Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil
Condition: Mild Cognitive Impairment
MeSH terms: Cognitive Dysfunction
Intervention: Donepezil; Atropine
Intervention description: 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.; A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
Intervention MeSH terms: Atropine; Donepezil; Ophthalmic Solutions
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 55 Years
Maximum age: 95 Years
Healthy volunteers: No
Keywords: Olfaction; Donepezil; Alzheimer's Disease; Mild Cognitive Impairment; Memory

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 <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.