Network-Level Mechanisms for Preclinical Alzheimer's Disease Development

In this study the investigators want to find out whether the use of a perturbation, such as
AGB101 low dose of levetiracetam extended release formulation, in healthy adults with the
Apolipoprotein e4 gene (APOE 4) can reduce abnormal hippocampal network activity. The
investigators also want to study whether this low dose of LEV can improve memory function.

Generic levetiracetam is a type of drug called an anti-epileptic or anti-seizure medication.
It is FDA approved worldwide for adults and children as young as one month with seizures. It
is a generic drug used in long-term epilepsy treatment. It is relatively safe and has an
acceptable side-effect profile.

AGB101 has been developed as a novel extended release formulation of low dose levetiracetam
(below clinically marketed doses for epilepsy) for slowing the progression of amnestic mild
cognitive impairment.

It is known that age and the APOE 4 gene are important risk factors for late-onset
Alzheimer's disease. Further studies have shown that cognitively normal, older adults with
the APOE 4 gene have more hyperfunctional brain network activity, increased alpha beta
accumulation, decreased memory function, and decreased brain volume, which is consistent with
Alzheimer's disease patterns.

Inclusion Criteria:

- Fluent in English

- At least eight (8) years of education

- Geriatric Depression Scale (GDS) (62) score < 6

- Hachinski Ischemic Score ≤ 4

- Normal general cognitive function as well as 1) normal memory function, documented by
MOCA score of 23 or greater, and a RBANS Delayed Memory Index score of 85 or greater.

Exclusion Criteria:

- Neurological disease, such as Parkinson's disease, multi-infarct dementia,
Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive
supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or a
history of significant head trauma or known structural brain abnormalities

- Major psychiatric disease or chronic unstable medical conditions

- History of drug abuse

- History of alcohol abuse (4 or greater drinks per day on average)

- Unable to complete MRI scans (no Pacemaker/Defibrillator)

- Known clinically significant abnormalities in B12 or thyroid function tests

- End Stage Renal Disease (ESRD)

- Hemodialysis (HD)