Reference Database & Longitudinal Registry of the Normal and Pathological Aging Brain

Currently, there is no reliable, bedside, and non-invasive method for assessing connectivity
changes in electrophysiological activity of the brain associated with brain-related
pathologies, e.g., concussion, ADHD, autistic spectrum disorders (ASD), etc. Event Related
Potentials (ERPs), which are temporal reflections of the neural mass electrical activity of
cells in specific regions of the brain that occur in response to stimuli, may offer such a
method, as they provide both a non-invasive and portable measure of brain function. The ERPs
provide excellent temporal information, but spatial resolution for ERPs has traditionally
been limited. However, by using high-density electroencephalograph (EEG) recording, spatial
resolution for ERPs is improved significantly. The paradigm for the current study will
combine neurophysiological knowledge with mathematical signal processing and pattern
recognition methods (BNA) to temporally and spatially map brain function, connectivity and
synchronization.

The need of objective measures that will help the clinician in its decision-making in
brain-related pathologies is recognized. BNA is a new imaging modality that has been
developed to fill this gap.

For ALL arms:

Inclusion Criteria:

- Currently resides in The Villages community

- Age 50-years and above.

- Able to speak, read and understand English

- Willingness to participate and able to give informed consent.

- If corrected vision: only Glasses should be used during the study testing

Exclusion Criteria:

- Currently with lice or open wounds on scalp.

- Any CNS neurologic disorder

- Significant sensory deficits.

- Use of a hearing aid that occupies the ear canal

- Any neuropsychological disorders

- History of special education

- Substance abuse in the last 3 months

- History of any clinically significant brain trauma as determined by the investigator.

- Clinically diagnosed with a concussion in the past year.

For Arm 1 Healthy

Inclusion Criteria:

- BDI score <14

- Subjects Not meeting diagnostic criteria for MDD per the DSM IV-TR,

- MMSE score ≥25

Exclusion Criteria:

- Any chronic disease or condition which affects the nervous system as determined by
clinical neurological evaluation, medical history or PI discretion.

- Any psychiatric disorder,

- History of any medication affecting CNS within the last 3 months

For Arm 2 Early Alzheimer's Disease

Inclusion Criteria:

- BDI score <14

- Subjects Not meeting diagnostic criteria for MDD per the DSM IV-TR, as determined by
clinical evaluation by a research clinician and the Mini International
Neuropsychiatric Interview (MINI).

- MMSE score <24

- MoCA<20

- Presence of an early and significant episodic memory impairment

Exclusion Criteria:

- Any chronic disease or condition other than current pathology

- Any other psychiatric disorder

- CNS medications within the short period of time prior to the EEG testing which are not
in a medically stable treatment phase.

For Arm 3 Depression

Inclusion Criteria:

- BDI score >14

- Subjects meeting full diagnostic criteria for MDD without psychotic features per the
DSM IV-TR

- HAM-D 17-item: Total score of 16 or higher at visit 1.

Exclusion Criteria:

- Any chronic disease or condition other than current pathology

- Any psychiatric disorder other than Depression

- CNS medications within the short period of time prior to the EEG testing which are not
in a medically stable treatment phase.

For Arm 4 Mild Cognitive Impairment

Inclusion Criteria:

- BDI score <14

- Subjects Not meeting diagnostic criteria for MDD per the DSM IV-TR

- MMSE scores according to Number of years of Education:

MMSE score Years of Education 17-18 ≤6 20-21 7-8 23-24 ≤10

-2026

Exclusion Criteria:

- Any chronic disease or condition other than current pathology

- Any other psychiatric disorder

- CNS medications within the short period of time prior to the EEG testing which are not
in a medically stable treatment phase.