Phase 4
N=41
Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil
Mild Cognitive Impairment
Bottom Line
View on ClinicalTrials.gov: NCT01845636 ↗Enrolled (actual)
41
Serious AEs
4.9%
Results posted
Mar 2018
Primary outcome: Primary: Selective Reminding Test (SRT) — 33.61; 36.23; 36.81; 37.13 Words
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Donepezil (Drug); Atropine (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- All
- Sponsor
- New York State Psychiatric Institute
- Primary completion
- Mar 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Selective Reminding Test (SRT) |
33.61; 36.23; 36.81; 37.13 | — |
| SECONDARY Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) |
10.67; 10.27; 8.80; 10.09 | — |
| SECONDARY Pfeffer Functional Activities Questionnaire (FAQ) |
3.73; 4.37; 4.40; 5.16 | — |
| SECONDARY Measurement of Everyday Cognition (Ecog) |
60.27; 62.80; 63.37; 65.39 | — |
| SECONDARY Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-plus) |
3.43; 3.31; 3.13 | — |
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.
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 1 pack daily.
Data sourced from ClinicalTrials.gov (NCT01845636). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.