Individualized Cognitive Training in HIV

This research directly meets the goals of the NIH Cognitive and Emotional Health Project and
the Healthy Brain Initiative which seek to "maintain or improve the cognitive performance of
all adults," especially for "populations experiencing the greatest disparities and risks in
cognitive health."

Significance: Using the Frascati criteria, 52% - 59% of people with HIV experience some form
of HIV-Associated Neurocognitive Disorder (HAND) which affects medication adherence,
instrumental activities of daily living (IADLs), and even mood maintenance and quality of
life. By 2020, 70% of adults with HIV in the United States will be 50 and older; thus,
cognitive aging in this group represents a major concern. In a prior study (R03MH076642-01A2)
conducted in the HAART era, when comparing cognitive functioning between older and younger
HIV-positive and HIV-negative adults, older adults with HIV performed the worst. In the HAART
era, these cognitive impairments continue to be observed in several cognitive domains
including memory, learning, executive functioning, and speed of processing.

Regrettably, few behavioral interventions aimed at improving cognition in this
pharmacologically-burdened population have been attempted. Pharmacological interventions have
short-lived effects, if any, and can produce adverse side effects in a population prone to
multiple comorbidities. Fortunately, computerized cognitive training interventions have been
shown to improve cognition without adverse side-effects. Yet, only two types of computerized
cognitive training interventions have been studied in adults with HIV. Becker and colleagues
partially randomized 60 adults with HIV and without HIV to engage in 14 computerized targeted
modules (e.g., knowledge, memory) over 24 weeks. No significant effects were found; however,
adherence was poor. In a prior study, investigators randomized 46 adults to either a speed of
processing training (10 hrs of training) group or a no-contact control group. Adherence was
excellent and improvements were observed on this cognitive domain which transferred to an
everyday functioning task.

Despite this lack of cognitive training studies in HIV, studies in older adults have shown
their efficacy in improving specific cognitive abilities, some as much as 1-1.5 standard
deviations (SD) above baseline performance or age/education-based norms. Using Frascati
criteria, HAND is diagnosed when a person performs at least 1 to 2 SD below their normative
mean on measures of two or more cognitive domains (e.g., verbal memory, speed of processing,
executive functioning); yet many individuals may be only a fraction of a SD below the cut
off. A meta-analysis of 52 cognitive training studies indicated the average cognitive
improvement following cognitive training was 0.22 SD. Although this seems to be a small to
moderate effect size, such cognitive training programs can change the diagnosis of HAND for
some by improving cognitive performance to within acceptable performance norms. In this
study, older adults (50+) with HAND will be enrolled to determine which cognitive domains are
attributable to their diagnosis. Then those cognitive domains in which they have impairments
will be targeted for training with the corresponding cognitive program. Such a tailored
approach to standard cognitive training programs may offer hope and symptom relief to those
individuals diagnosed with HAND. Furthermore, these changes may result in improved everyday
functioning and quality of life. This approach also represents a paradigm shift in changing
the way clinicians and researchers look at HAND in that this is not a static "progressive"
diagnosis; Antinori et al. observed a 20% fluctuation of HAND over as little as 1 year, with
some improving or declining in their cognitive performance. Such fluctuations, at least
partially, reflect positive neuroplasticity that can be manipulated with cognitive training
to improve cognition which can improve medication adherence and other IADLs. This study will
use a basic two group pre-post experimental design of 146 adults with HAND.

Inclusion Criteria:

- Must be 40+ years

- English speaking

- Have HIV-Associated Neurocognitive Disorder (HAND)

Exclusion Criteria:

- Because the study requires several weeks, participants not living in stable housing
(e.g., halfway house) will be excluded.

- Participants with significant neuromedical co-morbidities (e.g., schizophrenia,
epilepsy, bipolar disorder, multiple sclerosis, Alzheimer's disease or related
dementias, mental retardation)

- Currently undergoing radiation or chemotherapy

- A history of brain trauma with a loss of consciousness greater than 30 minutes

- Legally blind or deaf