Case History
Learning Objectives
Web References
Literature References

After the initial interview with the patient, she left the room with an aide. The patient is the mother of the physician who conducted the interview; he further expanded on the patient's condition. She has Alzheimer’s disease. Her symptoms began very slowly, first being noticed after the death of her husband about 3 years ago. The family realized at the time that she was not doing the shopping regularly, not cooking for herself and was losing weight. She was living the United Kingdom. The physician has lived in the U.S. since 1967. He still has 2 brothers living in the UK. However, because of their family and/or financial situations, they were not able to offer a supervised living situation for their mother, so a family decision was made to have her join the physician and his wife in the US.

The patient was very pleasant. When asked how old she was she thought she was 90 or 92. She did remember the date of her birth, August 9, 1908. As the physician pointed out, she will be 91 in August. She remembered that she was born in the UK and was born in the family house. She remembered that she went to school there but was not sure of the name of the school and wanted to be reminded. She was trained as a nurse. With prompting from the physician, she was able to recall the names of several hospitals that she worked at. She said that she gave up nursing to marry her husband. At that point, she confused the physician with her husband. He mentioned that this happens frequently. She initially thought that she had 3 or 4 children but was then able to remember the names of her three sons and the order in which they were born. The physician lives in the United States. The other two still live in the UK. The physician handles all his mothers’ financial issues. He has power of attorney for all her affairs in the U.S. and one of his brothers has power of attorney for all her affairs in the United Kingdom.

Although the patient likes living with the physician and his wife, she misses her relatives in the UK. They have been back to visit in the past and plan on visiting again this fall.

She realizes that her memory is “going slightly”. She likes the adult day care center she attends once a week. She is very social and gets along well with the other patients there. In the past she was very active with cooking and flower arranging and tries to help with flower arranging at the day care center. At home, she is not involved in major cooking but is able to assist the physician’ wife in doing things such as drying dishes and peeling potatoes. She is able to make herself breakfast as well as tea. She likes watching television, especially “the one who died” (Lawrence Welk). The family rents videotapes for her and she watches in the evening. She also reads the newspaper as well as some Agatha Christie novels, but does not remember anything she reads. When asked specifically about last evening’s paper, she did not recall anything she read. She is able to wash and dress herself but needs encouragement to bathe. the physician’ wife has to pester her to make sure that she bathes frequently. She has no problem with either bowel or bladder incontinence but does not do a good job cleaning herself after a bowel movement. She also needs help picking out her clothes to make sure they are appropriate. Occasionally she has put on her clothes backward.

The patient likes to help around the house with dusting. He states that she does this at least several hours everyday, always walking around with a dust rag. She likes to pet the 2 dogs that they have and when the weather is nice enjoys sitting in the garden. She is able to make her own bed. She frequently takes naps in the afternoon. She has exertional dyspnea and does not do a lot of walking.

At times she feels depressed. He noted that she cries at times. She has been on an antidepressant (sertraline (Zoloft) in the past. At times she gets frustrated and upset saying things such as “I’m useless” or “Perhaps I should join your father”. Her recent memory is very poor, remembering things only a few minutes. She tends to repeat herself frequently.

the physician stated that his mother has never been given medications that might potentially improve her memory, such as cholinergic drugs, antioxidants (Vitamin E) or herbal medications such as Ginkgo Biloba. He really was not sure that any of these would make a marked difference and were not likely to result in any major change in her function.

One of the major care issues is that as an elderly immigrant to the U.S., she has no health insurance. the physician has been able to prevail on friends and colleagues when testing is needed but is currently serving not only as her care giver but also her primarily care physician. He realizes this might not be the wisest decision but feels under the circumstances with the lack of any insurance that it is a choice that he has made. His wife is his mother’s health care proxy. They have discussed end of life issues with her. She does not want resuscitation. She does not want any tube feedings.

She has had very few medical problems recently. She had a fall with fracture of her tibial plateau. He was able to arrange to get x-rays and then to have her admitted directly into a nursing home where he works so she could receive rehab.

Her past and family history were reviewed. She had a hysterectomy in the past because of menorrhagia. She was a heavy smoker for many years and he suspects she has emphysema. She used to have severe reflux esophagitis and has a very large hiatal hernia, with about half her stomach in the chest. However, as she has aged, her reflux symptoms have disappeared. The physician suspects that she may have developed atrophic gastritis and therefore have less or little acid to reflux. Her reflux was so severe in the past that she required blood transfusions for anemia related to bleeding from her esophagitis. She also has a history of diverticulosis which is mostly inactive. Of note in the family history is that she had a brother who died in his 70’s of mental problems. Although the physician is not sure of the exact diagnosis, he stated that the brother became progressively more demented. He does not know of any evidence of strokes or Parkinson’s disease and suspects that he had Alzheimer’s disease.

His mother has deteriorated steadily over the past year. A recent score on a mini mental exam was 14/30. At this point she is never left alone. Either he or his wife or occasionally a sitter stays with her. Because she is pleasantly demented, they are able to take her along when they do things such as going to the theater or to dinner. They have to plan very carefully to make sure that someone is always available to care for her. They are starting to consider long term plans on whether she will need to be placed in an institution. Costs for this would be much less in the United Kingdom than they are in the U.S. He talked about the issue of guilt on the part of the family in terms of whether or not to place her in a facility.

Other changes that the physician noted was that recently she has become dysphasic. She has difficulty in word finding, especially in the morning. He noted that as patients with Alzheimer’s progress, eventually most of them become mute. He talked about the FASS staging system for Alzheimer’s which is on a stage of 1 to 7. He noted that stage 1 is normal. Stage 5 indicates needing help with selection of clothing, stage 6 refers to a need for help with self maintenance such as washing, and stage 7 indicates that language function is decreased or absent. He stated that if you understand child development, the progression in Alzheimer’s is essentially the reverse of the situation. He noted that babies early on develop the ability to hold their head up and this is one of the last functions lost in Alzheimer’s. Likewise, babies learn early on to smile and this is one of the last things to be lost in Alzheimer’s disease.

the physician discussed a little bit about his role as a physician helping other patients with Alzheimer’s disease. He stated that besides handling medical issues that they took a much more holistic approach. They discuss things such as support services, financial issues, legal affairs, end of life issues, as well as dealing with medical care.

Incidence

A major social and economic problem as the population ages

At least 2-4 million affected in the U.S. possibly twice as many (why are accurate stats

hard to obtain?)

50% of all nursing home patients have this disease

Epidemiology

Onset in patients after age 50

About 1% population at age 65; 50% people over age 80 are affected

More common in females

Clinical Findings

Definition of dementia

Clinical manifestations

Insidious onset with dementia

Loss of memory (recent?long-term) and cognitive function

Language disturbance, impaired spatial orientation

Diagnostic Tests

Mental status exam

Tests of cognition

Compare and contrast with normal aging changes

Tests to rule out reversible causes of dementia

Differential diagnosis - Pick’s, Parkinson’s, diffuse lewy body disease,

Huntington’s, normal pressure hydrocephalus, Creutzfeldt-Jakob, syphilis,

progressive multifocal leukoencephalopathy, chronic alcohol abuse and

Binswanger’s (subcortical arteriosclerotic) disease

CT scan showing cortical atrophy and large lateral ventricles

Course and Prognosis

Disease is progressive with 5-10 year survival (average)

Care &Therapy

Effect on caregivers - Living situation

Community resources - access

Medication - Tacrine

Pathology

Gross brain small with cerebral cortical atrophy and hydrocephalus ex vacuo

Marked loss of neurons in the cerebral cortex

Microscopically numerous senile (neuritic) plaques and neurofibrillary tangles (NFT)

Early plaques are diffuse and contain amyloid (few fibrils)

Mature plaques contain central amyloid core and surrounding degenerating neurites and glia

Stain with silver stains and congo red

Amyloid is also seen in the cerebral blood vessels (is this a systemic vascular process?)

NFT are masses of paired helical filaments

Stain with silver in light microscopic sections

Composed of hyperphosphorylated tau proteins

Are the plaques and NFT specific for Alzheimer’s disease?

Pathogenesis

This is complicated and there are probably several pathways to disease

Disease seems to begin with deposition of amyloid in the brain (beta A4 amyloid)

Amyloid appears to be neurotoxic and results in loss of cortical neurons

Amyloid may activate microglia which release cytokines that damage neurons

Neuronal injury may result in formation of neurofibrillary tangles (this is controversial)

It is not clear whether NFT cause (precede) nerve cell death or result from prior injury

Alzheimer’s disease is really a group of related disorders rather than a single disease

Some cases are genetically determined while many are sporadic

Several genetic abnormalities have been described

Chromosome 21 (trisomy in some cases) - Amyloid precursor protein (APP) is a normal membrane protein (function unknown) APP (563-770aa) is cleaved through the amyloid portion (39-43aa) by enzyme secretase Mutations of gene result in abnormal APP, which is cleaved in the wrong place so that intact beta amyloid is formed

Chromosome 14 - Presenilin 1 in ER membrane where amyloid is folded and cut

Chromosome 1 - Presenilin 2 in ER membrane where amyloid is folded and cut

Chromosome 19 - ApoE4 is a chaperone protein, which facilitates breakdown of intracellular proteins

Alzheimer's Association

DESCRIPTION: Not much substance

URL: http://www.alz.org

Alzheimer's Disease Research

DESCRIPTION: Lots of good information

URL: http://www.dundee.ac.uk/pharmacology/staff/kcb/alzres.htm

Alzheimer's Forum

DESCRIPTION: Excellent - huge store of information for patients, doctors, and researchers

URL: http://www.alzforum.org

6th International conference on Alzheimer's Disease

DESCRIPTION: Use the search facility to find specific topics

URL: http://www.alzh98.com/book

Resources for Neuroscience

DESCRIPTION: Large collection of links. This is part of the WWW Virtual Library.

URL: http://neuro.med.cornell.edu