The Study of Nasal Insulin in the Fight Against Forgetfulness (SNIFF)

Inclusion Criteria:

- Fluent in English or Spanish

- Diagnosis of aMCI by Petersen criteria or probable AD by National Institute of
Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related
Disorders Association (NINCDS-ADRDA) criteria

- Mini Mental State Examination (MMSE) score at screening is greater than or equal to 20

- Clinical Dementia Rating is 0.5-1 at screening

- Logical Memory is less than or equal to 8 for 16 or more years of education, less than
or equal to 4 for 8-15 years of education, less than or equal to 2 for 0-7 years of
education. Scores measured at screening on Delayed Paragraph Recall (Paragraph A only)
from the Wechsler Memory Scale-Revised

- Able to complete baseline assessments

- Modified Hachinski score of less than or equal to 4

- A study partner able to accompany the participant to most visits and answer questions
about the participant

- The study partner must have direct contact with the participant more than 2 days per
week (minimum of 10 hours per week) and provide supervision of drug administration as
needed

- Stable medical condition for 3 months prior to screening visit

- Stable medications for 4 weeks prior to the screening and baseline visits

- Stable use of permitted medications

- At least six years of education or work history

- Clinical laboratory values must be within normal limits or, if abnormal, must be
judged to be clinically insignificant by the investigator

- Visual and auditory acuity adequate for neuropsychological testing

Exclusion Criteria:

- A diagnosis of dementia other than probable AD

- Probable AD with Down syndrome

- History of clinically significant stroke

- Current evidence or history in past two years of epilepsy, focal brain lesion, head
injury with loss of consciousness or Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (DSM IV) criteria for any major psychiatric disorder
including psychosis, major depression, bipolar disorder, alcohol or substance abuse

- Sensory impairment that would preclude the participant from participating in or
cooperating with the protocol

- Diabetes (type 1 or type II) requiring pharmacologic treatment (including both insulin
dependent and non-insulin dependent diabetes mellitus)

- Current or past use of insulin or any other anti-diabetic medication

- Evidence of any significant clinical disorder or laboratory finding that renders the
participant unsuitable for receiving investigational drug including clinically
significant or unstable hematologic, hepatic, cardiovascular, pulmonary, endocrine,
metabolic, renal or other systemic disease or laboratory abnormality.

- Active neoplastic disease, history of cancer five years prior to screening (history of
skin melanoma or stable prostate cancer are not excluded)

- History of seizure within the past five years

- Pregnancy or possible pregnancy

- Contraindications to Lumbar Puncture (LP) procedure: prior lumbosacral spine surgery,
severe degenerative joint disease or deformity of the spine, platelets is less than
100,000 or history of bleeding disorder

- Use of anticoagulants warfarin (Coumadin) and dabigatran (Pradaxa) due to LP
requirement

- Contraindications for MRI (claustrophobia, craniofacial metal implants of any kind,
pacemakers)

- Residence in a skilled nursing facility at screening

- Use of an investigational agent within two months or screening visit

- Regular use of narcotics, anticonvulsants, medications with significant
anticholinergic activity, antiparkinsonian medications or any other exclusionary
medications