Study of Nasal Insulin to Fight Forgetfulness - Short-Acting Insulin Aspart

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.

This trial will consist of a randomized double-blind, placebo-controlled parallel group trial
in which 30 participants with AD or mild cognitive impairment (MCI) receive twice daily
intranasal administrations of insulin aspart (20 IU) or placebo (saline), two times per day
for 12 weeks. All participants will appoint a "support person" to answer a collateral
questionnaire and supervise the administration of the study drug. All participants and study
partners will undergo the intensive, structured training program in the self-management of
intranasal insulin administration. Cognitive testing and blood collection will occur at
baseline, after 6 weeks of treatment, and at the end of the 12 week treatment period.
Participants will also receive a lumbar puncture to measure AD biomarkers in the subject's
cerebral spinal fluid.

Inclusion Criteria:

- Previous or subsequent diagnosis of Alzheimer's disease or mild cognitive impairment

- Ability to communicate in English

Exclusion Criteria:

- Preexisting diabetes

- Clinically significant elevations in liver function test

- Clinically significant elevations in lipid profile

- Prior lumbar lumbar surgeries or other medical conditions that render lumbar punctures
unsafe

- Hemoglobin <8 g/dl

- Significant neurologic disease that might affect cognition, other than Alzheimer's
disease, including stroke, Parkinson's disease, multiple sclerosis, or recent severe
head injury (within the last year) with loss of consciousness >30 minutes or with
permanent neurologic sequelae

- Significant medical illness or organ failure, such as uncontrolled hypertension or
cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or
kidney disease

- Current use of antipsychotic, anticonvulsant, anxiolytic, anticoagulant or sedative
medications

- Current or previous use of glucose-lowering agents or insulin;

- Chronic use (≥ 3 times per week) of nasal sprays of any type for any indication

- Premenopausal status (defined as having had a period within the last year).