Safety and Effectiveness Study of Intranasal Insulin Glulisine on Cognitive and Memory in Mild-Mod AD Patients.

Inclusion Criteria:

• Male or female subject with a clinical diagnosis of probable AD in accordance withNational Institute of Neurological and Communicative Disorders and Stroke and theAlzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria andDementia Rating Scale (McKhann 1984).

• Mini-Mental State Examination (MMSE) score of 18-26.

• Hachinski Ischemia Score < 4.

• Age is > 65 and <85 years

• Females must be > 2 years post-menopausal or surgically sterile.

• Must be able to speak, read and understand English in order to comply with testing ofcognitive function, memory and physiology.

• Must have a dedicated family member /caregiver, able to attend all visits and reporton subject's status.

• Subject and family member/caregiver have both provided fully informed written consentprior to participation. In the event that subject is legally unable to provideinformed written consent due to deterioration in cognitive abilities, fully informedwritten consent must be provided by a legally authorized representative.

• On a stable dose (≥ 1 months) of a prescribed acetylcholinesterase inhibitor (e.g.donepezil, rivastigmine, galantamine) and/or memantine.

• A brain CT or MRI in the last 2 years compatible with the diagnosis of probableAlzheimer's Disease.

• A Clinical Dementia Rating (CDR) ranging from 1 to 2.

Exclusion Criteria:

• Medical history and/or clinically determined evidence of other central nervous system (CNS) disorders including brain tumor, active subdural hematoma, seizure disorder,multiple sclerosis dementia with Lewy bodies, vascular dementia, corticobasalsyndrome, progressive supranuclear palsy, Parkinson's disease, multiple systematrophy, frontotemporal dementia, normal pressure hydrocephalus, Huntington's disease,or Jakob-Creutzfeldt disease presenting as dementia.

• Personal medical history and/or clinically determined disorders: current B12deficiency, positive syphilis serology, chronic sinusitis or any untreated thyroiddisease, significant head trauma, or history of difficulty with smell and/or tasteprior to AD diagnosis.

• Diagnosis with any form of diabetes mellitus, actively takes insulin, or has HbA1c > 6.1 % at screening.

• Personal history of any of the following: moderate to severe pulmonary disease,congestive heart failure, significant cardiovascular and/or cerebrovascular events inprevious 6 months, condition known to affect absorption, distribution, metabolism, orexcretion of drugs such as any hepatic, renal or gastrointestinal disease or any otherclinically relevant abnormality that inclusion would pose a safety risk to the subjectas determined by Investigator.

• Heavy smoker (defined as smoking half a pack or more per day in the last 10 yearsprior to entry in the study).

• Personal history of any psychiatric illness, except major depressive disorder (according to Diagnostic and Statistical Manual (DSM)-IV TR) currently in remission orstable with treatment for > 2 years, or any other psychiatric condition that inclusionwould pose a safety risk to the subject as determined by Investigator. Patients withactive depression (Geriatric Depression Score>9) are excluded from the study.

• Currently taking any medications, herbals and food supplements that are determined byInvestigator to interfere with procedural testing of cognitive function as well asensure study safety.

• Recent change (< 1 months) in prescribed acetylcholinesterase inhibitor (e.g.donepezil, rivastigmine, galantamine) or memantine.

• Current or recent drug or alcohol abuse or dependence defined by DSM-IV TR.

• Systolic blood pressure > 160 or < 90 mmHg or diastolic blood pressure > 100 or < 60mmHg at Screening.

• Screening laboratory results that are medically relevant and which would pose a safetyrisk to the subject as determined by Investigator.

• Participation in any other research study at least 3 months prior to this study.

• Insulin allergy.

• History of significant traumatic brain injury

• History of acute and chronic rhinitis and/or sinusitis.

• Legally unable to provide informed written consent due to deterioration in cognitiveabilities.