Science and Technology Division
IS ALZHEIMER'S DISEASE?
MAGNITUDE OF THE PROBLEM
Number of Victims
Treatment and Care
Support for Caregivers
Causes of AD
FOR THE FUTURE
With the elimination of
many diseases, particularly those affecting children and the young, Canadians
are living longer. The percentage of Canadians over age 65, only 4% in
1900, is now 12% and is expected to increase to 23% within 40 years.(1)
This growth in longevity has brought with it a great increase in diseases
and disorders that cause dementia,(2)
the most common of which is Alzheimer's Disease (AD), first identified
in 1906 by Alois Alzheimer,(3)
a German neuropathologist. This paper will review some of the major aspects
of this dreaded disease and will also discuss the research efforts underway
throughout the world to establish the cause(s), develop an effective method
of diagnosis, and discover a cure.
IS ALZHEIMER'S DISEASE?
Alzheimer's disease is a
progressive degenerative disorder of the cerebral cortex that produces
dementia in middle to late life. Currently no definitive cause has been
found for this affliction and no effective treatment has been developed.
Clinically, AD results from a progressive loss of neurons from the cerebral
cortex and other brain areas. The brain of a person who has died from
this disease contains two characteristics: neuritic plaques (clumps of
beta-amyloid protein outside the brain cells, or neurons), and neurofibrillary
tangles (twisted, spaghetti-like fibres inside damaged neurons). Biochemical
abnormalities associated with neuron failure include deposition of amyloid
protein in cerebral blood vessels and senile plaques; disrupted nerve-cell-membrane
phospholipid metabolism; and decreases in neurotransmitter substances
such as acetylcholine, serotonin, norepinephrine, and somatostatin. It
is extremely difficult to diagnose this disease without a biopsy, since
other conditions, many of which are treatable, can have the same initial
symptoms. Two main variants of the disease are known. Early-onset AD,
which strikes victims in their 40s and 50s, accounts for only a tiny percentage
of AD victims; a subset of this type is hereditary and is known as Familial
AD. Late-onset AD, which appears after age 65, is the most common form
of the disease.
Memory loss is the most
prominent early symptom of AD, followed by a slow disintegration of personality
and physical control. Total nursing care is necessary in later stages
of the disease.
In descending order,
the patient goes from (1) decreased ability to handle a complex
job to (2) decreased ability to handle such complex activities
of daily life as (3) managing finances, (4) complex meal preparation
and (5) complex marketing skills. Next comes (6) loss of ability
to pick out clothing properly, (7) or to put on clothing properly,
followed by (8) loss of ability to handle the mechanics of bathing
properly. Then (9) progressive difficulties with continence and
(10) toileting occur, followed by (11) very limited speech ability
and (12) inability to speak more than a single word. Next comes
(13) loss of ambulatory capability. Last to go are such basic
functions as the ability to (14) sit up, (15) smile and (16) hold
up one's head.(4)
While the disease is progressing,
between 10% to 15% of patients hallucinate and suffer delusions, 10% have
seizures and 10% will become violent.(5)
The change in personality and temperament can be rapid. The rate of progression
of the disease varies between patients, with the average time from diagnosis
to death being eight years. The family usually cares for a patient at
home for an average of four years.(6)
This disease frequently
masquerades as other ailments. Its diagnosis remains difficult and no
simple clinical test has yet been developed. A complete medical team is
involved in the evaluation process, which begins with eliminating the
other possible causes of such symptoms as impaired intellectual functioning,
memory loss, difficulty in recognizing or recalling the names of objects,
and impaired ability to distinguish the relationships of objects. The
evaluation encompasses medical, neurological and psychiatric examinations,
a detailed history of the patient (including a complete inventory of all
the drugs he or she takes) and various tests. Once a patient has been
diagnosed as having AD, any change in his or her condition must be brought
to the attention of the attending physician.
MAGNITUDE OF THE PROBLEM
Number of Victims
The many studies on the
incidence of the disease all indicate that this increases immensely in
older age groups. The highest incidence was reported in a U.S. survey
conducted in East Boston by the Harvard Medical School. It showed the
incidence of AD to be 3% for people between the ages of 65-74, 18.7% for
those between 75-84, and 47.2% for those over 84.(7)
Other studies have shown similar trends (see figure below) but in some
cases a much lower overall incidence rate. Although the disease is not
of epidemic proportions, the estimated number of Canadians with AD ranges
from 300,000(8) to approximately
400,000.(9) With continuous
growth in the percentage of Canadians over age 65, this figure could easily
exceed 700,000 by the year 2020.
Source: M. Breteler et
al., "Epidemiology of Alzheimer's Disease," Epidemiologic
Reviews, Vol. 14, 1992.
The human and financial
costs of this affliction are enormous. The process of decline takes many
years, during the first few of which family members often take care of
the patient. Caregivers frequently retire early from paid employment to
look after their relative, particularly as the disease progresses. Even
when victims are being cared for at home, they frequently require costly
medical and other care. The immediate family members, particularly the
caregivers, also require help to enable them to cope with this "36-hour-day."
The suffering associated
with AD is horrendous, as much as for those watching a loved one's slow
decline, as for the victims, who may suffer more by being aware of their
eventual plight. Since the progression of the disease varies, the rapidity
with which victims lose their abilities differs. Even though memory is
lost, the relationship between the victim and the family can to some extent
be maintained over a period of time, as feelings and emotional responses
continue, but as the disease progresses a victim of AD eventually becomes
only a "shell." The grief of the victim's immediate family continues,
however, though society and friends do not always understand this.(10)
Even when using the most
conservative estimates of the average number of years spent in an institution,
typically three to four years, and the number of afflicted Canadians,
the costs to the health care system are immense.
At $33,000 (1989)
per patient per year in an institution and with an average stay
of 3 years until death, the cost of AD will amount to $3 billion
over the next three years; and if the entry into the disease state
remains constant, it will cost the Canadian taxpayer $1 billion
per year thereafter.(11)
Added to this cost are other
major expenses, mainly paid by the public heath care system and social
programs, including the support/assistance for the caregiver, the entire
medical support team, costly prescription drugs, and modifications to
living accommodations. Further cost is incurred if a family caregiver
must retire early to care for the victim.
Treatment and Care
Once a patient has been
diagnosed as having AD, an assessment is made of the disease's stage of
progression and of the strengths and weaknesses of the victim and the
victim's family. Several assessment systems are available to evaluate
the level of dysfunction in various areas. Based on this assessment, a
comprehensive care plan is prepared by a team consisting of a family member,
the paid caregiver with primary responsibility for direct care, other
care providers, and the victim's physician. Throughout the progression
of the disease, and depending on the needs of the patient, a wide range
of expensive medication, such as psychoactive drugs to lift depression
and sedatives to control violence, may be required.
a wide range of treatments have been tested, most have proven ineffective.
Care at present is mainly palliative. During the initial phases of the
disease, the patient can frequently be looked after at home by a caregiver,
paid or unpaid, with some social support and medical attention.
Simple changes in the home
can make life much easier for sufferers, help them maintain self-esteem
and a degree of independence, and prolong the period in a home environment.
Examples of low-cost changes and modifications to the environment include:
reducing the noise levels in the home (noises from television, radio,
and telephone as well as from speaking); avoiding vividly patterned and
striped rugs, drapes and upholstery; placing locks up high or down low
on outside doors and adding simple doorknob alarms; clearing floors of
throw rugs and clutter; and reducing the contents of closets to simplify
choices. These costs are paid for by the victim's family. Many of these,
and other more expensive modifications, are introduced in long-term care
settings. They aim at meeting the safety and security needs of the victim,
reducing his or her confusion and contributing to the effective functioning
of both victims and caregivers.
The patient's and the family's
condition are assessed every six months. In response to changing needs,
the extent and nature of the care are modified, normally in consultation
with the family. Other issues that may arise during the care of AD victims
are assessment of the victim's competence, power of attorney, and prevention
of and response to abuse of both the victim and the caregiver. Eventually
the victim's condition deteriorates to the point where home care is no
longer possible and he or she must be moved to long-term institutional
Support for Caregivers
Until an eventual cure and
treatment for AD are found, this disease will remain a significant problem
for Canadian society. Care, support and information for AD victims and
their families come primarily from the health care system and from the
Alzheimer's Society, which in Canada is organized at the national, provincial
and, frequently, the municipal level. The information and support the
society provides are crucial, particularly for the caregivers.
The caregiver needs information
on the disease, including details of dementia and appropriate methods
of care. The victim may become restless, or suspicious, may wander, or
have erratic sleep patterns. Such behaviour places an additional strain
on the caregiver. Some studies have shown that caregiver depression and
inappropriate living arrangements were the factors most associated with
violence towards AD victims.(12)
The caregivers themselves often suffer from depression or "burnout"
and their health deteriorates as a result of trying to help the AD victim.
Frequently, conflicts with attitudes and actions of other family members
can greatly increase the risk of depression for caregivers. AD support
groups offer families the emotional, spiritual and practical help they
need to cope with the disease. The caregiver has many needs, including
regular and increasingly lengthy relief from duties. The greater the level
of support, the longer a caregiver can cope with the patient.
Causes of AD
The underlying cause(s)
of AD remain unknown although theories and ideas abound. Many of the theories,
and much of the research, have focused on the beta-amyloid protein, the
building block of the plaque found in the brain of AD sufferers. Even
the role and toxicity of this protein remain controversial, however, and
how it is made and released in the brain is unknown. One of the newest
theories on the origin of beta-amyloid was recently reported in the journal
Science.(13) It suggests
that the beta-amyloid is produced in healthy brain cells and it is its
overproduction that creates a problem.
Research is continuing on
many different approaches to AD and new findings are being reported continually.
Some of the suspected causes include:
recent years a theory identifying aluminum as a possible trigger for
AD was put forward. There is some evidence of a link between the amount
of aluminum ingested and the incidence of AD. This evidence suggests
that: aluminum accumulates in at least four sites in AD-affected brain
tissue, at concentrations known to effect several biochemical reactions;
that there is an association between AD and aluminum exposure in drinking
water and antiperspirants; and that treatment with a trivalent metal
ion binding agent slows up to about half, but does not arrest, the
clinical progression of AD.(14)
In a recent study, however, researchers at Oxford University's Radcliffe
Infirmary, using nuclear microscopy to examine neuritic plaques from
the brains of AD victims, could not find any trace of aluminium.(15)
This method does not require any dyes and some researchers have speculated
that the aluminum found in other studies may have been simple background
contamination or have come from the reagent used in the dyes.(16)
The controversy surrounding the relationship between AD and aluminum
Infection: One of the most difficult ideas to disprove is that
AD might be caused by a slow-acting virus that could be present at
Recent studies have shown that within hours or days of a serious head
injury, beta-amyloid plaques are formed which are identical to those
found in AD sufferers. It is proposed that head injuries may be an
environmental trigger for AD.(18)
Research is now being done to find how head trauma triggers amyloid
Research has shown that one half of the members of each generation
of certain families succumb to early-onset AD, a type that accounts
for a tiny percentage of AD sufferers.(19)
The triggering mechanism is a mutation on chromosome 21 of the gene
responsible for encoding amyloid precursor protein (APP).(20)
Down's syndrome patients almost always suffer from brain lesions similar
to those associated with AD; this syndrome is caused when there are
three copies of chromosome 21 instead of the normal two. Chromosome
14 has also been linked to certain familial types of AD.(21)
Other research findings indicate that a "house cleaning gene"
located on chromosome 19 could be a genetic cause for late-onset AD.
Malfunction of the
Immune System: Some researchers believe that AD is an immune disorder
resulting from a malfunction of the body's immune system. This theory
stems from the similarity between the beta-amyloid protein found in
AD patients and the amyloid present in tissues of person suffering
from numerous kinds of immune-system breakdown.(22)
An early theory that suggested that AD begins with a chemical imbalance
is now being reinvestigated. It has been known since the mid 1970s
that AD is somehow related to a deficiency in acetylcholine, a neurotransmitter
especially important in the brain areas involved with memory. The
new theory centres on choline, the substance from which acetylcholine
is derived; recent findings indicate that the brains of AD sufferers
have 40% to 50% less choline than normal brain tissue. This theory
proposes that defects in the processing of choline and related molecules
cause the brain-cell membrane to decay.(23)
Malfunction of Age
Compensation Mechanism: Some research findings published in the
January 1993 issue of Neuroreport suggest that AD may be caused
by a natural mechanism that combats the effects of aging.(24)
The report explains that, as humans grow older, many neurons in the
brain begin to decline and the surviving neurons try to compensate
by growing to fill gaps left by the dead cells. This process, known
as "resprouting," is assisted by the production of beta
amyloid precursor protein (BAPP), of which excess amounts may lead
The actual cause for AD
has yet to be established but all or some of the above may be involved.
It may well be found that AD is a heterogeneous disorder in which a variety
of factors can stimulate the amyloid protein precursor and its derivatives
to process aberrantly, so that the beta amyloid protein is released and
deposited as amyloid, which then initiates the rest of the pathologic
Several promising new tools
are being developed to simplify early diagnosis of AD. Until a cure and
a treatment are found, however, early diagnosis can be a mixed blessing,
since the knowledge can hurt as much as help. In the past year, several
potential methods involving advanced biological testing or the use of
sophisticated equipment have been identified. Much more testing will be
required before any of these methods is available for general use.
A test involving the extraction
and analysis of a sample of cerebrospinal fluid for screening for AD at
an early stage was announced in August 1992 and is undergoing further
testing. The test is based on levels of APP, which in AD victims are as
much as 3.5 times lower than normal;(26)
the disease appears to progress more quickly, the lower the level of APP.
The test can apparently differentiate AD from other forms of dementia
and, it is hoped will allow researchers to check the effectiveness of
AD treatment. Last summer, the company that developed the test, SIBIA,
the corporate spin-off from the Salk Institute of Biotechnology in La
Jolla California, said it expected to bring a commercial version to market
in late 1993. The status and cost of the test are unknown, but the test
would be carried out in a hospital setting.
Images from a PET(27)
scanner of victims of AD show a reduction in brain activity that is most
severe in the parieto-temporal region of the cortex.(28)
Unfortunately, only a few specialist hospitals have the equipment needed
to exploit this discovery.
A promising diagnostic method,
normally taking less than 10 minutes, uses a single measurement from a
computerised tomography (CT) scan of the temporal medial lobe of the brain.
A long-term study found that the measurement of the thinnest point of
the lobe was lower for AD sufferers and that there was little overlap
between them and the control group. The test could detect 79% of sufferers
and reduce the "false positives" to 1%, but an additional test
would also be needed to identify all AD victims. Another useful aspect
of the test is its ability to distinguish between patients with AD and
those with dementia from other causes.(29)
Further evaluations are continuing with this approach.
Also being investigated
is a diagnostic method that uses the results of postmortem studies indicating
that an increased choline to N-acetylasparte (NAA) ratio is specific to
Alzheimer's disease. The process being developed involves the use of magnetic
resonance spectroscopy (MRS) to "see" the biochemical change
in the brain. The testing done so far, which compares the MRS brain images
of healthy elderly people with those of young people, rules out the chance
that the change in NAA ratio is a function of age. Comparisons between
healthy elderly people and elderly people with Alzheimer's disease showed
Once the actual cause(s)
of the disease are known, it is hoped that a simple test, possibly based
on the level of certain key proteins, may become available.
Until the definitive cause
of AD and the mechanism involved in it are discovered, the disease itself
cannot be cured. The current treatment consists mainly of palliative care
and maintenance of the patient. Several new developments for treating
the symptoms have been announced and further testing and evaluation are
The most widely employed
strategy for symptomatic treatment of AD is the replacement of neurotransmitters,
though few of the trials with various neurotransmitters have been successful.
The results of a major trial, conducted on 468 AD patients at 23 treatment
centres in 1990 and 1991, was published in November 1992; it confirmed
that a 12-week treatment with tacrine hydrochloride provided patients
with cognitive improvement.(31)
Based on the cognitive component of the Alzheimer's Disease Assessment
Scale, the mean response of the 12-week treatment would seem, on average,
to reverse six months of the progression, of the disease. The trial also
showed that the drug's major side effect, liver toxicity, was reversible.
Tacrine, and several other similar drugs, work by inhibiting an enzyme
that breaks down acetylcholine, which is involved in the memory areas
of the brain and is mentioned in the chemical imbalance theory.
Several studies show that
short-term treatment with selegine, developed for the treatment of Parkinson's
Disease and commonly known as L-deprenyl, improved the memory and attention
of AD patients.(32)
This neurotransmitter inhibits the production of the enzyme monoamine
oxidase-B, which is involved in dopamine degradation (the principal defect
in Parkinsons's disease) and is thought to cause disturbances to the catecholaminergic
system that lead to cognitive defects such as memory loss.(33)
New evidence from the Centre for Research in Neurodegenerative Diseases
at the University of Toronto suggests that the drug may bring hitherto
unrecognized benefits that compensate for some of the beneficial/nutritive
Clinical trials and testing
are continuing with these and other drugs. Researchers agree that it would
preferable to develop drugs to prevent damage rather than simply to boost
the effectiveness of one particular neurotransmitter.
Some other areas of intervention
The inhibition of abnormal protein deposition in the brains of AD
victims is currently under study as a potential therapeutic strategy.(35)
The detailed mechanism for the formation of beta-amyloid protein is
still being researched. Once the mechanism is known, treatment to
stop the build-up may be possible.
Some studies suggest that nerve growth factor (NGF) helps nourish
neurons and that early administration of NGF could reduce or prevent
the loss of neurons.(36)Research
indicates that NGF is particularly beneficial for the cholinergic
neurons in the basal forebrain, a portion of the brain involved in
the memory function and heavily affected by AD. Some innovative research
involving gene therapy(37)
to promote the production of NGF is taking place.(38)
Research into the broader
issue of cell death ("apoptosis") may one day provide some help
for those suffering from AD. Some very recent discoveries indicate that
the bcl-2 gene operates as a blocking agent for cell death without causing
cancer.(39) Other research
indicates the tantalizing possibility that the bcl-2 gene could be used
in fighting neuron death.(40)
AD is an enormous social
and economic problem. As the population ages, the number of victims will
steadily increase, imposing a massive burden on the health care system.
Until a cure and an effective treatment are found, AD poses social, legal,
and medical challenges as well as problems of scientific policy and resource
Social challenges include
ensuring a uniform level of supplemental support for caregivers and optimizing
the sharing of resources between expanded home care and institutional
care. Legal issues include power of attorney for the victim and voluntary
euthanasia, while medical issues include a lack of available institutions
for long-term care, particularly specialized units for AD sufferers, and
the need for increased education and awareness on the part of the medical
Another problem is the modest
level of funding assigned to AD research in Canada. The Medical Research
Council accounts for 80% of neuroscience research; it provided approximately
$26.5 million in fiscal year 1992-93 for all neuroscience research, including
that on AD.(41) This amount
of research is minuscule when compared with the multi-billion dollars
spent by Canadian taxpayers to treat the effects of AD.
FOR THE FUTURE
The cause of Alzheimer's
Disease remains uncertain, as does the cure. Many researchers are, however,
confident that the efforts of both government and the private sector should
result in more effective treatment by the end of the century.
"Alzheimer's: Is there
Hope?" U.S. News and World Report. 12 August 1991, p. 44.
Begins to Yield Its Secrets." Science, Vol. 259, 22 January
1993, p. 457.
Breteler, Monique M.B. et
al. "Epidemiology of Alzheimer's Disease." Epidemiologic
Reviews, Vol. 14, 1992, p. 72.
Brown, Phyllida. "Alzheimer's
May Not Be Linked To Aluminum." New Scientist, 7 November
1992, p. 16.
Brown, Phyllida. "Rescuing
Minds from Disease and Decay." New Scientist Supplement, 14 November
Brown, Phyllida. "Secret
Life of the Brain." New Scientist Supplement, 14 November
1992, p. 14.
"Cell Death Studies
Yield Cancer Clues." Science, Vol. 259, 5 February 1993, p.
Davies, Anna. "Capturing
Images of Alzheimer's." New Scientist, 17 April 1993, p. 18.
"Death Gives Birth
to the Nervous System. But How?" Science, 5 February 1993,
Scientific American, August 1992.
Eaton, Dr. William. "Unresolved
Grief of Family Members of Alzheimer Victims." OANHSS Quarterly,
April 1989, p. 5-8.
Evans, Denis A. et. al.
"Prevalence of Alzheimer's Disease in a Community Population of Older
Persons." Journal of American Medical Association, 10 November
Fallow, Marin et al.
"A Controlled Trial of Tacrine in Alzheimer's Disease." The
Journal of American Medical Association, Vol. 268, No. 18, 11 November
Medical Research Council
of Canada. President's Report 1989-1990. p.13.
The Merck Manual.
Fifteenth Edition. Merck, Sharp and Dohme Research Laboratories, 1987,
Murray, Terry. "Protein
in Alzheimer's Found in Healthy People." The Medical Post,
6 October 1992, p. 4.
Paveza, Gregory J. et
al. "Severe Family Violence and Alzheimer's Disease." Gerontologist,
August 1992, p. 493-497.
Roberts, Garth W. et
al. "On the Origin of Alzheimer's Disease: A Hypothesis."
Neuroreport, Vol. 4, No. 1, January 1993.
Schellengber, Gerard D.
et al. "Genetic Linkage Evidence for a Familial Alzheimer's
Disease Locus on Chromosome 14." Science, Vol. 25, 23 October
1992, p. 668.
Webb, Jeremy. "Brain
Scan Gives Fresh Angle on Alzheimer's." New Scientist, 28
November 1992, p. 19.
Weber, Susan. "Parkinson's
Drug May Benefit Alzheimer's Patients." The Medical Post,
8 September 1992, p. 24.
Weber, Susan. "Link
between Alzheimer's, Aluminum Questioned." The Medical Post,
24 November 1992, p. 21.
Worsnop, Richard L. "Alzheimer's
Disease." CQ Researcher, Congressional Quarterly Inc., Vol.
2, No. 27, 24 July 1992, p. 619-639.
"Would Decreased Aluminum
Ingestion Reduce the Incidence of Alzheimer's Disease?" Canadian
Medical Association Journal, 1 October 1991, p. 800.
Medical Research Council of Canada, President's Report 1989-1990,
Dementia is the deterioration of the intellectual, emotional and cognitive
faculties to the extent that daily function is impaired.
Richard L. Worsnop, "Alzheimer's Disease," CQ Researcher,
Congressional Quarterly Inc., Vol. 2, No 27, 24 July 1992, p. 619-639.
Ibid., p. 628.
"Alzheimer's: Is there Hope?" U.S. News and World Report,
12 August 1991, p. 44.
Ibid., p. 45.
Denis A. Evans et al.,"Prevalence of Alzheimer's Disease
in a Community Population of Older Persons," Journal of American
Medical Association, 10 November 1989.
"The Time to Act Is Now," A Report on the Workshop on
Aging and Mental Health, December 1989, p. 19.
Medical Research Council of Canada (1990), p. 13.
Dr. William Eaton, "Unresolved Grief of Family Members of Alzheimer
Victims," OANHSS Quarterly, April 1989, p. 5-8.
"The Time to Act Is Now," Report on the Workshop on Aging
and Mental Health, December 1989, p. 19.
Gregory J. Paveza, et al.,"Severe Family Violence and Alzheimer's
Disease," Gerontologist, August 1992, p. 493-497.
"Alzheimer's Pathology Begins to Yield Its Secrets," Science,
Vol 259, 22 January 1993, p. 457.
"Would Decreased Aluminum Ingestion Reduce the Incidence of Alzheimer's
Disease?" Canadian Medical Association Journal, 1 October
1991, p. 800.
Susan Weber, "Link between Alzheimer's, Aluminum Questioned,"
The Medical Post, 24 November 1992, p. 21.
Phyllida Brown, "Alzheimer's May Not Be Linked to Aluminum,"
New Scientist, 7 November 1992, p. 16.
Monique M.B. Breteler, et al., "Epidemiology of Alzheimer's
Disease," Epidemiologic Reviews, Volume 14, 1992, p. 72.
Worsnop (1992), p. 619-639.
Each human cell normally has 23 pairs of chromosomes, which consist of
coiled DNA(deoxyribonucleic acid) carrying genetic material.
Gerard D. Schellengber, et al.,"Genetic Linkage Evidence for
a Familial Alzheimer's Disease Locus on Chromosome 14," Science,
Vol 25, 23 October 1992, p. 668.
Worsnop (1992), p. 619-639.
Garth W. Roberts et al., "On the Origin of Alzheimer's Disease:
A Hypothesis," Neuroreport, Vol. 4, No 1, January 1993.
Terry Murray, "Protein in Alzheimer's Found in Healthy People,"
The Medical Post, 6 October 1992, p. 4.
"Doomsday Diagnostic?" Scientific American, August 1992.
PET: positron emission tomography (PET) is a research tool using the uptake
of tracer amounts of radioisotopes to measure blood flow, glucose, and
oxygen metabolism in the living brain. Because of its very high cost and
lack of availability, PET currently has little place in clinical diagnosis.
The Merck Manual, Fifteenth Edition, Merck, Sharp and Dohme Research
Laboratories, 1987, p. 1323.
Phyllida Brown, "Rescuing Minds from Disease and Decay," New
Scientist Supplement, 14 November 1992, p. 6.
Jeremy Webb, "Brain Scan Gives Fresh Angle on Alzheimer's,"
New Scientist, 28 November 1992, p. 19.
Anna Davies, "Capturing Images of Alzheimer's," New Scientist,
17 April 1993, p. 18.
Fallow, Marin et al., "A Controlled Trial of Tacrine in Alzheimer's
Disease," The Journal of American Medical Association, Vol.
268, No. 18, 11 November 1992.
Breteler (1992), p. 59-81.
Susan Weber, "Parkinson's Drug May Benefit Alzheimer's Patients,"
The Medical Post, 8 September 1992, p. 24.
Ibid., p. 75.
Gene therapy: modified genetic material is introduced to the body to produce
a desired result. This can be done using different vectors, including
Phyllida Brown,"Secret Life of the Brain," New Scientist
Supplement, 14 November 1992, p. 14.
"Cell Death Studies Yield Cancer Clues," Science, Vol.
259, 5 February 1993, p. 760.
"Death Gives Birth to the Nervous System. But How?," Science,
5 February 1993, p. 763.
Discussion with N. Morris, Medical Research Council, March 1993.