Clinical trials

Subjective cognitive impairment (SCI) is a non-clinical condition manifesting as a self-reported decline in cognitive function without objective clinical evidence, and is prevalent among older adults and strongly associated with declining mood. This study explores the potential of photobiomodulation (PBM) as a therapeutic intervention for SCI. PBM, using near-infrared light, is a non-invasive neuromodulation approach that has shown promise in improving neuronal function, blood flow, and reducing inflammation in both healthy adults and patients with neurological conditions, including dementia and depression. This study proposes investigating the potential of forehead (tPBM), intranasal (iPBM) and vagal (vPBM) PBM to enhance mood and cognitive function in individuals with SCI as a proof of concept for the future use of PBM as therapy for cognitive decline in general. This study will recruit approximately 80 participants with SCI for the study, and the total expected duration of the participant\'s participation in the study is 5 weeks. The active and sham Neuro 5T device consisting of a headset with a built-in controller, nasal and neck applicators will be used. The nasal and neck applicators each contains a single LED and will be placed into the nostril or neck and secured into place. The headset contains multiple LEDs in a wearable applicator and may be adjusted. The Neuro 5T also contains telemetry features to allow documentation of patient usage of the device. LEDs are semiconductor electronic components that emit light. Participants will be given PBM devices for in-home usage, 2 times a day, 7 days a week, for 5 weeks. Participants will undergo EEG, MRI, cognitive and nasal microbiome assessments before and after the 5-week period.

Major depressive disorder (MDD) is associated with significant cognitive impairment throughout the life-course, which may progress toward MCI and dementia with age. Antidepressant medications are the first line of treatment; however, they fail to adequately address cognitive deficits and prevent relapse. Sustained cognitive impairment into euthymic periods may relate to underlying neurobiological changes, which could potentially be addressed through Cognitive Behavioural Therapy (CBT). Notably, CBT has been shown to improve cognitive domains including divided attention, memory, and processing speed while preventing depression relapse. Midlife represents a critical period in which shared neurobiological factors (such as brain changes on a vascular, morphological, and functional level) underlying depression and cognitive impairment could accelerate toward MCI and dementia. An updated understanding of neurobiological correlates of midlife depression and CBT response through multimodal neuroimaging is critical to improving affective and cognitive outcomes in this population. The overarching objective of this project is to use multimodal neuroimaging to quantify the neurobiological and clinical impact of CBT in midlife depression. Specifically, we aim to: 1. Investigate the clinical impact of CBT on cognitive function and mood outcomes in midlife depression 2. Examine functional connectivity and microstructural determinants of CBT response in midlife depression using neuroimaging 3. Identify vascular modulators of neural connectivity and CBT response in midlife depression. We hypothesize that midlife depression will be associated with functional and structural neural connectivity changes, which will be accompanied by vascular pathology. Adequate CBT response (i.e., improvements in mood and cognitive function) will be associated with amelioration of neurobiological changes.

Previous preliminary results are sufficiently impressive to suggest that tDCS stimulation does have the potential to improve motor function when that ability is trained during stimulation. In the proposed study, the investigation will assess whether walking sessions combined with tDCS lead to improvements in motor function: gait, articulation, eye gaze, and motor dexterity. In addition, the investigators wish to examine if such results can be replicated in people with other conditions, such as cortical basal syndrome, and Parkinson's disease.

Participants (n=450; aged 50+; without a diagnosis of dementia; sufficiently fluent in English to complete the assessments and engage in programming) receive a comprehensive dementia risk assessment, including nonmodifiable and modifiable risk factors, from which they receive a Personalized Dementia Risk Report and Program Strategy, indicating their health conditions increasing and their risk level in five modifiable risk domains: physical activity, brain- healthy eating, cognitive engagement, social connections, and mental wellbeing. Equipped with this information, participants enroll in programs within the Centre to address their risk factors. Changes to their dementia risk, cognition, and Personalized Program Strategy are communicated through re-assessments of risk factors every six months (risk and cognition) and every year (comprehensive assessment).

There is currently little symptomatic therapy for Alzheimer's Disease (AD) and nothing effective for individuals with Frontotemporal dementia (FTD). However, neuromodulation with transcranial direct current stimulation (tDCS) has the potential to be a clinically effective therapy for both AD and FTD. The challenge now is to specify the parameters and conditions under which tDCS is most effective to transition from the laboratory to clinical medicine. tDCS studies typically report significant group effects despite the variability demonstrated among participants, with some showing clear, meaningful improvement, while others only show statistical improvement or none at all. These variable results may be related to the conventional stimulation intensity level of 2mA. The investigators predict that administering tDCS at 4.0 mA, a more significant number of participants would show a meaningful response, and those who improve at 2mA may improve even more from 4.0mA due to having a larger electric field produced. The investigators aim to test this hypothesis in people with Alzheimer's Disease.

There is currently little symptomatic therapy for Alzheimer's Disease (AD) and nothing effective for individuals with Frontotemporal dementia (FTD). However, neuromodulation with transcranial direct current stimulation (tDCS) has the potential to be a clinically effective therapy for both AD and FTD. The challenge now is to specify the parameters and conditions under which tDCS is most effective to transition from the laboratory to clinical medicine. tDCS studies typically report significant group effects despite the variability demonstrated among participants, with some showing clear, meaningful improvement, while others only show statistical improvement or none at all. These variable results may be related to the conventional stimulation intensity level of 2mA. The investigators predict that administering tDCS at 4.0 mA, a more significant number of participants would show a meaningful response, and those who improve at 2mA may improve even more from 4.0mA due to having a larger electric field produced. The investigators aim to test this hypothesis in people with Alzheimer's Disease.