This is created to understand about Alzheimer's disease and precautions one has to follow

1. Alzheimer's Disease
By
Prof. K.YELLAMMA
Professor (Rtd)
Division of Neurobiology, Department Zoology,
Sri Venkateswara University,
Tirupati -517502, INDIA.

2. • Neurological disorders such as Huntington’s Disease,
Parkinson’s Disease, Alzheimer’s Disease, Epilepsy,
Schizophrenia, Multiple Sclerosis, Cerebral Plasy ,
Neuropathy and spinocerebellar ataxias are quite diverse,
chronic, challenging to treat and often disabling.
• They can be caused by many different factors including
inherited genetic abnormalities, problems in the immune
system, injury to the brain or diabetes.
• Usually these diseases are caused by a genetic mutation in a
specific neuronal protein that leads to a loss of function of that
protein or slow accumulation of insoluble material in or
around the cell.
• Alzheimer” Disease is one such disease which is caused by
misfolding of a protein.
Introduction

3. Magnitude of Alzheimer’s Disease

4. • Alzheimer's Disease is one of the major
neurological disorders which occurs mainly in the
older people.
• This disease is also called as senile dementia
Alzheimer’s type (SDAT).
• As the age advances, the risk of developing this
disease increases.
• AD is to be more common in women.
• It is neither infectious nor contagious.
• It is the fourth most common cause of
death in the world after heart disease.

5. • AD occurs when neurons in the brain die or
break their connections with other neurons.
• The patients with AD lose their cognitive
abilities, i.e., their abilities
- to read, write, calculate and
- use language appropriately.
- they cannot feed or dress themselves,
- they don’t recognize their own families,
- they get lost when only a short distance
from home and
- ultimately do not even know their own
names.

6. EPIDEMIOLOGY
Incidence rates after age 65
Age Newly affected persons per
thousand per year
65-69 3
70-74 6
75-79 9
80-84 23
85-89 40
90- 69

8. • 1 in 8 persons at the age > 65
• Lifetime risk: Women > men
• One among top 10 leading causes of death for all ages.
• 6th leading cause of death in U.S. 2009, 7th leading cause of
death in world
• Scientists estimate that around 5.3 million people now have AD.
• In people over 65 years, the percentage of people with AD
doubles for every 5 years.
• By 2050, 13.2 million older Americans are expected to have AD
if the current numbers hold and no preventive treatments become
available.
• The national cost of caring for people with AD is about $100
billion every year.
Statistics of Alzheimer’s Disease

9. Postal stamp of US Govt WHO-AD Associations(71)
Alzheimer’s Day LOGO Alzheimer’s Day logo of UK Govt
25th September has been declared as World Alzheimer’s Day in 1994
71 Alzheimer’s Disease Associations around the world are Established in
conjunction with WHO. In view of this growing number of risks with AD, different
countries released stamps to create awareness among the people

10. ALZHEIMER’S DISEASE MYTHS
• Actually, Memory loss is a natural part of aging.
• Alzheimer’s Disease is not fatal
• Only older people get Alzheimer’s Disease
• Aluminium vessels can cause Alzheimer’s Disease
• Flu increase the risk of developing Alzheimer’s Disease
• Silver dental fillings increase the risk of developing Alzheimer’s
Disease
• Treatments are available to stop the progression of Alzheimer’s
Disease

11. HISTORY
• Dr. Alois Alzheimer (1864-1915),
was a German psychiatrist and
pathologist who first described
the disease.
• In 1906, he carried out an autopsy
on the brain of a 56 year old
woman, Auguste, D. of Frankfurt.
Who is suffering from “mental
illness”. This was the first case.
•Symptoms :
Memory loss, language problems,
and unpredictable behavior.
The neurons in the neocortex,
hippocampus, amygdala, and the
basal forebrain cholinergic system
are the most affected brain regions

12. • Auguste had died after several years of progressive mental
disorientation characterized by confusion and memory loss.
• In her cerebral cortex, the part of brain responsible for reasoning and
memory, he found strange bundles of nerves, which he termed
Neurofibrillary Tangles and accumulations of cellular debris around
the nerves, which he termed Senile Plaques.

13. CAUSES FOR AD
• Following are the different causes of AD:
• AGE
• FAMILY HISTORY
• HERIDITARY FACTORS
• DOWN’S SYNDROME
• WHIPLASH OR HEAD INJURIES
• ALUMINIUM
• POOR EDUCATION
• CONSUMPTION OF HIGH FAT, HIGH
CALORIFIC DIET
• PREVIOUS SERIOUS TRAUMA TO THE
HEAD
• SMOKING
• CARDIOVASCULAR DISORDERS
• HYPER CHOLESTEROLEMIA
• DIABETES MELLITUS
• MENOPAUSE AND
• SEDENTARY LIFE STYLE

14. TYPES OF AD
Basically there are 3 types of Alzheimer’s Disease:
1. Early - onset Alzheimer’s Disease
2. Late - onset Alzheimer’s Disease
3. Familial - Alzheimer’s Disease

15. Early - onset Alzheimer’s Disease
• Rare form of Alzheimer's disease
• Occurred before the age of 65
• Less than 10% cases have this type
• Adults with Down’s syndrome are often in their mid to late 40s or
early 50s when symptoms appeared
• It appears to be linked with a genetic defect on chromosome 14.

16. Late on set Alzheimer’s disease
• Most common form of Alzheimer’s disease
• Occurred after the age of 65
• About 90% of cases have this type
• Doubles every five years after the age of 65
• Strikes almost half of all the people over the age of 85, may or may
not be hereditary.
• Also known as “sporadic Alzheimer’s Disease”.

17. Familial Alzheimer’s Disease
• Very rare type of AD
• Attacks younger people mainly
in their 40’s and 50’s, rarely in
their 30’s.
• Affects only less than 1%.
• This type of AD runs in
families. These families
usually inherit a genetic fault
on specific chromosomes viz.
21,14 or 1.
• 50% offsprings of these AD
sufferers will carry the genetic
fault.

18. 8 years average. Range – 2-20 years

19. CHARACTERISTICS OF AD
• Aphasia - Loss or impairment of language caused by brain
dysfunction
• Aphraxia - Inability to execute learned movements on
command
• Agnosia - Inability to recognize
• Acalculia - Inability to perform arithmetical calculations
• Agraphia - Inability to write
• Alexia - Inability to read

20. The Disease Course
• The Disease is divided into four stages with progressive patterns of
cognitive and functional impairments.
• PRE-DEMENTIA: The symptoms are often mistaken as related to aging
or stress.The most noticeable deficit is memory loss, which I evident
with difficulty in remembering recently learned facts and inability to
acquire new information.
• EARLY- DEMENTIA: Characterised by difficulties with language,
executive functions, perceptions or execution of moments etc. As the
disease progress, people with Alzheimer’s Disease can not continue to
perform many tasks independently, particularly the most cognitively
demanding activities.
• MODERATE- DEMENTA: Characterised by the enability to perform
most common activities of daily living, speech difficulties (paraphasias.),
progressive loss of reading and writing skills, less coordinated motor
sequence activities etc.
• ADVANCED- DEMENTIA: During this last stage , the patient is
completely dependent upon caregivers. Language is reduced to simple
phrases or even single words, eventually leading to complete loss of
speech.

21. Amnesia Stage
Early clinical symptoms
- Short - term memory deficits (repeatedly asking the
same question every five minutes, forgetting a telephone
number during the act of dialing)
- Dyscalculia
(Impairment in basic visual
- motor integrative ability)
- Constructional Apraxia
(Inability to excecute learned
movements on command)
- Loss of spontaneity
This stage may last for 2-4 years before progressing to
confusional stage.

22. Confusional stage
• Dysphasia (Impairment in speaking and writing)
• Agnosia (Inability to recognize)
• Disorientation in time and place
• Severe mental confusion
• Personality changes
• Behavioural disturbances such as,
- extreme aggressiveness or wandering
- psychotic episodes etc.,

23. Dementia stage
• Patient is withdrawn and unresponsive
• Bedridden
• Incontinent and
• Unable to care for himself
• Maintained in a nursing facility
- Ultimately, the patient dies from secondary illness such as
Bronchopneumonia
Urinary infection or
Aspiration.

24. Genetic Loci of Alzheimer's Disease:
• Chromosome 21 (APP) : Early Onset FAD
• Chromosome 1 (PS2) : Volga German FAD
• Chromosome 14 (PS1) : Early Onset FAD
• Chromosome 19: Apolipoprotein (E risk factor)
• PS1 and PS2 (Presenilin 1 and 2)
• 5% of Alzheimer’s caused by mutation in these two or APP Can be inherited
in dominant fashion Leads to early onset (<65)
Genetics of Alzheimer's Disease

25. GENETICS
• Genetically. It is a heterogenous disorder
• More than one gene mutation can cause Alzheimer’s
Disease
• Mutations occurred in one of the following 3 genes
- Amyloid Precursor Protein (APP)
- Presenilin I
- Presenilin II
• Beta Amyloid is a fragment from a larger protein
called APP.
• Accumulation of Beta Amyloid, by over production
(or) failure to break down APP leads to Amyloid
deposition resulting in amyloid plaques,
neurofibrillary tangles and cell death.
• Apolipoprotein E (Apo E) gene can cause late onset
AD
• ApoE2, ApoE3 and ApoE4 are the 3 types of alleles for
Apolipoprotein E
E2 ---------> Protective
E3 ---------> most common form of gene
E4 ---------> confers an increased risk of AD

26. Genetic and Environmental Factors in Alzheimer’s Disease
Genes
-amyloid precursor
Presenilin – 1
Presenilin – 2
APOE-E 4
Alzheimer’s
Disease
Environment
Head trauma
Vascular factors
HSV-1
Total cholesterol
Hypertension
Protective
N.S.A.I.D.’s
Prednisone
Vitamin-C
Estrogen

27. Cytogenetic band: 21q21.2 19q13.2 17q21.1 12p13.3-p12.3 8p21-p12
Location : 26,174,732 bp to 50,100,878 bp to 41,327,623 bp to 27,510,367 bp to
26,465,003 bp 50,104,489 bp 41,458,611 bp 27,524,855 bp
Orientation Minus strand Plus strand Plus strand Minus strand
APP APOE Tau Alpha-2-
macroglobulin
Clusterin

28. Presence of similar genes in other mammals

30. Presenilin 1 Presenilin-2 Nicastrin APH-1A
1p36.13-q31.3
150,237,799 bp to
150,241,980 bp
minus strand
1q22-q23
160,313,054 bp to
160,328,742
plus strand
14q24.3
72,672,931 bp to
72,756,862 bp
Plus strand
1q31-q42
227,058,264 bp to
227,083,806
plus strand

37. Hypothesis to explain the Biochemical Basis of AD
• Cholinergic hypothesis:
The oldest, on which most currently available drug therapies are based is the
cholinergic hypothesis, which highlights that Alzheimer’s Disease is cuased by
reduced synthesis of the neurotransmitter, Acetylcholine. The most prominent
changes occur is the loss of cholinergic neurons in the basal forebrain that
project to the hippocampus and neocortex, which play an important role in
memory and cognitive function. The loss of cholinergic neurons results in
upto a 90% reduction in the activity of acetyltransferase, which is needed for
the synthesis of acetylcholine.
• Amyloid hypothesis:
This hypothesis, substantiates that Amyloid beta (ABeta) deposites are the
causative factor in the disease (Mudher and Lovestone, 2002).
• Tau hypothesis:
An extensive research investigation by Schmitz et al.,(2004) demonstrated that
hyperphosporylated tau begins to pair with other threads of tau and they tangled
up together inside nerve cell dodies in masses known as neuro fibrillary tangles
( Goedert et al., 1991) eventually leading to disintegration of microtubules
and collapsing of the neuron’s transport system (Iqbal et al., 2005).

38. NEUROCHEMICAL CHANGES
• The initial findings were reported by Bowen et al., 1976 who found a marked
loss of basal forebrain cholinergic neurons and also large reduction in
cholinergic markers such as the cortex, hippocampus and amygdala.
• The densities of cortical and hippocampal muscarinic M2 and nicotinic
receptors are reduced in the brains of Alzheimer’s Disease patients.
• There are indications that other neurotransmitter systems may also be
compromised in Alzheimer’s Disease.
• Noradrenergic deficits were also found in the cortex and in hypothalamus.
• The serotonergic system is likewise compromised in Alzheimer’s Disease.
• In the cortex, there is some loss of both presynaptic and post synaptic
serotonergic markers.
• Based on postmortem studies, however, changes in serotonergic
neurotransmission may be linked to the behavioural disturbances of
Alzheimer’s Disease such as depression, rather than cognitive dysfunction.

39. • Several investigators have reported significant losses of cortical
somatostatin neurons and receptors in Alzheimer’s disease.
• Nevertheless, glutamate concentration was reduced by 14% in
temporal lobe biopsy samples of patients with Alzheimer’s disease.
• The last 15–20 years have seen a wealth of studies to characterize the
neurochemical abnormalities of Alzheimer's disease, in particular
those involving the β-amyloid and tau proteins, as well as more
recently, apolipoprotein E4.
• Other studies have shown that the phosphorylation of tau, thought to
be an important step in the formation of tangles (which occur
predominately in EAA cortical pyramidal neurons), may also be
influenced by the phospholipase C second messenger system.

40. Other Hormones and Enzymes responsible for AD
Insulin
Insulin (1aiy) is a hormone that is central to regulating energy and glucose
metabolism in the body High insulin concentration stimulates nitric oxide
synthetase.
Combines nitric oxide with superoxide to produce peroxynitrite Peroxynitrite
causes Tyr nitration.
AD patients show high Tyr nitration in both neurons and glial cells
Acetyl Choline esterase
Acetylcholinesterase(1b41), also known as AChE, is an enzyme that degrades
(through its hydrolytic activity) the neurotransmitter Acetylcholine, producing
choline and an acetate group
Promotes aggregation of Beta –Amyloid

42. Changes in the structure of Microtubules
Changes in the structure of Microtubules

43. Putative Amyloid
Cascade
This hypothesis of the
amyloid cascade, which
progresses from the
generation of the beta-
amyloid peptide from the
amyloid precursor protein,
through multiple secondary
steps, to cell death, forms
the foundation for current
and emerging options for
the treatment of Alzheimer's
disease.
APP denotes amyloid
precursor protein, and AB
beta-amyloid.

44. • Beta-amyloid plaques, which are dense deposits of protein and cellular
material that accumulate outside and around nerve cells
• Neurofibrillary Tangles, which are twisted fibers that build up inside the
nerve cell
• Commonly found in cortical neurons, amygdala, hippocampus, forebrain.

46. Morphology and Distribution of Neuritic Plaques and Neurofibrillary Tangles
Pathologic diagnosis of AD
requires the presence of both
Neuritic Plaques and
Neurofibrillary Tangles in
abundance tan anticipated for
age-matched healthy controls.
Neuritic Plaques consist of a
central core of amyloid protein
surrounded by astrocytes,
microglia, and dystrophic
neurites often containing paired
helical filaments.
Neurofibrillary Tangles are the
second major histopathological
feature of AD. They contain
paired helical filaments of
abnormally phosphorylated Tau
protein that occupy the cell
body and extend into the
dendrites

47. Changes in the structure of Microtubules

48. APP
•APP is a cell surface receptor, interacts with many other proteins, and
may regulate neurite growth. Clearly, APP is an important player in Alzheimer's
Disease .
•APP is cleavage by betasecretase on the amino end & gamma-secretase on the
carboxy end
•Highly amyloidogenic A-beta 42 protein aggregates into diffuse plaques
•Normally, APP clips itself using two different pathways, -secretase and  -
secretase.
•Following the a-secretase pathway, APP is clipped between amino acids 612 and 613,
or between the 16th and 17th amino acids with regards to the A protein. A full-
length version of A is not formed.
•The -secretase pathway clips APP between amino acids 596 and 597 and
is followed by a presenilin-1 regulated -secretase pathway that clips
the A protein at amino acid 40. This forms a full-length
A protein (A 1-40).

49. • Ia a Major lipoprotein for lipid transport between neurons
•Protein portion of lipoproteins (LDL, HDL, etc.) transpors cholesterol which is
used for synapse plasticity and repair of damaged neurons
•It exists in 3 common forms
•ε2, ε3, ε4
•Apo ε4 most linked to leading to Alzheimers (1/3 of cases?)
•Apo ε2 may have protective effect
•ApoE helps to carry cholesterol and fat in bloodstream
ApoE
•Synthesized in the liver, by the brain astrocytes and oligodendrocytes
•Does not cross the Blood Brain Barrier
•Acts as the binding site for LDL receptors- Allows lipids to get into the cell
•Removes oxidized lipids from the brain

50. •The Tau (MAPT) protein appears to promote microtubule assembly
and stability.
•They are abundant in Neurons in the CNS & less in else where.
•Defective in Tau Protein are a cause of no longer stabilize
microtubules properly, it leads to Alzheimer’s Disease.
•MAPT undergoes complex alternative splicing and its transcripts are
differentially expressed in the nervous system depending on neuron
type and maturation.
•Abundant evidence exists linking mutations in MAPT to
neurodegenerative diseases in humans
Tau protein

51. Changes that occur during the progression of AD

55. •Secondary structure Identification: Sablet , PSI-Pred
•Domain Identification-
•Ramachandran Plot -Prochek
•Protein-Protein interaction-Hex
•Protein-Ligand interaction- AutoDock , Gold
•Active sites prediction- Qsite Finder, CASTp
Annotation of Proteins involved in
Alzheimer’s Disease
Ex: Beta Secretase, AChE(1b41) ect By using PDBSUM
Domain Fishing 1.0.

56. Beta secretase Acetylcholinesterase Insulin
Clusterin
APP
APoE
Tau Protein
Structural Details of the Proteins involved in Alzheimer’s Disease

57. •Gamma secretase is a multi-subunit protease complex, itself an integral membrane
protein
•The most well-known substrate of gamma secretase is amyloid precursor protein
•The gamma secretase complex minimally consists of four individual proteins:
presenilin, nicastrin, APH-1 (anterior pharynx-defective 1), and PEN-2 (presenilin
enhancer 2
APH-1A
Presenilin-1 Presenilin-2 Nicastrin PEN2
Gamma Secretase Complex

58. •The PSEN1 gene has multiple transcriptional variants and its functions
could include the cleavage of APP and notch receptor
protein .
•PSEN1 located on Chromosome 14.
•The PSEN2 gene has two transcriptional variants and its functions could
include the cleavage of APP and notch receptor protein
•PSEN1 located on Chromosome 1.
•Dominant mutations in the genes that encode presenilin proteins are the
most common cause of familial early-onset Alzheimer's Disease
Presenilin
Presenilins are a family of related multi-pass transmembrane proteins that
function as a part of the gamma-secretase protease complex

59. Nicastrin precursor
• Component of the gamma-secretase complex
• Binds to proteolytic processed C-terminal fragments C83 and
C99 of the amyloid precursor protein (APP)
• It probably represents a stabilizing cofactor required for the
assembly of
the gamma-secretase complex
APH-1 (anterior pharynx-defective 1)
• APH-1 (anterior pharynx-defective 1) is a protein gene product
originally identified in the Notch signaling pathway in
Caenorhabditis elegans as a regulator of the cell-surface
localization of nicastrin
• components of the gamma secretase complex along with the
catalytic subunit presenilin and the regulatory subunits nicastrin
and PEN-2

60. Steps involved in Drug Discovery
•Target Identification
•Active site Prediction
•Preparation of Lead Molecule
•Docking Studies
Computer aided Drug Discovery for AD
Causative proteins

61. • Alzheimer’s Disease is usually diagnosed
clinically from
• A detailed patient history
• Information from family and friends
• Physical and neurological exams and lab
tests
• Neuropsychological tests
• Imaging tools such as brain CT scan/
Magnetic Resonance Imaging (MRI), PET
scans are used primarily for research
purposes.
• The diagnosis can be confirmed with very
high accuracy post-mortem when brain
material is available and can be examined
histologically.

62. Alzheimer’s Disease:
Postmortem Analysis
Normal Advanced AD

65. • Specificity is good (96%)
• But the sensitivity is poor (63%)
• Using a standard cutoff score of 24 will leave a substantial proportion of
cases of early dementia undetected.
• Asking patients and knowledgeable informants about deficits may enhance
detection of early stages of AD
– abnormalities in learning and retaining new information
– difficulty handling complex tasks
– impaired reasoning ability
– changes in language or behavioral alterations
Diagnostic Criteria
• Cognitive impairment severe enough to cause social or occupational
disability in at least two domains
– Memory
– Language
– Calculations
– Orientation
– Judgment
Identification of AD

66. – Acetylcholinesterase inhibitors
– NMDA Receptor Antagonists
Memantine (Namenda)
– β-secretase (BACE) inhibitor?
– Anti-amyloid vaccine?
– Detoxification of β-amyloid?
– Metal ions reduction (Clioquinol)?
– Vitamin E intake
Treatments

67. • There was no cure for Alzheimer’s Disease; available treatments offer relatively small
symptomatic benefit. Current treatments can be divided into
• pharmaceutical, psychosocial and caregiving.
• Pharmaceutical: The following drugs are variously used for the treatment of Alzheimer’s
Disease
• Cholinergic Therapy of Possible Benefit in the Treatment of Alzheimer's Disease
Drug Mechanism of action
Tacrine (Cognex) Cholinesterase inhibitor
Donepezil (Aricept) Cholinesterase inhibitor
Epastigmine Cholinesterase inhibitor
Physostigmine (Synapton)* Cholinesterase inhibitor
Xanomeline† Cholinergic agonist
Milameline Cholinergic agonist
AF 102B Cholinergic agonist
SB202026 (Memric) Cholinergic agonist
Rivastigmine (ENA 713; Exelon) Cholinesterase inhibitor
Metrifonate
Indirect cholinesterase
inhibitor
Heptylphysostigmine Cholinesterase inhibitor

68. • Breaks acetylcholine
• Promotes aggregation of β-amyloid
Acetylcholineste
rase
O N+
O
acetylcholine
HO N+
choline
O
-
O
acetate
+
+H2O O N+
O
O
tetrahedral intermediate
H
H

69. Donepezil
(Aricept)
Galantamine
(Reminyl)
Rivastigmine
(Exelon)
Tacrine
(Cognex)
Acetylcholine
O N+
O
O
H
H
HO
NH
CH3
O
Br
N
NH2 H
Cl
H
O
H
N
O N
O
C4H6O6
O
H2
C
N
C
H2
O
CH3
O CH3
H
Cl
AchE Inhibitors

70. • Memantine/Auxura/Namenda
• Regulates Calcium influx
• Replaces Magnesium Ions
NMDA
Receptor
Antagonist

71. • Chelates copper and zinc in vitro
• Treatment reversed the deposition of amyloid in the brains of mice with AD
• Clioquinol cut amyloid deposits in half over a nine week period with no
adverse effects.
• Vitamin E (2000 IU/d) and selegiline (10 mg/d) have been shown to reduce
the rate of decline of functions in patients with AD.
– Combined therapy was not superior to either agent alone.
• Evidence to support the use of other antioxidants, anti-inflammatory agents,
or herbal medications such as ginkgo biloba is insufficient to recommend
use as standard therapies.
• Estrogen in standard doses has been shown not to improve cognition in
postmenopausal women with AD
N
OH
I
Cl

72. FUTURE HOPE
• Reducing amyloid production, aggregation or enhancing its removal are
promising avenues of treatment that will address the basic pathophysiology
of AD.
• Immunization, secretase inhibition, and other strategies to accomplish this
are being studied.
• Epidemiologic data suggest that some agents may decrease the likelihood
of developing AD.
– nonsteroidal anti-inflammatory agents
– hormonal treatments
– histamine H2 blockers
– antihypertensive agents
– statins
• Clinical trials of these compounds to test their roles in the treatment or
prevention of AD are planned or under way.

73. Care giving
• During the early and moderate stages,
modifications in the living environment
and lifestyle can increase patient safety
and reduce caretaker burden.
• But in the advanced stage, the patient
may also become incapable of feeding
themselves, so they required food in
smaller pieces and the use of feeding
tubes.
• As the disease progresses, different
medical issues can appear such as oral
and dental diseasees, pressure ulcers,
malnutrition, hygiene problems or
respiratory, skin or eye infections.
• At these stage, careful management can
prevent them, while professional
treatment is needed when they do arise.

74. AD Research: Managing Symptoms
Between 70 to 90% of people with AD eventually develop behavioral symptoms,
including sleeplessness, wandering and pacing, aggression, agitation, anger,
depression, and hallucinations and delusions. Experts suggest these general
coping strategies for managing difficult behaviors:
• Stay calm and be understanding.
• Be patient and flexible. Don’t argue or try to convince.
• Acknowledge requests and respond to them.
• Try not to take behaviors personally.
Experts encourage caregivers to try non-medical coping strategies first. However,
medical treatment is often available if the behavior has become too difficult to
handle. Researchers continue to look at both non-medical and medical ways to
help caregivers.

75. Who are the AD Caregivers?
• Spouses – the largest group. Most are older with their own
health problems.
• Daughters – the second largest group. Called the “sandwich
generation,” many are married and raising children of their
own. Children may need extra support if a parent’s attention
is focused on caregiving.
• Grandchildren – may become major helpers.
• Daughters-in-law – the third largest group.
• Sons – often focus on the financial, legal and business
aspects of caregiving.
• Brothers and Sisters – many are older with their own
health problems.
• Other – friends, neighbors, members of the faith
community.
Support for Caregivers

76. Alzheimer’s Disease Prevention
Initiative
No Disease,
No Symptoms
Early Brain
Changes,
No Symptoms
Mild Memory
Loss
Mild, Moderate
and Severe
Impairment
Disease Progression
Disease Progression
Mild
Cognitive
Impairment
Pre-
symptomatic
AD
Normal AD
Primary
Prevention
Secondary
Prevention Treatment

77. PREVENTION
• Intellectual activities such as playing chess or regular social interaction have
been linked to a reduced risk of AD.
• Cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes
and smoking are associated with a higher risk of onset and course of AD.
• The components of 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 AD.
• Long-term usage of non-steroidal anti-inflammatory drug is associated with a
reduced likelihood of developing AD.
• Curcumin from the curry spice turmeric has shown some effectiveness in
preventing brain damage in mouse models due to anti-inflammatory properties.
• A 21- year study found that coffee drinkers of 3-5 cups day at midlife had a 65%
reduction in risk of dementia in late life.
• 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 AD.
• Education delays the onset of AD syndrome.
• Physical activity is also associated with a reduced risk of AD.
• Some studies have shown an increased risk of developing AD with environmental
factors such as intake of metals particularly aluminium or exposure to solvents.

78. With the technical advancements available today, it is possible
to develop and synthezise new Drug molecule within a short
time

79. In -Vivo Studies

80. Clinical Trails

81. Drugs For the Disease-FDAApproved

83. THANK YOU
ACKNOWLEDGEMENTS
I thank various websites and also the Authors of the
Slide Share presentation which were available
through Google who indirectly contributed to the
preparation of this presentation .