An important new study led by the Center for Addiction and Mental Health (CAMH), and with collaboration between several Toronto Dementia Research Alliance (TDRA) sites; Baycrest, Sunnybrook Health Science Centre, Unity Health Toronto and University Health Network-; has shown that combination therapy can slow cognitive decline in older adults at risk for dementia.
The research was published today in JAMA Psychiatry: “Slowing cognitive decline in depressive disorders and mild cognitive impairment: a randomized controlled trial”, and reports the primary results of the Prevention of Alzheimer’s disease with cognitive remediation plus transcranial direct current stimulation in mild cognitive impairment and depression (PACt-MD) study.
PACt-MD was made possible by a grant from the Canada Brain Research Fund, a unique arrangement between Brain Canada and the Canadian government through Health Canada, the Chagnon Family and the CAMH Discovery Fund. The work focused on preventing cognitive decline in older adults with a condition that increases the risk of dementia: major depressive disorder in remission (rMDD), mild cognitive impairment (MCI), or both.
“Investing in long-term, comprehensive research like this is a commitment not only to science, but also to the millions of individuals, families and caregivers affected by dementia,” said the Honorable Mark Holland, Minister of Health. “This research contributes to advancing dementia care in Canada and improving the quality of life for people with dementia and caregivers.”
The study involved 375 older adults who received either a control intervention (“sham”) or a combination of two active therapies: the first involved specially designed Cognitive Remediation (CR) techniques; therapeutic interventions designed to improve cognitive functioning, such as puzzles and logic. problems. The second was transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. These therapies were given five days a week for eight weeks, followed by five-day “boosters” every six months. The study was randomised, controlled and double-blind, with assessments carried out at baseline, month 2 and annually for three to seven years.
The study found that participants who received CR plus tDCS experienced slower cognitive decline over a median follow-up period of four years compared to those who received the control intervention. The effects were more prominent in individuals with a low genetic risk for Alzheimer’s disease, and participants with rMDD (with or without MCI) showed better outcomes than those with MCI alone.
Cognitive decline is often the result of overlapping conditions, making combination therapies particularly relevant: they can improve patient outcomes by synergistically targeting different disease pathways.
We are very pleased to demonstrate, after seven years of close monitoring, that this combination of therapies is effective in slowing cognitive decline in some of our most vulnerable populations. This study shows promise that multifaceted, non-pharmacological approaches for people at high risk of developing dementia can help them live more independent lives for longer.”
Dr. Tarek Rajji, lead author and one of the principal investigators of the study
Dr. Rajji is a former CAMH Senior Scientist and is now Chairman of the Department of Psychiatry at the University of Texas Southwestern Medical Center.
Dr. Benoit Mulsant, senior author and research team leader, explained the focus on the prefrontal cortex: “While there are several hypothesized mechanisms underlying the increased risk of dementia in older adults with depression, reduced brain plasticity, or the ability to the brain to compensate for damage is considered a common pathway. In this study, we targeted the prefrontal cortex for treatment because this is believed to be a part of the brain that is highly adaptable to change and critical for executive functioning.” Dr. Mulsant is a senior scientist at CAMH and Labatt Family Chair for the Department of Psychiatry, Temerty Faculty of Medicine, at the University of Toronto.
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Magazine reference:
Rajji, T.K. et al. (2024). Slowing cognitive decline in major depressive disorder and mild cognitive impairment. JAMA Psychiatry. doi.org/10.1001/jamapsychiatry.2024.3241.