Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations

Background: Global brain atrophy is present in normal aging and different neurodegenerative disorders such as Alzheimer's disease (AD) and is becoming widely used to monitor disease progression. Summary: The brain volume/cerebrospinal fluid index (BV/CSF index) is validated in this study as a measurement of global brain atrophy. We tested the ability of the BV/CSF index to detect global brain atrophy, investigated the influence of confounders, provided normative values and cut-offs for mild, moderate and severe brain atrophy, and studied associations with different outcome variables. A total of 1,009 individuals were included [324 healthy controls, 408 patients with mild cognitive impairment (MCI) and 277 patients with AD]. Magnetic resonance images were segmented using FreeSurfer, and the BV/CSF index was calculated and studied both cross-sectionally and longitudinally (1-year follow-up). Both AD patients and MCI patients who progressed to AD showed greater global brain atrophy compared to stable MCI patients and controls. Atrophy was associated with older age, larger intracranial volume, less education and presence of the ApoE ε4 allele. Significant correlations were found with clinical variables, CSF biomarkers and several cognitive tests. Key Messages: The BV/CSF index may be useful for staging individuals according to the degree of global brain atrophy, and for monitoring disease progression. It also shows potential for predicting clinical changes and for being used in the clinical routine.

Reference: Camila Orellana, Daniel Ferreira, J.-Sebastian Muehlboeck, Patrizia Mecocci, Bruno Vellas, Magda Tsolaki, Iwona Kłoszewska, Hilkka Soininen, Simon Lovestone, Andrew Simmons, Lars-Olof Wahlund, Eric WestmanMeasuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations. Neurodegener Dis (DOI: 10.1159/000442443)

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MTA Atrophy 0-4

 

Visual assessment of the medial temporal lobe atrophy was performed on a single MR-slice posterior to the amygdala and the mamillary bodies.

The was positioned so the hippocampus, the pons and the cerebral peduncles were all visible. The visual assessment included hippocampus proper, dentate gyrus, subiculum, parahippocampal gyrus, entorhinal cortex and surrounding CSF spaces such as temporal horn and choroid fissure. The right and left side were rated separately. Scores range from 0 (no atrophy) to 4 (end stage atrophy).

Multimodal techniques for diagnosis and prognosis of Alzheimer's disease

a, Relationship of PIB PET to cerebrospinal-fluid Ab₄₂ concentration in cognitively normal individuals. Subjects with mean cortical PIB binding potentials >0.16 (calculated from an average of PIB retention in the prefrontal cortex, the lateral temporal cortex, the precuneus and the gyrus rectus, divided by PIB retention in the cerebellar cortex) are considered PIB-positive and uniformly have low CSF Ab₄₂ concentrations (<500 pg ml^-1); PIB-negative subjects with low Ab₄₂ concentrations may have non-fibrillar (diffuse) Ab₄₂ deposits that do not retain PIB. Whether non-demented individuals with high PIB and/or low cerebrospinal-fluid Ab₄₂ are more likely to develop dementia than those with low PIB and/or high cerebrospinal-fluid Ab₄₂ has not yet been reported on for large numbers of people, but an initial study supports this idea. b, Axial (horizontal) view of Alzheimer's brain, imaged to quantify amyloid (PIB PET), annual rates of regional atrophy (quantitative MRI) and hypometabolism in relation to dementia severity (fluorodeoxyglucose PET). The intensity of the PIB binding potential is depicted using a colour scale (approximated by the colours in a) in which red reflects greatest PIB retention, and black and dark blue reflect least PIB retention. The regional extent of atrophy is depicted colorimetrically, with rates ranging from 0.4% per year (dark blue) to 1% per year (yellow/green). Regional hypometabolism is also depicted colorimetrically, with red and yellow representing greater and lesser hypometabolism, respectively. The units of this scale reflect the slope of the regression between hypometabolism and dementia severity as measured by mini-mental status examination; high slope suggests a steeper decline in metabolism in relation to decreasing cognitive ability. c, Illustrations of left hemi-brain surfaces (medial, left; lateral, right), allowing comparison of averaged anatomical signal maps for amyloid (top), atrophy (second from top), hypometabolism (third from top) and default-network activity (bottom). Regional amyloid load (PIB binding potential) is depicted as percentage increase of PIB binding potential over that of the brainstem, ranging from 5% (red) to 40% (yellow/white). Colorimetric scales for atrophy and hypometabolism are as in b. The colour scale for regional default-network activity shows the degree of association, ranging from greatest association with default-network activity (light blue) to least statistically significant association (darker blue).