Effects of Memantine on Cerebrospinal Fluid Biomarkers of Neurofibrillary Pathology

Previous studies showed that memantine inhibits tau hyperphosphorylation in vitro. In this study, phosphorylated tau (P-tau) and total tau (T-tau) were measured before and after 6 month treatment with memantine in 12 subjects ranging from normal cognition with subjective memory complaints, through mild cognitive impairment to mild Alzheimer\u27s disease. Thirteen non-treated individuals served as controls. Treatment was associated with a reduction of P-tau in subjects with normal cognition. No treatment effects were seen among impaired individuals, suggesting that longer treatment time may be necessary to achieve biomarker effect in this group

Framingham cardiovascular risk profile correlates with impaired hippocampal and cortical vasoreactivity to hypercapnia

Vascular risk factors affect cerebral blood flow (CBF) and cerebral vascular reactivity, contributing to cognitive decline. Hippocampus is vulnerable to both Alzheimer's disease (AD) pathology and ischemia; nonetheless, the information about the impact of vascular risk on hippocampal perfusion is minimal. Cognitively, healthy elderly (NL=18, 69.9±6.7 years) and subjects with mild cognitive impairment (MCI=15, 74.9±8.1 years) were evaluated for the Framingham cardiovascular risk profile (FCRP). All underwent structural imaging and resting CBF assessment with arterial spin labeling (ASL) at 3T magnetic resonance imaging (MRI). In 24 subjects (NL=17, MCI=7), CBF was measured after a carbon dioxide rebreathing challenge. Across all subjects, FCRP negatively correlated with hippocampal (ρ=−0.41, P=0.049) and global cortical (ρ=−0.46, P=0.02) vasoreactivity to hypercapnia (VRh). The FCRP–VRh relationships were most pronounced in the MCI group: hippocampus (ρ=−0.77, P=0.04); global cortex (ρ=−0.83, P=0.02). The FCRP did not correlate with either volume or resting CBF. The hippocampal VRh was lower in MCI than in NL subjects (Z=−2.0, P=0.047). This difference persisted after age and FCRP correction (F[3,20]=4.6, P=0.05). An elevated risk for vascular pathology is associated with a reduced response to hypercapnia in both hippocampal and cortical tissue. The VRh is more sensitive to vascular burden than either resting CBF or brain volume