MRI Asymmetry Index of Hippocampal Subfields Increases Through the Continuum From the Mild Cognitive Impairment to the Alzheimer's Disease

Sarica, Alessia; Vasta, Roberta; Novellino, Fabiana; Vaccaro, Maria Grazia; Cerasa, Antonio; Quattrone, Aldo

doi:10.3389/fnins.2018.00576

Cited by 89 publications

(88 citation statements)

References 56 publications

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“…This interaction effect is not significant for right CA2_3 and CA4_DG, although they also showed significant atrophy and correlation with MoCA. This result may suggest asymmetry of AD pathology, as previously reported [43, 44]. …”

Section: Discussionsupporting

confidence: 83%

The Role of MRI Biomarkers and Their Interactions with Cognitive Status and APOE ε4 in Nondemented Elderly Subjects

et al. 2018

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Purpose: (1) To investigate atrophy patterns of hippocampal subfield volume and Alzheimer’s disease (AD)-signature cortical thickness in mild cognitive impairment (MCI) patients; (2) to explore the association between the neuropsychological (NP) and the brain structure in the MCI and older normal cognition group; (3) to determine whether these associations were modified by the apolipoprotein E (APOE) ε4 gene and cognitive status. Methods: The FreeSurfer software was used for automated segmentation of hippocampal subfields and AD-signature cortical thickness for 22 MCI patients and 23 cognitive normal controls (NC). The volume, cortical thickness, and the neuropsychological scale were compared with two-sample t tests. Linear regression models were used to determine the association between the NP and the brain structure. Results: Compared with the NC group, MCI patients showed a decreased volume of the left presubiculum, subiculum and right CA2_3 and CA4_DG (p < 0.05, FDR corrected). The volume of these regions was positively correlated with NP scores. Of note, these associations depended on the cognitive status but not on the APOE ε4 status. The left subiculum and presubiculum volume were positively correlated with the Montreal Cognitive Assessment (MoCA) scores only in the MCI patients. Conclusion: Atrophy of the hippocampal subfields may be a powerful biomarker for MCI in the Chinese population.

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Section: Discussionsupporting

confidence: 83%

The Role of MRI Biomarkers and Their Interactions with Cognitive Status and APOE ε4 in Nondemented Elderly Subjects

et al. 2018

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“…Owing to the fine level of segmentation afforded by the probabilistic atlas used, we were able to further examine if group differences were widespread across the ventral thalamus or localized to specific subnuclei, revealing that the left lateralization of thalamic atrophy in AD was largely restricted to the posterior ventrolateral and VM regions. Notably, these group differences were independent of the absolute subnuclei volume and global cerebral asymmetry and were significant even after accounting for hippocampal asymmetry which has been widely reported in AD [5,12,17].…”

Section: Discussionmentioning

confidence: 57%

Asymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid‐positive mild cognitive impairment is associated with key clinical features

Low

Mak

Malpetti

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction Although widespread cortical asymmetries have been identified in Alzheimer's disease (AD), thalamic asymmetries and their relevance to clinical severity in AD remain unclear. Methods Lateralization indices were computed for individual thalamic subnuclei of 65 participants (33 healthy controls, 14 amyloid‐positive patients with mild cognitive impairment, and 18 patients with AD dementia). We compared lateralization indices across diagnostic groups and correlated them with clinical measures. Results Although overall asymmetry of the thalamus did not differ between groups, greater leftward lateralization of atrophy in the ventral nuclei was demonstrated in AD, compared with controls and amyloid‐positive mild cognitive impairment. Increased posterior ventrolateral and ventromedial nuclei asymmetry were associated with worse cognitive dysfunction, informant‐reported neuropsychiatric symptoms, and functional ability. Discussion Leftward ventral thalamic atrophy was associated with disease severity in AD. Our findings suggest the clinically relevant involvement of thalamic nuclei in the pathophysiology of AD.

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“…One can speculate whether and to what degree faster LH degradation tracks to an asymmetric presence of other AD biomarkers, such as neurofibrillary tangles 64 , as patterns of cortical thinning in AD largely overlap with tau deposition 25,65 . Future research could also assess whether and how cortical asymmetry change in AD might co-occur with asymmetric neurodegeneration of subcortical brain structures vulnerable in AD 66,67 .…”

Section: Discussionmentioning

confidence: 99%

Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s Disease

Roe

Vidal-Piñeiro

Sørensen

et al. 2020

Preprint

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Normal aging and Alzheimer's Disease (AD) are accompanied by large-scale alterations in brain organization that undermine brain function. Although hemispheric asymmetry is a global organizing feature of cortex thought to promote brain efficiency, current descriptions of cortical thinning in aging and AD have largely overlooked cortical asymmetry. Consequently, the foundational question of whether and where the cerebral hemispheres change at different rates in aging and AD remains open. First, applying vertex-wise data-driven clustering in a longitudinal discovery sample (aged 20-89; 2577 observations; 1851 longitudinal) we identified cortical regions exhibiting similar age-trajectories of asymmetry across the adult lifespan. Next, we sought replication in 4 independent longitudinal aging cohorts. We show that higher-order regions of cortex that exhibit pronounced asymmetry at age ~20 also show asymmetry change in aging. Results revealed that both leftward and rightward asymmetry is progressively lost on a similar time-scale across adult life. Hence, faster thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This simple organizational principle showed high consistency across multiple aging cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating samples. Finally, we show that regions exhibiting gradual asymmetry-loss over healthy adult life exhibit faster asymmetry-change in AD.Overall, our results suggest a system-wide breakdown in the adaptive asymmetric organization of cortex across adult life which is further accelerated in AD, and may implicate thickness asymmetry as a viable marker for declining hemispheric specialization in aging and AD. The brain becomes progressively disorganized with age, and brain alterations accelerated in Alzheimer's disease may occur gradually over the lifespan. Although hemispheric asymmetry aids efficient network organization, efforts to identify structural markers of age-related decline have largely overlooked cortical asymmetry. Here we show the hemisphere that is thicker when younger, thins faster. This leads to progressive system-wide loss of regional thickness asymmetry across life. In multiple aging cohorts, asymmetry-loss showed high reproducibility topologically across cortex and similar timing-of-change in aging. Asymmetry-change was further accelerated in AD. Our findings uncover a new principle of brain aging -thicker homotopic cortex thins faster -and suggest we may have unveiled a structural marker for a widely-hypothesized decline in hemispheric specialization in aging and AD.

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MRI Asymmetry Index of Hippocampal Subfields Increases Through the Continuum From the Mild Cognitive Impairment to the Alzheimer's Disease

Cited by 89 publications

References 56 publications

The Role of MRI Biomarkers and Their Interactions with Cognitive Status and APOE ε4 in Nondemented Elderly Subjects

The Role of MRI Biomarkers and Their Interactions with Cognitive Status and APOE ε4 in Nondemented Elderly Subjects

Asymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid‐positive mild cognitive impairment is associated with key clinical features

Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s Disease

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