Clinical trial NCT01845636: Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil
Official title: Olfactory Deficits in Mild Cognitive Impairment as a Predictor of Improved Cognition on Donepezil
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Mild Cognitive Impairment
Keywords: Olfaction
Donepezil
Alzheimer's Disease
Mild Cognitive Impairment
Memory
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2013-05-03
Enrollment: 41
Sex: ALL
Minimum age (years): 55
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Odor identification deficits, which are a result of early Alzheimer's Disease (AD) pathology in the olfactory bulb and tract as well as olfactory projection areas in the medial temporal lobe (entorhinal and piriform cortex and hippocampus), lateral and central orbitofrontal cortex and several other regions, occur in AD and strongly predict mild cognitive impairment (MCI) conversion to AD. Our pilot data, along with converging findings in the literature, suggests that odor identification deficits, both incremental change over time and change in response to an anticholinergic challenge, may be clinically simple, relatively inexpensive, predictors of cognitive improvement with acetylcholinesterase inhibitor (ACheI) treatment with potential clinical implications for predicting improvement and monitoring ACheI therapy.

Detailed description: In this clinical trial, the investigators will evaluate, treat and follow a broad sample of 60 adult patients with amnestic MCI at New York State Psychiatric Institute/Columbia University Medical Center. Recruitment will be from clinics and/or advertisements. In the protocol, all 60 amnestic MCI patients will receive baseline memory and olfactory assessments and begin treatment 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 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 mild cognitive impairment for treatment based on the evaluation of olfaction tests to predict response to donepezil and other ACheI. Since mild cognitive impairment is widespread and Alzheimer's disease represents a major public health problem, this study has considerable public purpose and significance.

Eligibility criteria: Inclusion Criteria:

* Of either sex, age 55-95 years old
* Patients who meet criteria for amnestic mild cognitive impairment by meeting all of the following:

  (i) subjective memory complaints (ii) Wechsler Memory Scale-R Logical Memory combined Story A + B immediate recall score or combined Story A + B delayed recall score or Free and Cued Selective Reminding Test immediate recall or delayed recall score greater than 1.5 Standard Deviation (SD) below norms or Selective Reminding Test immediate recall or delayed recall score greater than 1.5 SD below norms iii) no functional impairment consistent with dementia
* Folstein Mini Mental State (MMSE) score ≥ 23 out of 30
* Clinical Dementia Rating (CDR) of 0.5 (questionable dementia)
* Availability of informant

Exclusion Criteria:

* Meets Criteria for dementia by Diagnostic and Statistical Manual IV (DSM-IV) criteria or probable Alzheimer's disease
* Meets DSM IV criteria for:

  (i)schizophrenia, schizoaffective disorder, other psychosis, or bipolar I disorder (ii)alcohol or substance dependence or abuse (current or within past 6 months)
* Current untreated major depression or suicidality
* Parkinson's disease, Lewy body disease, multiple sclerosis, central nervous system infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder.
* Mental Retardation
* Clinical stroke with residual neurological deficits. MRI findings of cerebrovascular disease (small infarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion.
* Patients receiving cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine will be excluded.
* Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases will be excluded, but past history of successfully treated cancer will not lead to exclusion.
* Medical contraindication to donepezil treatment or prior history of intolerability to donepezil treatment.
* Medications with anticholinergic effects that have been shown to adversely impact cognition will not be permitted. Benzodiazepines in lorazepam equivalents greater than or equal to 2 mg daily and narcotics will also not be permitted.
* Exclusion criterion for olfaction: history of anosmia due to any cause (e.g. traumatic or congenital) verified by UPSIT score of \<11 out of 40; head trauma with loss of consciousness; nasal sinus disease, current upper respiratory infection; severe allergies to odors; current smoker \> 1 pack daily.

Primary outcomes:
measure: Selective Reminding Test (SRT)
timeFrame: Week 0, Week 8, Week 26, Week 52
Secondary outcomes:
measure: Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
timeFrame: Week 0, Week 8, Week 26, Week 52
measure: Pfeffer Functional Activities Questionnaire (FAQ)
timeFrame: Week 0, Week 4, Week 8, Week 26, Week 52
measure: Measurement of Everyday Cognition (Ecog)
timeFrame: Week 0, Week 4, Week 8, Week 26, Week 52
measure: Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-plus)
timeFrame: Week 8, Week 26, Week 52
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: Columbia University
name: Davangere Devanand, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Gregory Pelton, M.D.
role: STUDY_DIRECTOR
References: