Study of Nasal Insulin to Fight Forgetfulness - Device Comparison Study

A growing body of evidence suggests that insulin plays a role in normal memory processes and
that insulin abnormalities may contribute to cognitive and brain changes associated with
Alzheimer's disease (AD). Interestingly, insulin administered to the nasal cavity is
transported within a few minutes into the brain, but does not affect blood sugar or insulin
levels.

The study will consist of a single site, randomized, double-blind trial comparing the acute
effects of intranasal insulin (20 International Units) or placebo delivered with either the
ViaNase or Impel devices on cerebral spinal fluid insulin levels, AD biomarkers and memory.
At study entry, participants will be randomized to either the ViaNase or Kurve arm, and will
complete two study visits, receive either an acute dose of insulin or of placebo (in
randomized order). A total of 20 adults who are cognitively normal or diagnosed with amnestic
mild cognitive impairment (aMCI) will be enrolled in this trial. Study Investigators expect
to enroll approximately 50% of participants from each group.

Inclusion Criteria:

- Fluent in English

- Cognitively normal or diagnosis of aMCI

- Stable medical condition for 3 months prior to screening visit

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

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

Exclusion Criteria:

- A diagnosis of dementia

- History of a clinically significant stroke

- Current evidence or history in past two years of epilepsy, head injury with loss of
consciousness, any major psychiatric disorder including psychosis, major depression,
bipolar disorder

- Diabetes (type I or type II) insulin dependent and non-insulin dependent diabetes
mellitus

- Current or past use of insulin or any other anti-diabetic medication within 5 years of
Screening visit.

- History of cancer five years prior to screening (history of skin melanoma or stable
prostate cancer are not exclusionary)

- History of seizure within past five years

- Pregnancy or possible pregnancy.

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

- Residence in a skilled nursing facility at screening

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

- Regular use of alcohol, narcotics, anticonvulsants, antiparkinsonian medications, or
any other exclusionary medications