Concordance and Discordance Between Brain Perfusion and Atrophy in Frontotemporal Dementia

The aim of this study was to determine if a dissociation between reduced cerebral perfusion and gray matter (GM) atrophy exists in frontotemporal dementia (FTD). The study included 28 patients with FTD and 29 cognitive normal (CN) subjects. All subjects had MRI at 1.5 T, including T1-weighted structural and arterial spin labeling (ASL) perfusion imaging. Non-parametric concordance/discordance tests revealed that GM atrophy without hypoperfusion occurs in the premotor cortex in FTD whereas concordant GM atrophy and hypoperfusion changes are found in the right prefrontal cortex and bilateral medial frontal lobe. The results suggest that damage of brain function in FTD, assessed by ASL perfusion, can vary regionally despite widespread atrophy. Detection of discordance between brain perfusion and structure in FTD might aid diagnosis and staging of the disease

Concordance and discordance between brain perfusion and atrophy in frontotemporal dementia.

The aim of this study was to determine if a dissociation between reduced cerebral perfusion and gray matter (GM) atrophy exists in frontotemporal dementia (FTD). The study included 28 patients with FTD and 29 cognitive normal (CN) subjects. All subjects had MRI at 1.5 T, including T1-weighted structural and arterial spin labeling (ASL) perfusion imaging. Non-parametric concordance/discordance tests revealed that GM atrophy without hypoperfusion occurs in the premotor cortex in FTD whereas concordant GM atrophy and hypoperfusion changes are found in the right prefrontal cortex and bilateral medial frontal lobe. The results suggest that damage of brain function in FTD, assessed by ASL perfusion, can vary regionally despite widespread atrophy. Detection of discordance between brain perfusion and structure in FTD might aid diagnosis and staging of the disease

Associations between white matter hyperintensities and β amyloid on integrity of projection, association, and limbic fiber tracts measured with diffusion tensor MRI.

The goal of this study was to assess the relationship between Aβ deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0-0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between Aβ deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. Aβ deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where Aβ deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ε4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue

Effects of PiB positivity and WMH pathology on FA in subset of subjects with apoE genotype^a.

a<p>PiB+WMH+: n = 13; PiB+WMH<b>−</b>: n = 14; PiB−WMH+: n = 14; PiB−WMH<b>−</b>: n = 16.</p>b<p>controlling for age, CDR, and presence of infarct, df = 1,41.</p>c<p><i>p</i>-values from MANCOVA controlling for age, CDR, presence of infarct, and apoE ε4 status, df = 1,40.</p

Sample characteristics by PIB and WMH pathology^a status.

a<p>Defined as WMH volume ≥0.5% of total intracranial volume (ICV).</p>b<p>unavailable for 9 participants.</p>c<p>derived from FLAIR segmentation, available for 24 PiB−, 26 PiB+, 28 WMH<b>−</b>, 22 WMH+.</p>d<p><i>p</i>-value from MANOVA, df = 1,55.</p>e<p><i>p</i>-value from Pearson Chi-Square test.</p

Examples of the (A) projection fiber ROIs: corona radiata in magenta; internal capsule in green, (B) limbic fiber ROIs: cingulate gyrus in green, parahippocampal white matter in magenta; fornix in red, (C) association fiber ROIs: superior longitudinal fasciculus in red; superior fronto-occipital fasciculus in green; inferior fronto-occipital fasciculus in purple, and (D) corpus callosum ROIs: genu in purple; body in green; splenium in red.

<p>ROIs are overlaid an intensity-averaged FA template generated from 23 Aging Brain research participants with no infarct and WMH <0.5% intracranial volume.</p

Least Squares Means FA values from 9 ROIs by PiB and WMH pathology status^a.

a<p>Least squares means of FA values in PiB −/+ and WMH −/+ groups controlling for age, CDR, and presence of infarct.</p>a<p><i>p</i>-values from MANCOVA, df = 1,50.</p

Description of infarcts in 22 participants.

1<p>basal ganglia and/or thalamus.</p>2<p>midbrain, pons, medulla and/or cerebellum.</p