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CBF measured with 3D pseudocontinuous ASL MR imaging helps detect functional changes in the prodromal and more advanced stages of AD and is a marker for disease severity.

Recent imaging studies have demonstrated functional brain network changes in patients with Alzheimer's disease (AD). Eigenvector centrality (EC) is a graph analytical measure that identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. This study used voxel-wise EC mapping (ECM) to analyze individual whole-brain resting-state functional magnetic resonance imaging (MRI) scans in 39 AD patients (age 67 ± 8) and 43 healthy controls (age 69 ± 7). Between-group differences were assessed by a permutation-based method. Associations of EC with biomarkers for AD pathology in cerebrospinal fluid (CSF) and Mini Mental State Examination (MMSE) scores were assessed using Spearman correlation analysis. Decreased EC was found bilaterally in the occipital cortex in AD patients compared to controls. Regions of increased EC were identified in the anterior cingulate and paracingulate gyrus. Across groups, frontal and occipital EC changes were associated with pathological concentrations of CSF biomarkers and with cognition. In controls, decreased EC values in the occipital regions were related to lower MMSE scores. Our main finding is that ECM, a hypothesis-free and computationally efficient analysis method of functional MRI (fMRI) data, identifies changes in brain network organization in AD patients that are related to cognition and underlying AD pathology. The relation between AD-like EC changes and cognitive performance suggests that resting-state fMRI measured EC is a potential marker of disease severity for AD.

ObjectivesTo investigate arterial spin-labelling (ASL) cerebral blood flow (CBF) changes in predementia stages of Alzheimer’s disease (AD).MethodsData were obtained from 177 patients with subjective complaints, mild cognitive impairment and AD from the Amsterdam Dementia Cohort. AD stages were based on diagnosis and cerebrospinal fluid biomarkers amyloid-β (Aβ) and total-tau (tau). General-linear-models were used to assess relationships between AD stages and total and regional CBF, correcting for age and sex.ResultsDecreasing CBF was related to more advanced AD stages in all supratentorial regions (p for trend < 0.05). Post-hoc testing revealed that CBF was lower in AD compared to controls and stage-1 predementia patients (i.e. abnormal Aβ and normal tau) in temporal and parietal regions, and compared to stage-2 predementia patients (i.e. abnormal Aβ and tau) in temporal regions. CBF values of stage-2 predementia patients were numerically in between those of stage-1 predementia patients and AD.ConclusionThe continuing decrease of CBF along the continuum of AD indicates the potential of ASL-CBF as a measure for disease progression.Key Points• Decreasing CBF relates to more advanced AD stages in all supratentorial regions.• The reduction of CBF does not reach a bottom level.• ASL-CBF has potential as a measure for disease progression in AD.

Our results suggest that CBF may have potential as a functional marker of disease severity.