IC‐P‐111: Cerebral hypoperfusion, gray‐matter atrophy, and white‐matter pathology in incipient Alzheimer's disease

Abstract

Background: Regional variation in the degree of functional (i.e., hypoperfusion and hypometabolism) and structural brain injury is seen in Alzheimer's disease (AD) patients, often accompanied by cerebrovascular burden. These AD pathological hallmarks need further characterization at prodromal disease stages (Mattsson et al., 2014) to develop sensitive biomarkers for early AD detection (Wierenga et al., 2014). We evaluated cerebral hypoperfusion, gray-matter atrophy, and white-matter lesions (WMLs) in incipient AD using magnetic resonance imaging (MRI). Methods: Cognitively-normal older adults (n=107, 6367 years) and mild cognitive impairment (MCI) patients (n=52, 6768 years) were examined. Cerebral perfusion (blood volume and blood flow, measured using dynamic-susceptibility contrast imaging), gray-matter atrophy (measured by volume and, if available, cortical thickness using structural MRI) were extracted within AD-sensitive regions of interest. Regional biomarker variation was compared between diagnostic groups (adjusting for age and sex) and relationships with WML volumes were assessed. Results: In MCI patients, region-specific cerebral hypoperfusion (mainly blood flow reduction, Figure 1) was detected in temporo-parietal regions and the basal ganglia compared to cognitively-normal older adults; region-specific atrophy occurred in the hippocampus (Figure 1). Both, hypoperfusion and atrophy (i.e., cortical thinning) were present in entorhinal cortex and isthmus cingulate. WMLs were correlated with hypoperfusion in temporo-partial regions and the basal ganglia and with atrophy in hippocampal and entorhinal regions across diagnostic groups. Conclusions: Our data indicate extensive cerebral blood flow alterations within AD-sensitive regions in incipient AD. We also document divergent patterns in the degree of regional hypoperfusion and atrophy, pointing toward applicability as sensitive and independent MRI-based biomarkers in early AD detection. Hypoperfusion and atrophy were both affected by white-matter pathology, suggesting additive effects of regional pathological mechanisms and cerebrovascular burden at prodromal stages of AD. (Figure Presented).