alzemers modified

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Presented by

K.SAIKRISHNAM.PHARM

(Pharmacology)

Under the Guidance of

Dr. K. PRASAD

M.PHARM., PhD

Shri Vishnu College of Pharmacy, Dept. of pharmacology , Vishnupur, Bhimavaram -2.


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AD STATISTICS INSIDE THE HUMAN BRAIN MECHANISM OF ACTION

TYPES OF AD

SEARCH FOR CAUSES

DIAGNOSIS

TREATMENT

RECENT DEVELOPMENTS CONCLUSION REFERENCES


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The Impact ofAlzheimer's Disease(AD)

Once considered a rare

disorder, Alzheimers diseaseis now seen as a major publichealth problem that isseriously affecting millions of

older People and their families.


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Although the risk of developing AD increases with

age in most people with AD, symptoms firstappear after age 60 AD is not a part of normalaging. AD is the most common cause of dementiaamong people age 65 and older.[2]

This incurable, degenerative, and terminal diseasewas first described by German psychiatrist andneuropathologist Alois Alzheimer in 1906 and was

named after him.[1]


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The World Health Organizationestimated that in 2005, 0.379% ofpeople worldwide had dementia,and that the prevalence wouldincrease to 0.441% in 2015 and to0.556% in 2030.[3]

Scientists estimate that around4.5 million people now have AD.

AD Statistics.


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To understandAlzheimersdisease, itsimportant toknow a bit about

the brainThe Brains Vital Statistics

Adult weight:about 3 pounds

Adult size:

a medium cauliflower Number of neurons:

100,000,000,000(100 billion)

Number of synapses(the gap between neurons):100,000,000,000,000

(100 trillion)Slide 8


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The Three Main layers

1. Cerebral Hemispheres

2. Cerebellum

3. Brain Stem

Other Crucial Parts Hippocampus: where short-term memories are converted

to long-term memories

Thalamus: receives sensory and limbic information andsends to cerebral cortex

Hypothalamus: monitors certain activities and controlsbodys internal clock

Limbic system: controls emotions and instinctive behavior(includes the hippocampus and parts of the cortex)


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The Brain in Action

Hearing Words Speaking Words Seeing Words Thinking about Words

Different mental activities take place in different parts

of the brain. Positron emission tomography (PET)scans can measure this activity. Chemicals taggedwith a tracer light up activated regions shown in redand yellow.


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Neurons

The brain has billionsof neurons, each withan axon and manydendrites.

To stay healthy,neurons mustcommunicate witheach other, carry out

metabolism, andrepair themselves.

AD disrupts all threeof these essential jobs.


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Plaques and Tangles[4]: The Hallmarks of AD

The brains of people with AD have an abundance oftwo abnormal structures:

An actual AD plaque An actual AD tangle

Beta-amyloid plaques[5] [6], which are densedeposits of protein and cellular material that

accumulate outside and around nerve cells Neurofibrillary tangles [7], which are twisted fibers

that build up inside the nerve cell


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Beta-Amyloid Plaques

Amyloid precursor protein (APP) isthe precursor to Amyloid plaque [8] [9].

1. APP sticks through the neuronmembrane.

2. Enzymes cut the APP intofragments of protein, includingbeta-Amyloid.

3. Beta-Amyloid fragments cometogether in clumps to form plaques.

1.

2.

3.

In AD, many of these clumps form,disrupting the work of neurons.This affects the hippocampus andother areas of the cerebral cortex.


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NeurofibrillaryTangles

Neurons have an internal support structure partly made up ofmicrotubules. A protein called tauhelps stabilize microtubules.In AD, tauchanges, causing microtubules to collapse, and tau

proteins clump together to form neurofibrillary tangles[10].


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Preclinical AD[10] [11] Signs of AD are firstnoticed in the entorhinalcortex, then proceed to thehippocampus.

Affected regions begin to

shrink as nerve cells die.

Changes can begin 10-20years before symptomsappear.

Memory loss is the firstsign of AD.


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Mild to Moderate AD[12] [113]

AD spreads through thebrain. The cerebral cortexbegins to shrink as more andmore neurons stop workingand die.

Mild AD signscan includememory loss, confusion,

trouble handling money,poor judgment, moodchanges, and increasedanxiety.

Moderate AD signscaninclude increased memoryloss and confusion, problemsrecognizing people, difficultywith language and thoughts,

restlessness, agitation,


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Severe AD [14] [15] In severe AD, extreme

shrinkage occurs in thebrain. Patients arecompletely dependent onothers for care.

Symptoms can includeweight loss, seizures, skininfections, groaning,moaning, or grunting,increased sleeping, loss of

bladder and bowel control. Death usually occurs from

aspiration pneumonia orother infections. Caregiverscan turn to a hospice for helpand palliative care.


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AD develops when genetic, lifestyle, and

environmental factors work together to causethe disease process to start.

In recent years, scientists have discoveredgenetic links [16] to AD. They are alsoinvestigating other factors that may play a rolein causing AD.


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Genetic Studies [17]

The two main types ofAD are early-onset andlate-onset:

Early-onset AD is rare,usually affecting people

aged 30 to 60 and usuallyrunning in families.Researchers haveidentified mutations inthree genes that causeearly-onset AD.

Late-onset AD is morecommon. It usually affectspeople over age 65.

Researchers have identified a gene that produces a protein calledapolipoprotein E (ApoE). Scientists believe this protein is involved in

the formation of beta-amyloid plaques.


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Studies at the Cellular and Molecular

Level

Homocysteine, an amino acid, is a risk factor for heartdisease. A study shows that an elevated level ofhomocysteine is associated with increased risk of AD.

Scientists are also looking at inflammation in certainregions of the brain and strokes as risk factors for AD.

Oxidative damage fromfree radical moleculescan injure neurons.

P t S f


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Physicians today use a

number of tools todiagnose AD:

a detailed patient history

physical and neurological

exams and lab tests

Advanced medical imaging withcomputed tomography (CT) ormagnetic resonance imaging(MRI), and with single photonemission computed tomography(SPECT) or positron emissiontomography (PET) can be usedto help exclude other cerebralpathology or subtypes of

dementia.[18]

Normal & AD MRI SCAN

Pet Scan ofNormal Brain

Pet Scan ofAlzheimers

Disease Brain


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TREATMENTFOR

Alzheimer'sDisease

DRUG


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DRUG

NAMEDRUG TYPE AND USE HOW IT WORKS COMMON SIDE EFFECTS

Namenda

(memantin

e)[19][20][21]

N-methyl D-aspartate

(NMDA) antagonist

prescribed to treat

symptoms of moderate tosevere Alzheimers

Blocks the toxic effects

associated with excess

glutamate and regulates

glutamate activation

Dizziness, headache,

constipation, confusion[22]

Razadyne

(galantami

ne)[23]

Cholinesterase inhibitor

prescribed to treat

symptoms of mild to

moderate Alzheimers

Prevents the breakdown of

acetylcholine and stimulates

nicotinic receptors to release

more acetylcholine in the brain

Nausea, vomiting,

diarrhea, weight loss, loss

of appetite

Exelon

(rivastigmi

ne)[24]


prescribed to treat

symptoms of mild to

moderate Alzheimers


acetylcholine and butyrylcholine

(a brain chemical similar to

acetylcholine) in the brain

Nausea, vomiting,

diarrhea, weight loss, loss

of appetite, muscle

weakness

Aricept

(donepezil)[25]


prescribed to treat

symptoms of mild to

moderate, and moderate

to severe Alzheimers


acetylcholine in the brain

Nausea, vomiting, diarrhea


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Dietary supplements[26]The following are the supplements to take:

Supplement Purpose

------------------- -----------------------------------------------

Vitamins C & E provides antioxidants to prevent Alzheimer'sCurcumin prevent Alzheimer's

Aspirin keeps blood thin - helps prevent heart attacks

Omega-3 (fish oil) prevent Alzheimer's

Iron pills maintain healthy red blood cells

Glucosamine sulfate prevents arthritisVitamin B complex prevent Alzheimer's

Sage leaf prevent Alzheimer's

DHEA hormone supplement

Blueberries prevent Alzheimer's

Citrical provides calcium for strong bonesDMAE active ingredient of skin care creams

Phosphatidyl choline prevent Alzheimer's - help retain acetylcholine in the brai

Lemonade prevent kidney stones

Huperzine-A prevent Alzheimer's (* NEW *)


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1. Scientists discover way to reverse loss of memory : It seems that in some

cases electrical stimulation of the brain can reverse memory loss. I guess thequestion is how many people can afford this type of treatment.?

2. Within 5 years there could be a vaccine which will break up the sticky globesof amyloid proteins which cause Alzheimer's disease, Known as CAD106, it isthe brainchild of scientists at Zurich-based biotechnology firm Cytos.

3. PBT2 - Australian doctors have produced a drug , PBT2, which not onlyprevents build up of the amyloid protein linked to the disease, but actuallyclears it out of the brain. Phase II clinical trails are beginning.

4. Huperzine A - It is an extract from a club moss (Huperzia serrata) that has

been used for centuries in Chinese folk medicine. Huperzine's action has beenattributed to its ability to strongly inhibit acetylcholinesterase, the enzyme thatbreaks down acetylcholine in the synaptic cleft. Acetylcholine is involved inmemory and learning.

RECENT DEVELOPMENTS


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1. By doing physical exercise like.

Walk, run, dance, swim, pump iron, whatever you can handle.

2. Bydoing mental exercise like.

Learn a new language. Play bridge, or chess. Do crossword

puzzles, Read.

3. By change your diet like.

The above mentioned diet have been found to be beneficial.

By doing these steps it will reduce risk of

suffering from this fatal disease.

CONCLUSION

REFERENCES


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1. Berchtold NC, Cotman CW (1998). "Evolution in the conceptualization of dementia and Alzheimer's

disease: Greco-Roman period to the 1960s". Neurobiol. Aging 19 (3): 17389. doi:10.1016/S0197-

4580(98)00052-9. PMID 9661992.

2. Brookmeyer R., Gray S., Kawas C. (September 1998). "Projections of Alzheimer's disease in the UnitedStates and the public health impact of delaying disease onset".American Journal of Public Health 88 (9):

133742. doi:10.2105/AJPH.88.9.1337. PMID 9736873.

3. World Health Organization (2006).Neurological Disorders: Public Health Challenges. Switzerland: World

Health Organization. pp. 204207. ISBN 978-92-4-156336-9.

http://www.who.int/mental_health/neurology/neurodiso/en/indzex.html.

4. Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J (June 2004). "The importance of neuritic plaques and

tangles to the development and evolution of AD".Neurology 62 (11): 19849. PMID 15184601

5. Hardy J, Allsop D (October 1991). "Amyloid deposition as the central event in the aetiology of

Alzheimer's disease". Trends Pharmacol. Sci. 12 (10): 38388. doi:10.1016/0165-6147(91)90609-V.

PMID 1763432.

6. Mudher A, Lovestone S (January 2002). "Alzheimer's disease-do tauists and baptists finally shakehands".Trends Neurosci. 25 (1): 2226. doi:10.1016/S0166-2236(00)02031- 2. PMID 11801334.

7. Mudher A, Lovestone S (January 2002). "Alzheimer's disease-do tauists and baptists finally shake

hands". Trends Neurosci. 25 (1): 2226. doi:10.1016/S0166- 2236(00)02031-2. PMID 11801334.

REFERENCES


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8. Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J (July 2006). "Synapse formation

and function is modulated by the amyloid precursor protein".J. Neurosci. 26 (27): 721221.

doi:10.1523/JNEUROSCI.1450-06.2006. PMID 16822978.

9. Turner PR, O'Connor K, Tate WP, Abraham WC (May 2003). "Roles of amyloid precursor protein and

its fragments in regulating neural activity, plasticity and memory". Prog. Neurobiol. 70 (1): 132.

doi:10.1016/S0301-0082(03)00089-3. PMID 12927332.

10. Hernndez F, Avila J (September 2007). "Tauopathies". Cell. Mol. Life Sci. 64 (17): 221933.

doi:10.1007/s00018-007-7220-x. PMID 17604998.

11. Frstl H, Kurz A (1999). "Clinical features of Alzheimer's disease".European Archives of

Psychiatry and Clinical Neuroscience 249 (6): 288290. doi:10.1007/s004060050101.

PMID 10653284.

12. Carlesimo GA, Oscar-Berman M (June 1992). "Memory deficits in Alzheimer's patients: a

comprehensive review".Neuropsychol Rev 3 (2): 11969. doi:10.1007/BF01108841.

PMID 1300219.

13. Jelicic M, Bonebakker AE, Bonke B (1995). "Implicit memory performance of patients with

Alzheimer's disease: a brief review".International Psychogeriatrics 7 (3): 385

392.

doi:10.1017/S1041610295002134. PMID 8821346.

14. Taler V, Phillips NA (Jul 2008). "Language performance in Alzheimer's disease and mild

cognitive impairment: a comparative review".J Clin Exp Neuropsychol 30 (5): 50156.

doi:10.1080/13803390701550128. PMID 1856925.

15. Frank EM (September 1994). "Effect of Alzheimer's disease on communication function".J S C MedAssoc 90 (9): 41723. PMID 7967534.


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16. Blennow K, de Leon MJ, Zetterberg H (July 2006). "Alzheimer's disease".Lancet368 (9533): 387403.

doi:10.1016/S0140-6736(06)69113-7. PMID 16876668.

17. Waring SC, Rosenberg RN (March 2008). "Genome-wide association studies in Alzheimer disease".Arch

Neurol 65 (3): 32934. doi:10.1001/archneur.65.3.329. PMID 18332245.

18. "Dementia: Quick reference guide" (PDF). London: (UK) National Institute for Health and Clinical

Excellence. November 2006. http://www.nice.org.uk/nicemedia/pdf/CG042quickrefguide.pdf. Retrieved 2008-

02-22.

19. Lipton SA (2006). "Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and

beyond".Nat Rev Drug Discov 5 (2): 160170. doi:10.1038/nrd1958. PMID 16424917.

20."Memantine". US National Library of Medicine (Medline). 2004-01-04.

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a604006.html. Retrieved 2010-02-03.21. Areosa Sastre A, McShane R, Sherriff F (2004). "Memantine for dementia". Cochrane Database Syst Rev (4):

CD003154. doi:10.1002/14651858.CD003154.pub2. PMID 15495043.

22. "Namenda Prescribing Information" (PDF). Forest Pharmaceuticals. http://www.frx.com/pi/namenda_pi.pdf.

Retrieved 2008-02-19.

23. "Galantamine".Medline Plus. US National Library of Medicine. 2007-01-08.

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a699058.html. Retrieved 2010-02-03

24. "Rivastigmine".Medline Plus. US National Library of Medicine. 2007-01-08.

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a602009.html. Retrieved 2010-02-03.

25. "Donepezil".Medline Plus. US National Library of Medicine. 2007-01-08.

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a697032.html. Retrieved 2010-02-03

26. www.fatsforhealth.com


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