the most common cause of dementia in all age groups.  AD is a slowly progressive neurodegenerative brain disorder that according to several imaging and neuropsychological studies, has a prodromal stage that can be traced back to 10 to 15 years prior to presentation of the symptoms.   AD is characterized by the presence of amyloid deposition and neurofibrillay tangles together with the loss of cortical neurons and synapses.  Post mortem studies suggest that temporal lobes are the first brain areas that are affected.  The cognitive deficits that are associated with AD become evident and gradually worsen years later. The combination of aging population and the promise, possibly in the near future, of disease-modifying therapies have made the characterization of the early stages of AD a topic of major research interest. The transitional stage between normal memory and dementia is called Mild Cognitive Impairment (MCI).  Although it has been difficult to develop robust and applicable criteria for MCI, it is generally agreed that it is a pre-dementia state that in majority of cases it evolves to a full blown dementia within five years from the diagnosis. In this stage there are memory lapses with preserved function.  Research has suggested that the early detection and treatment of AD provides symptomatic treatment and better quality of life, though does not prolong survival. For many patients the quality of life is important since the disease progresses slowly.  So the search for ideal marker or imaging indicator is underway.  For the early detection of AD, an ideal diagnostic tool must be sensitive to the earliest cognitive or biological changes that are found in AD but should be able to differentiate among early AD, normal aging, other organic brain disorders that cause memory loss and, importantly mimics of early dementia including depression.

Current research into ways for early detection of AD include; neuropsychological testing, structural imaging methods including; PIB ( Pittsburgh Compound B) a radioactive tracer that detects amyloid deposits in the brain of patients in pre-dementia stage, MRI, SPECT, PET and functional MRI. Other laboratory tests include blood and cerebrospinal fluid (CSF) levels of amyloid which seem to correlate with the presence of dementia, though can’t determine the stage of the disease. The Familial form of AD can be tested with genetic studies of APP (Amyloid Precursor Protein), PS1, PS2 genes.  Other genetic testing includes APO E4, which is only a succeptility gene. We must keep in mind; even positive results do not always translate into AD development, and may cause a whole host of medical-legal issues.  For example the future enrollment for health and long term insurance, employment and the stress that may cause within the family.  Since there is no cure, and no perfect treatment, routine screening after a certain age is not fully supported by health care professionals.

Currently we have two classes of drugs for the treatment of AD. The first class is the cholinesterase inhibitors that includes; Aricept, Exelon, and Razadyne.  These drugs inhibit the cholinesterase enzyme and increases the availability of acetylcholine, the hormone that is deficient in patients with AD. The other is Namenda an NMDA receptor antagonist that controls the toxic effect of excitatory neurotransmitter glutamate.  There has been numerous drugs that have been tested and are currently under investigation with disease modifying properties. These new classes of drugs mainly work in the mitochondrial level to prolong cell survival and prevent premature cell death.  There is also IVIG passive immunity vaccine that is currently under investigation with promising results.

Considerable progress has been made in recent years, in both the characterization of the cognitive profile of early AD and its neural basis. Much more work is still required, however, to clarify with greater accuracy and precision the transitional zone between healthy aging and the first manifestation of AD.  At present, it is clear that individuals in the prodromal stages of AD can show marked impairments on formal memory tests, although they continue to cope independently in their normal daily routine, and that this state can persist for several years before dementia develops. Reliably distinguishing such individuals from those in whom mild cognitive deficits will remain stable over time is an important challenge for ongoing research. At this point a purely objective marker would be advantages. Present evidence suggests that no single marker of MRI atrophy or even PET metabolic changes is likely to achieve perfect discriminant value for individual subjects at this prodromal stage on a single scan.  Serial studies over time are needed to identify the volume loss and structural changes. Future work focused on novel, disease- specific, MRI sequences or PET-SPECT radioligands might offer greater predictive value.

M. Reza Bolouri, M.D.

Be sure to ask your specialist, is it dementia or Alzheimer’s disease?  There are significant differences between the two and this directly affects a plan of care.

Dementia comes from the Latin word “demens,” which translated literally means “out of the mind.”  In other words, it describes someone whose mind is not working properly.

Dementia is not a disease, but a constellation of symptoms such as memory, language, judgment, executive function, mood and personality disturbances.  These symptoms typically leave the person with severe dementia unable to effectively communicate or interact with others.

Another more recent definition states that “dementia is a progressive brain disorder, severe enough to interfere with social and occupational functioning.”  Dementia can be caused by many conditions other than Alzheimer’s disease. These include:  strokes, Parkinson’s disease, head injury, alcohol, thyroid diseases, vitamin deficiency and infections. One of the primary benefits of a full dementia evaluation is to check for other causes of dementia to determine if there are other potentially reversible types of dementia. It has been proven that anyone can have dementia at any age stemming from a variety of causes that may not always include Alzheimer’s type dementia.

Alzheimer’s disease is the most common cause of dementia, and because of this, many people utilize these two terms interchangeably. It is a progressive brain disorder that affects multiple domains of brain function including, cognition, memory, language, judgment, and personality.  The diagnosed percentages of various types of dementia reveal that 60% of dementia patients have Alzheimer’s disease, whereas 15% have Lewy Body Dementia, 10% have vascular dementia, and rest is shared among other types, such as Frontal- temporal dementia, head injury related dementia, alcoholic dementia, Parkinson’s disease, and infections such as AIDS and Creutzfeldt-Jacob disease, a form of mad cow disease. Since Alzheimer’s dementia is more prevalent among the elderly, many incorrectly assume any memory problem to be Alzheimer’s type dementia.

It is important to note that while all Alzheimer’s patients have dementia, not all dementia patients have Alzheimer’s disease.  The proper treatment of dementia begins with a full evaluation by a specialist to better understand the specific type of dementia.  This then determines the best treatment plan for the patient.

M. Reza Bolouri, M.D.
Alzheimer’s Memory Center

The difference between age-related forgetfulness and MCI is that, in addition to memory impairment, people with MCI also experience difficulty with language, judgment, and problem solving.   According to the American College of Physicians, 20% of the population over the age of 70 has some form of MCI.  MCI can also be shown through non-memory related symptoms such as depression, anxiety, and personality changes that reflect a decline from previous level of functioning.  Although there are various subtypes of MCI, the most common form is called the amnesic type of MCI.  MCI has been extensively studied and it appears that it is a pre-dementia state leading to Alzheimer’s disease (AD) at a rate of about 20% per year. In other words, the majority of patients who have a diagnosis of MCI will likely develop AD within five years.   There is a smaller population who develop dementias other that AD and some will remain as MCI. The reason for these variations are not fully understood, but generally thought to be the type and location of the brain damage.  Genetic factors as well as the presence or absence of Amyloid plaques are thought to be the initial step in development of AD.  MCI has been studied using Pittsburgh compound B (PIB) that detects amyloid plaques in the brain of the patients destined to develop AD.  In patients with MCI, the amyloid plaques are present in smaller proportion as compared to the patients with AD.

The cause or causes of MCI are currently unknown; however the risk factors appear to be similar to AD.  These include: age, education, genetic susceptibility such as APO-E positivity and co-morbid medical conditions such as strokes, hypertension, heart disease, diabetes and high cholesterol.

There are currently no approved medicines for MCI.  However, in a recent study, Aricept did slow the progression of MCI to AD by about 6 months.  The effect was short-lived and lasted approximately 18 months.  Although there are genetic susceptibilities that play an important role in the development of MCI, one can lower the risk factors with intentional physical activity, mental stimulation, healthy diet habits, and properly treating medical co-morbidities such as hypertension, heart disease, high cholesterol and diabetes.

So what should you do if you suspect that you or a loved one may have MCI? The first step is to recognize the pattern of forgetfulness and determine if this is a recurring issue or just an isolated incident. If you notice a pattern that is also verified by others such as friends or family members, then it is time to ask your doctor and start the process of evaluation. Your doctor will determine if it needs further investigation.

M. Reza Bolouri, MD
Alzheimer’s Memory Center

Professionals who are typically involved in AD care include, but are not limited to: physicians, physician’s assistants, nurse practitioners, social workers, geriatric care managers, and care givers.  Given the complexity of the disease, it is crucial for each member of the care team to have a clear understanding of the nature of the disease, progression, fluctuation and overall management.

In the beginning or mild stage of AD, patients are initially not aware of occasional forgetfulness, and this can go unnoticed by patients, family members and even healthcare providers.  However, patients with more information on early detection are able to get help when it is most effective. Some patients go through a period of denial and blame their failing memory on aging or stress factors.

More than just the memory is affected in AD; other cognitive functions such as speech, word finding, judgment and problem solving are also affected. Typically, the primary caregiver will begin the search for help when it’s apparent that there is significant cognitive decline.

We live in a culture that views forgetfulness as a normal part of aging.  Some physicians might miss the early warning signs.  Others may feel that since AD it is an incurable disease, treatment is futile. As physicians, we need to build an alliance with patients and their caregivers in order to address relevant issues. These include medication management as well as addressing behavioral issues such as sleep disturbance, eating difficulties, weight loss, agitation, paranoid delusions, hallucinations and inter-current illnesses (i.e. urinary tract infections and pneumonia).

Although, the medications currently approved for the treatment of AD have only modest effect, research has shown that these drugs do in fact help improve the overall quality of life for patients.

There are demonstrated improvements in behavior, personality and cooperativeness when these medications are initiated. Evidence also proves that the earlier the treatment is initiated, the more robust the benefits.

Primary care physicians and geriatricians see approximately 85% of the patients with AD. Neurologists and psychiatrists see the remaining 15%. As the first line of caregiving defense, primary care physicians and personal caregivers should learn and utilize all available resources and research to help provide a comprehensive care plan that allows for the best quality of life for both the person with AD and their caregiver.

M. Reza Bolouri, MD
Alzheimer’s Memory Center

“Perspectives from Professionals Caring for Patients with Alzheimer’s Disease”

Alzheimer’s disease (AD) is the most common neuro-degenerative brain disorder. It affects 5.2 million Americans and 25 million people worldwide. By 2050, it is predicted that there will be an estimated 16 million Americans with AD. It is imperative for those who are involved in caring for people with AD to understand as much as possible about the disease and disease process in order to provide the best care possible for their patient.

Professionals who are typically involved in AD care include, but are not limited to: physicians, physician’s assistants, nurse practitioners, social workers, geriatric care managers, and care givers.  Given the complexity of the disease, it is crucial for each member of the care team to have a clear understanding of the nature of the disease, progression, fluctuation and overall management.

In the beginning or mild stage of AD, patients are initially not aware of occasional forgetfulness, and this can go unnoticed by patients, family members and even healthcare providers.  However, patients with more information on early detection are able to get help when it is most effective. Some patients go through a period of denial and blame their failing memory on aging or stress factors.

More than just the memory is affected in AD; other cognitive functions such as speech, word finding, judgment and problem solving are also affected. Typically, the primary caregiver will begin the search for help when it’s apparent that there is significant cognitive decline.

We live in a culture that views forgetfulness as a normal part of aging.  Some physicians might miss the early warning signs.  Others may feel that since AD it is an incurable disease, treatment is futile. As physicians, we need to build an alliance with patients and their caregivers in order to address relevant issues. These include medication management as well as addressing behavioral issues such as sleep disturbance, eating difficulties, weight loss, agitation, paranoid delusions, hallucinations and inter-current illnesses (i.e. urinary tract infections and pneumonia).

Although, the medications currently approved for the treatment of AD have only modest effect, research has shown that these drugs do in fact help improve the overall quality of life for patients.

There are demonstrated improvements in behavior, personality and cooperativeness when these medications are initiated. Evidence also proves that the earlier the treatment is initiated, the more robust the benefits.

Primary care physicians and geriatricians see approximately 85% of the patients with AD. Neurologists and psychiatrists see the remaining 15%. As the first line of caregiving defense, primary care physicians and personal caregivers should learn and utilize all available resources and research to help provide a comprehensive care plan that allows for the best quality of life for both the person with AD and their caregiver.

M. Reza Bolouri, MD

Alzheimer’s Memory Center