The Targeted Neurocognitive Training (TNT) Study

Summary

People with HIV (PWH) often suffer from cognitive impairments known as HIV-Associated Neurocognitive Disorder (HAND). Cognitive impairments in PWH are not fully captured by traditional neurocognitive assessment; thus, we must examine cognitive performance both within a task (inconsistency) and across cognitive domains (dispersion), called Intra-Individual Variability (IIV). IIV predicts cognitive impairment/decline, altered brain morphology, and neuropathology in many clinical populations. Conceptually, IIV results from "executive dyscontrol" or the efficiency (or inefficiency) with which executive control processes coordinate other cognitive processes/domains. Based on the Executive Dyscontrol Hypothesis and underlying calculations of IIV, one way to improve cognition in PWH is through interventions that target improvements in their most severely impaired cognitive domains. We hypothesize such improvements, in turn, should reduce the strain placed on executive functioning resources, freeing up resources needed to compensate for impairments in any domain and, in turn, reducing IIV. Computerized cognitive training, widely used in the study team's prior work, is ideally suited to target impairments in select cognitive domains using computerized cognitive training. In our systematic review of 13 cognitive training studies in PWH, we found cognitive training improved performance in the targeted domain. In this feasibility study, we will assess 150 PWH at baseline with the expectation to recruit 120 PWH with HAND. Then we will use a two-group pre-post experimental design of 120 adults with HAND including: 1) a Targeted Neurocognitive Training (TNT) group (n=60) to train each participant's two most impaired cognitive domains (e.g., attention \& memory) assessed from a neurocognitive battery at baseline, and 2) a no-contact control group (n=60). Aim 1 - Feasibility: To determine feasibility and acceptability of the intervention. Exploratory Aim 1 - Cognition: Compare adults who receive TNT to those who receive no training to determine whether they improve on the cognitive domains trained, show less cognitive IIV across domains and within a task, and demonstrate improved executive functioning. Exploratory Hypothesis 1: TNT will improve cognitive functioning in the targeted impaired cognitive domains. Exploratory Hypothesis 2: TNT will reduce cognitive IIV (both overall dispersion \& inconsistency). Exploratory Hypothesis 3: TNT will improve executive functioning. Exploratory Hypothesis 4: TNT will improve global cognition and reduce HAND severity. Innovation 1 - This is the first study to use IIV to guide cognitive training to target the most impaired cognitive domains to reduce cognitive IIV in HIV. Innovation 2 - This will be one of the first studies to prospectively include both types of cognitive IIV - dispersion and inconsistency - allowing us to examine the relationship between dispersion and inconsistency. Innovation 3 - The epicenter of HIV is in the Deep South where this study will occur.

Conditions

• HIV
• Aging
• Cognitive Function Abnormal
• Cognitive Training
• Older Adults

Interventions

BEHAVIORAL

Targeted Neurocognitive Training

Only two cognitive domains will be targeted for training (10 hrs of training in each, for a total of 20 hours). Two or more cognitive exercises may be employed within a cognitive domain. These exercises provide both immediate and intermittent feedback and are customized to the participants' individual ability; the difficulty and/or complexity of each game are systematically decreased/increased based on participants' performance to always be challenging, but not overly frustrating. Typically, in an hour session, one exercise (e.g., Mental Map) will be engaged at a time (20-30 minutes) before switching to another exercise (e.g., Hawkeye) in another domain for 20-30 minutes. This helps the participant remain engaged but avoid fatigue.

Sponsors & Collaborators

• University of Alabama at Birmingham

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-05-01

Primary Completion

2027-02-01

Completion

2027-07-01

Countries

• United States

Study Locations