Daniel Roquet

Brain perfusion in dementia with Lewy bodies and Alzheimer’s disease: an arterial spin labeling MRI study on prodromal and mild dementia stages

BackgroundWe aimed to describe specific changes in brain perfusion in patients with dementia with Lewy bodies (DLB) at both the prodromal (also called mild cognitive impairment) and mild dementia stages, relative to patients with Alzheimer’s disease (AD) and controls.MethodsAltogether, 96 participants in five groups (prodromal DLB, prodromal AD, DLB with mild dementia, AD with mild dementia, and healthy elderly controls) took part in an arterial spin labeling MRI study. Three analyses were performed: a global perfusion value comparison, a voxel-wise analysis of both absolute and relative perfusion, and a linear discriminant analysis. These were used to assess the global decrease in perfusion, regional changes, and the sensitivity and specificity of these changes.ResultsPatterns of perfusion in DLB differed from AD and controls in both the prodromal stage and dementia, DLB having more deficits in frontal, insular, and temporal cortices whereas AD showed reduced perfusion in parietal and parietotemporal cortices. Decreases but also increases of perfusion in DLB relative to controls were observed in both absolute and relative measurements. All these regional changes of perfusion classified DLB patients with respect to either healthy controls or AD with sensitivity from 87 to 100 % and specificity from 90 to 96 % depending on the stage of the disease.ConclusionsOur results are consistent with previous studies. We extend the scope of those studies by integrating prodromal DLB patients and by describing both hypo- and hyperperfusion in DLB. While decreases in perfusion may relate to functional impairments, increases might suggest a functional compensation of some brain areas.

Correcting for the echo-time effect after measuring the cerebral blood flow by arterial spin labeling.

To take into account the echo time (TE) influence on arterial spin labeling (ASL) signal when converting it in regional cerebral blood flow (rCBF). Gray matter ASL signal decrease with increasing TE as a consequence of the difference in the apparent transverse relaxation rates between labeled water in capillaries and nonlabeled water in the tissue (δR  2* ). We aimed to measure ASL/rCBF changes in different parts of the brain and correct them.

Insular atrophy at the prodromal stage of dementia with Lewy bodies: a VBM DARTEL study

Diffuse atrophy including the insula was previously demonstrated in dementia with Lewy bodies (DLB) patients but little is known about the prodromal stage of DLB (pro-DLB). In this prospective study, we used SPM8-DARTEL to measure gray matter (GM) and white matter (WM) atrophy in pro-DLB patients (n = 54), prodromal Alzheimer’s disease (pro-AD) patients (n = 16), DLB patients at the stage of dementia (mild-DLB) (n = 15), and Alzheimer’s disease patients at the stage of dementia (mild-AD) (n = 28), and compared them with healthy elderly controls (HC, n = 22). Diminished GM volumes were found in bilateral insula in pro-DLB patients, a trend to significance in right hippocampus and parahippocampal gyrus in pro-AD patients, in left insula in mild-DLB patients, and in medial temporal lobes and insula in mild-AD patients. The comparison between prodromal groups did not showed any differences. The comparison between groups with dementia revealed atrophy around the left middle temporal gyrus in mild-AD patients. Reduced WM volume was observed in mild-DLB in the pons. The insula seems to be a key region in DLB as early as the prodromal stage. MRI studies looking at perfusion, and functional and anatomical connectivity are now needed to better understand the role of this region in DLB.

Resting-state networks distinguish locked-in from vegetative state patients

Purpose Locked-in syndrome and vegetative state are distinct outcomes from coma. Despite their differences, they are clinically difficult to distinguish at the early stage and current diagnostic tools remain insufficient. Since some brain functions are preserved in locked-in syndrome, we postulated that networks of spontaneously co-activated brain areas might be present in locked-in patients, similar to healthy controls, but not in patients in a vegetative state. Methods Five patients with locked-in syndrome, 12 patients in a vegetative state and 19 healthy controls underwent a resting-state fMRI scan. Individual spatial independent component analysis was used to separate spontaneous brain co-activations from noise. These co-activity maps were selected and then classified by two raters as either one of eight resting-state networks commonly shared across subjects or as specific to a subject. Results The numbers of spontaneous co-activity maps, total resting-state networks, and resting-state networks underlying high-level cognitive activity were shown to differentiate controls and locked-in patients from patients in a vegetative state. Analyses of each common resting-state network revealed that the default mode network accurately distinguished locked-in from vegetative-state patients. The frontoparietal network also had maximum specificity but more limited sensitivity. Conclusions This study reinforces previous reports on the preservation of the default mode network in locked-in syndrome in contrast to vegetative state but extends them by suggesting that other networks might be relevant to the diagnosis of locked-in syndrome. The aforementioned analysis of fMRI brain activity at rest might be a step in the development of a diagnostic biomarker to distinguish locked-in syndrome from vegetative state.

Benefits from an autobiographical memory facilitation programme in relapsing- remitting multiple sclerosis patients: a clinical and neuroimaging study

ABSTRACT While the efficacy of mental visual imagery (MVI) to alleviate autobiographical memory (AM) impairment in multiple sclerosis (MS) patients has been documented, nothing is known about the brain changes sustaining that improvement. To explore this issue, 20 relapsing-remitting MS patients showing AM impairment were randomly assigned to two groups, experimental (n = 10), who underwent the MVI programme, and control (n = 10), who followed a sham verbal programme. Besides the stringent AM assessment, the patients underwent structural and functional MRI sessions, consisting in retrieving personal memories, within a pre-/post-facilitation study design. Only the experimental group showed a significant AM improvement in post-facilitation, accompanied by changes in brain activation (medial and lateral frontal regions), functional connectivity (posterior brain regions), and grey matter volume (parahippocampal gyrus). Minor activations and functional connectivity changes were observed in the control group. The MVI programme improved AM in MS patients leading to functional and structural changes reflecting (1) an increase reliance on brain regions sustaining a self-referential process; (2) a decrease of those reflecting an effortful research process; and (3) better use of neural resources in brain regions sustaining MVI. Functional changes reported in the control group likely reflected ineffective attempts to use the sham strategy in AM.

Functional Disconnectivity during Inter-Task Resting State in Dementia with Lewy Bodies

Aims: Limited research has been done on the functional connectivity in visuoperceptual regions in dementia with Lewy bodies (DLB) patients. This study aimed to investigate the functional connectivity differences between a task condition and an inter-task resting state condition within a visuoperceptual paradigm, in DLB patients compared with Alzheimer disease (AD) patients and healthy elderly control subjects. Methods: Twenty-six DLB, 29 AD, and 22 healthy subjects underwent a detailed clinical and neuropsychological examination along with a functional MRI during the different conditions of a visuoperceptual paradigm. Functional images were analyzed using group-level spatial independent component analysis and seed-based connectivity analyses. Results: While the DLB patients scored well and did not differ from the control and AD groups in terms of functional activity and connectivity during the task conditions, they showed decreased functional connectivity in visuoperceptual regions during the resting state condition, along with a temporal impairment of the default-mode network activity. Functional connectivity disturbances were also found within two attentional-executive networks and between these networks and visuoperceptual regions. Conclusion: We found a specific functional profile in the switching between task and resting state conditions in DLB patients. This result could help better characterize functional impairments in DLB and their contribution to several core symptoms of this pathology such as visual hallucinations and cognitive fluctuations.

Henry, where have you lost your Self?

The Self is a complex construct encompassing distinct components, including episodic and semantic autobiographical memory, the Self-concept, and the subjective sense of Self, which highest level consists of Self-awareness. The neuro-anatomical correlates are complex, and it is debated as to whether a common region could support these different components of the Self, with a particular interest for the cortical midline structures and the medial prefrontal cortex (MPFC). Alzheimers disease (AD) constitutes an interesting model for the study of Self as autobiographical memory typically deteriorates as the disease progresses. Here, we report the unexpected case of Henry, a patient with MCI due to AD who was unable to produce any personal autobiographical memories, nor describe his Self-concept, had a poor personal semantic memory, and disclosed unusual anosognosia for this stage of the disease. His cognitive performance was compared to a group of matched AD patients and a group of healthy controls confirming that the main components of his Self were degraded. We hypothesized that it was due to a marked atrophy within the cortical midline, as visually assessed on his MRI. We further elucidated these findings through Voxel-based morphometry analysis, which confirmed a significant atrophy of the MPFC that was specific to this patient. Moreover, this revealed significant atrophy within the bilateral insular cortex. Given the stage of the disease, the degradation of the Self is unlikely to be accounted for by deficient mnemonic processes, especially as the presence of discrete temporal atrophy was noted. We suggest that this specific pattern of MPFC and insular atrophy is responsible for the systematic collapse of the patients Self, through the breakdown of the subjective sense of Self, which is proposed as a prerequisite to all other components, according to the model proposed by Prebble, Addis, and Tippett (2013).

PRODROMAL AND NON-PRODROMAL DEMENTIA WITH LEWY BODIES AND ALZHEIMER'S DISEASE: A MULTIMODAL MRI APPROACH

2011); 17/41 (41%) had onset after and 24/41 (59%) before 65 years. We compared clinical, radiological, and CSF data at the initial valuation. Results: Late-onset bvFTLD (mean age at onset: 7063 years; probable bvFTLD1⁄459%) and presenile-onset bvFTLD (mean age at onset 5965 years; probable bvFTLD1⁄471%) had comparable mean disease duration at initial examination (363 years) and mean follow up duration (563 vs 564 years). MRI examination confirmed more frequent hippocampal atrophy (47% vs 21%) and less lobar atrophy (18% vs 58%) in late-onset bvFTLD; this was clinically correlated to more frequent hippocampal memory deficit (53% vs 12.5%). TEP-FDG or SPECT-HMPAO imaging detected focal hypometabolism/hypoperfusion in 53% vs 62.5% of the patients. Unexpectedly, no differences were found in CSF abeta1-42 (10976276 vs 10346236), T-tau (2896214 vs 2316100), P-tau (40617 vs 37615), and IATI index (260.6 vs 260.6); the ratio T-tau/abeta1-42 (0.2660.16 vs 0.2360.10) and P-tau/abeta1-42 (0.0460.01 vs 0.0460.01) were not different, either. In each group three subjects had high T-tau or P-Tau and one subject low abeta1-42. Conclusions:Late-onset bvFTLD is not rare in clinical practice; we confirmed more hippocampal and global atrophy compared to presenile-onset bvFTLD, clinically correlated to more frequent hippocampal memory loss. TEP-FDG and SPECT-HMPAO focal alterations were equally represented. Since no differences were found in CSF biomarkers, the differences between lateand presenile-onset bvFTLD could not be explained by co-existing AD pathology in older patients. They could instead be due to hippocampal sclerosis, known to be associated to FTLD. These data suggest the potential interest of CSF and metabolic markers in the differential diagnosis of late-onset bv-FTLD vs AD.