Design and Rationale of the PACt-MD Randomized Clinical Trial: Prevention of Alzheimer’s dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression

Article type: Research Article

Authors: Rajji, Tarek K.^{a; b} | Bowie, Christopher R.^{a; c} | Herrmann, Nathan^{b; d} | Pollock, Bruce G.^{a; b} | Bikson, Marom^e | Blumberger, Daniel M.^{a; b} | Butters, Meryl A.^f | Daskalakis, Zafiris J.^{a; b} | Fischer, Corinne E.^{b; g} | Flint, Alastair J.^{b; h} | Golas, Angela C.^{a; b} | Graff-Guerrero, Ariel^{a; b} | Kumar, Sanjeev^{a; b} | Lourenco, Lillian^a | Mah, Linda^{b; i} | Ovaysikia, Shima^a | Thorpe, Kevin E.^{j; k} | Voineskos, Aristotle N.^{a; b} | Mulsant, Benoit H.^{a; b; *} | for the PACt-MD Study Group

Affiliations: [a] Centre for Addiction and Mental Health, Toronto, Ontario, Canada | [b] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada | [c] Department of Psychology, Queen’s University, Kingston, Ontario, Canada | [d] Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada | [e] Department of Biomedical Engineering, The City College of New York, NY, USA | [f] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA | [g] Keenan Research Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada | [h] University Health Network, Toronto, Ontario, Canada | [i] Baycrest, Toronto, Ontario, Canada | [j] Dalla Lana School of Public Health, University of Toronto | [k] Applied Health Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada

Correspondence: [*] Correspondence to: Benoit H. Mulsant, 250 College Street, Toronto, Ontario, M5T 1R8, Canada. Tel.: +1 416 535 8501; E-mail: [email protected].

Note: [1] Except for the first four authors and the last author, all the authors have contributed equally and have been listed in alphabetical order.

Abstract: Background:By the time Alzheimer’s disease and related disorders (ADRD) are diagnosed, efficacy of treatments is limited. Preventive interventions are urgently needed. Objective:To design a randomized controlled trial to assess a novel intervention that aims to prevent ADRD in high-risk groups. Methods:We report on the rationale and describe the design of a multisite randomized controlled trial that aims to prevent ADRD in older persons with: (1) mild cognitive impairment (MCI); (2) remitted major depressive disorder (MDD) without MCI; or (3) remitted MDD with MCI. Results:PACt-MD (Prevention of Alzheimer’s dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression) is a trial that randomized 375 older participants with MCI, MDD, or MCI + MDD to cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) or sham-CR + sham-tDCS for 5 days/week for 8 weeks followed by boosters for 5 days/week once every 6 months until participants progress to MCI or ADRD, or the end of the study. Between boosters, participants are asked to train on CR daily. At baseline, end of 8 weeks, and yearly from baseline, participants undergo clinical, cognitive, and functional assessments. The primary aims are to compare the efficacy of CR + tDCS versus sham + sham in preventing: 1) long-term cognitive decline; and 2) incidence of ADRD or MCI. The secondary aim is to assess for cognitive improvement after the 8-week course. We will also explore the moderating and mediating effects of several biomarkers collected from the participants. Conclusion:PACt-MD is unique in combining brain stimulation and a psychosocial intervention to prevent ADRD. PACt-MD is also a platform for studying multi-domain biomarkers that will advance our understanding of the relationships among MCI, MDD, and ADRD.

Keywords: Alzheimer’s disease and related disorders, cognitive remediation, major depressive disorder, mild cognitive disorder, PACt-MD, prevention, transcranial direct current stimulation

Keywords: NCT02386670

DOI: 10.3233/JAD-200141

Journal: Journal of Alzheimer's Disease, vol. 76, no. 2, pp. 733-751, 2020