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					  ARICEPT
Drug of Choice
                    The Growing Elderly
                        Population
              800
                                                       690
              700
              600
   Millions




              500
                         380
              400
              300
              200
              100
                0
                        1997                           2020
                     Worldwide Population Aged 65+ Years

World Health Organization, World Health Report 1997.
                Prevalence of Dementia
                  Among the Elderly

           25                                                   20.8+
 Percent




           15
                                                      10.5

                                           5.6
           5                 2.8
                  1.4


                 65-69 yr   70-74 yr     75-79 yr    80-84 yr   85+ yr


Jorm et al. Acta Psychiatr Scand. 1987;76:465-479.
4
                Causes of dementia
        Reversible dementias   Irreversible dementias

       Common causes:             Common cause:
           Depression                 Alzheimer's disease
           Delirium               Other causes:
           Drug toxicity              Vascular dementia
                                       Lewy body disease
                                       Pick's disease
                                        (dementia of the frontal
                                        lobe type)
                                       Parkinson's disease
                                        with dementia
                Clinical features of AD
7
              Mild stage of AD (MMSE 21-30)

                        IMPAIRMENT
    Cognition            Function            Behavior
    * Recall/learning    * Work              * Apathy
    * Word finding       * Money/shopping    * Withdrawal
    * Problem            * Cooking           * Depression
      solving            * Housekeeping      * Irritability
    * Judgement          * Reading
    * Calculation        * Writing
                         * Hobbies

                                    Adapted from Galasko, 1997
                 Clinical features of AD
8
           Moderate stage of AD (MMSE 10-20)

                             IMPAIRMENT
    Cognition                 Function              Behavior
    * Recent memory           * IADL loss           * Delusions
      (remote memory          * Misplacing          * Depression
      unaffected)               objects             * Wandering
    * Language (names,        * Getting lost        * Insomnia
      paraphasias)            * Difficulty          * Agitation
    * Insight                   dressing            * Social skills
    * Orientation               (sequence and         unaffected
    * Visuospatial ability      selection)
                                           Adapted from Galasko, 1997
                Clinical features of AD
9
              Severe stage of AD (MMSE <10)

                            IMPAIRMENT
    Cognition                Function              Behavior
    * Attention              * Basic ADLs          * Agitation
    * Difficulty               -Dressing             - Verbal
      performing               -Grooming             - Physical
      familiar activities      -Bathing            * Insomnia
      (apraxis)                -Eating
    * Language                 -Continence
      (phrases, mutism)        -Walking
                               -Motor slowing
                                          Adapted from Galasko, 1997
      Global                 Cognitive
      Function               Function


                     Caregiver
                     Burden



     Activities of               Behavioural
     Daily Living                Abnormalities


10
          Alzheimer’s Disease:
            Treatment Goals


   Improve or stabilize deterioration of patient’s
    cognition, function, and behavior
   Improve patient’s quality of life
   Improve caregiver’s quality of life
12
                        Drugs:
     Enhancing acetylcholine (Cholinesterase inhibitors)
      [Tacrine (Cognex) — 1993]

      Donepezil (Aricept) — 1997

      Rivastigmine (Exelon) — 1998

      Galantamine (Reminyl) — 2000



     NMDA (glutamate) receptor antagonists
      Memantine (Ebixa) — 2002
Cognition
Aricept: Cognition improvement in
        mild-moderate AD




               Journal of Neurological Sciences 2005
                 Aricept : Cognition improvement in
                              severe AD
15                                                Severe Impairment Battery (SIB)
     LS mean change from baseline ± SE



                                         6                              p<0.0001
                                                             p=0.0051
                                                                                     p<0.0009   p<0.0001
                                         4        p=0.0078                                                   p=0.0001
                                                                                                                          Clinical
                                                                                                                        improvement
                                         2


                                         0                                                                               Baseline

                                         -2
                                                                                                                          Clinical
                                         -4          Donepezil                                                            decline

                                                     Placebo
                                         -6
                                              0      4          8         12           18         24       ITT LOCF



                                                                               Study week
Activities of Daily
      Living
                                                           Activities of Daily Living:
                                                     Disability Assessment for Dementia (DAD)
17
                                                                                                                 Clinical
       LS mean change from baseline ± SE



                                            4                       p=0.0037                                   improvement
                                            2                                                       p<0.0001
                                                                                        p<0.0001

                                            0                                                                   Baseline

                                            -2

                                            -4                                                                   Clinical
                                                                                                                 decline
                                            -6

                                            -8
                                                        Donepezil
                                           -10
                                                        Placebo
                                           -12
                                                 0                    12                  24       ITT LOCF
                                                                           Study week
     Donepeziln=134                                                 125                  121         (134)

     Placebo n=140                                                  129                  126         (140)
Behavioral
Problems
 Aricept: efficacy in treating
neuropsychiatric symptoms in
       moderate AD




                    Neurology 2004
        Aricept: Efficacy in treating
       neuropsychiatric symptoms in
                 Severe AD:

Aricept improves behavioral symptoms particularly:

   Depression
   Anxiety
   Apathy
   Delusions
   Visual Hallucinations


                                Am J Geriatr Psychiatry 2006
Aricept reduces concomitant
   psychotropic drug use:




                   Clin Ther. 1998
     Impact of Aricept on caregivers
22


     Impact on patient                  Impact on family/society

                                                 Pharmaco-
       Cognition                                 economic
                                                  Benefit

                            Patients
                                                  Reduced
                            Maintain
        Function                                  Caregiver
                         Independence
                                                   Burden
                            Longer

                                                  Delay to
        Behavior
                                                Nursing Home
                                                 Placement
     Aricept reduces Caregiver Burden
23




        More caregivers of placebo-treated patients
         reported spending most of each day caring for
         patients (at least 16 hours)
        Caregivers of donepezil-treated patients spent
         less time assisting patients with activities of daily
         living
        They spent 400 fewer hours in caregiving over 1
         year (=10 working weeks)
         Wimo et al., Dementia and Geriatric Cognitive.Disorders, 2003,15[1]:44-54
           Aricept delays Nursing Home
24




        Aricept 5 mg/d early in AD progression was
         strongly associated with delayed NHP


        Longer cumulative exposure to aricept appears
         to keep patients in the community longer,
         postponing and perhaps reducing nursing home
         costs

            Geldmacher D et al. J Amer Ger Soc. 2003; 51: 937-44.
                                                         Strength
 shown to increase time at home 8
        Delayed Time to First Dementia-Related Nursing Home Placement



            Persistent Aricept Treatment (n=310)                                     5.5
                                                                                      Nearly 2 more years
            Limited Aricept Treatment (n=113)                 3.7                     at home

        0            1               2               3               4               5

                                             Years (Median Times)

 Results from the Delay to Nursing Home Placement study

 *Data are from 2 cohorts of patients in a prospective, observational follow-up of 671 Alzheimer's disease patients from Aricept clinical trials for whom reason for and time of nursing home
 placement were obtained. Persistent group=at least 9 to 12 months of Aricept; 209 received >2 years of Aricept. Limited group= ≤6 months of Aricept.


 • Enables patients to remain longer in the familiarity of their own surroundings 8

 • Delays the social and economic cost of nursing home care 8*


     * Health services and patient families could save over €50,000 from a 21 month delay in admission to residential care 9




                               INITATE EARLIER, TREAT PERSISTENTLY
                               to help patients and caregivers stay together longer 8


25
            Pathophysiology
Cerebral Atrophy:

 Senile plaques
 Neurofibrillary tangles
 Cholinergic neurons degeneration
 Decrease in cholinergic function
 Decrease in Ach
 Symptoms of AD
                        AChE sites:
2.b. Pathophysiology of AD- The Acetylcholinesterase enzyme (ACHE)

                                 • ACHE could play a key role in the development of
                                 senile plaques by accelerating the Aβ deposition.


                                 •It does so by promoting the assembly of Aβ into
                                 amyloid fibrils forming Aβ-ACHE complexes:
                                 neurotoxicity↑.


                                 •The peripheral site is responsible for the adhesion
                                 function.


                                 •Thus ACHEIs able to interact with the peripheral site
                                 of the enzyme could exhibit an interesting
                                 neuroprotective effect.
28
    Aricept : neuroprotector effect
   Aricept : the only AChEI with a dual binding
    site.

   Aricept: the only AChEI to decrease
    neurotoxicity by blocking Aβ deposition.

   Aricept: model for the development of new
    Anti-Alzheimer drugs with same site of action.
Aricept: slows Hippocampal Atrophy
               in AD

   A prospective study, enrolling 147 AD patients,
    evaluated by MRI repeated at 1-year intervals.

   Aricept treatment slows the progression of
    hippocampal atrophy, suggesting a
    neuroprotective effect in AD.
                              Am J Psychiatry 2005
       Aricept Efficacy in VaD:
616 patients enrolled in a randomized, double-
  blind, placebo-controlled, 24-week study to
  receive: 5mg and 10mg Aricept:

• Significant improvement in cognition and global
  function.
• Excellent safety profile
• No drug interaction

                         Neurology 2003
              Aricept Efficacy:

   The only anti-Alzheimer’s drug FDA approved
    for mild, moderate and severe stages.
   Significant improvement in cognition, global
    function and behavioral symptoms.
   The only anti-Alzheimer’s drug with long-term
    proven efficacy and safety ( 5-year study)
   Proven efficacy in VaD.
   Treatment of choice in mixed dementia.
             Aricept Efficacy


The only dual binding site AChEI ( inhibits β-
 amyloid peptide aggregation).
 Unique neuroprotector effect.

 Brain atrophy reduction. .
                   Aricept Safety
   Aricept proven excellent Tolerability-Safety profile:

 93% of patients had concomitant medications.
 97% of patients had comorbid conditions.
 No significant Drug interactions in clinical practice.
 Adverse events are mild and transient (most common:
  nausea, diarrhea and vomiting).

                               Dement Geriatrr Cogn Disord 2003
            Aricept Compliance
   One simple single dose titration.
   Aricept 5mg is a therapeutic dose.
   Single daily dose.
   The most tolerated AChEI (least gastrointestinal
    side effect).
   The least expensive anti-Alzheimer’s drug in
    Lebanon.
Thank you

				
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