Clinical Trial: Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly

Brief 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 Summary:

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.


Sponsor: New York State Psychiatric Institute

Current Primary Outcome: Change over time in Selective Reminding Test (SRT) Scores [ Time Frame: Week 0, Week 8, Week 26, Week 52 ]

The 12-item, 6-trial SRT is a memory measure used to assess verbal list learning and memory. The total number of words learned over six trials (total immediate recall), and delayed recall (after a 15-minute delay) will be obtained.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) [ Time Frame: Week 0, Week 8, Week 26, Week 52 ]
    The modified ADAS-Cog is a cognitive battery that assesses learning, memory, language production, language comprehension, constructional praxis, ideational praxis, and orientation.
  • Clinician's Interview Based Impression (CIBIC-plus) [ Time Frame: Week 0, Week 2, Week 4, Week 8, Week 26, Week 52 ]
    The CIBIC-plus is a well-validated, reliable and widely used measure (range 1-7) of global improvement in AD and MCI trials.
  • Pfeffer Functional Activities Questionnaire (FAQ) [ Time Frame: Week 0, Week 4, Week 8, Week 26, Week 52 ]
    FAQ is a widely used 10-item instrument that takes 3 minutes to administer and focuses on instrumental, social and cognitive functioning.
  • Measurement of Everyday Cognition (Ecog) [ Time Frame: Week 0, Week 4, Week 8, Week 26, Week 52 ]
    This instrument has 40 items, takes 20 minutes to administer, and focuses on functional correlates of cognitive deficits.


Original Secondary Outcome: Same as current

Information By: New York State Psychiatric Institute

Dates:
Date Received: September 18, 2013
Date Started: October 2013
Date Completion: May 2018
Last Updated: December 27, 2016
Last Verified: December 2016