K.

SAIKRISHNA

Presented by

M.PHARM (Pharmacology)

Under the Guidance of Dr. K. PRASAD

M.PHARM., PhD

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

AD STATISTICS INSIDE THE HUMAN BRAIN MECHANISM OF ACTION TYPES OF AD

SEARCH FOR CAUSES DIAGNOSIS TREATMENT RECENT DEVELOPMENTS CONCLUSION REFERENCES

The Impact of Alzheimer's Disease (AD) Once considered a rare disorder, Alzheimers disease is now seen as a major public health problem that is seriously affecting millions of older People and their families.

What is Alzheimers disease?

This incurable, degenerative, and terminal disease was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him.[1]

Although the risk of developing AD increases with age in most people with AD, symptoms first appear after age 60 AD is not a part of normal aging. AD is the most common cause of dementia among people age 65 and older.[2]

AD Statistics.

The World Health Organization estimated that in 2005, 0.379% of people worldwide had dementia, and that the prevalence would increase to 0.441% in 2015 and to 0.556% in 2030.[3]

Scientists estimate that around 4.5 million people now have AD.

Brain
To understand Alzheimers disease, its important to know a bit about the brain
The 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

Inside the Human Brain

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 and sends to cerebral cortex Hypothalamus: monitors certain activities and controls bodys internal clock Limbic system: controls emotions and instinctive behavior (includes the hippocampus and parts of the cortex)

Inside the Human Brain

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 tagged with a tracer light up activated regions shown in red and yellow.

Inside the Human Brain

The brain has billions of neurons, each with an axon and many dendrites.
Neurons

To stay healthy, neurons must communicate with each other, carry out metabolism, and repair themselves.
AD disrupts all three of these essential jobs.

AD and the Brain

Plaques and Tangles[4]: The Hallmarks of AD

The brains of people with AD have an abundance of two abnormal structures: Beta-amyloid plaques[5] [6], which are dense deposits 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

An actual AD plaque

An actual AD tangle

AD and the Brain

Beta-Amyloid Plaques
1.

Amyloid precursor protein (APP) is the precursor to Amyloid plaque [8] [9]. 1. APP sticks through the neuron membrane. 2. Enzymes cut the APP into fragments of protein, including beta-Amyloid. 3. Beta-Amyloid fragments come together in clumps to form plaques.

2.

3.

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

AD and the Brain

Neurofibrillary Tangles

Neurons have an internal support structure partly made up of microtubules. A protein called tau helps stabilize microtubules. In AD, tau changes, causing microtubules to collapse, and tau proteins clump together to form neurofibrillary tangles [10].

AD and the Brain

Preclinical AD [10] [11]

Signs of AD are first noticed in the entorhinal cortex, then proceed to the hippocampus. Affected regions begin to shrink as nerve cells die.
Changes can begin 10-20 years before symptoms appear. Memory loss is the first sign of AD.

AD and the Brain

Mild to Moderate AD [12] [113]

AD spreads through the brain. The cerebral cortex begins to shrink as more and more neurons stop working and die.
Mild AD signs can include memory loss, confusion, trouble handling money, poor judgment, mood changes, and increased anxiety. Moderate AD signs can include increased memory loss and confusion, problems recognizing people, difficulty with language and thoughts, restlessness, agitation,

AD and the Brain

Severe AD [14] [15]

In severe AD, extreme shrinkage occurs in the brain. Patients are completely dependent on others for care. Symptoms can include weight loss, seizures, skin infections, groaning, moaning, or grunting, increased sleeping, loss of bladder and bowel control.

Death usually occurs from aspiration pneumonia or other infections. Caregivers can turn to a hospice for help and palliative care.

AD Research: the Search for Causes

AD develops when genetic, lifestyle, and environmental factors work together to cause the disease process to start. In recent years, scientists have discovered genetic links [16] to AD. They are also investigating other factors that may play a role in causing AD.

AD Research: the Search for Causes

Genetic Studies [17]

The two main types of AD are early-onset and late-onset:

Early-onset AD is rare, usually affecting people aged 30 to 60 and usually running in families. Researchers have identified mutations in three genes that cause early-onset AD. Late-onset AD is more common. It usually affects people over age 65. Researchers have identified a gene that produces a protein called apolipoprotein E (ApoE). Scientists believe this protein is involved in the formation of beta-amyloid plaques.

AD Research: the Search for Causes

Studies at the Cellular and Molecular Level

Oxidative damage from free radical molecules can injure neurons. Homocysteine, an amino acid, is a risk factor for heart disease. A study shows that an elevated level of homocysteine is associated with increased risk of AD. Scientists are also looking at inflammation in certain regions of the brain and strokes as risk factors for AD.

Diagnosing AD
Physicians today use a number of tools to diagnose AD:
a detailed patient history physical and neurological exams and lab tests

Pet Scan of Normal Brain

Pet Scan of Alzheimers Disease Brain

Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single photon emission computed tomography (SPECT) or positron emission tomography (PET) can be used to help exclude other cerebral pathology or subtypes of dementia.[18]

Normal

& AD MRI SCANS

TREATMENT FOR Alzheimer's Disease

DRUG NAME Namenda (memantin e) [19] [20] [21]

DRUG TYPE AND USE

N-methyl D-aspartate (NMDA) antagonist prescribed to treat symptoms of moderate to severe Alzheimers

HOW IT WORKS
Blocks the toxic effects associated with excess glutamate and regulates glutamate activation Prevents the breakdown of acetylcholine and stimulates nicotinic receptors to release more acetylcholine in the brain

COMMON SIDE EFFECTS

Dizziness, headache, constipation, confusion[22]

Razadyne Cholinesterase inhibitor (galantami prescribed to treat ne) [23] symptoms of mild to moderate Alzheimers Exelon (rivastigmi ne) [24] Cholinesterase inhibitor prescribed to treat symptoms of mild to moderate Alzheimers Cholinesterase inhibitor prescribed to treat symptoms of mild to moderate, and moderate to severe Alzheimers

Nausea, vomiting, diarrhea, weight loss, loss of appetite

Prevents the breakdown of Nausea, vomiting, acetylcholine and butyrylcholine diarrhea, weight loss, loss (a brain chemical similar to of appetite, muscle acetylcholine) in the brain weakness Prevents the breakdown of acetylcholine in the brain Nausea, vomiting, diarrhea

Aricept (donepezil)
[25]

Dietary supplements

[26]

The following are the supplements to take: Supplement Purpose ----------------------------------------------------------------Vitamins C & E provides antioxidants to prevent Alzheimer's Curcumin 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 arthritis Vitamin B complex prevent Alzheimer's Sage leaf prevent Alzheimer's DHEA hormone supplement Blueberries prevent Alzheimer's Citrical provides calcium for strong bones DMAE active ingredient of skin care creams Phosphatidyl choline prevent Alzheimer's - help retain acetylcholine in the brain Lemonade prevent kidney stones Huperzine-A prevent Alzheimer's (* NEW *)

RECENT DEVELOPMENTS
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 the question 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 globes of amyloid proteins which cause Alzheimer's disease, Known as CAD106, it is the brainchild of scientists at Zurich-based biotechnology firm Cytos.
3. PBT2 - Australian doctors have produced a drug , PBT2, which not only prevents build up of the amyloid protein linked to the disease, but actually clears 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 been attributed to its ability to strongly inhibit acetylcholinesterase, the enzyme that breaks down acetylcholine in the synaptic cleft. Acetylcholine is involved in memory and learning.

CONCLUSION
1. By doing physical exercise like. Walk, run, dance, swim, pump iron, whatever you can handle.

2. By doing 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.

REFERENCES
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/S01974580(98)00052-9. PMID 9661992.

2. Brookmeyer R., Gray S., Kawas C. (September 1998). "Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset". American Journal of Public Health 88 (9): 1337 42. 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 shake hands".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.

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): 385392. 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 Med Assoc 90 (9): 41723. PMID 7967534.

16. Blennow K, de Leon MJ, Zetterberg H (July 2006). "Alzheimer's disease". Lancet 368 (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 200802-22. 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