Most dementias are preceded by mild cognitive impairment (MCI), a transitional clinical stage characterized by cognitive decline that does not yet significantly interfere with activities of daily living. Obesity and diabetes are among the major risk factors for MCI and are strongly associated with unhealthy lifestyle patterns. The growing global prevalence of obesity has intensified the need for effective dietary strategies that promote both weight control and neuroprotection. Red fruits, which are rich in bioactive compounds such as anthocyanins, have demonstrated potential roles in modulating metabolic pathways and cognitive function. This systematic review aimed to identify and synthesize evidence from human studies published over the past two decades that examined the effects of red fruit consumption on obesity-related mechanisms and cognitive outcomes, as well as its influence on key neurodegenerative biomarkers, including TAU protein, β-amyloid, and neurofilament light chain. A systematic search was conducted in major scientific databases to identify human clinical trials evaluating the metabolic and neuroprotective effects of berry-derived compounds. Eligible studies were screened for outcomes related to cognitive performance, obesity-related parameters, and relevant molecular biomarkers. The included studies reported modest improvements in cognitive domains, with the most consistent effects observed in memory-related outcomes. Berry-derived bioactive compounds demonstrated potential in attenuating TAU protein hyperphosphorylation and reducing β-amyloid accumulation; however, the available evidence remains limited and requires further confirmation. Human clinical studies remain scarce, and although some trials reported favorable metabolic effects, these findings are still inconclusive. Reported outcomes included improvements in insulin sensitivity, regulation of leptin levels, and modulation of the gut-brain axis, which may collectively contribute to a reduced risk of obesity. Based on the studies evaluated in this review, there remains a limited number of human clinical trials that robustly support the neuroprotective and complementary metabolic effects of berry-derived bioactive compounds. Nevertheless, the available evidence suggests that dietary strategies incorporating wild fruits rich in polyphenols may represent a promising complementary approach for the prevention of mild cognitive impairment (MCI) and obesity, with potential implications for reducing the risk of dementia progression.
