Recent advances in the management of alzheimers disease

Recent advances in the
management of
Alzheimer’s disease
Presenter:- Dr Parthajyoti Neog, PGT
Moderator:- Dr. (Mrs.) Dolly Roy,
Asso. Prof., SMCH

Introduction
History
Clinical features
Pathophysiology
Diagnosis
Management
Recent advances
Conclusion

Alzheimer’s disease is defined as
premature aging of the brain, usually
beginning in mid-adult life and
progressing rapidly to extreme loss of
mental powers—similar to that seen in
very, very old age.
Introduction

 In Alzheimer’s disease, there is loss of
neurons in that part of the limbic
pathway that drives the memory
process.
Loss of this memory function is
devastating.

 It is a progressive and fatal
neurodegenerative disorder that results in
impairment of the person’s ability to
perform activities of daily living as well as
a variety of neuropsychiatric symptoms
and behavioral disturbances in the later
stages of the disease.

Approximately 10% of all person over
the age of 70 years have significant
memory loss, and in more than half
(60-70%) the cause is Alzheimer’s
disease

In 1906, Dr. Alois Alzheimer,
specifically identified a collection of
brain cell abnormalities as a disease.
History

The disease was first described as a
distinctive disease by Emil
Kraepelin after suppressing some
of the clinical (delusions and
hallucinations) and pathological
features (arteriosclerotic changes)
contained in the original report of
Auguste D.

In the 1960s, scientists discovered a link
between cognitive decline and the
number of plaques and tangles in the
brain.
Emil Kraepelin

The medical community then formally
recognized Alzheimer's as a disease and
not a normal part of aging.

Alois Alzheimer's
patient Auguste
Deter in 1902. Hers
was the first
described case of
what became known
as Alzheimer's
disease.

Stages of Alzheimer's disease
A) Effects of ageing on memory but not AD
i) Forgetting things occasionally
ii) Misplacing items sometimes
iii) Minor short-term memory loss
iv) Forgetting that memory lapses
happened.
Clinical Features

B) Early stage Alzheimer's
i) Absent-mindedness
ii) Forgetting appointments
iii) Slight changes seen by close loved
ones
iv) Some confusion in situations outside
the familiar

C) Middle stage Alzheimer's
i) Deeper difficulty remembering
recently learned information
ii) Deepening confusion in many
circumstances
iii) Speech impairment
iv) Repeatedly initiating the same
conversation

D) Late stage Alzheimer's
i) More aggressive or passive
ii) Some loss of self-awareness
iii) Debilitating cognitive deficit
iv) More abusive, anxious, or
paranoid

a) Genetics
b) Cholinergic hypothesis
c) Amyloid hypothesis
d) Tau hypothesis
e) Other hypothesis
Pathophysiology

Genetic factors play an important role
and about 15% of cases are familial.
Familial cases fall into two main groups:
early-onset disease with autosomal
dominant inheritance and a later-onset
group whose inheritance is polygenic.
Genetics

Mutations in several genes have been
described. The inheritance of one of the
alleles of apolipoprotein ε (apo ε4) is
associated with an increased risk of
developing the disease (2–4 times higher
in heterozygotes and 6–8 times in
homozygotes).

Most of autosomal dominant familial AD
can be attributed to mutations in one of
three genes: those encoding amyloid
precursor protein (APP) and presenilins 1
and 2.

The oldest, on which most currently
available drug therapies are based,
is cholinergic hypothesis, which proposes
that AD is caused by reduced synthesis of
theneurotransmitter acetylcholine.
Cholinergic hypothesis

The cholinergic hypothesis has not
maintained widespread support, largely
because medications intended to treat
acetylcholine deficiency have not been
very effective.

Amyloid hypothesis
In 1991, the amyloid hypothesis postulated
that extracellular amyloid beta (Aβ)
deposits are the fundamental cause of the
disease.

Support for this postulate comes from the
location of the gene for the amyloid
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 AD by 40 years of age.

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.

N-APP, a fragment of APP from the
peptide's N-terminus, is adjacent to beta-
amyloid and is cleaved from APP by one of
the same enzymes.

N-APP 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 ageing brain to cause damage.

Exactly how disturbances of
production and aggregation of the
beta-amyloid peptide gives rise to
the pathology of AD is not known.

The amyloid hypothesis traditionally
points to the accumulation of beta
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).

Other hypothesis
Herpes simplex virus type 1 has been
proposed to play a causative role in people
carrying the susceptible versions of the
apoE gene.

Some studies have shown an increased risk
of developing AD with environmental
factors such as the intake of metals,
particularly alluminium.

Some have hypothesised that
dietary copper may play a causal role.

There is tentative evidence that
exposure to air pollution may be a
contributing factor to the
development of Alzheimer's disease.

Biochemistry
Alzheimer's disease has been identified as
a protein misfolding disease (proteopathy),
caused by plaque accumulation of
abnormally folded amyloid beta protein,
and tau protein in the brain.

APP is critical to neuron growth,
survival and post-injury repair.

Plaques are made up of small peptides,
39–43 amino acids in length,
called amyloid beta (Aβ). Aβ is a
fragment from the larger amyloid
precursor protein (APP).

APP is a transmembrane protein that
penetrates through the neuron's
membrane.

In Alzheimer's disease, an unknown enzyme
in a proteolytic process causes APP to be
divided into smaller fragments.

One of these fragments gives rise to fibrils
of amyloid beta, which then form clumps
that deposit outside neurons in dense
formations known as senile plaques.

Alzheimer's disease is usually diagnosed
based on the person's medical history,
history from relatives, and behavioural
observations.
Diagnosis

Advanced medical imaging with
a) CT
b) MRI
c) SPECT
d) 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.

Challenging and gratifying despite the
absence of a cure or a robust
pharmacologic treatment.
Management

Focus is on long-term amelioration of
associated behavioral and neurologic
problems， as well as providing caregiver
support.

Building rapport with the patient, family
members, and other caregivers is
essential.

In the early stages of AD, memory aids
such as notebooks and posted daily
reminders can be helpful.

Family members should emphasize
activities that are pleasant while
curtailing those that increase stress on the
patient.

Kitchens， bath rooms， stairways， and
bed rooms need to be made safe， and
eventually patients will need to stop
driving.

Loss of independence and change of
environment may worsen confusion,
agitation, and anger.

Communication and repeated calm
reassurance are necessary.
 Use of adult day care centers can be
helpful.

Local and national support groups， such
as the Alzheimer's Association and the
Family Caregiver Alliance， are valuable
resources. Internet access to these resources
has become available to clinicians and
families in recent years.

Cholinesterase inhibitors:-
a) Tacrine (1993),
b) Donepezil (1996),
c) Rivastigmine (2000), and
d) Galantamine (2001).
Drug Treatment

Tacrine: It is the first centrally acting anti-ChE
to be introduced for AD.
 In clinical trials tacrine produced significant
improvement in memory, attention, praxis,
reason and language.
 However, it does not alter the course of
underlying disease process.
 Frequent side effects and hepatotoxicity have
restricted its use.

Donepezil (1996): This is a cerebroselective and
reversible anti-AChE drug.
 The benefit is ascribed to elevation of ACh level in the
cortex, especially in the surviving neurones that project
from basal forebrain to cerebral cortex and hippocampus.
 Because of long t½ (~70 hr), donepezil is administered once
daily at bed time; a distinct advantage over rivastigmine
and galantamine which need twice daily dosing. Moreover,
it can be used even in relatively severe case of AD.
 Donepezil is generally well tolerated and is not hepatotoxic.
 Dose: 5 mg OD HS (max 10 mg OD)

Rivastigmine (2000): This carbamate derivative of
physostigmine inhibits both AChE and BuChE.
 The carbamyl residue introduced by rivastigmine into
AChE molecule dissociates slowly resulting in inhibition
of cerebral AChE for upto 10 hours despite the 2 hr
plasma t½ of the drug.
 Rivastigmine is indicated in mild to moderate cases of
AD, but not in advanced disease.
 Dose: Initially 1.5 mg BD, increase every 2 weeks by 1.5
mg/day upto 6 mg/BD

Galantamine (2001): It is a natural alkaloid
which selectively inhibits cerebral AChE and
has some direct agonistic action on nicotinic
receptors as well.
 It is well tolerated, but needs twice daily
dosing.
 Dose: 4 mg BD (max 12 mg BD)

N-methyl-D-aspartate receptor
(NMDA) antagonist.
a) Memantine: It appears to restore the
function of damaged nerve cells and
reduce abnormal excitatory signals by the
modulation of the NMDA receptor
activity.

It is indicated in moderate-to-severe AD,
either to replace anti-AChEs or to
supplement them.
Dose: Initially 5 mg OD, increase
gradually upto 10 mg BD; stop if no
clinical benefit in 6 months.

Piracetam : This cyclic GABA derivative has no
GABA like activity and has been called ‘nootropic’
meaning a drug that selectively improves efficiency of
higher telencephalic integrative activities.
 Piracetam is not a vasodilator, does not affect
total/regional CBF, but may reduce blood viscosity. In
India and some other countries it has been promoted
for cognitive impairment and dementia in the elderly as
well as for mental retardation in children for over 30
years.

 Side effects are minor: gastric discomfort,
nervousness, excitement, insomnia, dizziness and
skin rash.
 Dose: 0.8–1 g TDS oral; children 20 mg/kg BD–
TDS; 1–3 g i.m. 6 hourly in stroke/head injury.

Pyritinol (Pyrithioxine) : It consists of two
pyridoxine molecules joined through a disulfide bridge,
but has no vit B6 activity.
 It is claimed to activate cerebral metabolism by
selectively increasing glucose transport across blood-
brain barrier and improving regional blood flow in
ischaemic brain areas.
 It has been promoted for: Sequelae of cerebrovascular
accidents, head injury, prolonged anaesthesia. Infants
and children with developmental disorders of CNS,
delayed milestones. Concentration and memory defects,
senility, organic brain syndromes.
 However, therapeutic benefit, if any, is uncertain.

 Dose: 100–200 mg TDS, children 50–100 mg TDS
orally; 200–400 mg every 4–6 hours (max. 1 g/day) has
been given i.v. for recovery from cerebral hypoxia due
to cardiac arrest, anaesthesia, brain operations and
stroke.
 Side effects: Only mild g.i. upset was noted initially.
Later skin rashes, itching and taste disturbances.
 It has been withdrawn in some countries.

Dihydroergotoxine (Codergocrine): It is a
semisynthetic ergot alkaloid having α adrenergic
blocking property; claimed to increase cerebral blood
flow selectively.
 Dose of 1.0–1.5 mg TDS oral/sublingual or 0.3 mg i.m.
OD, it has been recommended for MCI and dementia.
 Therapeutic value is not established.

Citicoline: It is a compound derived from choline and
cytidine, that is involved in biosynthesis of lecithin.
 Citicoline is believed to improve cerebral function by
increasing blood flow to the brain and enhancing
cerebral metabolism.
 In the absence of effective medicines and under
promotional pressure, citicoline is being commonly
prescribed for impaired brain function due to ischaemic
stroke, parkinsonism, head injury, etc.
 Dose: 0.5–1 g/day i.m. or i.v. inj, 200–600 mg/day oral in
divided doses.

Ginkgo biloba: The dried extract of this Chinese
plant contains a mixture of ginkgoflavon glycosides,
which have PAF antagonistic action.
 Since PAF has been implicated in cerebral thrombosis
and infarcts, it is professed that G. biloba will prevent
cerebral impairment in cerebrovascular insufficiency.
 It has been promoted for a variety of cognitive and
behavioural disorders in the elderly.
 Dose: 40–80 mg TDS for a minimum period of 4
weeks.

Piribedil: It is a dopaminergic agonist claimed to
improve memory, concentration, vigilance, giddiness and
tinnitus in the elderly due to circulatory insufficiency.
 Benefit is unsubstantiated.
 Minor efficacy in parkinsonism has also been reported.
Side effects are mild g.i. complaints.
 Dose: 50 mg OD, BD.

1) Cholinesterase inhibitor
 a) Phenserine: Phenserin treatments
increased cognition and regional cerebral
metabolic rate for glucose in AD patients.
 b) Dimebon: A cholinesterase inhibitor and also
a NMDA-antagonist, showed improved cognitive
and self-service functions while diminishing the
psychopathic symptoms in AD patients.

 c) Huperzine A: A Chinese herb with
reversibly and selectively acetylcholinesterase
inhibition activity, displayed good
pharmacokinetics with a rapid absorption and
a wide distribution in the body at a low to
moderate rate of elimination.
 Clinical trials have shown its cognitive
enhancement in AD at a dose of 0.4 mg and
seems to be a potential treatment option for
AD.

d) Ladostigil : A multimodal drug, combined
neuroprotective effects with monoamine oxidase
(MAO) -A and -B and cholinesterase inhibitory
activities in a single molecule, was tested and now
in Phase II clinical trial.
e) PMS777: A new cholinesterase inhibitor
with anti-PAF activity is also in clinical trial

 a) β-secretase inhibitors:
 i) BACE (β- site APP cleaving enzyme): Lateral
ventricular injection of this inhibitor led to a
significant dose- and time-dependent lowering of
brain Aβ40 and Aβ42, a robust decreased sAPPβ
and an increased sAPPα secretion.
 ii) KMI-429: Injection of this inhibitor into the
hippocampus of APP transgenic mice reduced Aβ
production.
2) Aβ-targeting strategies

 iii) GSK188909: Oral administration of this
non-peptidic BACE1 inhibitor results in a
significant reduction in the level of Aβ40 and
Aβ42 in the brain of transgenic mice.

b) γ-secretase inhibitors
i) BMS-299897
ii) MRK-560.
iii) LY450139 dihydrate

c) α-secretase activators/modulators
Since α-secretase and β-secretase compete
for the same substrate of APP, upregulation of
α-secretase activity may decrease the amount of
APP available for β-secretase, and thus decrease
Aβ secretion and have therapeutic potential.

 Many studies had indicated that members of
the adamalysin family of proteins, mainly
ADAM(A Disintegrin And Metalloproteinase)
10, ADAM 17 and ADAM 9, fulfill some of the
criteria required of α-secretase.
 i) Deprenyl: A neuroprotective agent used to
slow AD progress, was shown to increase α-
secretase activity by promoting ADAM10 and
PKCα/ε translocation

d)M1 muscarinic agonists
M1 muscarinic receptors play a role in an
apparent linkage of three major hallmarks of
AD: Aβ peptide; tau hyperphosphorylation and
loss of cholinergic function conductive to
cognitive impairments.

 i) Talsaclidine: It is a functionally selective
muscarinic M1 agonist that stimulates non-
amyloidogenic α-secretase processing in vitro.
In a double-blind, placebo-controlled, and
randomized clinical study in AD patients,
treatment with talsaclidine decreased CSF Aβ
about 20% as compared with the baseline,
suggesting its therapeutic potential.

 ii) AF102B: another M1 agonist, also decreased
CSF Aβ of AD patients.
 iii) AF267B: On clinical trial.

e) Aβ-aggregation inhibitor
 i) iAβ5p: This is the first drug was a β-sheet
breaker, which showed that intra hippocampal
injection of it resulted in improved spatial
memory and decreased amyloid plaque deposits.
 ii) Tramiprosate: It is a compound that binds
to soluble Aβ and inhibits the formation of
neurotoxic aggregates that lead to amyloid
plaque deposition in the brain.

f) Immunotherapy
 Passive immunotherapy in AD patients with
repeated intravenous administration of human
immunoglobulin against Aβ peptide resulted in
stopped cognitive decline and slight
improvement in functional scores.
i) LY2062430: On Phase I and II clinical trials.

ii) Bapineuzumab: After a phase II,
multicenter, randomized, double-blind,
placebo-controlled clinical trials it shows
decreased total and phosphorylated tau levels
in CSF without affecting Aβ level.

iii) AN1792A: Randomized, double-blind,
placebo controlled, phase II clinical trial with
this synthetic Aβ peptide in patients with mild to
moderate AD was initiated, but the trial was
later discontinued because of approximately 6%
of the immunized AD patients(18/300) developed
meningoencephalitis.

g) Aβ-degrading enzymes
i) Neprilysin (NEP),
ii) Insulindegrading enzyme (IDE),
iii) Plasmin,
iv) Endothelin converting enzyme (ECE) 1
and 2,
v) Angiotensin-converting enzyme.

 vi) Imatinib: A tyrosine kinase inhibitor, was
shown to elevate AICD ( APP intracellular
domain) in H4 human neuroglioma cells, and
this was accompanied by concomitant increases
of NEP protein, mRNA levels, and activity.
 vii) Valproic acid: A widely used drug in the
treatment of epilepsy, was capable of up-
regulating NEP expression, seen in
experimental rats.

 Estrogen and green tea all could increase
NEP activity and suggest their potential in
AD treatment but there is a long way before
their final clinical application.

h) Apolipoprotein E (ApoE) promotes Aβ
clearance
 The lipidated ApoE activates microglia and/or
astrocyte to degrade Aβ. It decreased brain
amyloid plaque burden and improved behavior
functions in AD transgenic mice.
 Bexarotene: Is a nuclear receptor modulator
and ApoE activator, whether it is effective in
AD prevention needs to be explored clinically.

i) Drugs influencing Aβ blood–brain
barrier transport
 The receptor for advanced glycation end
products (RAGE) resides in the blood vessel
wall cells and transport Aβ across the blood
brain barrier from systemic circulation to
facilitate their accumulation in brain.

 In contrast to RAGE, low-density lipoprotein
receptor-related protein-1 (LRP-1) mediates
transport of Aβ peptide out of brain.
 Thus inhibition of RAGE and/or activation of
LRP-1 may be a therapeutic target for AD, but
there are no clinical data available at present.

 3) Drugs development based on the
metals hypothesis:
 There is increasing evidence that metal (mainly
Cu, Zn and Fe) metabolism is involved in the
major phthophysiological events of AD: APP
processing and tau hyperphosphorylation.
Several chelators of Zn/Cu have been shown to
inhibit Aβ aggregation in vitro and in vivo.

 A phase II clinical trial with clioquinol, a
metal-protein-attenuating compound that
inhibits zinc and copper ions from binding to
Aβ, led to improved cognitive function,
decreased plasma Aβ42 level and zinc
concentration as compared with control group.

 Other metal chelators includs XH1, DP-109,
PBT2.
 PBT2 was an orally available, second generation
8-OH quinoline derivative of clioquinol, and is
advancing as a disease-modifying candidate
drug for Alzheimer’s disease.

4) HMG-CoA reductase inhibitors
(the “statins”):
 Clinical trial with atorvastatin for 1 year
provides some clinical benefit in AD patients.
Treatment with lovastatin resulted in decreased
plasma Aβ level.

5) Monoamine oxidase inhibitors
 MAO inhibitor deprenyl is an anti-Parkinson
drug used to inhibit dopamine degradation in the
brain. Also as a neuroprotective agent, deprenyl
has been used to slow the progress of
neurodegenerative diseases such as AD for many
years.

 Rasagiline: Another MAO-B inhibitor is a
bifunctional molecule which also has
acetylcholinesterase inhibition activity.

 6)Treatments based on tau pathology
a) Prevention of phosphorylation of tau
b) Prevention of the aggregation of tau
c) Prevention the misfolding of tau
d) Tau immunotherapy

 Protein phosphatase (PP)-2A: It may increase
dephosphorylation of tau. PP-2A also inhibits
kinases such as MAPK (mitogen activated
protein kinase), which phosphorylate tau.
a) Prevention of phosphorylation of tau

 Cyclin-dependent kinase-5 (CDK5): It is a
kinase suggested to phosphorylate tau in AD.
Transgenic mice in which CDK5 activity is
activated (by overexpression of the p25
activator) in adult brain show evidence of a
striking neurodegeneration with some tau
pathology.

As report, inhibitors of CDK5 appear
to have some influence on the
development of pathology in some tau
transgenic mice. There are as yet no
reports of the use of CDK5 inhibitors in
humans.

Glycogen synthase kinase (GSK)-3β: It has
also been suggested as a drug target to
inhibit tangle formation.
This kinase is blocked by
Lithium,
The M1 muscarinic agonist AF267B,
Propentofylline (PPF) and
SRN-003-556.

Recent studies using cell models have
demonstrated that certain drug inhibitors
are able to prevent tau protein
aggregation and even dissolve the
developed aggregates, which include-
b) Prevention of the aggregation of tau

 Phenothiazines,
 Anthraquinones,
 Polyphenols,
 Thiacarbocyanine dyes,
 N-phenylamines,
 Thiazolyl-hydrazides,
 Rhodanines,
 Quinoxalines,
 Aminothienopyridazines etc.

c) Prevention the misfolding of tau
 i) Chaperones: The results from a study
by Dou and colleagues suggested that
increasing the activation of molecular
chaperones might prevent the misfolding of
tau, which would then reduce the
development of NFTs.

ii) Heat shock proteins: They have been
shown to activate chaperones that prevent
misfolding and even promote tau binding
with microtubules.

7) Non-steroidal anti-inflammatory
drugs (NSAIDs)
More than 20 epidemiological studies,
some with a follow-up design and a good
estimation of NSAIDs use via prescription
data from pharmacies have suggested that
the prolonged intake of NSAIDs may be
associated with a reduced incidence of AD.

8) Estrogens
Merlo et al. reported that estrogen can
activate matrix metalloproteinases-2 and −9
to increase beta amyloid degradation.

9)Nicotine
 Published studies in humans have reported the
effects of intravenous or subcutaneous nicotine
administration on people with AD.
 Significant improvements were reported in
several cognitive tasks such as free recall,
visual attention and perception and in mood
although not on memory.

10) Melatonin
In AD patients, melatonin
supplementation has been suggested to
improve circadian rhythmicity, and to
produce beneficial effects on memory.

11) Cell transplantation and gene
therapy
 In AD rat model, transplantation of cholinergic-
rich tissue or peripheral cholinergic neurons
ameliorates abnormal behavior and cognitive
function. But no clinical trials in AD patients
have been initiated with this method.

a) Endogenous nerve growth factor (NGF):
NGF administration rescues neurons
from injury-induced cell damage and leads
to associated memory improvements and
thus NGF is good for gene therapy.

b) Besides NGF, another candidate for gene
therapy is Aβ-degrading enzymes and the
animal experiments are also positive. Clinical
trials are not being initiated yet.

12) Other pharmacological therapies
in clinical AD trails
a) Docosa-hexaenoic acid (DHA):
DHA is the most abundant omega 3 fatty acid
in the brain. Data from animal models support
the hypothesis that DHA maybe an effective
treatment for AD by means of antiamyloid,
antioxidant, and neuroprotective mechanisms.

b) Clioquinol: Metal chelation using
clioquinol has been reported in a pilot
study with 36 patients with AD to reduce
the rate of cognitive loss in a double-blind,
placebo-controlled, phase 2 clinical trial.

c) Resveratrol: Resveratrol, a red wine
polyphenol, recent studies on red wine
bioactive compounds suggest that
resveratrol modulates multiple mechanisms
of AD pathology.

Exert its neuroprotective role through
inhibition of Aβ aggregation, by
scavenging oxidants and exerting anti
inflammatory activities.

Vaccines
 AN-1792: Phase I studies of AN-1792 in humans
indicated that the vaccine was well tolerated, and
a portion of the patients developed amyloid
antibodies. As a result of these findings, a
multicenter Phase IIa study in patients with mild-
to-moderate Alzheimer’s disease was initiated.

Passive immunization: By using antibodies
to Aβ4-10.
Intravenous immunoglobulin (IVIg):
Initial results suggest that IVIg infusion
may have long-term benefits for the
treatment of cognitive decline in
Alzheimer’s disease.149 A Phase II study is
currently underway.150

The ultimate goal for Alzheimer’s disease
pharmacotherapy is not merely to
ameliorate symptoms, but to alter the onset
or progression of the disease.
Conclusion

There are four drugs (donepezil,
galantamine, rivastigmine, and
memantine) currently approved for the
treatment of Alzheimer’s disease, but the
numerous complex and interrelated
biochemical pathways underlying
neurodegeneration in Alzheimer’s disease
provide numerous potential targets for
therapeutic intervention.

Several investigational compounds have
demonstrated potential as therapeutic or
preventive therapies and merit additional
study. Gradual elucidation of the exact
mechanisms of neurodegeneration will
result in increasingly focused drug
development efforts.

References
1)Evaluating Prescription Drugs Used to Treat: Alzheimer's Disease Comparing
Effectiveness, Safety, and Price [PDF]. Consumer Reports Drug Effectiveness
Review Project May 2012 [Retrieved 1 May 2013]. Consumer Reports.
2)Hong-Qi et al. Translational Neurodegeneration 2012,
1:21http://www.translationalneurodegeneration.com/content/1/1/21: Current
advances in the treatment of Alzheimer’s disease: focused on considerations
targeting Aβ and tau.
3)Current Strategies for the Treatment and Prevention of Alzheimer’s Disease,
Primary Psychiatry | August 1, 2007 .
4) Goodman gilman’s The pharmacological basis of therapeutics, 12th edition.
5) Pharmacology and pharmacotherapeutics by R.S. Satoskar, 23rd edition.
6) Essential of Medical Pharmacology by K.D. Tripathi, 7th edition.

Recent advances in the management of alzheimers disease

Recent advances in the management of alzheimers disease

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