(P30-034-24) Homocysteine and Microvascular Abnormalities as Early Modifiable Biomarkers of Age-Related Cognitive Decline: A Study Protocol

Objectives: As the population ages, the prevalence of Alzheimer's disease and related dementias is expected to rise significantly. Early identification of individuals at risk is essential to prevent or slow disease progression. Cerebral microvascular alterations may precede neurodegeneration and may be correlated with peripheral microvascular alterations. This suggests that peripheral microvasculopathy may be utilized as an early biomarker of dementia risk. The bulbar conjunctiva, a vascularized mucus membrane covering the eye, is a unique candidate for this purpose since it has a direct connection to the cerebral circulation. Additionally, elevated plasma homocysteine (Hcy), a risk factor for vascular disease, is also linked to increased dementia risk, has been correlated with microvasculopathy in the bulbar conjunctiva, and may also serve as an early biomarker of dementia risk. The objective of this research protocol is to investigate the associations between peripheral microvascular abnormalities, plasma Hcy concentrations, and their independent and synergistic influences on cerebral vasculature and structure to establish early modifiable biomarkers of age-related cognitive decline.

Methods: Adults ≥60y, 20 cognitively healthy and 20 with cognitive impairment, will be recruited. Peripheral microvascular abnormalities will be quantified in real-time using computer-assisted intravital microscopy, a novel noninvasive technology. Additionally, plasma levels of Hcy and its determinants (folate, B12, B6, creatinine) will be measured. Microvascular abnormalities and the plasma analytes will be compared to cerebral vasculature and structure (subcortical infarcts, lacunes, white matter hyperintensities, enlarged perivascular spaces, cerebral microbleeds, cerebral perfusion, and total and regional brain volumes) using magnetic resonance imaging.

Results: N/A

Conclusions: This study will elucidate the relationships among peripheral microvascular abnormalities, Hcy, and cerebral vasculature and structure in older adults paving the way for targeted interventions to modify these biomarkers (e.g., B vitamin supplementation) and potentially prevent or slow disease progression.

Funding Sources: Rutgers University Brain Health Institute/Center for Advanced Human Brain Imaging Research