Cortical Thickness in Middle and Older Aged Adults With Bipolar Disorder Across Six International Sites.

Age-related changes in cognitive performance represent a growing public health challenge in aging societies. Even in the absence of overt neurodegenerative disease, older adults frequently report difficulties in memory, attention, and executive functioning, which can negatively impact on daily functioning, emotional well-being, and quality of life [,]. As life expectancy continues to increase, there is a growing need for safe and effective interventions aimed at preserving cognitive function and psychological well-being in elderly populations. In parallel with this demographic shift, there has been increasing interest in nutritional and botanical interventions as non-pharmacological strategies to support cognitive performance. Conventional pharmacological treatments have limited efficacy in non-pathological populations and may be associated with adverse effects, making them less suitable for preventive or long-term use [, , ]. Consequently, plant-derived extracts rich in polyphenols have gained attention due to their neuroprotective, anti-inflammatory, and antioxidant properties, as well as their favorable safety profiles [, , ]. Within this broad class of bioactive compounds, ellagitannins (ETs) have emerged as compounds of particular interest. ETs are a class of hydrolyzable polyphenols found in selected food sources, including berries from the Rubus genus (i.e., cloudberry, raspberry, blackberry) and the Fragaria genus (strawberry) []. Other sources are pomegranate, nuts, and seeds. Growing evidence from in vitro and animal studies suggests that ETs and their gut-derived metabolites, notably urolithins, exert neuroprotective effects through multiple mechanisms, including antioxidant activity, modulation of neuroinflammatory pathways, and protection against oxidative stress–induced neuronal damage []. Although direct evidence in humans remains limited, emerging clinical data indicates that dietary intake of ET-rich foods or extracts may positively influence cognitive performance. A small number of intervention studies have reported improvements in memory-related outcomes and other cognitive domains following ET consumption, supporting a potential role for these compounds in cognitive performance []. For example, pomegranate consumption, in the form of extract or juice, was reported to protect against post-surgery memory deficits and to enhance memory performance in older adults with memory complaints [,]. Moreover, a 12-week controlled trial using daily strawberry powder reported reduced memory interference and improved executive functioning in middle-aged adults with self-reported cognitive decline []. Additional randomized controlled trials with freeze-dried strawberry supplementation in older adults have shown enhancements in processing speed and antioxidant capacity, although effects on specific memory outcomes vary [].