The APOE 4 allele is a risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE 4-carriers and 18 matched noncarriers (age range: 20 -35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased ''default mode network'' (involving retrosplenial, medial temporal, and medial-prefrontal cortical areas) coactivation in 4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in 4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE 4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.hippocampus ͉ memory ͉ neuroimaging ͉ resting connectivity A polipoprotein E (apoE, protein; APOE, gene) is a very-lowdensity lipoprotein that removes cholesterol from the blood and carries it to the liver for processing (1). In the central nervous system, apoE has a key role in coordinating the mobilization and redistribution of cholesterol, phospholipids, and fatty acids, and it is implicated in mechanisms such as neuronal development, brain plasticity, and repair functions (2). The human APOE gene, which is encoded on chromosome 19, has 3 allelic variants ( 2, 3, and 4). The 4 allele has been associated with a higher risk of cardiovascular disease (3), both early-onset (4) and late-onset (5) Alzheimer's disease (AD), poor outcome from traumatic brain injury (6), and age-related cognitive impairment (7).Neuroimaging studies of the APOE polymorphism in healthy subjects have largely focused on gray matter (GM) alterations in middle or late life, particularly in brain regions associated with the greatest AD pathological findings. Even in asymptomatic subjects, hippocampal and frontotemporal GM reduction has been observed in APOE 4-carriers relative to noncarriers (8). Moreover, a reduction of resting glucose metabolism was reported in young and middle-aged cognitively normal APOE 4-carriers in brain regions known to be affected by AD, including the posterior cingulate, parietal, temporal, and prefrontal cortices (9-11). fMRI task-based studies (mainly investigating memory processes) have shown greater activation in middle-aged and elderly APOE 4-carriers relative to noncarriers (12-16). Although these studies suggest an influence of the APOE 4 allele on brain structure and metabolism, they do not make clear at what age these influences initially manifest. Furthermore, although differences in structure, resting metabolism, and function have each been reported in 4-carriers relative to noncarriers, it remains to be established to what extent these characteristics interact.Thus far, reports of structural and functional eff...
ObjectiveTo investigate the pattern of cortical thinning in Parkinson's disease (PD) across different disease stages and to elucidate to what extent cortical thinning is related to cognitive impairment.DesignNinety-six subjects including 39 controls and 57 PD patients participated in this study. PD subjects were divided into three groups (early, n=24; moderate, n=18; with dementia, n=15). High field structural brain MRI images were acquired in a 3T scanner and analyses of cortical thickness and surface were carried out. Vertex-wise group comparisons were performed and cortical thickness was correlated with motor and cognitive measures.ResultsWe found a positive correlation between Mini-Mental State Examination scores and cortical thickness in the anterior temporal, dorsolateral prefrontal, posterior cingulate, temporal fusiform and occipitotemporal cortex. Unified Parkinson's Disease Rating Scale-III (motor subsection) scores showed a robust negative correlation with caudate volumes. We found that disease stage in PD was associated with thinning of the medial frontal (premotor and supplementary motor cortex), posterior cingulate, precuneus, lateral occipital, temporal and dorsolateral prefrontal cortex. Discriminant analysis and a receiver operating characteristics approach showed that mean cortical thickness and hippocampus volume have 80% accuracy in identifying PD patients with dementia. PD stage and PD dementia can be characterised by a specific pattern of cortical thinning.ConclusionsWe conclude that measuring cortical thickness can be useful in assessing disease stage and cognitive impairment in patients with PD. In addition, cortical thickness may be useful in identifying dementia in PD.
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