Definition of Alzheimer

Alzheimer's disease, also called Alzheimer disease, senile dementia of the Alzheimer type
(SDAT), primary degenerative dementia of the Alzheimer's type (PDDAT), or simply Alzheimer's,
is the most common form of dementia. This incurable, degenerative, and terminal disease was
first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was
named after him(http://www.alzinfo.org). Alzheimers disease is the most common form of
dementia, a group of disorders that impairs mental functioning. At the moment, Alzheimers is
progressive and irreversible. Abnormal changes in the brain worsen over time, eventually
interfering with many aspects of brain function. Memory loss is one of the earliest symptoms,
along with a gradual decline of other intellectual and thinking abilities, called cognitive
functions, and changes in personality or behavior(www.wikipedia.com).
Although the course of Alzheimer's disease is unique for every individual, there are many
common symptoms(http://www.alzheimers.org.uk)The earliest observable symptoms are often
mistakenly thought to be 'age-related' concerns, or manifestations of stress. As the disease
advances, symptoms include confusion, irritability and aggression, mood swings, language
breakdown, long-term memory loss, and the general withdrawal of the sufferer as their senses
decline (Waldemar G, Dubois B, Emre M, et al. (January 2007). Gradually, bodily functions are
lost, ultimately leading to death. Individual prognosis is difficult to assess, as the duration of the
disease varies. AD develops for an indeterminate period of time before becoming fully
apparent, and it can progress undiagnosed for years. The mean life expectancy following
diagnosis is approximately seven years (Mls PK, Marttila RJ, Rinne UK (August 1986). Fewer
than three percent of individuals live more than fourteen years after diagnosis(Mls PK,
Marttila RJ, Rinne UK (March 1995).
Because Alzheimer cannot be cured and is degenerative, management of patients is essential.
The role of the main caregiver is often taken by the spouse or a close relative. Alzheimer's
disease is known for placing a great burden on caregivers; the pressures can be wide-ranging,
involving social, psychological, physical, and economic elements of the caregiver's life. In
developed countries, Alzheimer is one of the most costly diseases to society(Bonin-Guillaume S,
Zekry D, Giacobini E, Gold G, Michel JP (January 2005)).

Alois Alzheimer's patient Auguste Deter in 1902. Hers was

the first described case of what became known as
Alzheimer's disease.

Comparison of a normal aged brain (left) and an Alzheimer's

patient's brain (right). Differential characteristics are pointed out.

Dementia related to Alzheimer

Dementia is a condition in which there is a gradual loss of brain function; it is a decline in
cognitive/intellectual functioning The main symptoms are usually loss of memory, confusion,
problems with speech and understanding, changes in personality and behavior and an
increased reliance on others for the activities of daily living (Royal College of Psychiatrists). It is
not a disease in itself but rather a group of symptoms which may result from age, brain injury,
disease, vitamin or hormone imbalance, or drugs or alcohol. A person with dementia may also
exhibit changes in mood, personality or behavior. The loss of mental functions must be severe
enough to interfere with daily living. Confusion and disorientation may be present.
Its is not widely understood but Alzheimer's and dementia are not two different diseases but
instead, Alzheimer's is a form of dementia. Dementia is defined as a server impairment of loss
of intellectual capacity due to loss or destruction of neurons in the brain. Alzheimer's is just one
of many forms of dementia and is characterized by the deposits of protein fragments called
"beta-amyloid" plaques and twisted strands of the protein tau also known as
tangles.Alzheimer's is the most common form of dementia accounting for between 60 and 80%
of all cases (http://www.seniorhomecareinformation.com)

Symptoms of Alzheimer
The disease course is divided into four stages, with progressive patterns of cognitive and
functional impairments.

Pre-dementia
The first symptoms are often mistaken as related to aging or stress(Waldemar G, Dubois B,
Emre M, et al. (January 2007)) Detailed neuropsychological testing can reveal mild cognitive
difficulties up to eight years before a person fulfills the clinical criteria for diagnosis of
Alzheimer(Bckman L, Jones S, Berger AK, Laukka EJ, Small BJ (Sep 2004). These early
symptoms can affect the most complex daily living activities The most noticeable deficit is
memory loss, which shows up as difficulty in remembering recently learned facts and inability
to acquire new information.
Subtle problems with the executive functions of attentiveness, planning, flexibility, and abstract
thinking, or impairments in semantic memory (memory of meanings, and concept
relationships), can also be symptomatic of the early stages of Alzheimer Apathy can be
observed at this stage, and remains the most persistent neuropsychiatric symptom throughout
the course of the disease. The preclinical stage of the disease has also been termed mild
cognitive impairment, but whether this term corresponds to a different diagnostic stage or
identifies the first step of Alzheimer is a matter of dispute(Petersen RC (February 2007).

Early
In people with Alzheimer the increasing impairment of learning and memory eventually leads to
a definitive diagnosis. In a small portion of them, difficulties with language, executive functions,
perception (agnosia), or execution of movements (apraxia) are more prominent than memory
problems. Alzheimer does not affect all memory capacities equally. Older memories of the
person's life (episodic memory), facts learned (semantic memory), and implicit memory (the
memory of the body on how to do things, such as using a fork to eat) are affected to a lesser
degree than new facts or memories (Carlesimo GA, Oscar-Berman M (June 1992)).
Language problems are mainly characterised by a shrinking vocabulary and decreased word
fluency, which lead to a general impoverishment of oral and written language. In this stage, the
person with Alzheimer's is usually capable of adequately communicating basic ideas. While
performing fine motor tasks such as writing, drawing or dressing, certain movement
coordination and planning difficulties (apraxia) may be present but they are commonly
unnoticed. As the disease progresses, people with Alzheimer can often continue to perform
many tasks independently, but may need assistance or supervision with the most cognitively
demanding activities (Frstl H, Kurz A (1999)).
3

Moderate
Progressive deterioration eventually hinders independence; with subjects being unable to
perform most common activities of daily living. Speech difficulties become evident due to an
inability to recall vocabulary, which leads to frequent incorrect word substitutions
(paraphasias). Reading and writing skills are also progressively lost. Complex motor sequences
become less coordinated as time passes and Alzheimer progresses, so the risk of falling
increases. During this phase, memory problems worsen, and the person may fail to recognise
close relatives. Long-term memory, which was previously intact, becomes impaired (Carlesimo
GA, Oscar-Berman M (June 1992))
Behavioural and neuropsychiatric changes become more prevalent. Common manifestations
are wandering, irritability and labile affect, leading to crying, outbursts of unpremeditated
aggression, or resistance to caregiving. Sundowning can also appear. Approximately 30% of
patients develop illusionary misidentifications and other delusional symptoms. Subjects also
lose insight of their disease process and limitations (anosognosia). Urinary incontinence can
develop. These symptoms create stress for relatives and caretakers, which can be reduced by
moving the person from home care to other long-term care facilities.

Advanced
During this last stage of Alzheimer, the patient is completely dependent upon caregivers.
Language is reduced to simple phrases or even single words, eventually leading to complete
loss of speech(Frank EM (September 1994)). Despite the loss of verbal language abilities,
patients can often understand and return emotional signals. Although aggressiveness can still
be present, extreme apathy and exhaustion are much more common results. Patients will
ultimately not be able to perform even the most simple tasks without assistance. Muscle mass
and mobility deteriorate to the point where they are bedridden, and they lose the ability to
feed themselves. Alzheimer is a terminal illness with the cause of death typically being an
external factor such as infection of pressure ulcers or pneumonia, not the disease itself.

Histopathologic image of senile plaques seen in the cerebral

cortex of a person with Alzheimer's disease of presenile onset.
Silver impregnation.

Alzheimer's and the brain

The brain has 100 billion nerve cells (neurons). Each nerve cell connects with many others to
form communication networks. Groups of nerve cells have special jobs. Some are involved in
thinking, learning and remembering. Others help us see, hear and smell.
To do their work, brain cells operate like tiny factories. They receive supplies, generate energy,
construct equipment and get rid of waste. Cells also process and store information and
communicate with other cells. Keeping everything running requires coordination as well as
large amounts of fuel and oxygen.
Scientists believe Alzheimer's disease prevents parts of a cell's factory from running well. They
are not sure where the trouble starts. But just like a real factory, backups and breakdowns in
one system cause problems in other areas. As damage spreads, cells lose their ability to do their
jobs and, eventually die, causing irreversible changes in the brain.

The role of plaques and tangles

Plaques and tangles tend to spread through the cortex as Alzheimer's progresses.
Two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells.

Plaques are deposits of a protein fragment called beta-amyloid that build up in the spaces
between nerve cells.
Tangles are twisted fibers of another protein called tau that build up inside cells.
Though most people develop some plaques and tangles as they age, those with Alzheimer's
tend to develop far more. They also tend to develop them in a predictable pattern, beginning in
areas important for memory before spreading to other regions.
Scientists do not know exactly what role plaques and tangles play in Alzheimer's disease. Most
experts believe they somehow play a critical role in blocking communication among nerve cells
and disrupting processes that cells need to survive.
It's the destruction and death of nerve cells that causes memory failure, personality changes,
5

problems carrying out daily activities and other symptoms of Alzheimer's disease.

Causes of Alzheimer
The causes of Alzheimers disease are not yet fully understood, but scientists are zeroing in on
the answers. This is one of the most exciting and most important areas of research, because
understanding the causes should lead to more targeted treatments and ways to prevent the
disease.
What is clear is that Alzheimers develops as a result of a complex cascade of biological
processes that take place over many years inside the brain. The "amyloid cascade hypothesis" is
the most widely discussed and researched hypothesis about the cause of Alzheimer's disease
( Hardy J, Allsop D (October 1991). The strongest data supporting the amyloid cascade
hypothesis comes from the study of early-onset inherited (genetic) Alzheimer's disease.
Mutations associated with Alzheimer's disease have been found in about half of the patients
with early-onset disease. In all of these patients, the mutation leads to excess production in the
brain of a specific form of a small protein fragment called ABeta (A). Support for this postulate
comes from the location of the gene for the amyloid beta precursor protein (APP) on
chromosome 21, together with the fact that people with trisomy 21 (Down Syndrome) who
have an extra gene copy almost universally exhibit Alzheimer by 40 years of age. Also APOE4,
the major genetic risk factor for Alzheimer, leads to excess amyloid buildup in the brain before
Alzheimer symptoms arise. Thus, A deposition precedes clinical Alzheimer. Further evidence
comes from the finding that transgenic mice that express a mutant form of the human APP
gene develop fibrillar amyloid plaques and Alzheimer's-like brain pathology with spatial learning
deficits (Games D, Adams D, Alessandrini R, et al. (February 1995)).
Several competing hypotheses exist trying to explain the cause of the disease. The oldest, on
which most currently available drug therapies are based, is the cholinergic hypothesis, which
proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The
cholinergic hypothesis has not maintained widespread support, largely because medications
intended to treat acetylcholine deficiency have not been very effective. Other cholinergic
effects have also been proposed, for example, initiation of large-scale aggregation of amyloid,
leading to generalised neuroinflammation (Wenk GL (2003).
An experimental vaccine was found to clear the amyloid plaques in early human trials, but it did
not have any significant effect on dementia. Researchers have been led to suspect non-plaque
A oligomers (aggregates of many monomers) as the primary pathogenic form of A. These
toxic oligomers, also referred to as amyloid-derived diffusible ligands (ADDLs), bind to a surface
receptor on neurons and change the structure of the synapse, thereby disrupting neuronal
communication.[ One receptor for A oligomers may be the prion protein, the same protein
that has been linked to mad cow disease and the related human condition, Creutzfeldt-Jakob
6

disease, thus potentially linking the underlying mechanism of these neurodegenerative

disorders with that of Alzheimer's disease ( Lauren J, Gimbel D, et al. (February 2009).
A 2004 study found that deposition of amyloid plaques does not correlate well with neuron
loss. This observation supports the tau hypothesis, the idea that tau protein abnormalities
initiate the disease cascade. In this model, hyperphosphorylated tau begins to pair with other
threads of tau. Eventually, they form neurofibrillary tangles inside nerve cell bodies (Goedert
M, Spillantini MG, Crowther RA (July 1991).When this occurs, the microtubules disintegrate,
collapsing the neuron's transport system. This may result first in malfunctions in biochemical
communication between neurons and later in the death of the cells. Herpes simplex virus type
1 has also been proposed to play a causative role in people carrying the susceptible versions of
the apoE gene.
Another hypothesis asserts that the disease may be caused by age-related myelin breakdown in
the brain. Demyelination leads to axonal transport disruptions, leading to loss of neurons that
become stale. Iron released during myelin breakdown is hypothesized to cause further damage.
Homeostatic myelin repair processes contribute to the development of proteinaceous deposits
such as amyloid-beta and tau.
In 2009, this theory was updated, suggesting that a close relative of the beta-amyloid protein,
and not necessarily the beta-amyloid itself, may be a major culprit in the disease. The theory
holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the
fast-growth phase of early life may be triggered by aging-related processes in later life to cause
the neuronal withering of Alzheimer's disease. N-APP, a fragment of APP from the peptide's Nterminus, is adjacent to beta-amyloid and is cleaved from APP by one of the same enzymes. NAPP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor
6 (DR6, also known as TNFRSF21). DR6 is highly expressed in the human brain regions most
affected by Alzheimer's, so it is possible that the N-APP/DR6 pathway might be hijacked in the
aging brain to cause damage. In this model, beta-amyloid plays a complementary role, by
depressing synaptic function (Nikolaev, Anatoly; Todd McLaughlin, Dennis O'Leary, Marc
Tessier-Lavigne (19 February 2009)).
Stunning progress has been made recently in unraveling this cascade, and scientists now have a
much clearer picture of what happens to the brain when Alzheimers strikes.

Microscopy image of a neurofibrillary tangle,

conformed by hyperphosphorylated tau protein.
7

Alzheimer Diagnosis
There are many causes for dementia symptoms and this may determine how to treat it. There
are even conditions that can mimic Alzheimers symptoms that are reversible. In addition,
treatments currently available for Alzheimers while limited in their effectiveness and in the
number of people they help have the best chance of working when begun early in the
disease. This should become even more so in the future as new treatments are developed that
will alter the disease process itself, not just treat the symptoms. Early diagnosis also enables
people and families to take immediate action to prepare for worsening symptoms and make
appropriate plans for the future. While there have been significant advances in diagnostic
testing methods for Alzheimers that use brain scans and spinal taps may detect certain
biomarkers of the disease even in its pre-clinical stage, currently, there is no single test that can
diagnose Alzheimers disease with 100% accuracy. Doctors must use a variety of assessments
and laboratory measurements to make what we call a differential diagnosis. (See
Alzheimers Diagnostic Tests below.) They focus on ruling out all other possible causes for the
symptoms. A diagnosis is said to be either possible (not all other causes can be ruled out) or
probable (all other causes have been ruled out). Presently, a definitive diagnosis of Alzheimers
is possible only by examining brain tissue after death .

PET scan of the brain of a person with AD showing a

loss of function in the temporal lobe

Alzheimers Diagnostic Tests

Diagnosing Alzheimers will likely involve several types of evaluations and may take more than
one day. In many cases, specialists may be seen, such as a neurologist, psychologist or
psychiatrist, in addition to your primary care doctor, as they may have the knowledge and
training needed to evaluate symptoms correctly, accurately, and efficiently.
Evaluations commonly performed include:
Medical history: an interview or questionnaire to identify past medical problems, difficulties in
daily activities and any medications (prescriptions, vitamins, supplements and over-the-counter
medications), among other things. It is important to inform the doctor of any family history of
Alzheimers or other related medical issues. The doctor may wish to speak to a close family
member to supplement information, as it is important to get a thorough picture of a persons
medical history (http://www.alzinfo.org)
Physical examination: should include evaluations of hearing and sight, heart and lungs, as well
as temperature, blood pressure and pulse readings. The doctor might also ask about diet and
nutrition and use of alcohol and tobacco products. Standard laboratory tests: might include
blood and urine tests designed to help eliminate other possible conditions. These will measure
things like blood count, thyroid and liver function, and levels of glucose and other blood-based
indicatorsof illness. A depression screening should also be conducted. In some cases, a small
sample of spinal fluid may be collected for testing (http://www.alzinfo.org)
Neuropsychological testing: Doctors use a variety of tools to assess memory, problem-solving,
attention, vision-motor coordination and abstract thinking, such as performing simple
calculations in your head. The goal is to better characterize the types of cognitive symptoms
present, which might provide clues to the underlying cause. The most commonly used test is
called a mini-mental state exam, or MMSE. During the MMSE, the doctor or health professional
will ask a number of questions which test a variety of common mental skills. Some examples of
questions on the MMSE will ask about the date or the persons location and also ask the person
to count backward or copy a drawn figure (http://www.alzinfo.org)
Brain-imaging scan: MRI and CT scans look at the structure of the brain and are used to rule out
brain tumors or blood clots in the brain as the reason for symptoms. PET scans can look at how
certain parts of the brain are working or how active they are. Many scientists are trying to
determine if other brain-imaging techniques might be able to identify telltale signs of early
Alzheimers reliably enough to be used as diagnostic tools (http://www.alzinfo.org)

Prevention
At present, there is no definitive evidence to support that any particular measure is
effective in preventing Alzheimer (Daviglus ML et al. (April 2628, 2010). Global studies of
measures to prevent or delay the onset of Alzheimer have often produced inconsistent results.
However, epidemiological studies have proposed relationships between certain modifiable
factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities
among others, and a population's likelihood of developing Alzheimer. Only further research,
including clinical trials, will reveal whether these factors can help to prevent Alzheimer (Szekely
CA, Breitner JC, Zandi PP (2007)).
Although cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes, and
smoking, are associated with a higher risk of onset and course of Alzheimer, statins, which are
cholesterol lowering drugs, have not been effective in preventing or improving the course of
the disease. The components of a Mediterranean diet, which include fruit and vegetables,
bread, wheat and other cereals, olive oil, fish, and red wine, may all individually or together
reduce the risk and course of Alzheimer's disease. Its beneficial cardiovascular effect has been
proposed as the mechanism of action (Solfrizzi V, Capurso C, D'Introno A, et al. (January 2008).
There is limited evidence that light to moderate use of alcohol, particularly red wine, is
associated with lower risk of Alzheimer.
Reviews on the use of vitamins have not found enough evidence of efficacy to recommend
vitamin C, E, or folic acid with or without vitamin B12, as preventive or treatment agents in
Alzheimer. Additionally vitamin E is associated with important health risks. Trials examining
folic acid (B9) and other B vitamins failed to show any significant association with cognitive
decline. Docosahexaenoic acid, an Omega 3 fatty acid, has not been found to slow
decline(Quinn JF, Raman R, Thomas RG, et al. (November 2010)).
Long-term usage of non-steroidal anti-inflammatory drug (NSAIDs) is associated with a reduced
likelihood of developing Alzheimer. Human postmortem studies, in animal models, or in vitro
investigations also support the notion that NSAIDs can reduce inflammation related to amyloid
plaques. However trials investigating their use as palliative treatment have failed to show
positive results while no prevention trial has been completed (Szekely CA, Town T, Zandi PP
(2007)) . Curcumin from the curry spice turmeric has shown some effectiveness in preventing
brain damage in mouse models due to its anti-inflammatory properties. Hormone replacement
therapy, although previously used, is no longer thought to prevent dementia and in some cases
may even be related to it. There is inconsistent and unconvincing evidence that ginkgo has any
positive effect on cognitive impairment and dementia, and a recent study concludes that it has
no effect in reducing the rate of Alzheimer incidence. A 21-year study found that coffee
drinkers of 35 cups per day at midlife had a 65% reduction in risk of dementia in late-life
(Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M (January 2009). People who
engage in intellectual activities such as reading, playing board games, completing crossword
puzzles, playing musical instruments, or regular social interaction show a reduced risk for
10

Alzheimer's disease. This is compatible with the cognitive reserve theory, which states that
some life experiences result in more efficient neural functioning providing the individual a
cognitive reserve that delays the onset of dementia manifestations. Education delays the onset
of Alzheimer syndrome, but is not related to earlier death after diagnosis. Physical activity is also
associated with a reduced risk of Alzheimer.
Medical marijuana appears to be effective in delaying Alzheimer's Disease. The active ingredient
in marijuana, THC, prevents the formation of deposits in the brain associated with Alzheimer's
disease. THC was found to inhibit acetylcholinesterase more effectively than commercially
marketed drugs. THC was also found to delay amylogenesis (Eubanks LM, Rogers CJ, Beuscher
AE, et al. (November 2006) .Some studies have shown an increased risk of developing
Alzheimer with environmental factors such the intake of metals, particularly aluminium, or
exposure to solvents. The quality of some of these studies has been criticised, and other studies
have concluded that there is no relationship between these environmental factors and the
development of Alzheimer.
While some studies suggest that extremely low frequency electromagnetic fields may increase
the risk for Alzheimer's disease, reviewers found that further epidemiological and laboratory
investigations of this hypothesis are needed. Smoking is a significant Alzheimer risk factor.
Systemic markers of the innate immune system are risk factors for late-onset Alzheimer.

In Alzheimer's disease, changes in tau protein

lead to the disintegration of microtubules in brain
cells.

11

Conclusion

In conclusion, Alzheimers disease is the most common form of dementia, a group of disorders
that impairs mental functioning. People usually misunderstood about this particular disease
where they thought that Alzheimer will only attack the older. But until today, there still no
prove and research that can explain the exact cause of Alzheimer. Alzheimer disease come in
many stages before it getting worst. It is important to someone who has early symptom of
Alzheimer to do the diagnostic test and get treatment . Treatment will help to slow down the
disease but they will find no cure instead of lot of cost needed to take care for someone with
Alzheimer. I believe by producing this folio people will acknowledge Alzheimer disease and all
the misunderstanding about Alzheimer will unfold. Last but not the least, hopefully non-stop
research in finding cure for Alzheimer will meet its end and give patients a new hope for living.

12

Reference
1) http://www.alzinfo.org/aboutalzheimers/?mtc=google&kwd=alzheimers_disease&gclid=CIyO_5r37aYCFYd66wodNUEUGg
2) http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=100
3) Waldemar G, Dubois B, Emre M, et al. (January 2007). "Recommendations for the diagnosis and
management of Alzheimer's disease and other disorders associated with dementia: EFNS
guideline".
4) Mls PK, Marttila RJ, Rinne UK (August 1986). "Survival and cause of death in Alzheimer's
disease and multi-infarct dementia". Acta Neurol Scand 74 (2): 1037.
5) Mls PK, Marttila RJ, Rinne UK (March 1995). "Long-term survival and predictors of mortality in
Alzheimer's disease and multi-infarct dementia". ActaNeurol Scand 91 (3)
6) Bonin-Guillaume S, Zekry D, Giacobini E, Gold G, Michel JP (January 2005). "Impact conomique
de la dmence (English: The economical impact of dementia)" (in French). Presse Med 34 (1)
7) http://www.seniorhomecareinformation.com/dementia/the-relationship-between-alzheimersand-dementia/
8) Bckman L, Jones S, Berger AK, Laukka EJ, Small BJ (Sep 2004). "Multiple cognitive deficits during
the transition to Alzheimer's disease". J Intern Med 256 (3): 195204.
9) Petersen RC (February 2007). "The current status of mild cognitive impairmentwhat do we tell
our patients?". Nat Clin Pract Neurol 3 (2): 601
10) Frstl H, Kurz A (1999). "Clinical features of Alzheimer's disease". European Archives of
Psychiatry and Clinical Neuroscience 249 (6): 288290
11) Carlesimo GA, Oscar-Berman M (June 1992). "Memory deficits in Alzheimer's patients: a
comprehensive review". Neuropsychol Rev 3 (2): 11969.
12) Frank EM (September 1994). "Effect of Alzheimer's disease on communication function". J S C
Med Assoc 90 (9): 41723.
13) http://www.alzinfo.org/07/about-alzheimers/alzheimers-diagnostic-tests
14) Daviglus ML et al. (April 2628, 2010). "NIH State-of-the-Science Conference: Preventing
Alzheimer's Disease and Cognitive Decline". http://consensus.nih.gov/2010/alzstatement.htm.
15) Szekely CA, Breitner JC, Zandi PP (2007). "Prevention of Alzheimer's disease". Int Rev Psychiatry
19 (6): 693706.
16) Solfrizzi V, Capurso C, D'Introno A, et al. (January 2008). "Lifestyle-related factors in
predementia and dementia syndromes". Expert Rev Neurother 8 (1): 13358.
17) Quinn JF, Raman R, Thomas RG, et al. (November 2010). "Docosahexaenoic acid
supplementation and cognitive decline in Alzheimer disease: a randomized trial". JAMA 304
(17): 190311.
18) Szekely CA, Town T, Zandi PP (2007). "NSAIDs for the chemoprevention of Alzheimer's disease".
Subcell Biochem 42: 22948.

13

19) Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M (January 2009). "Midlife coffee
and tea drinking and the risk of late-life dementia: a population-based CAIDE study". J
Alzheimers Dis 16 (1): 8591.
20) Eubanks LM, Rogers CJ, Beuscher AE, et al. (November 2006). "A molecular link between the
active component of marijuana and Alzheimer's disease pathology" (Free full text). Molecular
Pharmaceutics 3 (6): 7737.
21) Hardy J, Allsop D (October 1991). "Amyloid deposition as the central event in the aetiology of
Alzheimer's disease". Trends Pharmacol. Sci. 12 (10): 38388.
22) Games D, Adams D, Alessandrini R, et al. (February 1995). "Alzheimer-type neuropathology in
transgenic mice overexpressing V717F beta-amyloid precursor protein". Nature 373 (6514):
52327.
23) Lauren J, Gimbel D, et al. (February 2009). "Cellular prion protein mediates impairment of
synaptic plasticity by amyloid-beta oligomers
24) Goedert M, Spillantini MG, Crowther RA (July 1991). "Tau proteins and neurofibrillary
degeneration". Brain Pathol 1 (4): 27986.

14

15