Alzheimer disease

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Alzheimer disease

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

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