Learning Objectives
- dementia is a progressive loss of multiple thought processes, not just a loss of memory
- be thoughtful of alternative causes of the symptoms
- lifestyle adaptation and safety are important to dementia care
History
CM, an 81 year old lady, visits the office with her son and daughter in law. When asked why she is visiting, she is at first unsure, but eventually describes that her long time primary care provider is concerned about her memory function. She says she has stopped driving. She has never been in charge of the finances, and since she has been a widow, her daughter has made sure the finances are balanced. She says she has generally been good at cooking and cleaning, and when she has a ride to the store, she is able to collect her own groceries, she says. She visits with her friends at their homes, church or at assisted living facilities a few times per week. She regularly walks her dog around the neighborhood every day. Her daughter says she is concerned because her mother seems to not keep her clothes as clean as the past, and she seems uninterested in making a complete meal for herself. She feels there has been a gradual, progressive problem for over one year. When confronted about these things, CM denies them, saying there is no need to take such measures for just one person. CM’s daughter also remarks that there are often times her entire home needs to be cleaned up, possibly due to negligence.
CM has a past medical history of appendectomy and hysterectomy. She has no allergies to medications and she takes no medications.
Her mother passed away due to breast cancer. Her father was an alcoholic and died from hepatic insufficiency.
CM has been a lifelong nonsmoker and she has never had alcohol. She lives by herself.
Review of systems indicates she has lost about 10 pounds over the past three years. She denies trouble swallowing, or trouble with bowel or bladder functions. She has normal breathing and heart beat. The remainder of a ten system review is negative.
Examination
CM has a pulse of 75, a blood pressure of 142/83, and a temperature of 98.4 degrees Fahrenheit. She has a normal, calm, healthy appearance, appropriate for her age. Her funduscopic evaluation is normal. She has a normal heart beat and rhythm. Her language appears fluent. She is able to name objects easily. She remembers lists of words poorly, and her serial calculation ability is impaired. She is oriented to herself, the date and location, but she has trouble drawing figures, including a clock. She is able to follow commands, read and write. Her cranial nerve evaluation is normal. She has normal strength and tone. Reflexes are normal, except in the Achilles, where they are absent. The toes have a downgoing Babinski response. She has normal finger nose finger movements, and she is able to walk easily, without any abnormality.
In summary, CM is brought to your attention for memory symptoms, but her history reveals suspicion for inability to perform daily tasks. Her examination is remarkable for deficits in recall, visual reconstruction and either calculation or attention, depending on how the findings are interpreted. Given the time frame these symptoms have occurred for, this collection of findings is suspicious for illness like Alzheimers disease.
Localization and Neuroanatomy
Alzheimers disease is a progressive degenerative disorder. Over the course of the disease, the volume of the brain decreases. In typical cases, there is pathological formation of amyloid protein deposits and neurofibrillary tangles. At early stages, neuronal death is greatest in the entorhinal cortex, a temporal lobe region responsible for spatial processing and memory tasks.
Diagnosis
The differential diagnosis of a condition that affects memory, attention, calculation- that is to say- multiple spheres of cognitive ability- is widely varied. Conditions to consider include Alzheimers disease, frontotemporal dementia, Lewy Body dementia, neoplastic disease of the brain, metabolic disorders, such as thyroid disorders, uremia, and liver disease, vitamin deficiency, leukemia, cerebrovascular disease, and medication side effects.
What makes this case suspicious for Alzheimers disease is the gradual progressive nature, the normal physical, if not cognitive examination, and the fact that CM does not take medications. Symptoms lasting longer than 12 months are especially suspicious, as many of the other disorders tend to accumulate other symptoms during this time frame. The Alzheimers Association has recommended that the illness be considered when memory disrupts daily life. Examples include difficulty driving to a common location, completing daily activities at work or for leisure, withdrawing from regular duties or activities, showing poor judgment when dealing with money or making decisions, misplacing important items in unusual places, or difficulty in planning or making decisions.
Many patients wonder if milder symptoms indicate Alzheimers disease. This includes forgetting people’s names, losing track of certain items, especially when distracted, or making rare word selection errors. These symptoms do not usually indicate Alzheimers disease.
**Special note: a rapidly progressive dementia, over several months, is very suspicious for neoplastic disease, and sometimes for rare disorders such as Creutzfeld Jakob disease.
In the office setting, there are several clinical tools that are helpful for building a case for dementia. These include the MMSE (mini mental state exam), the MoCA (Montreal Cognitive Assessment), and the FAQ (functional assessment questionnaire). These are collections of tasks and questions that are helpful for comparing a patient’s symptoms to what might be expected for normal, or near normal function. They are not perfect, and experience is needed to administer them and score them, especially when patients struggle with the test, or if they have a language deficit.
The MMSE is copyrighted and cannot be reproduced here. It contains testing of serial subtraction, naming, repetition, drawing, reading, following commands, attention, and recall. It is perhaps the most commonly used screening test for cognitive disorders in the U.S., and it is especially helpful in distinguishing mild and moderate dementia. A person could still be affected by dementia and perform normally on the test, and a normal person can miss some of the questions also.
The MoCA exam is designed to distinguish patients who are normal from those with mild cognitive impairment, a condition considered to be a precursor to dementia. This test is distinct from the MMSE in that the drawing tasks are more difficult, the recall and attention are more difficult, repetition and fluency tests are more difficult, and there are tests for abstraction (i.e. what is the similarity between a table and a couch- they are pieces of furniture). This is a helpful exam for evaluating a patient who does not seem to have many cognitive deficits.
The FAQ (functional assessment questionnaire) is a simple series of questions that any medical provider may ask. It includes questions about tasks including traveling away from home (using a car or bus), paying attention to the date, news, a TV show, magazine, or book, preparing a balanced meal, using the stove, writing checks or paying taxes, remembering family celebrations, such as birthdays, and awareness of medications and their regimens. The benefit of the FAQ is to determine the daily impact of the patient’s symptoms on important activities. Not only does it help to distinguish mild, moderate and severe dementia symptoms, it may also help in guiding the practical forms of assistance needed by the patient. One disadvantage of this test is that it does not distinguish dementia from other illnesses that affect these activities.
Laboratory testing is an important part of assessment of causes of a cognitive disorder. These include complete blood count, comprehensive metabolic profile (electrolytes, renal and hepatic function), thyroid function, vitamin B12 level, and syphilis screening test (although it appears this condition has become relatively rare). Significant abnormalities in these screening tests lead to a diagnosis other than dementia. These are often correctable with medical treatment.
A review of the medication list is important. Sedating medications, such as those used to treat pain or mood disorders, are often a contributor to cognitive symptoms. Sometimes the metabolism of medications may change in a patient, leading to surprising side effects that were not suspected for years.
A helpful screening test for some causes of cognitive deficits is an MRI of the brain. For patients who cannot have this test, a CT scan may also be helpful. The MRI is exceptional at determining the presence of cerebrovascular disease and neoplastic disease. The CT scan has a lesser sensitivity and specificity at determining these disorders.
In some cases, these tests are insufficient. There are specialized tests which may be more helpful, and these are often used by neurology providers. These include neuropsychological testing, PET scan, and fMRI.
Neuropsychological testing is perhaps the ultimate tool for office-based cognitive evaluation. It is a series of tasks and questions, associated with a detailed interview, administered by a psychology technician or clinical PhD. It is often tailored to the test taker’s education level and abilities. Using a series of exam tools, the patient’s score can be compared to the expected score, and to the scores of many other users. Multiple cognitive abilities can be examined this way, including complex attention, perceptual ability, multiple functions of language, planning, learning and storing of thoughts, and abstract reasoning. The difficulty with neuropsy testing is its availability. Technicians tend to administer just one test per day, and the wait list for this test can be long.
A recently available clinical test for Alzheimers disease is the PET scan. (PET indicates positron emission tomography). This test was specially approved to identify patients with frontotemporal dementia, who sometimes have many of the symptoms of Alzheimers disease. Although there is an abnormality on the PET scan in the setting of AD, which is diagnostic, the PET is not meant to aid in the diagnosis of AD at this time. The PET study uses a specially prepared sugar molecule to measure what regions of the brain are metabolically active. Patients with dementia disorders tend to have regions of brain surface that are metabolically inactive, sometimes in a manner specific to their illness. Patients with Alzheimers disease should have hypometabolism of specific cortical regions of the brain, as opposed to patients with other illnesses.
A special variation of an MRI study, called functional MRI or fMRI, has been useful in research studies of memory disorders. For Alzheimers disease, these studies have shown changes in blood flow within the hippocampus, a region of the brain known to be important to forming memories. There is hope that this kind of study will help to predict the outcome of treatment for patients with cognitive disorders. For the time being, fMRI should be considered a research tool, rather than a clinical tool, except in special circumstances.
Treatment
When a patient is suspected of having any cognitive disorder, including a mild one, there are home remedies which may be helpful. These include regular aerobic exercise, social activities, and eating a healthy diet. It has been shown in many studies that negligence of these activities is harmful to cognitive function, and for that reason they should be strongly encouraged. Alzheimers disease is however a degenerative, incurable illness, and these remedies should not be expected to cure it.
First line agents to treat Alzheimers disease include donepezil, rivastigmine and galantamine. These treatments are designed to enhance acetylcholine signaling within the memory center of the brain. They interfere with cerebral degradation of the neurotransmitter acetylcholine. Common side effects of these medications include loss of appetite, diarrhea and nausea. We have observed that these medications produce modest effects on the preservation of function. For some people, they seem to be more effective than for others. These medicines should not be used with the goal of improving memory or cognitive function.
For moderate or severe Alzheimers disease, a medication such as memantine may be considered. This medication is a glutamate receptor antagonist, and it is meant to protect diseased neurons from toxic effects of glutamate stimulation. This medicine may be used with or without anticholinergics. It is felt to have a modest effect on the progression of the illness at more advanced stages, it has not been shown to have a benefit for people with milder forms of Alzheimers disease. Common side effects of this medicine include dizziness, drowsiness and confusion.
Recently, medications designed to reduce amyloid have been become available. As of 2023, these medicines are controversial, given their cost, risk of adverse effects, and overall benefit to the patient. We remain hopeful that additional information and innovation will lead to safe, effective and practical remedies for this terrible illness.
The most important issues about Alzheimers disease are to maintain safety and independence without exposing the patient to hazards. Patients who display altered judgment or slow processing may not be fit to continue their driving habits. Sometimes providers must declare a patient unsafe for driving. There are special driving tests to help evaluate patients when it is uncertain what their function is. These may be driving simulators or proctored exams.
Patients with cognitive disorders may struggle to support themselves without help. Activities such as obtaining and cooking food, housecleaning, using medications, and bathing may be very difficult. Assisted living, either in a nursing home, assisted living community, at home with the care of a family member, or a professional in home assistant may be advisable when this support is needed. Patients with a cognitive disorder may not be able to recognize the need for these services, but they should be encouraged to take part in them.
Power of attorney and guardianship ought to be considered when cognition is affected. Patients may be unable to make their own medical decisions, and should be accompanied by a guardian to clinic visits. They may be unable to operate a bank account or pay for bills, and a legal guardian should be appointed to look after their financial interests.
Patients with severe dementia may die due to complications of their illness. This may be due to choking, pneumonia, poor nutrition due to loss of interest in food or eating, or breakdown of the skin due to poor mobility. Patients with severe dementia may not recover well from other medical illnesses. Sometimes treatment of severe pneumonia in a patient with advanced dementia is futile. Although there may be recovery from the pneumonia, the risk of choking might lead to future illness. Patients with severe dementia might not care for advanced or invasive medical care. Their durable power of attorney, or legal guardian, may be called on to decide if these medical measures should be extended.
Patients with dementia may be able to make their own medical decisions for years, if they are diagnosed at an early stage of the illness. At this stage they should be asked to participate in planning for contingencies, such as choosing a guardian and discussing medical care wishes. It is advisable that a patient discuss their wishes for medical resuscitation (DNR/DNI) if their illness were to progress.
Medical illnesses may influence concomitant AD. Type II diabetes mellitus increases the risk of developing AD. Patients with illnesses in addition to AD should maintain routine goals of treatment in order to prevent worsening of their cognitive illness.
Review Questions
- Alzheimers disease would be suspected in a person who:
a. has difficulty remembering where there car keys were placed
b. is living in a nursing home
c. is 85 years old and forgets the name of the governor
d. has trouble naming objects in a room and remembering a 3 digit number
e. uses a walker to prevent falling - Conditions that should be excluded before making a diagnosis of Alzheimers disease include:
a. vitamin B12 deficiency
b. uremia
c. hyponatremia
d. stroke
e. all of the above - A patient with Alzheimers disease may benefit from nonmedical interventions. What are the best examples of this?
a. creating a living will and DNR order
b. visiting with people who have advanced Alzheimers disease
c. identifying a durable power of attorney
d. selling their residence and moving to a care facility
e. both A and C