|Amyloid plaques stained by the Campbell-Switzer technique. |
The histological fields are representative of the amyloid plaque burden shown in 40 µm coronal sections of the frontal lobe.
Tuesday, November 15, 2011
Alzheimer's Disease and Non-Demented High Pathology Control Nonagenarians: Comparing and Contrasting the Biochemistry of Cognitively Successful Aging
Saturday, October 22, 2011
Neuropathologic Correlates of Hippocampal Atrophy in the Elderly: A Clinical, Pathologic, Postmortem MRI Study
The volume of the hippocampus measured with structural magnetic resonance imaging (MRI) is increasingly used as a biomarker for Alzheimer's disease (AD). However, the neuropathologic basis of structural MRI changes in the hippocampus in the elderly has not been directly assessed. Postmortem MRI of the aging human brain, combined with histopathology, could be an important tool to address this issue. Therefore, this study combined postmortem MRI and histopathology in 100 elderly subjects from the Rush Memory and Aging Project and the Religious Orders Study.
|A typical three-dimensional region of interest created by manually outlining the hippocampal formation in consecutive T2-weighted sagittal images of a human cerebral hemisphere.|
First, to validate the information contained in postmortem MRI data, we tested the hypothesis that postmortem hippocampal volume is smaller in subjects with clinically diagnosed Alzheimer's disease compared to subjects with mild or no cognitive impairment, as observed in antemortem imaging studies. Subsequently, the relations of postmortem hippocampal volume to AD pathology, Lewy bodies, amyloid angiopathy, gross infarcts, microscopic infarcts, and hippocampal sclerosis were examined. It was demonstrated that hippocampal volume was smaller in persons with a clinical diagnosis of AD compared to those with no cognitive impairment (P = 2.6×10−7) or mild cognitive impairment (P = 9.6×10−7). Additionally, hippocampal volume was related to multiple cognitive abilities assessed proximate to death, with its strongest association with episodic memory. Among all pathologies investigated, the most significant factors related to lower hippocampal volume were shown to be AD pathology (P = 0.0018) and hippocampal sclerosis (P = 4.2×10−7). Shape analysis allowed for visualization of the hippocampal regions most associated with volume loss for each of these two pathologies. Overall, this investigation confirmed the relation of hippocampal volume measured postmortem to clinical diagnosis of AD and measures of cognition, and concluded that both AD pathology and hippocampal sclerosis affect hippocampal volume in old age, though the impacts of each pathology on the shape of the hippocampus may differ.
Reference: Dawe RJ, Bennett DA, Schneider JA, Arfanakis K, 2011 Neuropathologic Correlates of Hippocampal Atrophy in the Elderly: A Clinical, Pathologic, Postmortem MRI Study. PLoS ONE 6(10): e26286. doi:10.1371/journal.pone.0026286 Free full text
Tuesday, October 4, 2011
Cerebrospinal Fluid Levels of sAPPα and sAPPβ in Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates
AbstractWe measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.Full text
Saturday, September 24, 2011
Early detection of Alzheimer’s disease (AD) is important to reveal preclinical pathological alterations, to monitor disease progression, and to evaluate response to therapy. The study of cerebral glucose metabolism through 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) plays a leading role in early detection of AD because the decrease of cerebral glucose metabolism largely precedes the onset of AD symptoms. This technique demonstrated high sensitivity in early diagnosis of AD, allowing a qualitative and quantitative estimate of cerebral glucose metabolism. Furthermore FDG-PET imaging may help to discriminate the subjects of a high-risk population (like patients with mild cognitive impairment) who more probably will develop AD: an early stage of AD generally shows hypometabolism of medial temporal lobes and parietotemporal posterior cortices; other cerebral cortices are later involved. The combination of FDG-PET with other biomarkers, such as genotype, cerebrospinal fluid markers, and amyloid plaque imaging, may increase the preclinical diagnostic accuracy and offer promising approaches to assess individual prognosis in AD patients.
Multiple Indices of Diffusion Identifies White Matter Damage in Mild Cognitive Impairment and Alzheimer’s Disease
The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer’s disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa.
Saturday, September 17, 2011
Combined imaging markers dissociate Alzheimer’s disease and frontotemporal lobar degeneration – an ALE meta-analysis
To compare and dissociate the neural correlates of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD), we combine and synthesize here recent comprehensive meta-analyses. Systematic and quantitative meta-analyses were conducted according to the QUOROM statement by calculating anatomical likelihood estimates (ALE). AD (n = 578) and the three subtypes of FTLD, frontotemporal dementia, semantic dementia (SD), and progressive non-fluent aphasia (n = 229), were compared in conjunction analyses, separately for atrophy and reductions in glucose metabolism. Atrophy coincided in the amygdala and hippocampal head in AD and the FTLD subtype SD. The other brain regions did not show any overlap between AD and FTLD subtypes for both atrophy and changes in glucose metabolism. For AD alone (n = 826), another conjunction analysis revealed a regional dissociation between atrophy and hypoperfusion/hypometabolism, whereby hypoperfusion and hypometabolism coincided in the angular/supramarginal gyrus and inferior precuneus/posterior cingulate gyrus. Our data together with other imaging studies suggest a specific dissociation of AD and FTLD if, beside atrophy, additional imaging markers in AD such as abnormally low parietal glucose utilization and perfusion are taken into account. Results support the incorporation of standardized imaging inclusion criteria into future diagnostic systems, which is crucial for early individual diagnosis and treatment in the future (Full text).
Multi-modal MRI analysis with disease-specific spatial filtering: initial testing to predict mild cognitive impairment patients who convert
Background: Alterations of the gray and white matter have been identified in Alzheimer’s disease (AD) by structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). However, whether the combination of these modalities could increase the diagnostic performance is unknown. Methods: Participants included 19 AD patients, 22 amnestic mild cognitive impairment (aMCI) patients, and 22 cognitively normal elderly (NC). The aMCI group was further divided into an “aMCI-converter” group (converted to AD dementia within 3 years), and an “aMCI-stable” group who did not convert in this time period. A T1-weighted image, a T2 map, and a DTI of each participant were normalized, and voxel-based comparisons between AD and NC groups were performed. Regions-of-interest, which defined the areas with significant differences between AD and NC, were created for each modality and named “disease-specific spatial filters” (DSF). Linear discriminant analysis was used to optimize the combination of multiple MRI measurements extracted by DSF to effectively differentiate AD from NC. The resultant DSF and the discriminant function were applied to the aMCI group to investigate the power to differentiate the aMCI-converters from the aMCI-stable patients. Results: The multi-modal approach with AD-specific filters led to a predictive model with an area under the receiver operating characteristic curve (AUC) of 0.93, in differentiating aMCI-converters from aMCI-stable patients. This AUC was better than that of a single-contrast-based approach, such as T1-based morphometry or diffusion anisotropy analysis. Conclusion: The multi-modal approach has the potential to increase the value of MRI in predicting conversion from aMCI to AD (Full text).