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Atrophy of amygdala and abnormal memory-related alpha oscillations over posterior cingulate predict conversion to Alzheimer's disease.

ABSTRACT: Synaptic dysfunction, a key pathophysiological hallmark of Alzheimer's disease (AD), may account for abnormal memory-related EEG patterns in prodromal AD. Here, we investigate to what extent oscillatory EEG changes during memory encoding and/or retrieval enhance the accuracy of medial temporal lobe (MTL) atrophy in predicting conversion from amnestic mild cognitive impairment (aMCI) to AD. As expected, aMCI individuals that, within a 2-year follow-up period, developed dementia (N?=?16) compared to healthy older (HO) (N?=?26) and stable aMCI (N?=?18) showed poorer associative memory, greater MTL atrophy, and lower capacity to recruit alpha oscillatory cortical networks. Interestingly, encoding-induced abnormal alpha desynchronized activity over the posterior cingulate cortex (PCC) at baseline showed significantly higher accuracy in predicting AD than the magnitude of amygdala atrophy. Nevertheless, the best accuracy was obtained when the two markers were fitted into the model (sensitivity?=?78%, specificity?=?82%). These results support the idea that synaptic integrity/function in the PCC is affected during prodromal AD and has the potential of improving early detection when combined with MRI biomarkers.

SUBMITTER: Prieto Del Val L

PROVIDER: S-EPMC4992828 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Atrophy of amygdala and abnormal memory-related alpha oscillations over posterior cingulate predict conversion to Alzheimer's disease.

Prieto Del Val Laura L Cantero Jose L JL Atienza Mercedes M

Scientific reports 20160822

Synaptic dysfunction, a key pathophysiological hallmark of Alzheimer's disease (AD), may account for abnormal memory-related EEG patterns in prodromal AD. Here, we investigate to what extent oscillatory EEG changes during memory encoding and/or retrieval enhance the accuracy of medial temporal lobe (MTL) atrophy in predicting conversion from amnestic mild cognitive impairment (aMCI) to AD. As expected, aMCI individuals that, within a 2-year follow-up period, developed dementia (N = 16) compared ...[more]

PMID: 27546195

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Project description:The posterior cingulate cortex (PCC) is a critical brain network hub particularly sensitive to Alzheimer's disease (AD) and can be subdivided into ventral (vPCC) and dorsal (dPCC) regions. The aim of the present study was to highlight functional connectivity (FC) disruption, atrophy, and hypometabolism within the ventral and dorsal PCC networks in patients with amnestic mild cognitive impairment (aMCI) or AD. Forty-three healthy elders (HE) (68.7 ± 6 years), 34 aMCI (73.4 ± 6.8 years) and 24 AD (70.9 ± 9.1 years) patients underwent resting-state functional MRI, anatomical T1-weighted MRI and FDG-PET scans. We compared FC maps obtained from the vPCC and dPCC seeds in HE to identify the ventral and dorsal PCC networks. We then compared patients and HE on FC, gray matter volume and metabolism within each network. In HE, the ventral PCC network involved the hippocampus and posterior occipitotemporal and temporoparietal regions, whereas the dorsal PCC network included mainly frontal, middle temporal and temporoparietal areas. aMCI patients had impaired ventral network FC in the bilateral hippocampus, but dorsal network FC was preserved. In AD, the ventral network FC disruption had spread to the left parahippocampal and angular regions, while the dorsal network FC was also affected in the right middle temporal cortex. The ventral network was atrophied in the bilateral hippocampus in aMCI patients, and in the vPCC and angular regions as well in AD patients. The dorsal network was only atrophied in AD patients, in the dPCC, bilateral supramarginal and temporal regions. By contrast, hypometabolism was already present in both the vPCC and dPCC networks in aMCI patients, and further extended to include the whole networks in AD patients. The vPCC and dPCC connectivity networks were differentially sensitive to AD. Atrophy and FC disruption were only present in the vPCC network in aMCI patients, and extended to the dPCC network in AD patients, suggesting that the pathology spreads from the vPCC to the dPCC networks. By contrast, hypometabolism seemed to follow a different route, as it was present in both networks since the aMCI stage, possibly reflecting not only local disruption but also distant synaptic dysfunction.

Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of toxic misfolded proteins, which are believed to have propagated from disease-specific epicenters through their corresponding large-scale structural networks in the brain. Although previous cross-sectional studies have identified potential AD-associated epicenters and corresponding brain networks, it is unclear whether these networks are associated with disease progression. Hence, this study aims to identify the most vulnerable epicenters and corresponding large-scale structural networks involved in the early stages of AD and to evaluate its associations with multiple cognitive domains using longitudinal study design. Annual neuropsychological and MRI assessments were obtained from 23 patients with AD, 37 patients with amnestic mild cognitive impairment (MCI), and 33 healthy controls (HC) for 3 years. Candidate epicenters were identified as regions with faster decline rate in the gray matter volume (GMV) in patients with MCI who progressed to AD as compared to those regions in patients without progression. These epicenters were then further used as pre-defined regions of interest to map the synchronized degeneration network (SDN) in HCs. Spatial similarity, network preference and clinical association analyses were used to evaluate the specific roles of the identified SDNs. Our results demonstrated that the hippocampus and posterior cingulate cortex (PCC) were the most vulnerable AD-associated epicenters. The corresponding PCC-SDN showed significant spatial association with the patterns of GMV atrophy rate in each patient group and the overlap of these patterns was more evident in the advanced stages of the disease. Furthermore, individuals with a higher GMV atrophy rate of the PCC-SDN also showed faster decline in multiple cognitive domains. In conclusion, our findings suggest the PCC and hippocampus are two vulnerable regions involved early in AD pathophysiology. However, the PCC-SDN, but not hippocampus-SDN, was more closely associated with AD progression. These results may provide insight into the pathophysiology of AD from large-scale network perspective.

Project description:ObjectivesTo investigate the global cortical and regional quantitative features of cortical neural architecture in the brains of patients with posterior cortical atrophy (PCA) and typical Alzheimer's disease (tAD) compared with elderly healthy controls (HC).MethodsA novel diffusion MRI method, that has been shown to correlate with minicolumnar organization changes in the cerebral cortex, was used as a surrogate of neuropathological changes in dementia. A cohort of 15 PCA patients, 23 tAD and 22 healthy elderly controls (HC) were enrolled to investigate the changes in cortical diffusivity among groups. For each subject, 3 T MRI T1-weighted images and diffusion tensor imaging (DTI) scans were analysed to extract novel cortical DTI derived measures (AngleR, PerpPD and ParlPD). Receiver operating characteristics (ROC) curve analysis and the area under the curve (AUC) were used to assess the group discrimination capability of the method.ResultsThe results showed that the global cortical DTI derived measures were able to detect differences, in both PCA and tAD patients compared to healthy controls. The AngleR was the best measure to discriminate HC from tAD (AUC?=?0.922), while PerpPD was the best measure to discriminate HC from PCA (AUC?=?0.961). Finally, the best global measure to differentiate the two patient groups was ParlPD (AUC?=?0.771). The comparison between PCA and tAD patients revealed a different pattern of damage within the AD spectrum and the regional comparisons identified significant differences in key regions including parietal and temporal lobe cortical areas. The best AUCs were shown by PerpPD right lingual cortex (AUC?=?0.856), PerpPD right superior parietal cortex (AUC?=?0.842) and ParlPD right lateral occipital cortex (AUC?=?0.826).ConclusionsDiagnostic group differences were found, suggesting that the new cortical DTI analysis method may be useful to investigate cortical changes in dementia, providing better characterization of neurodegeneration, and potentially aiding differential diagnosis and prognostic accuracy.

Project description:IntroductionIn vivo clinical, anatomical and metabolic differences between posterior cortical atrophy (PCA) patients presenting with different Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers profiles are still unknown.MethodsTwenty-seven PCA patients underwent CSF examination and were classified as 1) PCA with a typical CSF AD profile (PCA-tAD; abnormal amyloid and T-tau/P-tau biomarkers, n = 13); 2) PCA with an atypical AD CSF profile (PCA-aAD; abnormal amyloid biomarker only, n = 9); and 3) PCA not associated with AD (PCA-nonAD; normal biomarkers, n = 5). All patients underwent clinical and cognitive assessment, structural MRI, and a subset of them underwent brain 18F-FDG PET.ResultsAll patients' groups showed a common pattern of posterior GM atrophy and hypometabolism typical of PCA, as well as equivalent demographics and clinical/cognitive profiles. PCA-tAD patients showed a group-specific pattern of hypometabolism in the left fusiform gyrus and inferior temporal gyrus. PCA-aAD did not present a group-specific atrophy pattern. Finally, group-specific gray matter atrophy in the right dorsolateral prefrontal cortex, left caudate nucleus and right medial temporal regions and hypometabolism in the right supplementary motor area and paracentral lobule were observed in PCA-nonAD patients.ConclusionOur findings suggest that both PCA-tAD and PCA-aAD patients are on the AD continuum, in agreement with the recently suggested A/T/N model. Furthermore, in PCA, the underlying pathology has an impact at least on the anatomo-functional presentation. Brain damage observed in PCA-tAD and PCA-aAD was mostly consistent with the well-described presentation of the disease, although it was more widespread in PCA-tAD group, especially in the left temporal lobe. Additional fronto-temporal (especially dorsolateral prefrontal) damage seems to be a clue to underlying non-AD pathology in PCA, which warrants the need for longitudinal follow-ups to investigate frontal symptoms in these patients.

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Atrophy of amygdala and abnormal memory-related alpha oscillations over posterior cingulate predict conversion to Alzheimer's disease.

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Atrophy of amygdala and abnormal memory-related alpha oscillations over posterior cingulate predict conversion to Alzheimer's disease.

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