Citicoline Effects on Cortical Membrane Structure and Function

To determine the effect of citicoline supplementation on cortical structure and function in
healthy middle-aged adults. Test 1: The effect of citicoline (500 mg/d) compared with placebo
on event-related anterior cingulate cortex (ACC) activation during sustained attention by
fMRI. Test 2: The effect of citicoline (500 mg/d) compared with placebo on reaction time and
increasing accuracy on the sustained attention task (CPT-IP). Test 3: The effect of
citicoline compared with placebo on phosphodiester (PDE) and b-NTP levels in the ACC by
31P-MRS. Test 4: ACC activation and CPT-IP performance (fMRI) and ACC PDE levels (31P-MRS)
following high-dose citicoline (500 mg/d) compared with placebo at Week 3. Test 5: The effect
of low-dose citicoline (250 mg/d) compared with placebo on an ACC activation and CPT-IP
performance (fMRI) and ACC PDE levels (31P-MRS). Test 6: Among all subjects (n=60), the
relationship between baseline red blood cell (RBC) omega-3 fatty acid (EPA+DHA) levels and
ACC activation, ACC PDE levels, or the effects of citicoline.

Inclusion Criteria:

- Provision of written informed consent;

- Ages 40-60 years old;

- Right handed.

- If female, not pregnant (as determined by a positive pregnancy test); and agrees to
use one of the following methods of birth control: abstinence from sexual intercourse,
barrier (diaphragm or condom), or oral/injectable contraceptive;

Exclusion Criteria:

- Contraindication to an MRI scan (i.e., braces, claustrophobia, pacemaker etc);

- A history of a major medical (e.g., diabetes) or neurological illness (e.g.,
epilepsy);

- Body mass index (BMI) ≥ 30;

- An IQ <75 and >130;

- A positive urine drug test (nicotine dependence is permitted);

- Personal history of a DSM-5 Axis I psychiatric disorder;

- Requiring treatment with a drug which might obscure the action of the study treatment.