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Combination therapy slows cognitive decline, research shows

Dual therapies could help older adults with depression who face higher risk of dementia, new study finds

Caregiver nurse wearing blue scrubs and elderly woman retirement playing wooden shape puzzles game learning origami as for physiotherapy activity for dementia as a part of a physical therapy session medical health care plan
In the study, older adults with remitted major depressive disorder, mild cognitive impairment, or both received either a control intervention or a combination of two therapies: cognitive remediation puzzles and logic problems, along with a mild form of electrical neuromodulation targeting the prefrontal cortex of the brain. (Photo Credit: Getty Images)

DALLAS – Oct. 30, 2024 – A novel combination therapy slowed cognitive decline in elderly patients with a history of depression – a major risk factor for developing Alzheimer’s and other forms of dementia, a study led by UT Southwestern Medical Center’s new Chair and Professor of Psychiatry found.

Published in JAMA Psychiatry, the study demonstrates for the first time that combining targeted electrical stimulation with specialized mental training can improve cognitive function in adults with remitted major depressive disorder after just two months of treatment and delay cognitive decline to baseline for up to six years.

Tarek Rajji, M.D.
Tarek Rajji, M.D., Chair and Professor of Psychiatry at UT Southwestern, holds the Stanton Sharp Distinguished Chair in Psychiatry and is a member of the Peter O’Donnell Jr. Brain Institute.

Tarek Rajji, M.D., who joined UT Southwestern on Oct. 1, performed the research with colleagues at the Centre for Addiction and Mental Health (CAMH) and the Toronto Dementia Research Alliance (TDRA) at the University of Toronto, where he previously served as Professor of Psychiatry and Director of the Geriatric Psychiatry Division. He also was Executive Director of the TDRA and Chair of the Medical Advisory Committee for the CAMH, Canada’s largest mental health teaching hospital.

“A history of depression – even at younger ages – doubles the risk of dementia in older adults, and no intervention to date has been shown to reduce this risk,” Dr. Rajji said. “Our study found that combining neuromodulation with specialized cognitive training can have a positive impact in older patients with depression, slowing cognitive decline and helping them maintain function for a significant period. It’s a major step forward in reducing the risk of Alzheimer’s and other forms of dementia in patients with a history of depression.”

The randomized trial studied 375 older adults with remitted major depressive disorder, mild cognitive impairment, or both. Study participants received either a control intervention or a combination of two therapies: cognitive remediation puzzles and logic problems, along with transcranial direct current stimulation, a mild, noninvasive form of electrical neuromodulation targeting the prefrontal cortex, a critical region of the brain for cognitive compensation in aging adults.

Participants received treatment five days a week for eight weeks, with follow-up sessions every six months.

The participants who received cognitive remediation plus transcranial direct current stimulation experienced slower cognitive decline compared with those in the control group. Positive outcomes were even more pronounced in participants with remitted major depressive disorder, either with or without cognitive impairment, than those who only had cognitive impairment. 

“The combined therapy strategy has been used in older adults with mild cognitive impairment for short-term treatment,” Dr. Rajji said. “This is the first time it has been evaluated in older adults with depression who either have mild cognitive impairment or do not, in addition to patients with mild cognitive impairment on its own, with up to six years of follow-up.”

The next step is to confirm the study’s findings using a larger and more diverse sample of participants.

“UT Southwestern is an ideal place to build on this work going forward, especially considering our expanding research in neuromodulation that is taking place across various departments,” Dr. Rajji said. “It’s also possible we could develop a complementary intervention for home use that would allow many more individuals to be helped.” 

Dr. Rajji holds the Stanton Sharp Distinguished Chair in Psychiatry and is a member of the Peter O’Donnell Jr. Brain Institute.

About UT Southwestern Medical Center   

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.