This document provides an overview of Alzheimer's disease including its causes, symptoms, stages, diagnosis, and treatment approaches. It discusses how Alzheimer's is characterized by plaques and tangles in the brain made up of beta-amyloid and tau proteins. Current treatment aims to improve cognitive function and behaviors through cholinesterase inhibitors and memantine, though none can stop or reverse the disease. Non-pharmacological interventions like education, communication, and stimulation therapies may provide additional support.

2. Presented by
Kirmal Masih
Medicinal Chemistry
March 25th

3. Alzheimer's disease (AD), also known as
Senile Dementia of the Alzheimer Type
(SDAT) or simply Alzheimer’s is the most
common form of dementia.
This incurable, degenerative, terminal
disease was first described by a German
psychiatrist and neuropathologist Alois
Alzheimer in 1906 and was named after
him.

4. Alzheimer's disease (AD) is a slowly
progressive disease of the brain that is
characterized by impairment of
memory and eventually by
disturbances in reasoning, planning,
language, and perception.
Many scientists believe that
Alzheimer's disease results from an
increase in the production or
accumulation of a specific protein (β-
amyloid protein) in the brain that leads
to nerve cell death.

5. • Generally, it is diagnosed in people over
65 years of age, although the less-
prevalent early onset of Alzheimer’s can
occur much earlier.
• In 2006, there were 26.6 million
sufferers worldwide.
• Alzheimer’s is predicted to affect 1 in 85
people globally by 2050.

7. 1) Early Stage
This is considered as a mild/early stage and
the duration period is 2-4 years.
Frequent recent memory loss, particularly
of recent conversations and events.
Repeated questions, some problems
expressing and understanding language.
Writing and using objects become difficult
and depression and apathy can occur.
Drastic personality changes may accompany
functional decline.
Need reminders for daily activities and
difficulties with sequencing impact driving
early in this stage.

8. 2) Second stage
This is considered as a middle/moderate stage and
the duration is 2-10 years.
Can no longer cover up problems.
Pervasive and persistent memory loss impacts life
across settings.
Rambling speech, unusual reasoning, confusion
about current events, time, and place.
Potential to become lost in familiar settings, sleep
disturbances, and mood or behavioral symptoms
accelerate.
Nearly 80% of patients exhibit emotional and
behavioral problems which are aggravated by
stress and change.
Slowness, rigidity, tremors, and gait problems
impact mobility and coordination.
Need structure, reminders, and assistance with
activities of daily living.

9. 3) Moderate stage
Increased memory loss and confusion.
Problems recognizing family and friends.
Inability to learn new things.
Difficulty carrying out tasks that involve
multiple steps (such as getting dressed).
Problems coping with new situations.
Delusions and paranoia.
Impulsive behavior.
In moderate AD, damage occurs in areas of
the brain that control language, reasoning,
sensory processing, and conscious thought

10. 4) Last stage
This is considered as the severe stage and
the duration is 1-3 years.
Confused about past and present. Loss of
recognition of familiar people and places
Generally incapacitated with severe to total
loss of verbal skills.
Unable to care for self. Falls possible and
immobility likely.
Problems with swallowing, incontinence, and
illness.
Extreme problems with mood, behavioral
problems, hallucinations, and delirium.
Patients need total support and care, and
often die from infections or pneumonia

11. Alzheimer's disease is usually diagnosed
clinically from the patient history,
collateral history from relatives, and
clinical observations, based on the
presence of characteristic neurological
and neuropsychological features and the
absence of alternative conditions.

12. Advanced medical imaging with
computed tomography (CT) or magnetic
resonance imaging (MRI), and with single
photon emission computer tomography
(SPECT) or positron emission
tomography (PET) can be used to help
exclude other cerebral pathology or
subtypes of dementia.
The diagnosis can be confirmed with
very high accuracy post-mortem when
brain material is available and can be
examined histologically.

13. .
PET scan of the brain of a person with AD showing a loss
of function in the temporal lobe.

14. Neuropsychological tests such as the
mini-mental state examination (MMSE)
are widely used to evaluate the cognitive
impairments needed for diagnosis. More
comprehensive test arrays are necessary
for high reliability of results, particularly
in the earliest stages of the disease.
Psychological tests for depression are
employed, since depression can either
be concurrent with AD, an early sign of
cognitive impairment, or even the cause.

15. • When available as a diagnostic tool,
SPECT and PET neuroimaging are used to
confirm a diagnosis of Alzheimer's in
conjunction with evaluations involving
mental status examination. In a person
already having dementia, SPECT appears
to be superior in differentiating
Alzheimer's disease from other possible
causes, compared with the usual
attempts employing mental testing and
medical history analysis.

16.  Scientists don’t yet fully understand
what causes AD, but it is clear that it
develops because of a complex series
of events that take place in the brain
over a long period of time. It is likely
that the causes include genetic,
environmental, and lifestyle factors.


17.  Some drug therapies propose that AD
is caused by reduced synthesis of the
neurotransmitter acetylcholine.
 Other cholinergic effects have also
been proposed, for example, initiation
of large-scale aggregation of amyloid
leading to generalized
neuroinflammation.

18. • Alzheimer's disease is characterized by a
build-up of proteins in the brain. Though
this cannot be measured in a living
person, extensive autopsy studies have
revealed this phenomenon. The build-up
manifests in two ways:
 Plaques– deposits of the protein β-
amyloid that accumulate in the spaces
between nerve cells
 Tangles – deposits of the protein tau
that accumulate inside of nerve cells

19. Microscopy image of a neurofibrillary tangle, conformed by
hyperphosphorylated tau protein.

20.  Alzheimer's disease is characterised by loss of neurons and
synapses in the cerebral cortex and certain subcortical
regions. This loss results in gross atrophy of the affected
regions, including degeneration in the temporal lobe and
parietal lobe, and parts of the frontal cortex and cingulate
gyrus.

21. Both amyloid plaques and neurofibrillary
tangles are clearly visible by microscopy
in brains of those afflicted by AD.
Plaques are dense, mostly insoluble
deposits of amyloid – β peptides and
cellular material outside and around
neurons.

22. Tangles (neurofibrillary tangles) are
aggregates of the microtubule-associated
protein tau which has become
hyperphosphorylated and accumulate
inside the cells themselves.
Although many older individuals develop
some plaques and tangles as a
consequence of ageing, the brains of AD
patients have a greater number of them
in specific brain regions such as the
temporal lobe.

23. Alzheimer's disease has been identified as
a protein misfolding disease (proteopathy),
caused by accumulation of abnormally
folded A-β and tau proteins in the brain.
Plaques are made up of small peptides, 39–
43 amino acids in length, called 𝜷-amyloid
(also written as A-β or Aβ).
β-amyloid is a fragment from a larger
protein called amyloid precursor protein
(APP), a transmembrane protein that
penetrates through the neuron's
membrane.

24. • APP is critical to neuron growth, survival
and post-injury repair. In Alzheimer's
disease, an unknown process causes
APP to be divided into smaller fragments
by enzymes through proteolysis.
• One of these fragments gives rise to
fibrils of β-amyloid, which form clumps
that deposit outside neurons in dense
formations known as senile plaques

25. AD is also considered a tauopathy due to
abnormal aggregation of the tau protein.
Every neuron has a cytoskeleton, an
internal support structure partly made
up of structures called microtubules.
These microtubules act like tracks,
guiding nutrients and molecules from
the body of the cell to the ends of the
axon and back. A protein called tau
stabilizes the microtubules when
phosphorylated, and is therefore called a
microtubule-associated protein.

26. • In AD, tau undergoes chemical changes,
becoming hyperphosphorylated; it then
begins to pair with other threads,
creating neurofibrillary tangles and
disintegrating the neuron's transport
system.

27.  Exactly how disturbances of production and aggregation of
the β amyloid peptide gives rise to the pathology of AD is
not known.
 The amyloid hypothesis traditionally points to the
accumulation of β- amyloid peptides as the central event
triggering neuron degeneration.
 Accumulation of aggregated amyloid fibrils, which are
believed to be the toxic form of the protein responsible for
disrupting the cell's calcium ion homeostasis, induces
programmed cell death (apoptosis).
 It is also known that A β selectively builds up in the
mitochondria in the cells of Alzheimer's-affected brains,
and it also inhibits certain enzyme functions and the
utilization of glucose by neurons.

28.  Various inflammatory processes and cytokines may also
have a role in the pathology of Alzheimer's disease.
Inflammation is a general marker of tissue damage in any
disease, and may be either secondary to tissue damage in
AD or a marker of an immunological response
 Alterations in the distribution of different neurotrophic
factors and in the expression of their receptors such as the
brain derived neurotrophic factor (BDNF) have been
described in AD

30. • Apolipoprotein E (APOE) found on chromosome 19
appears to be a predisposing genetic risk factor for the
late onset of AD – the most typical AD.
• APOE helps carry cholesterol in the bloodstream.
• APOE comes in several different forms, or alleles.
• Three forms—APOE ε2, APOE ε3, and APOE ε4—occur
most frequently.

31. Treatment for
Alzheimer’s Disease

32. Treatment Goal
• Currently there is no current therapy to treat
Alzheimer’s disease. Current therapy is
aimed at prolonging the patient’s cognitive
function and secondary goals include
symptomatically treating psychiatric and
behavioral abnormalities
• Current therapy has not been shown to
prolong life, cure AD, halt or reverse the
pathophysiological degradation of the
disease

33. Natural Disease
Progression
• Alzheimer’s Disease Assessment Scale-
Cognition (ADAS-cog) scores worsen by an
average of 4 points over 6 months and 7
points over 1 year
• 4 points represents a clinically significant
change
• In clinical practice a Mini Mental Status
Examination (MMSE) is used due to time
requirements of the ADAS-cog
– An untreated patient has an average decline of
2-4 points per year

35. Brain Comparison

36. Ideal Treatment
• Improving symptomatic decline by
improving cognitive function, daily
activities, and behavior
– Current therapy
• Arrests the neurodegenerative molecular
process
– Research needed

37. Treatment Algorithm
• Cholinesterase Inhibitor
• NMDA Antagonist
• Cholinesterase Inhibitor + NMDA
antagonist
• Titrate doses to recommended
maintenance therapy as tolerated
• Symptomatic approach is used to treat
behavioral symptoms

38. Cholinesterase Inhibitors

39. Cholinesterase Inhibitors
• Donepezil (Aricept)- used in mild to severe
disease
• Galantamine (Razadyne)- used in mild to
moderate disease
• Rivastigmine (Exelon)- used in mild to
moderate disease
• Combination of more than one cholinesterase
inhibitor is not recommended
• Choice of therapy often selected based on ease
of use for the patient, cost and safety issues
• Switching can occur if patients are not
tolerating the initial treatment or a treatment
failure
– If MMSE decline is greater than 2-4 points in
one year changing therapy is warranted

40. Cholinesterase Inhibitors
• Donepezil, Rivastigmine and Galantamine
• All show similar efficacy and adverse event
profiles with gastrointestinal complaints
being the most common symptom
• Dose titration over several months can help
tolerability of urinary incontinence,
dizziness, headache, syncope, bradycardia,
muscle weakness, salivation and sweating
• Abrupt discontinuation is discouraged due
to worsening of cognition or behavioral
problems in some medications
• Avoid use with anti-cholinergic medications
which is especially important when trying to
treat behavioral abnormalities.

41. Cholinesterase Inhibitors
Mechanism of Action
• Donepezil- specifically and reversibly inhibits
acetylcholinesterase
• Rivastigmine- inhibits both
butylcholinesterase and acetylcholinesterase
• Galantamine- selective, competitive,
reversible acetylcholinesterasse inhibitor
and also enhances the action of
acetylcholine on nicotinic receptors
• Clinical relevance is unknown

42. NMDA Antagonist

43. N-methyl-D Aspartate
(NMDA) Antagonist
• Memantine- used in moderate to severe
disease
– Not recommended in early stages of the
disease
– Only NMDA-antagonist available
– Blocks glutamatergic neurotransmission by
antagonizing NMDA receptors
• Glutamate an excitatory
neurotransmitter in the brain
– Most common side effects include
constipation, confusion, dizziness,
headache, hallucinations, coughing, and
hypertension

44. Dosage Forms
• Galantamine (Razadyne)- capsule, tablet, and solution
• Donepezil (Aricept)- tablet (oral disintegrating tablet)
• Rivastigmine (Exelon)- capsule, patch, and solution
• Memantine (Namenda)- tablet and solution

45. Treatment for Non-cognitive
Symptoms
• Psychosis
• Disruptive behavior
• Depression
• Environmental interventions then pharmacological
therapy
• Limited clinical data; therefore, treatment is empirical
• General guidelines: reduced doses, close monitoring
closely, slow dose titrations, and careful documentation
• Cholinesterase inhibitors and memantine should be
considered as first line therapy in patients with
behavior abnormalities in the beginning stages of AD

46. Antipsychotics
• Haloperidol
• Olanzapine
• Quetiapine
• Risperidone
• Ziprasidone
• Treatment of psychosis: hallucinations,
delusions, suspicions
• Treatment of disruptive behaviors: Agitation
and aggression
• Not FDA approved

47. Concern with
Antipsychotics
• Worsening cognitive impairment,
oversedation, falls, tardive dyskinesia,
neuroleptic malignant syndrome,
hyperlipidemia, weight gain, diabetes
mellitus, cerebrovascular accidents
• A dose reduction or discontinuation should
be considered periodically in patients
• Physical restraints should be limited to
patients who pose imminent harm to
themselves or others.

48. Antidepressants
• Citalopram
• Escitiolopram
• Fluoxetine
• Paroxetine
• Sertraline
• Venlafaxine
• Trazadone
• Treatment of depression: poor appetite, insomnia,
hopelessness, anhedonia, withdrawal, suicidal
thoughts, agitation, or anxiety
• As many as 50% of AD patients suffer from depression

49. Anticonvulsants
• Carbamazepine
• Valproic Acid
• Treatment of agitation or aggression

50. Standard of treatment
• None exists
• Duration of treatment ranges from clinician
to clinician. May be months to years
• No clear standard of care for dosing from
clinical trials
• No clear standard of when to discontinue
therapy in very severe stages of AD
– Many clinicians do discontinue therapy when the
patient becomes bed ridden

51. Key Non-pharmacological Methods
•Education
•Preparation
•Communication

52. • Educating patient and family at the time of
diagnosis
– Discussion of the course of illness
– Expectations from treatment
– Legal and financial planning including a durable
power of attorney
– Quality of life issues
– Re-enforcing the importance of communication
between the patient and family members
– Decreasing environmental triggers and personal
discomfort

53. Non-Pharmacological
Interventions
• Physical well-being
• Increased overall well being
• Stimulation oriented treatments: recreational activity, art
therapy, music therapy, pet therapy and aromatherapy
may be useful, but lack of sufficient evidence to validate
effectiveness but used in clinical practice

54. Caregivers
• Find time to rest, relax and tend to personal affairs
because stress will impact the health and quality of life of
both the patient and the caregiver
• Help patients to discover a structured level of autonomy
using reminders and explanations
• Be aware of signs and symptoms of decline
• Knowing when to institutionalize a patient

55. Interventions
• Patients should be assessed every 3-6 months
• Patients may need to stop driving even at mild levels of
treatment
• Sleep disturbances common in people with dementia,
proper sleep hygiene should be implemented before
beginning pharmacological therapy

56. Behavioral Management
• Sleep disturbances
• Wandering
• Urinary Incontinence
• Agitation
• Aggression
• May be useful to try this before beginning drug therapy

57. Epidemiological
Correlations
• Brain Vascular Health
• Lipid lowering agents
• Non inflammatory agents
• Vitamin B 6, B12 and B12
deficiency
• Hyerhomocysteinemia

58. Brain Vascular Health
• New studies have evidence brain vascular
disease plays an important role in the
progression of dementia
• Brain vascular disease may accelerate
deposition of β amyloid plaques and increase
amyloid toxicity to neurons and the neural
synapses
• Brain vascular health includes managing blood
pressure, glucose, cholesterol and
homocysteine.
– Elevated homocysteine levels correlate with
decreased performance on cognitive tests
• Importance of stating physically, mentally, and
socially active

59. Folate, Vitamin B1, Vitamin
B6
• Defects in these vitamins are associated
with neurological and psychological
dysfunction
• In elderly patients there is increased
concern of satiety, atrophic gastritis,
and decreased function of the olfactory
functions
• Increased homocysteine has a direct
correlation with a deficiency and these
vitamins

60. Estrogen Therapy
• Epidemiological studies post menopausal women who
took estrogen replacement therapy had a lower incidence
of AD
• Studies did not show an improvement in behavioral or
functional outcomes when estrogen used to treat
cognitive decline
• Estrogen has a risk of stroke and other cardiovascular
events

61. Anti-inflammatory Agents
• Epidemiological studies suggest patients on anti-
inflammatory agents have a lower incidedence of AD
• Treatment less than 2 years proved beneficial in some
patients
• Clinical studies does not show evidence of cognitive
benefit and tolerability was an issue

62. Lipid Lowering Agents
• Epidemiological studies and AD show a
correlation between higher midlife total
cholesterol rates and AD
• Correlation between people on lipid
lowering therapy and lower incidences' of
AD
– Pravastatin and lovastatin but not simvastatin
were associated with a lower incidence of AD
– More trials are needed to address the impact of
cognitive benefit, the duration of treatment, class
effect, and optimal dosing for its role in AD
• Role of therapy should remain for people
with indications for their use

63. Therapies in the Pipeline
• Vitamin E
• Atomexetine
• IGIV 10%
• Thiazolidinediones (anti-
inflammatory effects)
• Over 900 studies
occurring now phase 1-4
and
• Ginkgo Biloba
• Huperzine A
• Semagacestat (LY450139)
• Coenzyme Q10
• Acupuncture
• Over 100 studies phase 3

64. Vitamin E
• Antioxidant- may be useful because of the
accumulation of free radicals associated with
AD
• Favorable side effect profile and low cost
• Impaired hemostasis, fatigue, nausea,
diarrhea, abdominal pain, and thinning of
the blood
• Increased mortality in older patients
• Doses above 400 international units per day
should be avoided in patients with AD
• May be beneficial in combination with
Selegeline: Phase III study-PREADVISE-
examining anti-oxidant effects of Selegeline

65. Ginkgo Biloba
• Increased blood flow, decreased viscosity of
the blood, antagonizing platelet activating
factor receptors, increased tolerance to
anoxia, inhibiting monoamine oxidase, anti-
infective properties, preventing damage of
membranes caused by free radicals
• If used for dementia should be used as soon
as deterioration of cognitive functioning
occurs
• Side effects are typically mild and rare
• Herbal products are typically poorly
standardized

66. Huperzine A
• An alkyloid isolated from the Chinese club
moss, Huperzia serrata
• Reversibly inhibits acetylcholinesterase and
is administered orally in doses 50-200 mcg 2-
4 times daily
• May be more promising for symptomatic
treatment of Alzheimer’s disease
• Promising product from clinical studies, but
lack of product purity
• Concurrent use with other available
cholinesterase inhibitors should be avoided

67. Semagacestat
(LY450139)
• Inhibiting the enzyme gamma-secretase
lowers the production of beta amyloid.
Semagacestat (LY450139) a functional
gamma-secretase inhibitor lowers the beta
amyloid in the blood and spinal fluid in
humans.
• Effect of LY450139 a gamma-secretase
inhibitor on the progression of Alzheimer’s
disease as compared with Placebo- Currently
Phase III
• 60 mg orally titrated up to 140 mg

68. Immune Globulin Intravenous
(Human), 10% (IGIV, 10%)
• A Randomized, Double-Blind, Placebo-
Controlled, Two Dose-Arm, Parallel Study of
the Safety and Effectiveness of Immune
Globulin Intravenous (Human), 10% (IGIV,
10%) for the Treatment of Mild to Moderate
Alzheimer's Disease – Phase III trial
• The purpose of this study is to determine
whether IGIV, 10% treatment, administered
at two different doses results in a
significantly slower rate of decline of
dementia symptoms in subjects with mild to
moderate (AD).
• Approved in 2005 for primary
immunodeficiency

69. Coenzyme Q10
• A natural antioxidant in the body
• Role of therapy currently being explored, but limited
clinical trials in humans for AD

70. Helpful links
• www.aoa.gov
• www.nia.nih/gov/alzheimers
• www.alzforum.org
• www.aarp.gov
• www.thefamilycaregiver.org
• www.ec-online.net

71. Economic Impact
• US health care cost is greater than $100
billion
• Annual cost for caring for an individual with
advanced AD is approximately $50,000
• According to CDC, there is 231,900 patients
in nursing homes with AD which accounts
for 15.5% of the nursing home population
• 4th leading cause of death in adults

72. Resources
• http://www.gammagardliquid.com/about-
gammagard-liquid/dosage-
administration.html
• http://www.nlm.nih.gov/medlineplus/drugin
fo/natural/1003.html
• cdc.gov
• www.ncbi.nlm.nih.gov
• www.novartis.com
• www.alz.org
• www.clinicaltrials.gov

73. Resources
• National Guideline Clearinghouse (NGC).
Guideline synthesis: Management of Alzheimer's
disease and related dementias. In: National
Guideline Clearinghouse (NGC). Rockville (MD):
2006 Nov (revised 2010 Sep). [cited 2011 June
13]. Available: http://www.guideline.gov.
• Dipiro J,Talbert R, Yee G., Matzke G, Wells B,
Posey L. Pharmacotherapy: A Pathophysiologic
Approach. 7th. New York: McGraw-Hill, 2008.
1051-1066
• B Vitamins, Homocysteine, and Neurocognitive
Function in the Elderly. American Journal of
Clinical Nutrition. February 2000;71(2):614s-
620s. Accessed June 15, 2011.

74. treatment
• Current therapy is aimed at prolonging the patient’s
cognitive function and secondary goals include
symptomatically treating psychiatric and behavioral
abnormalities
• Current therapy has not been shown to prolong life, cure
AD, halt or reverse the pathophysiological degradation of
the disease

75.  Aricept Used to delay or slow the
symptoms of AD
Donepezil • Loses its effect over time
• Used for mild, moderate and severe
AD
• Does not prevent or cure AD
 Celexa
Citalopram Used to reduce depression and anxiety
• May take 4 to 6 weeks to work
• Sometimes used to help people get to sleep
 Used to reducedepression and anxiety
• May take 4 to 6 weeks to work
• Sometimes used to help people get to sleep
 Depakote® (DEP-uh-cote)

76.  Depakote Used to treat severe aggression
Sodium Valproate • Also used to treat depression
and anxiety
 Exelon Used to delay or slow the
symptoms of AD
Rivastigmine • Loses its effect over time
• Used for mild to moderate AD
• Can get in pill form or as a skin
patch
• Does not prevent or cure AD

77.  Namenda Used to delay or slow the
symptoms of AD
Memantine • Loses its effect over time
• Used for moderate to severe AD
• Sometimes given with Aricept®,
Exelon®
• Does not prevent or cure AD
 Razadyne Used to prevent or slow the
symptoms of AD
Galantamine • Loses its effect over time
• Used for mild to moderate AD
• Can get in pill form or as a skin
patch
• Does not prevent or cure AD
 Zoloft Used to reduce depression and
anxiety
Sertraline • May take 4 to 6 weeks to work
• Sometimes used to help people
get to sleep
 Trileptal Used to treat severe aggression
Oxcarbazepine • Also used to treat depression
and anxiety

78. 
Tegretol Used to treat
severe aggression
Carbamazepine • Also used to
treat depression and anxiety
 Remeron Used to reduce
depression and anxiety
Mirtazepine • May take 4 to
6 weeks to work
• Sometimes used
to help people get to sleep

79.  Although there is currently no way to cure Alzheimer's
disease or stop its progression, researchers are making
encouraging advances in Alzheimer's treatment, including
medications and non-drug approaches to improve
symptom management.
 Mild/Moderate AD:
Cholinesterase inhibitors increase the levels of
acetylcholine in the brain, which plays a key role in
memory and learning. This kind of drug postpones the
worsening of symptoms for 6 to 11 months in about half of
the people who take it. Cholinesterase inhibitors most
commonly prescribed for mild to moderate Alzheimer's
disease include Aricept (donezepil HCL), Exelon
(rivastigmine), and Razadyne (galantamine).

80. • Moderate/Severe AD:
Namenda (memantine) regulates glutamate in the brain,
which plays a key role in processing information. This drug
is used to treat moderate to severe Alzheimer's disease
and may delay the worsening of symptoms in some
people. It may allow patients to maintain certain daily
functions a little longer than they would without the
medication.

81. Razadyne
• Razadyne (galantamine HBr) is FDA-approved for mild and
moderate stages of the disease.
• Razadyne is a cholinesterase inhibitor that prevents the
breakdown of acetylcholine in the brain. Acetylcholine
plays a key role in memory and learning; higher levels in
the brain help nerve cells communicate more efficiently.
Razadyne also stimulates nicotinic receptors to release
more acetylcholine in the brain.

82.  Razadyne delays the worsening of Alzheimer's symptoms
for 6 to 11 months in about half of the people who take it.
 Razadyne is available in tablet and capsule form, and is
commonly started at 4 mg twice a day. If it's well tolerated
after 4 weeks, the dosage may be increased to 8 mg twice
a day.
 Razadyne also comes in an extended release, once-a-day
tablet.
 Razadyne is available in generic form (galantamine HBr).

83. Exelon (Rivastigmine)
Exelon is FDA approved for mild and moderate stages of
the disease; it is also approved for the treatment of mild
to moderate dementia due to Parkinson's disease.
Exelon is available as a capsule, liquid, and patch.

84. • Exelon is a cholinesterase inhibitor that
prevents the breakdown of acetylcholine
and butyrylcholine in the brain by
blocking the activity of two different
enzymes. Acetylcholine and
butyrylcholine play a key role in memory
and learning.
• When given orally, bioavailability is about
40% in the 3 mg dose. The compound can
cross the blood-brain barrier.

85. Aricept (Donepizel)
• One of the most widely used drugs to treat the symptoms
of Alzheimer's disease. Aricept is FDA-approved for mild,
moderate, and severe stages of the disease.

86. • Aricept is available in tablet form or an orally
disintegrating tablet form, and is commonly started at 5
mg a day.
• Can cross the blood-brain barrier.

87. Namenda (Memantine)
• Namenda is an N-methyl D-aspartate (NMDA) antagonist
that regulates the activity of glutamate in the brain.
Glutamate plays a key role in memory and learning, but
excess glutamate can lead to the disruption of nerve cell
communication or nerve cell death.

88. • Studies involving Namenda have shown that the drug can
slow the rate of decline in thinking and the ability to
perform daily activities in individuals who have moderate
to severe Alzheimer's disease
• A dysfunction of glutamatergic neurotransmission is
thought to be involved in the etiology of AD.
• Namenda is available in generic form (memantine HCL).

89.  A molecule designed by a Purdue University researcher to
stop the debilitating symptoms of Alzheimer's disease has
been shown in its first phase of clinical trials to be safe and
to reduce biomarkers for the disease.
 The molecule, called a β-secretase inhibitor, prevents the
first step in a chain of events that leads to amyloid plaque
formation in the brain. This plaque formation creates
fibrous clumps of toxic proteins that are believed to cause
the devastating symptoms of Alzheimer's.

90. • Researchers at Mount Sinai School of Medicine have
found that a compound called NIC5-15, might be a safe
and effective treatment to stabilize cognitive performance
in patients with mild to moderate Alzheimer's disease.
The two investigators, Giulio Maria Pasinetti, M.D., Ph.D. ,
and Hillel Grossman, M.D., presented Phase IIA
preliminary clinical findings at the Alzheimer's Association
2009 International Conference on Alzheimer's Disease
(ICAD) in Vienna on July 1

91. • NIC5-15's potential to preserve cognitive performance will
be further evaluated in a Phase IIB clinical trial. Early
evidence suggests that NIC5-15 is a safe and tolerable
natural compound that may reduce the progression of
Alzheimer's disease-related dementia by preventing the
formation of β-amyloid plaque, a waxy substance that
accumulates between brain cells and impacts cognitive
function.

92.  http://www.sciencedaily.com/releases/2008/01/08012310
1629.htm
 http://www.sciencedaily.com/releases/2009/07/09071214
5228.htm
 http://www.nia.nih.gov/Alzheimers/Publications/CaringAD
/other/medicines.htm
 http://en.wikipedia.org/wiki/Rivastigmine
 http://en.wikipedia.org/wiki/Galantamine
 http://en.wikipedia.org/wiki/Donepezil
 http://en.wikipedia.org/wiki/Mementine
 Newsweek; 06/15/98, Vol. 131 Issue 24, p52, 2p,

93. • Harvard Mental Health Letter; Apr2010, Vol. 26 Issue 10,
p7-7, 1/2p
• Asian Journal of Animal & Veterinary Advances; 2010, Vol.
5 Issue 1, p13-23, 11p, 1 Chart, 2 Graphs
• Medical Device Daily; 2/16/2010, Vol. 14 Issue 30, p1-6,
2p

94. • An Introduction to Medicinal Chemistry by Graham L.
Patrick, pp. 589-590.
• Abbott, Alison. Neuroscience: The plaque plan. Nature
(London, United Kingdom) (2008), 456(7219), 161-164.
• Bolognesi, Maria L.; Matera, Riccardo; Minarini, Anna;
Rosini, Michela; Melchiorre, Carlo. Alzheimer's disease:
new approaches to drug discovery. Current Opinion in
Chemical Biology (2009), 13(3), 303-308.

95. • What are the three stages of Alzheimer’s Disease?
• What are some of the diagnostic tools of diagnosing Alzheimer’s
Disease?
• What drugs are used to treat mild/moderate Alzheimer’s
Disease?
• Which drug is most commonly used to treat Alzheimer’s
Disease?
• Have current pharmaceutical agents been successful in slowing
the progress of Alzheimer’s Disease?
• Why is it important to develop ‘biomarkers’ for Alzheimer’s
Disease?