Brain Changes With Game Training in Aging

Neuroplasticity is an important process associated with memory and learning, and may be
impaired in early Alzheimer's disease (AD). Video games are one potential strategy for
investigating adaptive cognitive learning. Recent neuroimaging studies in healthy young
adults have been able to detect brain changes associated with learning and memory from a
racing video game over relatively short training periods of a couple hours. This strategy
offers significant promise for characterizing the potential for neuroplasticity in patients
at risk for AD including amnestic mild cognitive impairment (aMCI).

This project will apply video game training with magnetic resonance imaging (MRI) brain
scanning to investigate adaptive learning, working memory and neuroplasticity as a function
of aging and in patients with aMCI. A total of forty participants will be studied. Twenty
subjects will undergo the video game training. Twenty subjects will be passive controls.

Specific Aims:

To characterize the microstructural brain changes after video game training in aging subjects
and determine how patients with amnestic MCI (aMCI) and early AD are affected. For this
study, adult participants ages 50 and older including patients with aMCI and early AD will
undergo two neuroimaging sessions spaced roughly two hours apart that are bracketed around
roughly 90 minutes of car racing game play. We will use diffusion-weighted imaging to detect
longitudinal changes in microstructure of the hippocampus and parahippocampus. A primary
objective of this study is to demonstrate that these training and imaging methods are
translatable to patients with MCI. We will investigate the following two important
hypotheses.

Hypothesis 1: Following car racing video game play, participants, on average, will
demonstrate significant microstructural changes in hippocampal and parahippocampal brain
regions measured with MRI.

Hypothesis 2: The microstructural changes in the hippocampus and parahippocampus measured
with MRI will be significantly correlated with (a) cognitive memory performance as assessed
by recent memory assessments, and (b) improvements in video game performance in all
participants.

The primary outcome measures for both Hypotheses are the changes in the MRI measurements
following car racing video game play.

A long-term objective of this project is to determine whether imaging short term
neuroplasticity is predictive for individual patients of either future conversion to AD or
the effectiveness of cognitive training therapies. More generally, neuroimaging markers of
learning-induced brain plasticity would provide extremely useful tools for investigations of
aging, dementias, and neurodegenerative diseases.

Inclusion Criteria:

1. 50-80 years of age

2. Part of existing aging research sample cohorts at University of Wisconsin - Madison

3. Successful research MRI study within prior two years

4. May include participants with

1. No diagnosed cognitive impairment

2. amnestic MCI

3. mild AD (single or multi-domain) with predominant amnesia

Exclusion Criteria:

1. Contraindications to MRI (see Risks of MRI below)

2. Significant experience with playing race car video games in previous 2 years.

3. Severe AD

4. Lack of capacity as determined by the Capacity Assessment of Understanding
questionnaire

5. Women who may be pregnant