Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD

Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer's disease

Recent studies have shown that increased cognitive intraindividual variability (IIV) across accuracy scores from tests representing different cognitive domains (across-domain IIV) might indicate prodromal Alzheimer's disease (AD). Although IIV has been proposed to index cognitive control processes, IIV across accuracy scores from cognitive control tasks (within-domain IIV) has not been examined in healthy controls subjects (HCS), mild cognitive impairment (MCI), and AD patients in a single comparative study. This study examines the discriminative properties of within-domain IIV, and across-domain IIV in 149 HCS, 31 MCI, and 26 AD. Three tasks representing different cognitive domains were identified to calculate across-domain IIV. Three other tasks representing cognitive control were identified to calculate within-domain IIV. The intraindividual standard deviation was calculated across accuracy scores. To compare IIV between groups, ANCOVAs with the covariates age, gender, education, and mean performance were computed. IIV scores in general were higher in AD vs. HCS (p < 0.01). Only across-domain IIV was higher in AD vs. MCI (p = 0.001), and only within-domain IIV was higher in MCI vs. HCS (p = 0.05). Within-domain IIV may constitute a cognitive marker for the detection of prodromal AD at the MCI stage, whereas across-domain IIV may detect beginning AD at the MCI stage