Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly
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.
Mild Cognitive Impairment
Delirium, Dementia, Amnestic, Cognitive Disorders
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly|
- Change over time in Selective Reminding Test (SRT) Scores [ Time Frame: Week 0, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]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.
- Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) [ Time Frame: Week 0, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]This instrument has 40 items, takes 20 minutes to administer, and focuses on functional correlates of cognitive deficits.
- Mini-Mental State Examination - MMSE [ Time Frame: Week 0, Week 26, Week 52 ] [ Designated as safety issue: No ]
- Trail Making Test (Parts A and B) [ Time Frame: Week 0, Week 52 ] [ Designated as safety issue: No ]Parts A and B are composed of 25 circles. Patients are asked to scan the entire page and identify the next number or letter in a sequence.
- Wechsler Adult Intelligence Scale (WAIS) -III Digit Symbol Subtest [ Time Frame: Week 0, Week 52 ] [ Designated as safety issue: No ]
- Controlled Word Association (CFL) [ Time Frame: Week 0, Week 52 ] [ Designated as safety issue: No ]
- Boston Naming Test (BNT) [ Time Frame: Week 0, Week 52 ] [ Designated as safety issue: No ]
- Wechsler Memory Scale (WMS)-R Digit Span [ Time Frame: Week 0, Week 52. ] [ Designated as safety issue: No ]
- Treatment Emergent Symptom Scale (TESS) [ Time Frame: Week 0, Week 4, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]TESS is widely used to evaluate somatic side effects. For each item, a rating is made on a 3-point scale, with an additional rating on the likelihood that the medication caused the side effect.
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||May 2018|
|Estimated Primary Completion Date:||May 2018 (Final data collection date for primary outcome measure)|
Experimental: Donepezil Treatment & Atropine Challenge
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item UPSIT immediately before and 45 minutes after atropine administration. Immediately after the atropine challenge, donepezil treatment is started and continues for 52 weeks.
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 Name: Aricept
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01951118
|United States, New York|
|New York State Psychiatric Institute||Recruiting|
|New York, New York, United States, 10032|
|Contact: Jennifer Ferrar, B.S. 646-774-7204 firstname.lastname@example.org|
|Contact: Daniel Valmas, B.A. 646-774-7202 email@example.com|
|Principal Investigator: Davangere Devanand, M.D.|
|Sub-Investigator: Gregory Pelton, M.D.|
|Sub-Investigator: Edward Huey, M.D.|
|Sub-Investigator: Karen Bell, M.D.|
|Principal Investigator:||Davangere Devanand, M.D.||Columbia University|