Clinical and Biological Effects of Citrus-phytochemicals in Subjective Cognitive Decline.

Subjective cognitive decline (SCD) is receiving increasing attention as a risk factor for incident dementia due to AD. SCD manifests prior to the onset of clinical impairment, and as such could serve as a potential target population for early intervention trials. The pathogenesis of AD is complex and involves a dysregulation of the neuroendocrine immune (NEI) system, a network of signaling molecules, such as neurotransmitters, hormones and cytokines. As a result, it may be unlikely that cognitive decline may be mitigated by drugs acting on a single specific target. Plant extracts acting at different levels of the NEI regulation could represent appealing therapeutic strategies for cognitive decline. Citrus-derived phytochemicals, like auraptene and naringenin, showed antioxidant, anti-inflammatory, and neuroprotective effects in preclinical studies of AD mouse models and preservation of cognition in elderly without cognitive impairment. This is a pilot randomized controlled trial to determine clinical and biological effects of Citrus-phytochemicals in individuals with SCD. Participants will be randomized to receive Citrus-phytochemicals standardized in auraptene and naringenin or placebo for 9 months. Cognitive tests and blood-based biological markers will be done at baseline and at the end of treatment as outcome measures.