The overall objective of the study is to assess the potential effects of the long-acting GLP-1 analogue exenatide in preventing/slowing the progression of cognitive dysfunction and related biomarkers in dysglycemic/prediabetic patients with mild cognitive impairment (MCI).

Type 2 Diabetes Mellitus (T2DM) and Alzheimer's Disease (AD) are two of the most common diseases of aging.The presence of T2DM almost doubles the risk of developing AD and is associated with a faster rate of cognitive decline in those with mild cognitive impairment (MCI). Blood glucose levels are directly associated with accelerated cognitive decline also in subjects with impaired fasting glucose and in individuals without clinical DM. Impaired insulin signaling is critically involved in the natural history of both T2DM and AD and it may represent a common mechanistic link ("common soil") between dysglycemic/prediabetic states and AD development and progression.

The overall objective of the study is to assess the potential effects of the long-acting GLP-1 analogue exenatide in preventing/slowing the progression of cognitive dysfunction and related biomarkers in dysglycemic/prediabetic patients with mild cognitive impairment (MCI).

All eligible patients at V0 will undergo baseline assessments (V1) and will be allocated according to the procedure of randomization to one of the study arms. Follow-up (FU) visits for all subjects will be at 16 (V2) and at 32 weeks (V3) after randomization. Additionally, subjects on active treatment will be admitted weekly to the Outpatient Diabetes Unit of the AOUPR for GLP-1 subcutaneous injections and to check for possible side effects. Subjects in the control arm will be seen at the Center for Dementia (AOUPR) according to their usual schedule.

Laboratory and diagnostic:

At each study visits patients will undergo:

• anthropometric and hemodynamic assessment: weight and height for Body Mass Index (BMI) calculation, waist circumference, ambulatory blood pressure, heart rate;
• blood test collection of metabolic profile: blood collection for metabolic/hormonal profile: fasting plasma glucose, HbA1c, insulin, C-peptide, glucagon, active GLP-1, total gastric inhibitory polypeptide (GIP), total cholesterol, HDL-cholesterol, triglycerides, AST, ALT, pancreatic amylase, lipase, creatinine, eGFR.
• cognitive function tests: ADAS-cog and the quality score of MMSE, Phonemic verbal fluency test; Semantic verbal fluency test; Geriatric Depression Scale (GDS) ; Clinical Dementia Rating Scale (CDR); Neuropsychiatric Inventory (NPI); Activities of Daily Living (ADL); Instrumental Activities of Daily Living (IADL).

ADAS-cog was designed to measure the severity of the most important symptoms of Alzheimer's disease. It consists of 11 7 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of AD.

- Functional Magnetic Resonance Imaging (MRI)(only at V1 and V3).

Inclusion Criteria:

• patients capable of giving informed consent
• dysglycemia/prediabetes defined as fasting plasma glucose between 100 and 125 mg/dl and/or 2-hour plasma glucose between 140 and 199 mg/dl after a 75 g OGTT and/or a HbA1c value between 5.7 and 6.4%
• diagnosis of MCI according to the Petersen clinical criteria (the expected corrected scores at the MMSE are from 24 to 27)
• age >50<80 yrs
• stable medication for the past 3 months
• Caucasian ethnicity

Exclusion Criteria:

• age <50>80 yrs
• incapability to give informed consent
• diabetes defined according to American Diabetes Association (ADA) criteria
• clinically significant liver or kidney dysfunction defined as s-ALT > 2 times upper reference or estimated creatinine-clearance (eGFR) < 60 mL / min/1.73m2, assessed by with CKD-EPI formula
• endocrinological diseases other than well controlled hypothyroidism, personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia (MEN) syndrome, severe gastro-intestinal diseases (i.e gastroparesis, dumping syndromes), current or history of chronic or acute pancreatitis
• any contraindication to the use of exenatide as per the Summary of Product Characteristics
• known abuse of alcohol or drugs
• ferro-magnetic prosthesis, pacemaker or other metals incorporated in the body
• significant neurologic disease other than MCI (i.e. Parkinson's disease, multiple system atrophy, normal pressure hydrocephalus, progressive supranuclear palsy, subarachnoid hemorrhage, brain neoplasms, Huntington disease, epilepsy or head trauma)
• BMI ≤22 Kg/m2 in subject ≥ 70 yrs
• MRI/CT showing unambiguous etiological evidence of cerebrovascular disease with regard to MCI
• severe sensory defects; current presence of clinically significant psychiatric disorder
• warfarin treatment, clinically significant systemic condition
• history of cancer within the last 5 yrs
• known allergy to exenatide or any of the other components.