Brain Structural and Perfusion Signature of Amyotrophic Lateral Sclerosis With Varying Levels of Cognitive Deficit

Abstract

ObjectiveTo characterize the patterns of brain atrophy and perfusion as measured by arterial spin labeling (ASL)-MRI, in amyotrophic lateral sclerosis (ALS) patients with varying levels of cognitive deficit, including ALS with frontotemporal dementia (FTD).MethodsA total of 55 ALS patients and 20 healthy controls (HCs) were included, and all participants underwent neuropsychological assessments and MRI scans. According to their cognitive performance, ALS patients were further subclassified into ALS with normal cognition (ALS-Cn, n = 27), ALS with cognitive impairment (ALS-Ci, n = 17), and ALS-FTD (n = 11). Voxel-based comparisons of gray matter (GM) changes and cerebral blood flow (CBF) were conducted among the subgroups.ResultsThe whole-brain comparisons of GM changes and CBF among ALS-Ci, ALS-Cn, and HCs were not significantly different. However, the ALS-FTD patients demonstrated a similar pattern of GM loss and hypoperfusion with more significant alterations in the left frontal and temporal lobe compared with the HCs, ALS-Cn, and ALS-Ci patients. Decreased CBF was found in many of the same brain areas wherein structural alterations occurred, although isolated GM loss and hypoperfusion were also observed. In addition, for both GM and CBF abnormalities, a similar pattern of changes was found in the comparisons of ALS-FTD vs. ALS-Ci, ALS-FTD vs. ALS-Cn, and ALS-FTD vs. HCs, with the differences being most significant between ALS-FTD and HCs.ConclusionThe cognitive status of ALS patients is associated with different patterns of GM changes and cerebral perfusion. ASL-MRI might be a useful tool with which to investigate the pathological burden of ALS and to disclose the early signature of possible cognitive impairment.

Brain Cortical Complexity Alteration in Amyotrophic Lateral Sclerosis: A Preliminary Fractal Dimensionality Study

“…In line with our results, previous studies have constantly found ALS-associated cortical thinning [4,6], hypometabolism [41], and reduced restingstate neural activity [13] in the posterior cingulate cortex. Consistent with our finding of FD reduction in the insula, researchers have described insula impairment in ALS, such as cortical thinning [5], energy hypometabolism [47], and decreased cerebral blood flow [43]. Given that the posterior cingulate cortex and insula are functionally associated with several high-order cognitive processes such as memory and attention [48][49][50][51], it is speculated that FD reduction in these brain regions may be the neurobiological bases of the cognitive dysfunctions in ALS.…”

“…We also observed a decline of FD in the cingulate gyrus and sulcus (middle part). In fact, middle cingulumassociated cortical atrophy [13,43], functional disconnection [44], and hypoperfusion [43] have been observed in ALS. The middle cingulate cortex has widespread connection with the motor cortex and spinal cord, as well as numerous pyramidal neurons [45].…”

Defining novel functions for cerebrospinal fluid in ALS pathophysiology

“…Whilst neuroimaging studies have demonstrated abnormal CSF dynamics in ALS patients, further studies may be required to specifically determine the influence of these different factors on glymphatic clearance in ALS patients 199]. Abnormal vascular changes in ALS and FTD have further been evidenced through arterial-spin coupling [53,177]. In the SOD1 mouse model, blood-spinal cord barrier (BSCB) breakdown may precede hypoperfusion [215], a feature which has previously been linked to disease severity in ALS patients [2,40].…”

“…Multiple studies employing single-photon emission computed tomography (SPECT) have demonstrated hypoperfusion in the brain of both ALS and FTD patients, with greater involvement of the frontal and temporal lobes [ 1 , 82 , 199 ]. Abnormal vascular changes in ALS and FTD have further been evidenced through arterial-spin coupling [ 53 , 177 ]. In the SOD1 mouse model, blood-spinal cord barrier (BSCB) breakdown may precede hypoperfusion [ 215 ], a feature which has previously been linked to disease severity in ALS patients [ 2 , 40 ].…”

Peer Review #1 of "Static and dynamic alterations in the amplitude of low-frequency fluctuation in patients with amyotrophic lateral sclerosis (v0.1)"

“…As an effective index to measure local brain activity, amplitude of low frequency fluctuation (ALFF) (Guo et al 2012;Liu et al 2013;Yu-Feng et al 2007) has been extensively employed in ALS research. Using this approach, scholars have discovered that patients with ALS showed aberrant activation in the precentral gyrus, frontal gyrus, and occipital regions; this finding suggests that ALS is a disease involving many system with brain impairment spreading beyond the motor cortex (Bueno et al 2019;Ma et al 2016;Shen et al 2018). In addition, the increased ALFF in the frontal lobe could be a candidate biomarker in ALS (Luo et al 2012).…”