New Clinical Trial Explores Digital Intervention for Apathy in Late-life Depression

Geriatric neuropsychologist and neuroscience researcher Lauren Oberlin, PhD, is leading a new NIH-funded, randomized controlled clinical trial at the AdventHealth Neuroscience Institute called THRIVE: Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics. The study will examine whether digital cognitive training – a behavioral intervention involving a customized suite of computerized cognitive exercises – improves mood, cognitive function, and functional connectivity of select brain networks in older adults with apathy and major depression.

A Disorder of Motivation -- Understanding and Treating Apathy

Late-life depression, defined as major depressive disorder that occurs in those aged 60 or older, is a leading cause of disability and medical morbidity for that population. A clinical syndrome, apathy is defined as a motivational disturbance accompanied by a persistent reduction in goal-directed behavior that results in initiation deficiencies, flattening of affect, and emotional indifference.

“Apathy is a challenging and highly prevalent psychiatric syndrome in older adulthood, afflicting 30-50% of patients with late-life depression” explains Dr. Oberlin. “Motivational disturbances of apathy can result in poor self-care, physical inactivity, social isolation and disconnection as well as neglect of medical recommendations. This can accelerate disease trajectories and lead to poor health outcomes and disability.”

Dr. Oberlin shares that effective treatments for apathy are scarce and can have side effects.

“Selective serotonin reuptake inhibitors (SSRI’s) are the first-line pharmacotherapy for late-life depression, but they often do not improve apathy and may even exacerbate it,” she says. “Digital cognitive training is a novel approach developed by cognitive neuroscientists to stimulate neuroplasticity. Emerging data from our lab and others suggests that it improves mood and cognitive control functions in major depression, including reduced disability and depression severity. There is also strong empirical support from randomized controlled trials showing that digital cognitive training exercises significantly reduce age-related declines in attention, working memory, and executive functioning.”

About the THRIVE Trial

The purpose of the new THRIVE study is to examine whether a targeted and remotely delivered digital cognitive training intervention can modulate the network connectivity of depressed apathetic persons and reduce apathy and its accompanying cognitive deficits. The exercises were custom designed to engage brain networks specifically impacted in apathy of late-life depression by targeting core cognitive operations supported by these networks, including salience processing, sustained attention, and cognitive control.

“This non-invasive behavioral intervention involves 25-30 minutes of user-friendly, computer-based brain games 5 days a week for 4 weeks,” comments Dr. Oberlin. “These cognitive exercises were designed to challenge but not overwhelm. They are remotely delivered on a web-based platform, making them highly accessible and easily completed in participants’ own homes. Participants already receiving other treatments for their mood (medication, psychotherapy) are eligible and may continue their usual treatments during the study."

The primary aim of the THRIVE trial is to test target engagement of key brain networks measured via resting state functional magnetic resonance imaging (fMRI) data. Researchers will examine whether the intervention, relative to the expectancy-matched control, leads to alterations in resting state functional connectivity (rsFC) among the salience network, executive control network, and reward networks over 4 weeks. Study participants will complete research assessments, including measures of mood, cognitive function, and daily function, at baseline (pre-treatment), week 2 (study midpoint), post-treatment, and at week 8 (4-week post-intervention follow-up). MRI scans will be collected at baseline and at treatment end for measurement of rsFC. Participants also have weekly visits with a study clinician for clinical monitoring and to help support intervention engagement and adherence.

“We are excited about this new trial as it has the potential to identify a novel intervention for apathy that can be used alongside current treatments to improve clinical outcomes for older adults struggling with apathy and depression,” adds Dr. Oberlin.

Learn more about the THRIVE research study here.