#introduction #factors #pathophysiology #treatments #anti alzheimer drugs #experimenta drugs #laboratory tests

1. Alzheimer's disease
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introduction...
Alzeihmere disease is a degenerative brain disorder
• It is the most common form of dementia
• Usually starts in late middleage or in old age
• result in -prgressive memory loss
-impaired thinking
-disorientation
-changes in personality and mood(1)
• There is degeration of brain nervous especially in the cerebralcortex and presence of nuerofibrillary tangles and plaque
containg beta amyloid cells .( 1 )

2. Incidences……
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More than 5 million Americans haveAlzheimer’s disease, the most common form of dementia. (2)
Alzheimer’s accounts for 60 to 80 percent of all dementia cases. That includes 11 percent of those age 65 and older and
one-third of those 85 and older .(3)
• About 3,60,000 new cases of alzeihmere’s are diagnosed each year .
• About 3% of men and women ages 65 to 74 have alzeihmere’s disease(2)

3. Various Factors……
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Environmental factors…
• Cigarettesmoking.
• Certainninfections
• Metalss industrialor other toxins
Use of cholesterol lowering drugs.

4. 2 -Risk factors
1. Down’s syndrome - Down syndrome is a chromosomal disorder caused when an error in cell division results in an extra 21st
chromosome. There can be impairments in cognitive ability and physical growth, mild to moderate developmental disabilities,
and a higher risk of some health problems (5)
2. Family history
3. Chronic high blood pressure
4. Head injuries.
5. Gender
6. Smoking anddrinking

5. 3 – Neurochemical factors
•Acetylcholine
•Somatostatin
•Sunstance P
•Norepinephrine .
Pathology -
•There are 3 consistent neuropathologicall hallmarks:
•Amyloid-rich senile plaques
•Neurofibrillary tangles
•Neuronal degeneration
These changes eventually lead to clinicall symptoms, but they begin years before the onset of symptoms(7)

6. Pathophysiology…
Alzeihmere’s disease attacks nervous and brain cells
as well as neuratransmitters
The destruction of these part causes clumps of
protein to form around the brain cells. These clumos
are known as plaques and bundles.( 8 )
The plaques and bundles start to destroy more
connection between the brain cells ,which make the
condition worse.(12)

7. Comparison between normal brain and
AD affectedbrain
Normal brain AD effectedbrain

8. Anti-Alzeimhere‘s drugs….
1.
2
• The anti alzeihmere’s drugs are classified into two types…
1. Approved drugs.
2. Experimental drugs.
• Apprroved drugs – itmay be classified into 2 types…
Cholinesterase inhibitors..
1 donepezil
2 rivastigmine
3 galantamine
NMDA antagonist …..
1 memantine

9. Experimental drugs….
•
• Antioxidants - ginkgo boliba.
-vitamin E .
•Gaama agonists -
durgs -pioglitazone .
gaama secretaseinhibitors –
drugs -semagesastat .

10. •
•Statins
- simvastatin
-pravastatin
Others
-heavy metalchelators
-estrogen
-antiinflammatory drugs

11. Cholinesterase inhibitors…..
1 donepezil
2 rivastigmine
3 galantamine
4 tacrine
Cholinergic hypothesis–
role –
acetylcholine is a important neuratransmitters in brain regoin involved in memories
Impact –
loss of acetylcholine in AD correlates with impairmentof memories
Treatment approah –
•Enhancement of cholinergic function
may stablize or imorove congitive
function and may effect behavior and daily function .

12. Tacrine
• Aminoacridine
• Dose dependent affect 40- 160mg per day
• half life:3-5 years .
• Metabolized byCYP450
• Adverse effects.
-nousea
-vomiting
-diarrhoea
-hypotoxicity
•nolonger actively marketed

13. Donepezil
•
•
Long plasma half life – 70 hrs
Dose 5-6 mg daily
• Severals controls trail have shown modest benefit in cognition and behavior
• Not hepatotoxic
• Adverse effect
-nousea
-diarrhoea
-vomiting
-fatigue
-muscle cramp
- bradycardia
.

14. Rivastigmine
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•
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High effinity for brain Ache from peripheral
Inhibit both acetylcholinesterase and butrylcholinestrase
half lifeof 2 hrs..
Doaing of 3-12 per mg daily
• Metabolism is almost totally independent of the hepatic cytochrome P450 system
• GI adverse events are common ,including weight loss.

15. Signs andsymptoms
1. Signs -
warning signs of alzeihmere’s disease
• Memory loss
• difficult to performing familiar tasks
• problem withlanguage
• disorientation with time and place
• problem with abstractthinking
• misplacing things
• changes in mood and behavior
• changes inpersonality
• loss ofinitiative

16. symptoms
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Confusion
• Disturbance in short term memory
• Problem with attention and orientation
Persoinality changes
Language difficulties
Unexplained mood swings.

17. Treatment….
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There is no known cure for Alzheimer's. The death of brain cells cannot be reversed.
However, there are therapeutic interventions that can make it easier for people to livewith the disease.
According to theAlzheimer'sAssociation, the following are important elements of dementia care(14)
• effective management of any conditions occurring alongside theAlzheimer's
• activities and day-care programs(15)
involvement of support groups and services

18. Diagnosis…..
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•
There is no single test for Alzheimer's disease, so doctors willlook at the signs and symptoms, take a medical history, and rule out
other conditions before making a diagnosis.
• They may also check the person's neurological function, for example, by testing their balance, senses, and reflexes.
• Other assessments may include a blood or urine test, a CT or MRI scan of the brain, and screening for depression.(5),(9)
Sometimes the symptoms of dementia are related to an inherited disorder such as Huntington's disease, so genetic testing may
be done.

19. Refrences :
1.Mangialasche, F.,Solomon, A., Winblad, B., Mecocci, P. & Kivipelto, M.Alzheimer's disease: clinical trials and drug
development. Lancet Neurol. 9, 702–716 (2010)
2.Berk, C., PaulSabbagSabbagh, M.Investigational drugs in Alzheimer's disease: current progress. Expert Opin.
Investig. Drugs 23, 837–846 (2014).
3.Selkoe, D. J. & Hardy, J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol. Med. 8, 595–608
(2016).This article reviews new evidence supporting the concept that an imbalance between production and
clearance of Aβ is a very early, often initiating factor, in AD — a widely debated issue.
4.Yankner, B. A. & Mesulam, M. M.Seminars in medicine of the Beth Israel Hospital, Boston. β-Amyloid and the
pathogenesis of Alzheimer's disease. N. Engl. J. Med. 325, 1849–1857 (1991).
5.Roher, A. E. et al.Amyloid β peptides in human plasma and tissues and their significance for Alzheimer's disease.
Alzheimers Dement. 5, 18–29 (2009). This study evaluates Aβ levels in brain, peripheral organs and tissues,
suggesting that brain as well as plasma Aβ levels are the consequence of intricate relationships between central and
peripehralsources.
6.Li, Q. X., Fuller, S. J., Beyreuther, K. & Masters, C. L. The amyloid precursor protein of Alzheimer disease in human
brain and blood. J. Leukoc. Biol. 66, 567–574 (1999).
7.Toledo, J. et al. Factors affecting Aβ plasma levels and their utility as biomarkers in ADNI. Acta Neuropathol.122,
401–413

20. 8.Mehta, P. D.,Pirttila, T.,Patrick, B. A., Barshatzky, M. & Mehta, S. P.Amyloid β protein 1–40 and 1–42 levels in matched
cerebrospinal fluid and plasma from patients with Alzheimer disease. Neurosci. Lett. 304, 102–106 (2001).
9.Delvaux, E., Bentley, K., Stubbs, V.,Sabbagh, M. & Coleman, P. Differentialprocessing of amyloid precursor protein in brain and in
peripheralblood leukocytes. Neurobiol. Aging 34, 1680–1686 (2013).
10.Evin, G., Zhu, A., Holsinger, R. M., Masters, C. & Li, Q.-X. Proteolytic processing of theAlzheimer's disease amyloid precursor
protein in brain and platelets. J. Neurosci. Res. 74, 386–392 (2003
11.Biere,A. L. et al.Amyloid β-peptide is transported on lipoproteins and albumin in human plasma. J. Biol. Chem. 271,
32916–32922 (1996).
12.Kuo, Y. M. et al.Amyloid-β peptides interact with plasma proteins and erythrocytes: implications for their quantitation in plasma.
Biochem. Biophys. Res. Commun. 268, 750–756 (2000).