Brainstem atrophy in the early stage of Alzheimer’s disease: a voxel-based morphometry study

Ji, Xiaoxi; Wang, Hui; Zhu, Minwei; He, Yun; Zhang, Hong; Chen, Xiaoguang; Gao, Wenpeng; Fu, Yili; Initiative, Alzheimer’s Disease Neuroimaging

doi:10.1007/s11682-019-00231-3

Cited by 36 publications

(30 citation statements)

References 39 publications

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“…Pontine atrophy has also been found in AD population (Mann, 1983;Lee et al, 2015), but it was less reported as compared with medial temporal lobe atrophy. A recent study showed that compared to the control group, bilateral volume loss in the pons was found in the mild AD group (Ji et al, 2020).…”

Section: Discussionmentioning

confidence: 95%

“…Second, the sample size was relatively small, particularly for the AD_IFG group, which limited the interpretation and generalizability of our results. However, as several studies have associated pontine degeneration with dysglycemia and AD (Ichikawa et al, 2012a;Ji et al, 2020;Lee et al, 2015), it may be possible to extend these findings to patients with comorbid dysglycemia and AD. However, further studies are needed on a larger cohort to confirm these preliminary findings.…”

Section: Discussionmentioning

confidence: 98%

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Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

Wang

Wong

Shi

et al. 2020

PeerJ

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Objectives Alzheimer’s disease (AD), impaired fasting glucose (IFG), and Type 2 diabetes mellitus (T2DM) were reported associated with smaller brain volumes. Nevertheless, the association of hyperglycemia with brain volume changes in AD patients remains unclear. To investigate this issue, structural magnetic resonance imaging was used to compare brain volumes among AD patients with different fasting glucose levels. Methods Eighty-five AD patients were divided into three groups based on their fasting glucose level as suggested by the American Diabetes Association: normal fasting glucose group (AD_NFG, n = 45), AD_IFG group (n = 15), and AD_T2DM group (n = 25). Sagittal 3D T1-weighted images were obtained to calculate the brain volume. Brain parenchyma and 33 brain structures were automatically segmented. Each regional volume was analyzed among groups. For regions with statistical significance, partial correlation analysis was used to evaluate their relationships with fasting glucose level, corrected for Mini-Mental State Examination score, age, education level, cholesterol, triglyceride, and blood pressure. Results Compared with the AD_IFG and AD_NFG groups, the volume of pons in AD_T2DM group was significantly smaller. Fasting glucose was negatively correlated with pontine volume. Conclusions T2DM may exacerbate pontine atrophy in AD patients, and fasting glucose level is associated with pontine volume.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

Wang

Wong

Shi

et al. 2020

PeerJ

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“…To this end, we adopted a neuroimaging voxel-based morphometry (VBM) approach utilizing 3T T1-weighted structural MRI scans from 686 subjects [ n = 395 (HC), n = 156 (MCI), and 135 (AD)] provided by Alzheimer’s Disease Neuroimaging Initiative—ADNI (ADNI2 and ADNI3 phases) [ 62 , 63 ]. Structural volumetric analyses on 3T T1-weighted MRIs with this methodology have been already carried out by several studies showing accurate reliability investigating the integrity of the Brainstem [ 64 , 65 , 66 , 67 ], the LC also in the ADNI [ 68 , 69 , 70 , 71 ] and the other neuromodulators’ seeds such as the Raphe Nuclei [ 72 , 73 , 74 , 75 ], the ventral tegmental area (VTA) [ 76 , 77 , 78 , 79 ] and the nucleus basalis of Meynert (NBM) [ 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ]. The main objectives of this study were threefold.…”

Section: Introductionmentioning

confidence: 99%

Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age and Disease: An MRI Structural Study for the Alzheimer’s Disease Neuroimaging Initiative

Plini

O’Hanlon

Boyle

et al. 2021

Cells

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The noradrenergic theory of Cognitive Reserve (Robertson, 2013–2014) postulates that the upregulation of the locus coeruleus—noradrenergic system (LC–NA) originating in the brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 mild cognitive impairment, 135 Alzheimer’s disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD—an objective measure, which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the serotoninergic (5-HT), dopaminergic (DA) and cholinergic (Ach) systems were contrasted with the noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems. Results supported by Bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g., cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

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“…To this end, we adopted a neuroimaging voxel-based morphometry (VBM) approach utilizing 3T T1-weighted structural MRI scans from 686 subjects [n=395 (HC), n=156 (MCI), and 135 (AD)] provided by Alzheimer Disease Neuroimaging Initiative -ADNI (ADNI2 and ADNI3 phases) [49,50]. Structural volumetric analyses on 3T T1-weighted MRIs with this methodology have been already carried out by several studies showing accurate reliability investigating the Brainstem [51,52,53,54], the LC also in the ADNI [55,56,57,58] and the other neuromodulators' seeds such as the Raphe Nuclei [59,60,61,62], the Ventral Tegmental Area [63,64,65,66] and the Nucleus Basalis of Meynert [67,68,69,70,71,72,73,74]. The main objectives of this study were threefold.…”

Section: Introductionmentioning

confidence: 99%

Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age, Mild Cognitive Impairment and Alzheimer’s Disease: An MRI Structural Study On the Adni Cohort

Plini¹,

O’Hanlon²,

Boyle³

et al. 2021

Preprint

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The Noradrenergic Theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the up-regulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test this theory, a study was conducted on a sample of 686 participants (395 Controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC vol-ume, attentional performance and a biological index of brain maintenance (BrainPAD – a measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on reserve indices including education and occupational attainment. Volumetric variation across groups was also explored. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic hypothesis. Results showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on upregulation of the noradrenergic system (e.g. attention training, physical exercise and pharmacological intervention) may yield important clin-ical benefits to mitigate cognitive impairment with age and disease.

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Brainstem atrophy in the early stage of Alzheimer’s disease: a voxel-based morphometry study

Cited by 36 publications

References 39 publications

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age and Disease: An MRI Structural Study for the Alzheimer’s Disease Neuroimaging Initiative

Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age, Mild Cognitive Impairment and Alzheimer’s Disease: An MRI Structural Study On the Adni Cohort

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