Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil

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.

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.