Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly
Condition: Alzheimer Disease; Mild Cognitive Impairment; Delirium, Dementia, Amnestic, Cognitive Disorders
MeSH terms: Alzheimer Disease; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      Olfactory identification deficits occur in patients with Alzheimer's disease (AD), are
      associated with disease severity, predict conversion from mild cognitive impairment (MCI) to
      AD and are associated with healthy elderly subjects developing MCI. Odor (olfactory)
      identification deficits may reflect degeneration of cholinergic inputs to the olfactory bulb
      and other olfactory brain regions. Acetylcholinesterase inhibitors (ACheI) like donepezil
      show modest effects in improving cognition but can be associated with adverse effects and
      increased burden and costs because of the need for prolonged, often lifelong, treatment.
      Converging findings on odor identification test performance (UPSIT, scratch and sniff 40-item
      test) from four pilot studies, including two of our own, suggest that acute change in the
      UPSIT in response to an anticholinergic challenge (atropine nasal spray), incremental change
      over 8 weeks, and even the baseline UPSIT score by itself, may predict cognitive improvement
      with ACheI treatment in MCI and AD. If change in odor identification deficits can help to
      identify which patients should receive ACheI treatment, this simple inexpensive approach will
      advance the goal of improving personalized treatment, improve selection and monitoring of
      patients for ACheI treatment, reduce needless ACheI exposure with risk of side effects, and
      decrease health care costs.
    

Detailed description: 
      In this clinical trial, the investigators will evaluate, treat and follow two broad samples
      of adult patients at New York State Psychiatric Institute/Columbia University Medical Center.
      Study 1 will include 70 patients with amnestic Mild Cognitive Impairment (MCI). Study 2 will
      include 100 patients with probable Alzheimer's Disease (AD). Recruitment will be from clinics
      and/or advertisements. In the protocol, all 170 patients will receive baseline memory and
      olfactory assessments and are treated with donepezil. Patients will be followed for a total
      of 1 year. During this time, patients will be monitored closely by the study physician and
      will receive memory and olfactory assessments at weeks 0, 8, 26, and 52. In addition, an
      olfactory challenge test will be done at baseline.

      This project will be of value in the selection of patients with MCI and AD for treatment
      based on the evaluation of olfaction tests to predict response to donepezil. Since mild
      cognitive impairment is widespread and Alzheimer's disease represents a major public health
      problem, this study has considerable public purpose and significance.
    

Intervention name(s): Donepezil
Intervention type(s): Drug
Intervention description(s): Donepezil 5mg will be given for 4 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg of donepezil per day will be continued for the study duration, and this is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease. For patients who do not tolerate donepezil or have a history of intolerance to donepezil or cannot take donepezil for other reasons, treatment with other cholinesterase inhibitors (galantamine or rivastigmine) is permitted at any stage of the protocol. Data will be analyzed in two ways: for donepezil alone, and for any cholinesterase inhibitor (donepezil or rivastigmine or galantamine) as the intervention.
Other intervention name(s): Aricept
Intervention MeSH terms: Donepezil
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Smell; Olfaction Disorders; Atropine; Donepezil; Cholinesterase Inhibitors; Cognition Disorders