Efficacy and Safety of Rivastigmine Transdermal Patch in Patients With Mild to Moderate Alzheimer's Disease

• Change From Baseline in the Alzheimer's Disease Assessment Scale - Japan Cognitive Subscale (ADAS-J Cog) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  The Alzheimer's Disease Assessment Scale - Japan cognitive subscale (ADAS-J cog) was used to measure change in cognitive function. The ADAS-J cog score ranges from 0-70, with higher total scores indicating more impairment. A negative change score indicates improvement from baseline.
  
  
• Overall Clinical Rating of Change From Baseline to Week 24 Measured by the Clinician's Interview-Based Impression of Change Plus - Japan (CIBIC Plus-J) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

  The overall clinical rating of change from baseline to week 24 measured by the 7-point CIBIC plus-J scale. The Clinician's Interview-Based Impression of Change plus Caregiver Input consists of 3 subscales: Disability Assessment of Dementia Scale, Behavioral Pathology in Alzheimer's Disease Rating Scale and Mental Function Impairment Scale, as well as the Clinician's Global Impression of Change (CGIC). Participants are scored according to the following:

  1. Markedly improved
  2. Moderately improved
  3. Minimally improved
  4. Unchanged
  5. Minimally worse
  6. Moderately worse
  7. Markedly worse
  
  

• Change From Baseline in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  The Disability Assessment for Dementia (DAD) was used to assess levels of difficulty in activities of daily living (ADL). The DAD is administered through an interview with the caregiver. A total score is obtained by adding the rating for each question and converting this to a total score out of 100 (%). Higher scores represent less disability in ADL while lower scores indicate more dysfunction. A positive change score indicates an improvement from baseline.
  
  
• Change From Baseline in CIBIC Plus-J Score Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  BEHAVE-AD was used to assess patient behavior and psychiatric symptoms. It covers symptoms in seven categories: paranoid and delusional ideation, hallucinations, activity disturbances, diurnal rhythm disturbances, aggressiveness, affective disorders and anxieties, and phobias. Caregivers rate behavioral symptoms on a 0-3 scale. The total score can range from 0 to 66, with a lower score indicating better function. A negative change score indicates an improvement from baseline.
  
  
• Change From Baseline in CIBIC Plus-J Score Mental Function Impairment Scale (MENFIS) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  MENFIS was used to assess patient cognitive and psychiatric function, and evaluates core symptoms of dementia including cognitive, motivational and emotional aspects. The total score ranges from 0 to 78. The higher the score, the greater the functional deficit. A negative change score indicates an improvement from baseline.
  
  
• Change From Baseline in Mini-Mental State Examination (MMSE) [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline.
  
  
• Extension Phase: Change From Extension Phase Baseline to End of Extension in Mini-Mental State Examination (MMSE) [ Time Frame: Extension Phase Baseline and Week 52 of extension phase ] [ Designated as safety issue: No ]
  The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement. This outcome measured the change in MMSE from the beginning of the open-label extension phase through to Week 52 of the extension phase.
  
  
• Extension Phase: Change From Extension Phase Baseline to End of Extension in CIBIC Plus-J Score Disability Assessment for Dementia (DAD) [ Time Frame: Extension Phase Baseline and Week 52 of extension phase ] [ Designated as safety issue: No ]
  The Disability Assessment for Dementia (DAD) was used to assess levels of difficulty in activities of daily living. The DAD is administered through an interview with the caregiver. A total score is obtained by adding the rating for each question and converting this to a total score out of 100 (%). Higher scores represent less disability in activities of daily living while lower scores indicate more dysfunction. A positive change score indicates an improvement from baseline.
  
  
• Extension Phase: Change From Extension Phase Baseline to End of Extension in Modified Crichton Scale [ Time Frame: Extension Phase Baseline and Week 52 of extension phase ] [ Designated as safety issue: No ]
  The Modified Crichton Scale includes a total of seven items evaluated in eight grades that assess basic activities of daily living, communication functions, psychiatric symptoms and quality of life; the total score can range from 0 to 56, with a lower score indicating better function. A negative change score indicates an improvement from baseline.
  
  

Patients were randomly assigned in a double-blind manner to one of the 3 treatment arms (placebo, rivastigmine 5 cm^2 and rivastigmine 10 cm^2) in a ratio of 1:1:1. During the Double-blind treatment phase, patients entered a 16-week Titration Period followed by an 8-week Maintenance Period. During the open-label extension phase, all patients started treatment with a 2.5 cm^2 patch and the dose was increased to 10 cm^2 over a 16-week titration period, followed by a maintenance period of 36 weeks.