ObjectivesTo assess and compare cortical thickness (CTh) of patients with prodromal Dementia with Lewy bodies (pro-DLB), prodromal Alzheimer's disease (pro-AD), DLB dementia (DLB-d), AD dementia (AD-d) and normal ageing.MethodsStudy participants(28 pro-DLB, 27 pro-AD, 31 DLB-d, 54 AD-d and 33 elderly controls) underwent 3Tesla T1 3D MRI and detailed clinical and cognitive assessments. We used FreeSurfer analysis package to measure CTh and investigate patterns of cortical thinning across groups.ResultsComparison of CTh between pro-DLB and pro-AD (p<0.05, FDR corrected) showed more right anterior insula thinning in pro-DLB, and more bilateral parietal lobe and left parahippocampal gyri thinning in pro-AD. Comparison of prodromal patients to healthy elderly controls showed the involvement of the same regions. In DLB-d (p<0.05, FDR corrected) cortical thinning was found predominantly in the right temporo-parietal junction, and insula, cingulate, orbitofrontal and lateral occipital cortices. In AD-d(p<0.05, FDR corrected),the most significant areas affected included the entorhinal cortices, parahippocampal gyri and parietal lobes. The comparison of AD-d and DLB-d demonstrated more CTh in AD-d in the left entorhinal cortex (p<0.05, FDR corrected).ConclusionCortical thickness is a sensitive measure for characterising patterns of grey matter atrophy in early stages of DLB distinct from AD. Right anterior insula involvement may be a key region at the prodromal stage of DLB and needs further investigation.
BackgroundLittle is known about the patterns of brain atrophy in prodromal dementia with Lewy bodies (pro-DLB).MethodsIn this study, we used SPM8 with diffeomorphic anatomical registration through exponentiated lie algebra to measure grey matter (GM) volume and investigate patterns of GM atrophy in pro-DLB (n = 28) and prodromal Alzheimer’s disease (pro-AD) (n = 27) and compared and contrasted them with those in elderly control subjects (n = 33) (P ≤ 0.05 corrected for family-wise error).ResultsPatients with pro-DLB showed diminished GM volumes of bilateral insulae and right anterior cingulate cortex compared with control subjects. Comparison of GM volume between patients with pro-AD and control subjects showed a more extensive pattern, with volume reductions in temporal (hippocampi and superior and middle gyri), parietal and frontal structures in the former. Direct comparison of prodromal groups suggested that more atrophy was evident in the parietal lobes of patients with pro-AD than patients with pro-DLB. In patients with pro-DLB, we found that visual hallucinations were associated with relative atrophy of the left cuneus.ConclusionsAtrophy in pro-DLB involves the insulae and anterior cingulate cortex, regions rich in von Economo neurons, which we speculate may contribute to the early clinical phenotype of pro-DLB.
Our data, in conjunction with those of the 12 previously described subjects, suggest the existence of a currently unrecognized inaugural epilepsy syndrome of sporadic AD. Such a syndrome could be called the epileptic variant of AD because seizures are its sole feature for more than 2.5 years.
BackgroundTheory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have been published. The aim of our study was to assess ToM in patients with DLB and to search for neural correlates of potential deficits.MethodsThirty-three patients with DLB (DLB group) and 15 patients with Alzheimer’s disease (AD group), all in the early stage of the disease, as well as 16 healthy elderly control subjects (HC group), were included in the study. After a global cognitive assessment, we used the Faux Pas Recognition (FPR) test, the Reading the Mind in the Eyes (RME) test and Ekman’s Facial Emotion Recognition test to assess cognitive and affective components of ToM. Patients underwent cerebral 3-T magnetic resonance imaging, and atrophy of grey matter was analysed using voxel-based morphometry. We performed a one-sample t test to investigate the correlation between each ToM score and grey matter volume and a two-sample t test to compare patients with DLB impaired with those non-impaired for each test.ResultsThe DLB group performed significantly worse than the HC group on the FPR test (P = 0.033) and the RME test (P = 0.015). There was no significant difference between the AD group and the HC group or between the DLB group and the AD group. Some brain regions were associated with ToM impairments. The prefrontal cortex, with the inferior frontal cortex and the orbitofrontal cortex, was the main region, but we also found correlations with the temporoparietal junction, the precuneus, the fusiform gyrus and the insula.ConclusionsThis study is the first one to show early impairments of ToM in DLB. The two cognitive and affective components both appear to be affected in this disease. Among patients with ToM difficulties, we found atrophy in brain regions classically involved in ToM, which reinforces the neuronal network of ToM. Further studies are now needed to better understand the neural basis of such impairment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-016-0179-9) contains supplementary material, which is available to authorized users.
BackgroundCortical and subcortical cognitive impairments have been found in dementia with Lewy bodies (DLB). Roughly, they comprise visuoconstructive and executive dysfunction, whereas memory would remain relatively spared. However, the cognitive profile of patients with prodromal DLB remains poorly illustrated to date.MethodsWe included 37 patients with prodromal DLB (age 67.2 ± 8.6 years, 18 men, Mini Mental State Examination [MMSE] score 27.4 ± 2) and 29 healthy control subjects (HCs; age 68.8 ± 7.9 years, 15 men, MMSE score 29.0 ± 0.9). They were presented with an extensive neuropsychological test battery to assess memory; speed of processing; executive function; visuoperceptual, visuospatial and visuoconstructive abilities; language; and social cognition.ResultsCompared with HCs, patients had lower scores on a visual recognition memory test (Delayed Matching to Sample-48 items; p ≤ 0.021) and lower free recall (all p ≤ 0.035), but not total recall, performance on a verbal episodic memory test (Free and Cued Selective Reminding Test). Short-term memory (p = 0.042) and working memory (p = 0.002) scores were also lower in patients. Assessment of executive function showed no slowing but overall lower performance in patients than in HCs (all p ≤ 0.049), whereas assessment of instrumental function yielded mixed results. Indeed, patients had lower scores on language tests (p ≤ 0.022), apraxia for pantomime of tool use (p = 0.002) and imitation of meaningless gesture (p = 0.005), as well as weakened visuospatial abilities (p = 0.047). Visuoconstruction was also impaired in patients. However, visuoperceptual abilities did not differ between groups. Finally, theory of mind abilities were lower in patients than in HCs (p < 0.05), but their emotion recognition abilities were similar.ConclusionsThis study presents the cognitive profile in patients with prodromal DLB. In line with the literature on DLB with dementia, our results show lower performance on tests of executive function and visuoconstruction. However, we found, from a prodromal stage of DLB, memory (free recall and visual recognition) and social cognition deficits, as well as weakened visuospatial and praxic abilities.
CSF biomarkers of Alzheimer's disease are well validated in clinical research; however, their pragmatic utility in daily practice is still unappreciated. These biomarkers are used in routine practice according to Health Authority Recommendations. In 604 consecutive patients explored for cognitive disorders, questionnaires were prospectively proposed and filled. Before and after CSF biomarker results, clinicians provided a diagnosis and an estimate of their diagnostic confidence. Analysis has compared the frequency of diagnosis before and after CSF biomarker results using the net reclassification improvement (NRI) method. We have evaluated external validity comparing with data of French Bank National of AD (BNA). A total of 561 patients [Alzheimer's disease (AD), n = 253; non-AD, n = 308] were included (mean age, 68.6 years; women, 52 %). Clinically suspected diagnosis and CSF results were concordant in 65.2 % of cases. When clinical hypothesis and biological results were discordant, a reclassification occurred in favour of CSF biomarkers results in 76.9 %. The NRI was 39.5 %. In addition, the results show a statistically significant improvement in clinician confidence for their diagnosis. In comparison with BNA data, patients were younger and more frequently diagnosed with AD. Clinicians tend to heavily rely on the CSF AD biomarkers results and are more confident in their diagnoses using CSF AD biomarkers. Thus, these biomarkers appear as a key tool in clinical practice.
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.
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