Task-dependent posterior cingulate activation in mild cognitive impairment

Neuroimaging research has demonstrated that the posterior cingulate cortex (PCC) is functionally compromised in individuals diagnosed with amnestic mild cognitive impairment (MCI), a major risk factor for the development of Alzheimer\u27s disease (AD). In functional MRI studies with healthy participants, this same region is active during self-appraisal (requiring retrieval of semantic knowledge about the self) as well as episodic recognition of previously learned information. Administering both types of tasks to people with MCI may reveal important information on the role of the PCC in recollection. This study investigated fMRI activation in the PCC in individuals with MCI and matched controls across two tasks. The first task was a visual episodic recognition task. The second task was an autobiographical self-appraisal task in which subjects rated themselves on a set of trait adjectives. Results of a conjunction analysis revealed the PCC as the sole region commonly active during both tasks in the healthy older adults. Furthermore, additional analysis revealed an interaction in the PCC, indicating a task-dependent response in the MCI group. MCI participants showed PCC activation during self-appraisal, but not episodic retrieval. This result suggests in MCI that the PCC shows functional degradation during episodic retrieval; however, the PCC\u27s role in retrieval and evaluation of highly elaborated information regarding the self is more well-preserved. © 2005 Elsevier Inc. All rights reserved

Structural MRI discriminates individuals with Mild Cognitive Impairment from age-matched controls: A combined neuropsychological and voxel based morphometry study

Background: Several previous studies have reported that amnestic mild cognitive impairment (aMCI), a significant risk factor for Alzheimer\u27s disease (AD), is associated with greater atrophy in the medial temporal lobe (MTL) and posterior cingulate gyrus (PCG). Method: In the present study, we examined the cross-sectional accuracy (i.e., the sensitivity and specificity) of voxel-based morphometry (VBM) in discriminating individuals with MCI (n = 15) from healthy age-matched controls (n = 15). In addition, we also sought to determine whether baseline GM volume predicted aMCI patients that converted to AD from those that did not approximately 2 years after the baseline visit. Results: MCI patients were found to display significantly less GM volume in several hypothesized regions including the MTL and PCG relative to the age-matched controls (p \u3c 0.01). Logistic regression analysis and receiver operating characteristic (ROC) curves for GM volume in the anterior MTL and PCG revealed high discriminative accuracy of 87%. By contrast, baseline GM volume in anterior MTL and PCG did not appear to be sensitive to changes in clinical status at the follow-up visit. Conclusion: These results suggest that VBM might be useful at characterizing GM volume reductions associated with the diagnosis of aMCI. © 2006 The Alzheimer\u27s Association

Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study

BACKGROUND: The presence of the apolipoprotein E (APOE) ε4 allele is a major risk factor for the development of Alzheimer's disease (AD), and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI (fMRI) is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the ε4 allele on hippocampal activation has not been firmly established. METHODS: The present study examined the effects of APOE genotype on brain activation patterns in the medial temporal lobe (MTL) during an episodic encoding task using a well-characterized novel item versus familiar item contrast in cognitively normal, middle-aged (mean = 54 years) individuals who had at least one parent with AD. RESULTS: We found that ε3/4 heterozygotes displayed reduced activation in the hippocampus and MTL compared to ε3/3 homozygotes. There were no significant differences between the groups in age, education or neuropsychological functioning, suggesting that the altered brain activation seen in ε3/4 heterozygotes was not associated with impaired cognitive function. We also found that participants' ability to encode information on a neuropsychological measure of learning was associated with greater activation in the anterior MTL in the ε3/3 homozygotes, but not in the ε3/4 heterozygotes. CONCLUSION: Together with previous studies reporting reduced glucose metabolism and AD-related neuropathology, this study provides convergent validity for the idea that the MTL exhibits functional decline associated with the APOE ε4 allele. Importantly, these changes were detected in the absence of meaningful neuropsychological differences between the groups. A focus of ongoing work in this laboratory is to determine if these findings are predictive of subsequent cognitive decline

The influence of Alzheimer disease family history and apolipoprotein E ε4 on mesial temporal lobe activation

First-degree family history of sporadic Alzheimer disease (AD) and the apolipoprotein E ε4 (APOE4) are risk factors for developing AD. Although the role of APOE4 in AD pathogenesis has been well studied, family history remains a rarely studied and poorly understood risk factor. Both putatively cause early brain changes before symptomatic disease, but the relative contribution of each to brain function is unknown. We examined 68 middle-aged participants with a parent diagnosed with AD[family history (-FH)] and 64 age- and education matched controls without a first-degree family history of any dementia [no family history (+FH)]. All underwent cognitive testing, APOE genotyping, and a functional magnetic resonance imaging encoding task that required discrimination of novel items from previously learned items. A 2 x 2 factorial ANOVA (presence/absence of parental family history and presence/absence of the APOE4) was used to detect group effects. A greater response to novel items was detected in the mesial temporal lobe and fusiform gyrus bilaterally among persons without a first-degree family history of AD. In hippocampal areas, the -FH + ε4 group exhibited the greatest signal change, and the +FH + ε4 group exhibited the least. These findings indicate that FH of AD is an important predictor of hippocampal activation during encoding and that FH may modulate the effect of APOE4 in these middle-aged adults, suggesting that an as yet unspecified factor embodied in first-degree family history of AD is influencing the expression of APOE4 on brain function. Copyright © 2006 Society for Neuroscience

Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study-2

<p><b>Copyright information:</b></p><p>Taken from "Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study"</p><p>BMC Medicine 2006;4():1-1.</p><p>Published online 13 Jan 2006</p><p>PMCID:PMC1373642.</p><p>Copyright © 2006 Trivedi et al; licensee BioMed Central Ltd.</p>hippocampus (right panel) for ε3/3 homozygotes (black circles, solid lines) and ε3/4 heterozygotes (white squares, hashed lines)

Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study-1

<p><b>Copyright information:</b></p><p>Taken from "Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study"</p><p>BMC Medicine 2006;4():1-1.</p><p>Published online 13 Jan 2006</p><p>PMCID:PMC1373642.</p><p>Copyright © 2006 Trivedi et al; licensee BioMed Central Ltd.</p>e local maxima in the right hippocampus (: 30, -14, -16), and at the same location in the left hippocampus (: -30, -14, -16). Data are presented as mean signalchange for each group. Error bars represent the standard error of the mean. * denotes significant difference between the two groups

Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study-0

<p><b>Copyright information:</b></p><p>Taken from "Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study"</p><p>BMC Medicine 2006;4():1-1.</p><p>Published online 13 Jan 2006</p><p>PMCID:PMC1373642.</p><p>Copyright © 2006 Trivedi et al; licensee BioMed Central Ltd.</p>he ε3/3 homozygotes activated to a greater extent than the ε3/4 heterozygotes (panel C). The left side of each coronal section represents the left hemisphere. The dark-shaded area represents the MTL region to which the statistical analyses were confined. The lighter-shaded areasrepresent regions outside of the MTL mask