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Alzheimer disease

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  • kindly send this presentation because it helps me to my study. this is my email ralirio4586@yahoo.com thank you.
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  • hi... i am doing project on alzeimers. Your ppt is being very helpful to me. please let me download the presentation. my e-mail i.d is gudiadas1991@gmail.com.
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  • 1. BELIEVE ME My Grand Father is the Best
    • I am not telling this just because he is my grandfather.
    • He spends a lot of time with me.
    • He bought me a new blue bicycle last month.
    • He sits with me for my homework everyday.
    • He tells me stories from Egyptian nights.
    • He plays cricket with me in the rains.
    • But… now I am afraid. Yesterday he had gone alone for his evening walk and has not returned yet.
    • What might be the reason I do not know.
    • Or… has he lost his way home?
    • If you meet him tell him I am very angry and that my exams are starting from tomorrow…
    • And I am missing him very much...!
  • 2. ALZHEIMER DISEASE
    • Presented By:
    • Mr. Debadyuti Sahu
    • Thanks To:
    • Dept. of Pharmacology
    • Special Thanks To:
    • Dr. M. C. Das
    • Dr. Bandana Rath
  • 3. DEMENTIA
    • A syndrome consisting of progressive impairment in to or more areas of cognition (i.e. memory, language, visuo-spatial, and perceptual ability, thinking and problem solving, personality) sufficient to interfere with work, social function or relationships in the absence of delirium or major non-organic psychiatric disorder (eg. Depression, schizophrenia).
    • COGNITIVE CONTINUUM
    • NORMAL
    • MCI
    • DEMENTIA
    • FUNCTIONAL CONTINUUM
  • 4. CAUSES OF DEMENTIA
    • REVERSIBLE DEMENTIA
    • ALCOHOLISM
    • DRUG/NARCOTIC/ HEAVY
    • METAL INTOXICATION
    • PSYCHIATRIC
    • NORMAL PRESSURE
    • HYDROCEPHALOUS
    • VITAMIN DEFICIENCY
    • ENDOCRINE DISORDERS
    • INFECTIOUS CAUSES
    • NEOPLASTIC CONDITIONS
    • ORGAN FAILURES
    • ACUTE INTERMITTENT PORPHYRIA
    • IRREVERSIBLEDEMENTIA
    • ALZHEIMER DISEASE
    • VASCULAR COGNITIVE IMPAIRMENT
    • PARKINSON DISEASE
    • VIRAL & PRION INFECTIONS
    • DEGENERATIVE DISORDERS
    • DIALYSIS DEMENTIA (Al)
    • METABOLIC DISORDERS
  • 5. PREVALENCE OF DIFFERENT TYPES OF DEMENTIA
  • 6. ALZHEIMER DISEASE
    • AD is the prototypical and single most common cause of dementia.
    • It is a major public health problem affecting
    • >4 million persons-
    • 4 th leading cause of death
    • 3 rd most expensive illness (US)
    • (average cost for the illness from diagnosis to death is $174,000 )
    • This most common late life neurodegenerative disease is 10 times commoner than Parkinson disease.
    • Prevalence: 8-10% (>65 years)
    • 30-45% (>80 years)
  • 7. ALZHEIMER DISEASE contd…
    • It is a progressive irreversible neurodegenerative disorder with no known cause or cure characterized by a progressive deterioration in cognitive and functional abilities, likely as a result of degeneration of the cholinergic neurons in the cortical and limbic areas of the brain.
    • May be- (a) Early onset type (before age 60)(<10%)
    • (b) Late onset type
    • According to progress of disease:
    • (i) Rapidly progressive
    • (ii) Slowly progressive
    • If AD develops rapidly, it is likely to continue to progress rapidly. If it has been slow to progress, it will likely continue on a slow course.
    • FAMILIAL AD : Rare (<5%)
  • 8. RISK FACTORS
    • ADVANCING AGE
    • POSITIVE FAMILY HISTORY
    • FEMALE GENDER
    • DOWN'S SYNDROME
    • DOWN'S SYNDROME IN A FIRST-DEGREE RELATIVE
    • WOMEN UNDER 35 WHO GIVE BIRTH TO A CHILD WITH DOWN'S SYNDROME
    • PREVIOUS SERIOUS, TRAUMATIC BRAIN INJURY
    • SMOKING
    • ENVIRONMENTAL:
    • HEAVY METALS
    • VIRUSES
    • HIGH SYSTOLIC BLOOD PRESSURE.
    • HIGH BLOOD CHOLESTEROL LEVELS
  • 9. 10 WARNING SIGNS OF AD
    • COGNITION FUNCTION
    • MEMORY LOSS
    • LANGUAGE
    • PROBLEM
    • DISORIENTATION
    • IMPAIRED JUDGEMENT
    • TENDENCY TO MISPLACE OBJECTS
    • FUNCTION
    • DIFFICULTY IN PERFORMING EVERYDAY TASK
    • PROBLEMS PERFORMING COMPLEX TASKS
    • BEHAVIOUR
    • CHANGES IN MOOD OR BEHAVIOUR
    • CHANGES IN PERSONALITY
    • LOSS OF INITIATIVES
  • 10. CLINICAL FEATURES
    • ANTEROGRADE
    • Memory impairment
    • RETROGRADE
    • Cognitive disturbances (one or more )
    • Aphasia
    • Apraxia
    • Agnosia
    • Disturbance in executive functioning (i.e., planning, organizing, sequencing, abstracting)
  • 11. DIAGNOSIS
    • Neurological Exam
    • Psychological and mental status testing (MMSE, etc.)
    • Neuro-imaging study:
    • CT Scan
    • MRI Scan
    • Electroencephalogram (EEG)
    • Blood tests and urine tests (Usually NORMAL)
    • Functional imaging study
    • ApoE Genotyping
  • 12. STAGES OF AD
    • EARLY STAGE
    • 1 st cognitive, then daily functions are affected
    • Anosognosia
    • MIDDLE STAGE
    • Unable to work, confused, easily lost
    • Language impaired
    • (naming comprehension
    • frequency)
    • APHASIA, APRAXIA
    • VISUOSPATIAL DEFICIT
    • END STAGE
    • Rigid, mute, inconsistent, bedridden
    • Hyperactive tendon reflex
    • Myoclonic jerk
    • Requires help for everything
    • LATE STAGE
    • Wandering attitude
    • Loss of judgment, reason, cognitive ability
    • Delusion
    • Shuffling gait
    • Disrupted sleep-wake pattern
  • 13. CROSS SECTION OF BRAIN IN AD
  • 14. PATHOGENESIS
    • CHOLINERGIC DEFICIT
    • ACh,
    • Choline Acetyl Transferase
    • & Nicotinic Cholinergic Receptors
    • HYPERPHOSPHORYLATED
    • TAU PROTEIN
    • capacity for binding to
    • microtubule
    • Loss of neurons
    • AFFECTED AREAS:
    • HIPPOCAMPUS
    • NUCLEUS BASALIS OF MEYNERT
    • TEMPORAL CORTEX
  • 15.  
  • 16. BETA AMYLOID PLAQUE FORMATION
  • 17.  
  • 18. Current Biomarkers for Alzheimer's disease
    • Beta-amyloid measured in cerebrospinal fluid
    • Tau protein measured in cerebrospinal fluid
    • Neural thread protein/AD7C-NTP measured in
    • cerebrospinal fluid and in urine.
    • In people with Alzheimer's disease their
    • cerebrospinal fluid contains a reduced level of
    • 42-amio-acid beta-amyloid and an increase in
    • tau protein.
  • 19. TREATMENT
    • AD cannot be cured- it is permanent and invariably ends in death. After diagnosis, survival of patient averages 8-10 years (Max. 20 years).
    • PRINCIPLES OF TREATMENT:
    • Choline Esterase Inhibitors
    • Symptomatic management of behavioral problems
    • Building rapport with the patient, family members and the caregiver.
  • 20. CHOLINE ESTERASE INHIBITOR
    • TACRINE
    • FIRST USED CENTRALLY ACTING ANTI-ChE USED IN AD.
    • SIGNIFICANTLY IMPROVES MEMORY, ATTENTION, PRAXIS, REASON AND LANGUAGE, BUT CANNOT ALTER UNDERLYING PATHOLOGICAL PROCESS.
    • Approved by the FDA in 1993
    • Effective for: Early to moderate Alzheimer’s disease
    • ADR:
    • GI DISTURBANCES & POLYURIA
    • SERUM TRANSAMINASE & HEPATITIS
    • EXPENSIVE
  • 21. RIVASTIGMINE
    • CARBAMATE DERIVATIVE OF PHYSIOSTIGMINE-INHIBITS BOTH AChE & BuChE. Approved by the FDA in 2000
    • CEREBROSELECTIVE, because
    • MORE SELECTIVE FOR G1 ISOFORM OF AChE.
    • HIGHLY LIPID SOLUBLE
    • MOA:
    • INTRODUCES CARBAMYL RESIDUE TO AChE- SINCE DISSOCIATION IS SLOW, ACTION PERSISTS FOR 10 HOURS IN SPITE OF 2 HOUR t 1/2 .
    • ADVANTAGES:
    • MILD PERIPHRAL SIDE EFFECTS
    • NOT CAUSE HEPATIC DAMAGE
    • Effective for: Early to moderate Alzheimer’s disease
    • ADAS-cog improves 3.8 (average)
    • DOSING:
    • START 1.5 mg BD, INCREASE DOSE BY 1.5 mg EVERY 2 WEEKS TO MAX. 6mg/DAY.
  • 22. DONEPAZIL
    • CEREBROSELECTIVE REVERSIBLE AChEI
    • Improves both cognitive & non-cognitive functions
    • Elevates Ach level in surviving neurons that project from basal fore brain to cerebral cortex & hippocampus.
    • Approved by the FDA in 1996
    • ADVANTAGES:
    • ONCE DAILY DOSING
    • WELL TOLERATED- NOT HEPATOTOXIC
    • MILD PERIPHERAL SYPTOMS
    • DOSING: 5 mg OD
  • 23. GALANTAMINE
    • NATURAL ALKALOID
    • SELECTIVE INHIBITION OF CEREBRAL AChE
    • DIRECT AGONISTIC ACTION ON NICOTINIC RECEPTORS
    • Approved by the FDA in 2001
    • Effective for: Early to moderate Alzheimer’s disease
    • IMPROVES BOTH COGNITIVE AS WELL AS BEHAVIOURAL FUNCTIONS
    • TWICE DAILY DOSING
  • 24. NMDA RECEPTOR ANTAGONISTS
    • Protect the neurons against excess amounts of glutamate.
    • The attachment of glutamate to cell surface &quot;docking sites&quot; called N-methyl-D-aspartate (NMDA) receptors permits calcium to flow freely into the cell, which in turn may lead to cell death & degeneration.
    • Approved by the FDA in 2003 ( MIMENTINE )
    • Effective for: Moderate to advanced Alzheimer’s disease
    • Side effects: Dizziness, headache, constipation, confusion
  • 25. NEWER APPROCHES
    • Nonsteroidal Anti-inflammatory Drugs :
    • Study suggests that inflammatory process in brain may be responsible for AD changes.
    • NATURO-PATHY
    • Ginkgo Biloba extract:
    • Mixture of ginkgoflavon glycosides (eg. Ginkgolide-B)
    • MOA: PAF antagonist- improves microcirculation in hypoxic brain areas.
    • DOSING: 40 mg TDS for a minimum period of 4 weeks
  • 26. ANTI-OXIDANTS
    • VITAMINE-E – 1000U BD
    • VITAMINE-C
    • SELEGENILE
    • OESTROGEN IN POSTMENOPAUSAL WOMEN
    • OTHER USEFUL DRUGS UNDER TRIAL
    • STATINS
    • SSRI
  • 27. ALZHEIMER VACCINE
    • ANTIBODY AGAINST A B AMYLOID THAT CAN CROSS BBB CAN BE USED TO ELIMINATE THE NEURITIC PLAQUE.
    • BUT THE 1 ST TRIAL FAILED DUE TO FATAL MENINGOENCEPHALOPATHY INDUCED BY TE VACCINE.
    • IT IS A POTENTIAL FIELD IN TREATMENT OF AD TO WORK WITH.
  • 28. NON-PHARMACOLOGICAL THERAPY
    • A PERSON IS AT RISK FOR ALZHEIMER, LIFESTYLE CHANGES SHOULD BE MADE
    • Changing nutritional habits is key. It is very important to limit consumption of red meat and to increase intake of Omega-3 fatty acids , which are found in fish . The regular intake of Vitamin E , and also Vitamin C , is recommended.
    • Physical exercise and increased consumption of vegetables and fruits should be favored.
    • Essential fatty acids in the blood and also lipid-peroxidation parameters should be checked every 6-12 months.
  • 29. THANK YOU THANK YOU