Precuneus Structure Changes in Amnestic Mild Cognitive Impairment

Brain, 2009

A sensitive marker for monitoring progression of early Alzheimer's disease would help to develop and test new therapeutic strategies. The present study is aimed at investigating brain metabolism changes over time, as a potential monitoring marker, in patients with amnestic mild cognitive impairment, according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen amnestic mild cognitive impairment patients underwent magnetic resonance imaging and 18 FDG-positron emission tomography scans both at inclusion and 18 months later. Baseline and follow-up positron emission tomography data were corrected for partial volume effects and spatially normalized using magnetic resonance imaging data, scaled to the vermis and compared using SPM2. 'PET-PAC' maps reflecting metabolic per cent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than non-converters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18 FDG-positron emission tomography for monitoring early Alzheimer's disease progression. Abbreviations: aMCI = amnestic mild cognitive impairment; BA = Brodmann areas; 18 FDG = 2-[ 18 F]-Fluoro-2-Deoxy-D-Glucose; PAC = per cent annual change; VOI = volume of interest

Brain Research, 2004

Structures of the medial temporal lobes are recognized to play a central role in memory processing and to be the primary sites of deterioration in Alzheimer disease (AD). Mild cognitive impairment (MCI) represents potentially an intermediate state between normal aging and AD. Proton magnetic resonance spectroscopy (MRS) was used to examine brain metabolic changes in patients with AD and MCI in the medial temporal lobes (MTLs), parietotemporal cortices (PTCs) and prefrontal cortices (PFCs). Fourteen patients with MCI, 14 patients with mild AD and 14 age-and sex-matched control subjects were studied. Patients with AD and MCI demonstrated significant reductions of NAA/H 2 O and Cho/H 2 O in the left MTL relative to control subjects. Patients with AD showed mI/H 2 O increases relative to patients with MCI and control subjects in all six regions investigated, and a statistically significant mI/H 2 O increase was measured in the right PTC. Patients with AD and MCI demonstrated the same metabolic pattern in the left MTL, suggesting a similar pathological process underlying memory impairment. Increased mI signal appears to be a neurochemical abnormality associated mostly with AD and the dementia process. Some interhemispheric metabolite asymmetries were increased in AD patients. D

European Journal of Nuclear Medicine and Molecular Imaging, 2008

Purpose The purpose of the study was the identification of group and individual subject patterns of cerebral glucose metabolism (CMRGlu) in patients with Alzheimer's disease (AD) and with amnestic mild cognitive impairment (aMCI). Methods [ 18 F]fluorodeoxyglucose positron emission tomography (PET) studies and neuropsychological tests were performed in 16 aMCI patients (ten women, age 75± 8 years) and in 14 AD patients (ten women, age 75± 9 years). Comparisons between patient subgroups and with a control population were performed using Statistical Parametric Mapping. Results Clusters of low CMRGlu were observed bilaterally in the posterior cingulate cortex (PCC), in the precuneus, in the inferior parietal lobule and middle temporal gyrus of AD patients. In aMCI patients, reduced CMRGlu was found only in PCC. Areas of low CMRGlu in PCC were wider in AD compared to aMCI and extended to the precuneus, while low CMRGlu was found in the lateral parietal cortex in AD but not in aMCI patients. Individual subject pattern analysis revealed that 86% of AD patients had low CMRGlu in the PCC (including the precuneus in 71%), 71% in the temporal cortex, 64% in the parietal cortex and 35% in the frontal cortex. Among the aMCI patients, 56% had low CMRGlu in the PCC, 44% in the temporal cortex, 18% in the frontal cortex and none in the parietal cortex. Conclusion This study demonstrates that both AD and aMCI patients have highly heterogeneous metabolic impairment. This potential of individual metabolic PET imaging in patients with AD and aMCI may allow timely identification of brain damage on individual basis and possibly help planning tailored early interventions.

Alzheimer's & Dementia, 2008

Background: Mild cognitive impairment (MCI) has been associated with increased risk to develop Alzheimer's disease (AD), with episodic memory impairment being of the earliest symptoms preceding dementia. Hippocampus has been shown to be involved in episodic memory and is altered in MCI. Recent studies have shown that functional connectivity 1 of hippocampus activity within a larger cortical default network is altered in MCI and AD. Here we investigated to what extent hippocampus functional connectivity as assessed during episodic memory retrieval is altered. Since hippocampus has been found to be reduced in MCI we investigated in addition to what extent grey matter volume changes may influence functional connectivity changes of hippocampus. Methods: Functional MRI was acquired during delayed forced-choice word recognition task in healthy controls (HC, n ϭ 10) and MCI (n ϭ 8) subjects. Hippocampus volume was manually outlined on T1 weighted volumetric MRI scans according to an established volumetric protocol and used as mask to extract the average positive hippocampus activity during trials of successful retrieval. Hippocampus connectivity was assessed voxel-based by regression of hippocampus volume onto brain activity in the rest of the brain voxelby-voxel controlling for age and, optionally, hippocampus volume differences. Results: Functional hippocampus connectivity during a forcedchoice visual verbal recognition memory task was found to be bilaterally dramatically reduced in spatial extent in MCI subjects when compared to HC. HC showed increased hippocampus connectivity within large-scale neuronal network including prefrontal, lateral temporal, posterior parietal, occipital, cerebellar brain areas. Notably, whereas HC showed only positive hippocampus correlations, MCI patients showed only negative hippocampus correlations primarily confined to medial and anterior prefrontal cortex. Hippocampus connectivity in MCI within right dorso-lateral prefrontal cortex and middle anterior cingulate gyrus was no longer different from HC when hippocampus volume was controlled for. Conclusions: The current findings show that hippocampus related network is markedly altered in MCI, partially dependent upon hippocampus volume deficits, that may underly episodic memory deficits in MCI.

PLoS ONE, 2013

Background: Alzheimer's disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD.

Journal of the American Geriatrics Society, 2000

Given the predicted increase in prevalence of Alzheimer's disease (AD) in the coming decades, early detection and intervention in persons with the predementia condition known as mild cognitive impairment (MCI) is of paramount importance. Recent years have seen remarkable advances in the application of neuroimaging and other biomarkers to the study of MCI. This article reviews the most recent developments in the use of magnetic resonance imaging (MRI) to characterize brain changes and to prognosticate clinical outcomes of patients with MCI. The review begins with description of methods and findings in structural MRI research, delineating findings regarding both gross atrophy and microstructural brain changes in MCI. Second, we describe the most recent findings regarding brain function in MCI, enumerating findings from functional MRI and brain perfusion studies. Third, we will make recommendations regarding the current clinical use of MRI in identification of MCI. As a conclusion, we will look to the future of neuroimaging as a tool in early AD detection.

NeuroImage, 2004

Purpose. Mild cognitive impairment (MCI) is thought to be the prodromal phase to Alzheimer's disease (AD). We analyzed patterns of gray matter (GM) loss to examine what characterizes MCI and what determines the difference with AD. Materials and methods. Thirty-three subjects with AD, 14 normal elderly controls (NCLR), and 22 amnestic MCI subjects were included and underwent brain MR imaging. Global GM volume was assessed using segmentation and local GM volume was assessed using voxelbased morphometry (VBM); VBM was optimized for template mismatch and statistical mass. Results. AD subjects had significantly (12.3%) lower mean global GM volume when compared to controls (517 F 58 vs. 590 F 52 ml; P b 0.001). Global GM volume in the MCI group (552 F 52) was intermediate between these two: 6.2% lower than AD and 6.5% higher than the controls but not significantly different from either group. VBM showed that subjects with MCI had significant local reductions in gray matter in the medial temporal lobe (MTL), the insula, and thalamus compared to NCLR subjects. By contrast, when compared to subjects with AD, MCI subjects had more GM in the parietal association areas and the anterior and the posterior cingulate. Conclusion. GM loss in the MTL characterizes MCI, while GM loss in the parietal and cingulate cortices might be a feature of AD.

2013

Alzheimer's & Dementia, 2008

Alzheimer's & Dementia, 2010

Background-Studies show white matter hyperintensities, regardless of location, primarily affect frontal lobe metabolism and function. This report investigates how regional white matter integrity (measured as fractional anisotropy (FA)) relates to brain metabolism in order to unravel the complex relationship between white matter change and brain metabolism.