4. INTRODUCTION
Alzheimer’s disease (AD) is the commonest progressive,
dementing neurodegenerative disease in elderly, which
affects innumerable people each year, and these numbers are
likely to further increase as the population ages.
In addition to the financial burden of AD on health care
system, the disease has powerful emotional impact on
caregivers and families of those afflicted.
4
5. BRIEF HISTORY
Alois Alzheimer, a German physician,
is credited with being the first to
describe AD.
In 1906, Dr. Alzheimer observed a
patient, Auguste Deter, in a local
asylum who exhibited strange
behaviors. He followed her care and
noted her memory loss, language
difficulty and confusion. Alois Alzheimer
5
6. After her death at the age of 51, he examined her brain
tissue. The slides showed what are now known as plaques
and tangles.
In 1911, Doctors were using Dr. Alzheimer’s research to base
diagnosis.
In the 1960’s British pathologists determined that AD was not
a rare disease of the young but rather what had been termed
“senility.”
In the 1990’s researchers identified that the beta amyloid
protein was a factor in AD.
6
9. MC cause of dementia, > 65yr.
Starting with 0.5% prevalence at 55 yrs., it goes on doubling
every five years (60yrs-1%; 65yrs. – 2%; 70 yrs. -4%; 75yrs.-8%
and so on)
Risk at the age of 80 years is around 15 to 20%
About 7.7 million new cases of dementia each year. A new
case detected in every 4 seconds somewhere in world.
EPIDEMIOLOGY
WHO
9
10. The incidence rates per 1000 person-years for AD
was
11.67 for ≥55 years
15.54 for aged ≥65 years.
Neurol India. 2012 Nov-Dec;60(6):625-30. doi: 10.4103/0028-3886.105198.
10
11. COMMON TYPES OF DEMENTIAS
Type of Dementia % in total Cases
Alzheimer’s Dementia 50-55
Vascular Dementia 30-35
Lewy body Dementia 5-7
Pick’s Dementia 3-5
Other Dementias 10-15
11
12. Ziegler-Graham K et al. Alzheimer’s & Dememtia 2007;3(Suppl):S168–9
New Estimate of Dementia Worldwide
12
15. RISK FACTORS
Age : every 5 yr beyond 65, the % of people with AD doubles
Family history : strong genetic component
1. Early onset – fully penetrant
2. Late onset – reduced penetrant
Gender – women, ? Estrogen
Tobacco
Head injury
15
19. AD is characterized by generalized cerebral cortical atrophy,
neuronal loss, widespread cortical neuritic plaques and
neurofibrillary tangles.
Following mechanisms have been attributed for the
development of Alzheimer’s dementia
Amyloid cascade theory
Neuronal loss
Cholinergic hypothesis
Excitotoxicity
Genetic factors
PATHOGENESIS AND PATHOPHYSIOLOGY
19
20. Alzheimer’s disease begins with the abnormal build-up of an
amyloid protein in the brain from APP(amyloid precursor
protein).
APP normally found in the cell membranes of neurons and
normally metabolised by a protease enzyme α–secretase.
In AD, the metabolism of APP is altered by two other enzymes β
and γ secretase and is called β amyloid (Aβ).
AMYLOID CASCADE THEORY
20
21. Amyloid-β is originated by the alternative cleavage of the
amyloid precursor protein (APP) into smaller peptides (Aβ1-
40 and Aβ1-42) by two other enzymes β and γ secretase
Aβ1-42 is more prone to form insoluble aggregates (and
therefore more toxic) than Aβ1-40.
Once Aβ is formed, it accumulates into insoluble sheets
(called β-pleated sheets).
21
22. The interaction between genetic and environmental factors,
along with the homeostatic changes that pertain to the
ageing, seems to affect the balance between production and
clearance of toxic Aβ peptides.
These deposits are neurotoxic and activate inflammatory
reaction resulting in the formation of senile or neuritic plaque.
This is accompanied by hyperphosphorylation of tau protein,
supporting the microtubules.
22
23. Hyperphosphorylated Tau aggregates into oligomers to form
NFTs.
Several protein kinases are involved in this process, namely
glycogen synthase kinase-3 beta (GSK3β), cyclin-dependent
kinase-5 (CDK5), and extracellular signal-related kinase-2
(ERK2).
GSK-3β, the most important Tau kinase in neurons, is
overactive in AD
23
Journal of Alzheimer’s Disease 33 (2013) S185 -S194
DOI 10.3233/JAD-2012-129028
26. The classic gross neuro-
anatomical observation is
Diffuse atrophy with
widening cortical sulci
Enlarged cerebral
ventricles.
There is a progressive
loss of neurons and their
supportive glial cells.
The loss is more marked
in the entorhinal cortex,
hippocampus and basal
forebrain.
NEURONAL LOSS
26
27. Source: Image from the Alzheimer’s Society of Saskatchewan with permission from Alzheimer’s Broken Brain.
Alzheimer’s Brain Normal Brain
27
29. Levels of acetylcholine, noradrenaline, serotonin, γ-
aminobutyric acid (GABA), glutamate, somatostatin,
neuropeptide Y, and substance P have all been documented
to be reduced in the brains of AD patients.
Reductions in acetylcholine and choline acetyltransferase are
the most profound.
Neuronal loss in the basal forebrain, which is the major
region from which cholinergic projections originate.
CHOLINERGIC HYPOTHESIS
29
30. Excessive release of glutamate into the synapses.
Excessive influx of calcium into the cells leading to cell death
called excitotoxicity.
Also lead to excessive production of Aβ and tau
phosphorylation.
EXCITOTOXICITY
30
31. Growing evidence for the role of additional factors such as
oxidative stress, neuroinflammation, and mitochondrial
dysfunction in the pathogenesis of AD.
31
32. GENETICS
Four genes
1. Presenelin 1- chr 14
2. Presenelin 2- chr 1
3. Amyloid beta protein precursor- chr 21
4. Apolipoprotien E gene – chr 19
Typically divided into – early onset and late onset
Arch. Neurol. 1998;55:294-296
32
33. GENETICS OF EARLY ONSET
APP gene
Increase the production of amyloid.
Age of onset range from – 39 to 68 yrs
6 different mutation – all are fully penetrant.
APOE-4 mutation further decrease the age of onset.
Arch. Neurol. 1998;55:294-296
33
34. THE PRESENELIN GENES
Half of the early onset AD patient
Increase the production of amyloid and promote apoptosis.
It increase the production of Aß 1 -42,which is more
hydrophobic more prone to agreggation, hence more toxic
All PS1 mutation are fully penetrant and autosomal dominant
Age of onset in PS1 mutation range from 32 to 56 yrs
Age of onset in PS2 mutation range from 40 – 85 yrs
Arch. Neurol. 1998;55:294-296
34
35. GENETICS OF LATE ONSET AD
APOE GENE
Has 3 alleles – 2,3 and 4…. 4 is associated with pathology
Normal gene promote proteolysis and clearence of amyloid,
and mutant gene promote aggregation and deposition of
amyloid.
Increase the risk of disease.
Age of onset 60s
It decrease the age of onset with APP mutation.
Arch. Neurol. 1998;55:294-296
35
39. Who should be evaluated for AD
Age more than 60yr
People with risk factors – head injury, CV risks
People with memory or cognitive complaints, with or without
change in functioning.
Memory difficulty noted by friends, relatives or spouse.
Patient with depression or anxiety without memory
complaints
39
40. ASSESMENT
History
1. Patient
2. Relatives
Comprehensive physical and neurological examination
Cognitive evaluation
Functioning status
Lab work
Imaging
40
41. HISTORY
Memory impairment – trouble remembering recent
conversation, events, appointments, frequently misplaces
objects.
Executive impairment – deterioration of complex task
performance, decreased ability to solve problems, impaired
driving.
DRUGS
Focal motor or sensory symptoms
Behavior personality and mood changes
41
42. TOOLS
Screening
Mini Mental State Examination (MMSE) (Folstein et al. 1975)
Hindi Mental State Examination (HMSE) (Ganguli et al. 1995)
Hindi Cognitive Screening Test (Tiwari and Tripathi, 2011)
St. Louis University Mental State (SLUMS) Exm. (JE Morley,
2000)
Clock Drawing Test (CDT) (Shulman et al. 1993)
Bender Gestalt Test (BGT) (Lauretta Bender, 1938)
Hachinski Ischemic Scale (1975)
42
47. Features Score
1. Abrupt 2
2. Stepwise deterioration 1
3. Fluctuating course 2
4. Nocturnal confusion 1
5. Relative preservation of
personality
1
6. Depression 1
7. Somatic Complaints 1
8. Emotional incontinence 1
Features Score
9. History or presence of
hypertension
1
10. History of strokes 2
11. Evidence of associated
atherosclerosis
1
12. Focal neurologic symptoms 2
13. Focal neurologic sign 2
Total Score 18
Hachinski Ischemic Scale (1975)
Scoring
0-4: Alzheimer's Dementia;
5-6: diagnosis unclear;
7 or more : Vascular Dementia
47
48. 48
Score Error(s)
1 No error
2 Minor visuospatial error
3 Inaccurate
representation of “10
past 11”
4 Moderate visuospatial
disorganization of
times
5 Several disorganization
6 No reasonable
representation of a
clockScore≥ 3: Cognitive deficit
CLOCK DRAWING TEST
51. LABORATORY EAVALUATION
CBC, full chemistry, TSH.
Serum B12 and folic acid
No value of genetic testing at present
CSF markers – used only for research purpose not
recommended for clinical diagnosis
• Amyloid beta 42 - low
• Total tau - elevated
• Phosphorylated tau - elevated
51
52. CSF marker may assist in differentiating from other dementia.
A study in 2014 recommended the ratio of tau to A beta 42
with a cut of point of > 0.52 for differentiating AD from other
dementia…its more sensitive than individual marker.
Its also important in predicting progression of MCI and
dementia.
F.H. Duits et al. / Alzheimer’s & Dementia -(2014) 1–11
52
54. IMAGING
STRUCTURAL IMAGING – CT, MRI
May reveal atrophy, white matter changes
Not sensitive/specific to AD.
In AD – diffuse cerebral atrophy, enlarged sulci, increased
size of ventricles, loss of hippocampal volume.
54
56. FDG - PET
Functional imaging of brain metabolism.
It measures synaptic activity in different part of brain
In AD – temporal and parietal glucose hypometabolism.
Can differentiate AD from FTD.
IOFLUPANE
SPECT for evaluation of presynaptic dopamine
transporters, useful in differentiating AD from lewy body
dementia
56
58. AMYLOID IMAGING
11C – labelled pittsburgh compound B
First PET ligand to visualise beta amyloid in living patient
It have short half life.
Flourine 18 agents have longer half life and FDA
approved.
Sensitivity – 80 to 93%
Specificity – 91 to 96%
58
60. PET TAU IMAGING
In vivo marker of abnormally phosphorylated TAU
protein.
Tangles correlate best with cognitive impairment
Amyloid may be present for years in the absence of
impairment
Combined amyloid and TAU imaging my help in early
diagnosis and intervention.
60
69. Mild NCD
69
A. Evidence of modest cognitive decline from a previous
level of performance in one or more cognitive
domains based on:
1. Concern of the individual, a knowledgeable informant, or
the clinician that there has been a mild decline in
cognitive function; and
2. A modest impairment in cognitive performance,
preferably documented by standardized
neuropsychological testing or, in its absence, another
quantified clinical assessment.
B. The cognitive deficits do not interfere with capacity
for independence in everyday activities
70. 70
C. The cognitive deficits do not occur exclusively in
the context of delirium.
D. The cognitive deficits are not better explained by
another mental disorder.
Specify:
Without behavioral disturbance
With behavioral disturbance
71. 71
Specify whether due to
Alzheimer’s disease
FTD
LBD
Vascular
TBI
Substance/medication use
………
Unspecified
72. Major NCD
72
A. Evidence of significant cognitive decline from a
previous level of performance in one or more
cognitive domains based on:
1. Concern of the individual, a knowledgeable informant, or
the clinician that there has been a significant decline in
cognitive function; and
2. A substantial impairment in cognitive performance,
preferably documented by standardized
neuropsychological testing or, in its absence, another
quantified clinical assessment.
B. The cognitive deficits interfere with independence in
everyday activities.
73. 73
C. The cognitive deficits do not occur exclusively in
the context of delirium.
D. The cognitive deficits are not better explained by
another mental disorder.
Specify:
Without behavioral disturbance
With behavioral disturbance
74. 74
Specify whether due to
Alzheimer’s disease
FTD
LBD
Vascular
TBI
Substance/medication use
………
Unspecified
76. Major or Mild NCD Due to Alzheimer’s
76
A. The criteria are met for major or mild
neurocognitive disorder.
B. There is insidious onset and gradual progression
of impairment in one or more cognitive domains.
C. Criteria are met for either probable or possible
Alzheimer’s disease as follows:
For major neurocognitive disorder
For mild neurocognitive disorder
77. 77
For major neurocognitive disorder
Probable alzheimer’s disease is diagnosed if either of the
following is present; otherwise, possible Alzheimer’s
disease should be diagnosed.
1. Evidence of a causative Alzheimer’s disease genetic
mutation from family history or genetic testing.
2. All 3 of the following are present:
A. Clear evidence of decline in memory and learning and
at least one other cognitive domain.
B. Steadily progressive, gradual decline in cognition,
without extended plateaus.
C. No evidence of mixed etiology
78. 78
For mild neurocognitive disorder
Probable alzheimer’s disease is diagnosed if Evidence of a
causative Alzheimer’s disease genetic mutation from family
history or genetic testing.
Possible alzheimer’s disease is diagnosed if there is no
Evidence of a causative Alzheimer’s disease genetic
mutation from family history or genetic testing.
79. DIAGNOSIS
(ALZHEIMERS ASSOCIATION 2011)
3 stages of AD
Preclinical AD requires measureable changes in
biomarkers and/or poor performance on challenging
cognitive tests.
MCI - mild changes in memory and other cognitive
abilities; these changes can be detected through careful
evaluation, but do not interfere with day-to-day activities.
Dementia - changes in two or more aspects of cognition
and behaviour that interfere with function in everyday life.
Alzheimer’s & Dementia 7 (2011) 257–262
79
81. S.N Pseudodementia Dementia
1 Informant aware of memory disturbance
and can date the onset accurately
Onset is insidious and informant usually can
not date onset.
2 Patient complains enthusiastically about
the memory loss
Unlikely
3 Questions about cognitive functions lead
to DON’T KNOW RESPONSE
accompanied by irritation
Try their best but are incorrect
4 History is usually short and often there is
a previous history of depressive episode
History is long and depressive episode may
or may not be present
5 Depressed patients perform better on
memory tests.
Don’t perform well.
6 Memory complains are accompanied by
insomnia, diurnal variation etc.
May or may not be present
81
82. Feature Dementia Delirium
Onset Insidious Sudden
Duration Months to years Hours to week
Attention Preserved Fluctuates
Memory Impaired Impaired recent and
immediate
Speech Word finding difficulty Incoherent
Sleep & wake cycle Fragmented sleep Disrupted sleep, day night
reversal
Thoughts Impoverished Disorganized
Awareness Unchanged Reduced
Alertness Usually normal Hypervigilant or reduced
vigilance
82
83. 83
Characteristics Alzheimer’s Disease Vascular Dementia
Sex Women Men
Age Generally over age 75 years Generally over age 60 years
Onset & progression Gradually progressive Episodic with stepwise
deterioration
History of hypertension Less common Common
History of stroke(s),transient
ischemic attack(s),or other
focal neurological symptoms
Less common Common
Hypertension Less common Common
Focal neurological signs Uncommon Common
Emotional lability Less common More common
Cognitive deficits Uniform patchy
84. Features Pick’s disease AD
Personality change Early Late
Amnesia Late Early
Language disturbances Early Late
Stereotypes Early Mid or late
Apraxia, agnosia, alexia Late Variable
Kluver-Bucy syndrome Early Late
Visuospatial disorientation Rare Common
Age of risk Mean 50, up to 80yrs Risk increases with age
CT Scan Fronto-Temporal atrophy Widespread atrophy
Gross Pathology Anterior hemi. Atrophy, Posterior hemispheric
atrophy,
Histopathology pick’s body Neurofibrillary tangle
84
86. MANAGMENT
Treatment of AD
Treatment of secondary symptoms
Experimental therapy
Preventive measures
86
87. Treatment of AD
Cholineesterase inhibitors - mild-moderate AD
Donepezil
Rivastigmine
Galantamine
NMDA antagonists – severe AD
Memantine
87
88. 88
Characteristic DONEPAZIL RIVASTIGMINE GALANTAMINE MEMANTINE
Chemical class Piperidine Carbamate Phenanthrene
alkaloid
Similar to
amantadine
Primary
mechanism
AchE inh AchE inh AchE inh NMDA
antagonist
Other
mechanism
None BuchE IN Nicotine
modulator
HT3 receptor
antagonist
Half life 70 h 90 min 7 h 70 h
Metabolism Hepatic Renal Hepatic Hepatic
89. Current status of AChE Inhibitors
Treatment over 6 month produce improvement in cognitive
function.
Benefits were also noted on ADL and behaviour.
Direct comparison – equivocal result.
Delay institutionalization
Decrease troublesome behaviours
Combining memantine with AChE inhibitors - slowed
cognitive and functional decline.
89
91. TREATMENT OF SECONDARY SYMPTOMS
Neuroleptic agents
FDA in 2005 black box warning for atypical neuroleptics
2008 - haloperidol, chlorpromazine and thioridazine
included
Typical antipsychotics – cardiac arrythmia and EPS
Atypical – thromboembolism and aspirational pnemonia.
Cognitive decline with both
91
92. Antidepressants
Sertaline & fluvoxetine – no benefits (wintraub & petrecca
et al study)
Mirtazipine has no benefial effect ( Banerjee et al)
Recommendation – not effective – not recommended.
Anticonvulsants
Very limited evidence to support use
92
94. 94
To date there is no effective approach in terms of cure or
prevention of dementia.
The available pharmacological therapy is largely
symptomatic, with temporary clinical benefits on
cognitive, functional and behavioural manifestations of
the disease.
There is an urgent need to develop new drugs with
disease-modifying properties for AD.
95. 95
A disease-modifying drug is a agent intended to slow
the progression of the neurodegenerative process by
inhibiting critical events in the pathophysiology of the
disease.
Patients treated with such agents would be expected to
have a more benign course of the disease when
compared to placebo-treated individuals
96. 96
Many drugs have been proposed and tested in
neurobiological models of AD.
However, the promising effects of these compounds
in animal models failed to prove beneficial to
humans.
In addition, other drugs that underwent clinical
experimentation delivered negative results, either
due to limited efficacy or toxicity.
99. Therapeutic targets for disease
modification in AD
99
More than 200 pharmaceutical compounds are
currently undergoing phase 2 and 3 trials.
Grossly divided into :
Anti amyloid
Drug that target other pathways
100. Anti-amyloid compound
100
1. Block/inhibit the overproduction or aggregation
Gamma secretase inhibitors
Beta secretase inhibitors
2. Favour its clearance from the brain
Active immunisation
Passive immunisation
103. ACTIVE IMMUNIZATION
103
Induces an IgM response to generate antibodies against
pathogenic Aβ, which further mobilize microglia to clean
plaques through phagocytosis
AN 1792 – PHASE 2
The trial was interrupted due to the occurrence of
meningoencephalitis in 6% of subjects.
CAD106 - PHASE 1
Able to reduce Aβ accumulation in cortical and subcortical
brain regions
Bioorg Med Chem Lett 2011; 21 : 2655-8.
S, Jacobson LH, et al.. J Neurosci 2011; 31 : 9323-31.
104. PASSIVE IMMUNISATION
104
Intravenous administration of full monoclonal
antibodies or antibody fragments which directly
target Aβ.
BAPINEUZUMAB
Undergoing phase 3 studies.
Researchers reported that it failed to protect against
cognitive and functional decline of AD patients undergoing
a phase 3 trial.
Neurology 2009; 73 : 2061-70.
105. 105
SOLANEZUMAB
Phase 3 trials failed to demonstrate clinical benefits.
But In a study conducted in Japan with AD patients
associated with increased clearance of Aβ from the brain.
PONEZUMAB
Targets the amino-terminal portion of Aβ1-40
Phase 2 studies did not confirm clinical efficacy.
The European Federation of Neurological Societies annual 23. meeting, in Stokholm, Sweden; 2012.
Clin Neuropharmacol 2013; 36 : 14-23.
106. Inhibitor of production and accumulation
of Aβ
106
γ-secretase inhibitors
Semagacestat –
Phase III trials found no efficacy.
Even it was associated with increasing cognitive
impairment and worsening daily living activities, as well
with increasing risk for skin cancer.
Avagacestat –
Inhibitor of Ab 40 and Ab 42 formation
Phase 2 study
107. Tau-oriented strategies
107
LITHIUM AND VALPROATE - Inhibit GSK – prevent Tau
phosphorylation in animal models
Valproate was not associated with reduction of cognitive or
functional decline.
Long-term lithium treatment was associated with
stabilization of cognitive and functional parameters, in
addition to a reduction in CSF concentrations of
phosphorylated Tau.
Phase 2 study in patients with mild AD treated with lithium
for a shorter (10 wk) period, no significant differences were
observed in biological or clinical outcomes.
Neurology 2011; 77 : 1263-71.
J Clin Psychiatry 2009; 70 : 922-31
Br J Psychiatry 2011; 198 : 351-6.
109. Others
109
Ginkgo biloba
Previously - effective in mild to moderate Alzheimer’s
disease with an advantage over placebo.
Recent cochrane review – no evidence of efficacy
Several reports of bleeding.
Pharmacopsychiatry 2003; 36:297–303.
Cochrane Database Syst Rev 2009; 1:CD003120
110. Antibiotics
Higher than normal titres of Chlamydia in people
with AD
Multicentre Canadian double blind placebo
controlled RCT
101 patients with mild to moderate AD (MMSE 11-25)
Daily doxycycline 200mg plus rifampin 300mg or placebo
for 3 months
110
111. Standardized ADAS Cog significant @ 6 but not 12 months
Standardized MMSE score higher @12 (but not 3 or 6) months
Intriguing results!
Larger study in planning stages
Loeb M, Molloy DW et al JAGS 2004;52:381
111
112. vitamin E
High dose Vit E (2000U/day) for 2 yr slowed progression of
AD ( large double blind placebo trial ,Sano et al 1997)
Alzheimer Disease Cooperative Study ( 769 pts) showed no
benefit vs placebo (Peterson et al 2005)
Cause cardiovascular side effects
Not recommended currently
112
Cochrane Database Syst Rev 2008; 3:CD002854.
113. Estrogen replacement therapy
RCT with 351 pts for 2 weeks showed no beneficial effects
Cholesterol lowering agents
RCT, double blinded study with 748 pts for 6 months failed
to prove efficacy
113
McGuinness B et al. Statins for the treatment of dementia. Cochrane
Database Syst Rev 2010; 8:CD007514.
114. Anti inflammatory agents
NSAIDs delay onset of AD
Breitner et al showed NSAIDs don’t protect against AD in
very old
A double blind,placebo controlled trial ( Grundman et al
2003) showed rofecoxib & naproxen don’t delay AD
progression.
114
115. 115
Omega-3 supplementation
174 patients in a placebo-controlled RCT
No significant overall effects on neuropsychiatric
symptoms, on ADL or on caregiver’s burden
Positive effects were seen on depressive symptoms
Freund-Levi Y et al. Int J Geriatr Psychiatry 2008; 23:161–169.
116. 116
Dimebon (latrepirdine)
Non-selective antihistamine previously approved in Russia
Weak inhibitor of BuchE and AchE , weakly blocks the
NMDA receptor signalling pathway.
A company sponsored study completed in Russia included
183 patients - significant benefits compared with placebo.
In the recent CONNECTION study, dimebon was not more
effective than placebo.
Doody RS et al. Lancet 2008; 372:207–215.
117. 117
Huperzine A
Alkaloid isolated from the Chinese herb Huperzia serrata
AChE inhibitor used since 1994 in China.
A recent meta-analysis found that huperzine A 300–500 g
daily for 8–24 weeks in Alzheimer’s disease led to
significant improvements in MMSE and ADL.
Wang BS et al. J Neural Transm 2009; 116:457–465.
118. 118
Cerebrolysin
Porcine brain-derived peptide
Cerebrolysin was superior to placebo in improving
global outcome measures and cognitive ability in
several RCTs of up to 28 weeks.
A large RCT comparing cerebrolysin, donepezil or
combination therapy showed beneficial effects on
global measures and cognition for all three treatment
groups compared with baseline.
Plosker GL et al. Spotlight on cerebrolysin in dementia. CNS Drugs
2010; 24:263–266.
119. STEM CELL THERAPY
South Florida university
Mouse model study in 2009
Several infusions of stem cells from umblical cord
Myeloid protein reduced by 62%
Cerebral amyloid angiopathy reduced by 82%
Hope to begin human trials.
119
120. Conclusions
120
Most phase 3 trials with candidate drugs for AD in the
last decade failed to present unequivocal clinical
benefits, or were suspended due to severe adverse
events.
To date, treatment of AD relies on the symptomatic
effects of cholinesterase inhibitors and NMDA-receptor
antagonists.
121. Preventive measures
121
Exercise regularly
Eat a healthy diet rich in fruits and vegetables
Engage in social and intellectually stimulating
activities
Control type 2 diabetes
Lower high blood pressure levels
122. 122
Lower high blood cholesterol levels
Maintain a healthy weight
Stop smoking
Get treatment for depression