Vision-based Speed of Processing Cognitive Training and Mild Cognitive Impairment

Mild Cognitive Impairment (MCI), especially amnestic type, is considered a symptomatic
pre-Alzheimer's disease (AD) phase, and is prevalent in the aging population. Vision-based
speed of processing (VSOP) cognitive training is one of the most widely applied behavioral
interventions in community-dwelling older Americans free of AD, holding potential to slow
cognitive decline. Its particular relevance to MCI is supported by converging evidence from
our preliminary studies, including a recently completed pilot intervention study. However, we
know little about the mechanisms underlying the benefits of VSOP training, limiting our
ability to further exploit VSOP or other forms of cognitive training. In particular, we do
not know if and how the effects of VSOP training on cognitive performance are mediated by
neuroplasticity-related brain changes. Since recent evidence suggests that neuroplasticity is
inducible throughout adult life, even in MCI, it is possible that VSOP training promotes
neuroplasticity and slows neurodegeneration. In this early stage and new investigator
application, we will focus on assessing whether and how VSOP training, relative to mental
leisure activities (MLA), alters cognitive and neural functions in older adults with MCI, up
to 6 months after training. The study will enroll and randomize 84 participants with amnestic
MCI to VSOP training or MLA control groups. Three specific research aims are to (1) determine
whether VSOP training improves processing speed and attention that are associated with
changes of brain structural and functional connectivity; (2) test a novel neurophysiological
pathway of VSOP training effect on brain structure and function; (3) examine the effect of
VSOP training on untrained cognitive and functional domains and the role of
neurophysiological changes underlying possible transfer effects. By examining multiple neural
and novel physiological mechanisms linking a promising VSOP training intervention to
improvements in cognitive performance, this application seeks to challenge and shift current
research on cognitive training that merely examines training effects on cognitive outcomes.
Discovery of neural, and physiological-related mechanisms in VSOP training will have
important implications beyond this particular intervention. Findings from recent behavioral
studies (e.g., cognitive intervention, physical exercise, nutrition, and bio-feedback
intervention) suggest that for cognitive decline to be mitigated in individuals at risk for
AD, it will be necessary for interventions to target the neural and peripheral physiological
pathways that are susceptible to AD neuropathology. Confirmation of the study hypotheses
could support immediate translation to clinical practices by demonstrating the efficacy,
sustainability, and generalizability of cognitive training.

Inclusion Criteria:

- a clinical diagnosis of "mild cognitive impairment due to Alzheimer's disease" using
the most recent NIA and Alzheimer's Association workshop criteria within 3 months: a)
must have memory deficit (1-1.5SD below age- and education-corrected population
norms); b) may have deficits in other cognitive domains (e.g., executive function); c)
preserved BADL, defined as requiring occasional assistance on less than two items on
the Minimum Data Set-Home Care interview, d) absence of dementia using NINCDS-ADRDA
criteria;

- if on AD medication (i.e., memantine or cholinesterase inhibitors), no changes of
doses in the 3 months prior to recruitment;

- capacity to give consent based on clinician assessment; and

- other: age ≥60 years, English-speaking, adequate visual acuity for testing, and
community-dwelling.

Exclusion Criteria:

- current enrollment in another cognitive improvement study;

- major depression: 15-item Geriatric Depression Scale scored > 7;

- MRI contraindications, e.g., metallic implant, pacemaker, claustrophobia; and

- major vascular diseases: stroke, myocardial infarction, congestive heart failure.