Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages.

To 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.Study 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.Comparison 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).Cortical 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

Flow Chart of the present study on cortical thickness in prodromal and dementia stages of Lewy body dementia and Alzheimer's disease.

<p>AD = Alzheimer’s disease; DLB = Dementia with Lewy bodies; MCI = Mild Cognitive Impairment. Prodromal DLB means patients with McKeith's criteria of DLB with cognitive impairment but without dementia. Psychiatric pathologies included two patients with depression, one with bipolar disorder, and one histrionic personality disorder; and one cognitive impairment due to severe sleep apnoea, one vitamin B12 encephalopathy, and one mitochondriopathy for patients with MCI. Other brain pathologies included one Parkinson's disease dementia, one DLB with primary Sjögren's syndrome, one with chronic brain autoimmune encephalitis and one dementia without evolution for more than 10 years, for patients with dementia</p

Patterns of Cortical thinning between Pro-AD and Pro-DLB and between AD-d and DLB-d (A = Anterior, P = Posterior, FDR = False Discovery Rate).

<p>Patterns of Cortical thinning between Pro-AD and Pro-DLB and between AD-d and DLB-d (A = Anterior, P = Posterior, FDR = False Discovery Rate).</p

Cortical thinning patterns in pro-DLB, pro-AD, DLB-d and AD-d compared to healthy older controls (A = Anterior, P = Posterior, FDR = False Discovery Rate).

<p>Cortical thinning patterns in pro-DLB, pro-AD, DLB-d and AD-d compared to healthy older controls (A = Anterior, P = Posterior, FDR = False Discovery Rate).</p

Location and peak vertex significance of cortical thinning in pro-DLB, DLB-d, pro-AD and AD-d compared to healthy subjects as well as pro-DLB relative to pro-AD, and DLB-d compared to AD-d.

<p>Table depicts anatomical region, FreeSurferTalairach coordinates, number of vertices within each cluster (NVtxs), surface area (Area) (mm2) and peak significance expressed as a—log10P value (e.g.,-log10P = 3 corresponds to p = 0.001…etc). All results are significant (p<0.05 FDR corrected) except where noted by asterisk (*) which were uncorrected.</p><p>Location and peak vertex significance of cortical thinning in pro-DLB, DLB-d, pro-AD and AD-d compared to healthy subjects as well as pro-DLB relative to pro-AD, and DLB-d compared to AD-d.</p

Right Anterior Insula: Core Region of Hallucinations in Cognitive Neurodegenerative Diseases

International audienceObjectives: We investigated the neural basis of hallucinations Alzheimer's disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.Methods: AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. “Core regions” (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.Results: Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).Conclusion: Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases