Detecting an Early Response to Donepezil With Measures of Visual Attention
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Intervention: Donepezil Hydrochloride; Placebo
Intervention description: 5mg of Donepezil Hydrochloride by mouth; prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Intervention MeSH terms: Donepezil
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double Blind Placebo Control
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Study drug was prepared by research pharmacist who was the only person privy to group assignment. Drug and Placebo pills looked identical.
Enrollment: 25.0
Sex: All
Minimum age: 50 Years
Maximum age: 95 Years
Healthy volunteers: No
Keywords: Alzheimer Disease; Attention; Donepezil hydrochloride

Summary:

      Acetylcholinesterase inhibitors (AChE-I) comprise a class of drugs used to treat Alzheimer's
      disease (AD), but controversy about their usefulness remains. Modest response rates of
      treated versus placebo groups, small effect sizes with respect to efficacy, drug costs, and
      clinical relevance of the effects are problematic. Standard efficacy measures of efficacy are
      not sufficiently sensitive, and trying to assess cognitive change after 4-6 months of therapy
      confounds the drug effect and the natural progression of the disease.

      Surprisingly, attention has never been included in the assessment of AChE-I drugs. The
      rationale for using attentional measures are that (1) Attentional deficits are recognized as
      a critical cognitive change in the earliest phases of AD; (2) Attentional function is
      directly mediated by the cholinergic system, and responds rapidly to cholinergic
      augmentation, particularly on tasks that tax available attentional capacity are dose
      dependent; and (3) Acetylcholine is depleted in AD. However, the link between attention and
      cholinergic depletion in AD has not been fully explored, especially with regard to response
      to cholinergic treatment.

      The study tests if attentional performance can be a more sensitive marker of response. In a
      longitudinal study we measure attentional, as well as cognitive and behavioral performance in
      de novo AD patients undergoing donepezil treatment. The investigators develop visual
      attentional measures and contrast them to global and domain-specific cognitive scores on
      three occasions (T1) baseline pre-treatment, (T2) after approximately 6 weeks, and (T3) after
      6 months treatment. The T1-to-T2 arm is a double-blind placebo control period, after which
      members of the placebo group start open-label treatment. The assessment at 6 months allows us
      to determine whether the changes seen earlier at T2 can predict patients who respond, or
      determine which measures best predict response.

      We hypothesize that attention measures are more sensitive than standard global measures or
      other cognitive domains and that the change of attentional function can be detected after
      only after approximately 6 weeks treatment.

      Knowledge from this project will facilitate and inform our decisions about individual
      patients undergoing pharmacological treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Clinical diagnosis of Alzheimer's Disease

          -  Mini Mental State Examination score >15 / 30

          -  Can swallow pills

        Exclusion Criteria:

          -  No other dementia due to Parkinson's disease, Lewy Body dementia, Normal Pressure
             Hydrocephalus, Fronto-temporal dementia, or prominent cerebral vascular accident

          -  No prior or concurrent use of cholinesterase inhibitors

          -  No prior or concurrent use of memantine hydrochloride

          -  No other concurrent anticholinergic treatments