Discriminative analysis of early-stage Alzheimer’s disease and normal aging with automatic segmentation technique in subcortical gray matter structures: a multicenter <i>in vivo</i> MRI volumetric and DTI study

Li, Ya-di; He, Huijin; Dong, Haibo; Feng, Xiaoyuan; Xie, Guoming; Zhang, Lingjun

doi:10.1177/0284185113492971

Cited by 22 publications

(26 citation statements)

References 37 publications

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“…The mean diffusivity (MD), which represents the mean magnitude of water diffusivity, is used to evaluate GM tissue density (Li et al, 2013) with the lower the MD, the more integral the GM.…”

Section: Methodsmentioning

confidence: 99%

Neural substrates of verbal memory impairments in adults with type 2 diabetes mellitus

Yau

Kluger

Borod

et al. 2014

Journal of Clinical and Experimental Neuropsychology

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Background Verbal memory impairment is well documented in type 2 diabetes mellitus (T2DM) but to date, the neural substrates remain unclear. The present study evaluated verbal memory and ascertained the degree of frontal and temporal lobe involvement in the anticipated verbal memory impairment among adults with T2DM. Methods Forty-six late middle-aged and elderly adults with T2DM and 50 age-, sex-, and education-matched adults without T2DM underwent medical evaluation, verbal memory assessment, and brain MRI evaluations. Results As anticipated, participants with T2DM had clear verbal memory impairments. Consistent with prior reports, we found volume reductions restricted to the hippocampus. Our diffusion tensor imaging analysis revealed that participants with T2DM had extensive cerebral gray and white matter microstructural abnormalities predominantly in the left hemisphere, with a larger concentration present in the temporal lobe. In contrast, we uncovered mostly non-specific microstructural abnormalities in the absence of tissue loss in the frontal lobe. Of great importance, we present the first evidence among participants with T2DM linking verbal memory impairment and compromised microstructural integrity of the left parahippocampal gyrus, a key memory-relevant structure. Conclusions Our results suggest that the hippocampus and parahippocampal gyrus may be particularly vulnerable to the deleterious effects of T2DM. The parahippocampal gyrus in particular may play a crucial role in the verbal memory impairments frequently reported in T2DM. Future studies should employ methods such as resting state functional magnetic resonance imaging and diffusion tensor imaging tractography to better characterize network connectivity, which may help further characterize the verbal memory impairment frequently reported in T2DM.

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Section: Methodsmentioning

confidence: 99%

Neural substrates of verbal memory impairments in adults with type 2 diabetes mellitus

Yau

Kluger

Borod

et al. 2014

Journal of Clinical and Experimental Neuropsychology

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“…Among these brain regions, the number of senile plaques has been reported to be the highest in amygdala (Arriagada et al, 1992). Accordingly, a recent diffusion-tensor imaging study has revealed significant decrease in the relative volume of amygdale in early stage AD subjects (Li et al, 2013). The amygdala has long been known to be vulnerable to Alzheimer-type pathology (Hopper and Vogel, 1976), and it has been described as one of earliest locations to develop Alzheimer pathology in Down syndrome (Mann et al, 1986).…”

Section: Aβ and Excitatory Neurotransmissionmentioning

confidence: 99%

GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimerâ€™s disease

Nava-Mesa¹,

Jiménez‐Díaz²,

Yajeya³

et al. 2014

Front. Cell. Neurosci.

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, brain atrophy due to neuronal and synapse loss, and formation of two pathological lesions: extracellular amyloid plaques, composed largely of amyloid-beta peptide (Aβ), and neurofibrillary tangles formed by intracellular aggregates of hyperphosphorylated tau protein. Lesions mainly accumulate in brain regions that modulate cognitive functions such as the hippocampus, septum or amygdala. These brain structures have dense reciprocal glutamatergic, cholinergic, and GABAergic connections and their relationships directly affect learning and memory processes, so they have been proposed as highly susceptible regions to suffer damage by Aβ during AD course. Last findings support the emerging concept that soluble Aβ peptides, inducing an initial stage of synaptic dysfunction which probably starts 20–30 years before the clinical onset of AD, can perturb the excitatory–inhibitory balance of neural circuitries. In turn, neurotransmission imbalance will result in altered network activity that might be responsible of cognitive deficits in AD. Therefore, Aβ interactions on neurotransmission systems in memory-related brain regions such as amygdaloid complex, medial septum or hippocampus are critical in cognitive functions and appear as a pivotal target for drug design to improve learning and dysfunctions that manifest with age. Since treatments based on glutamatergic and cholinergic pharmacology in AD have shown limited success, therapies combining modulators of different neurotransmission systems including recent findings regarding the GABAergic system, emerge as a more useful tool for the treatment, and overall prevention, of this dementia. In this review, focused on inhibitory systems, we will analyze pharmacological strategies to compensate neurotransmission imbalance that might be considered as potential therapeutic interventions in AD.

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“…For example, the effects of brain injury may be detected sooner with diffusion scans before conventional MRI (Neil, et al., 2002; Sundgren, et al, 2004). A number of studies have examined variation in hippocampus MD in studies of memory (den Heijer, et al, 2012; Piras, et al, 2010), MCI, and AD (Kantarci, et al, 2005) (Cherubini, et al, 2010; Fellgiebel, et al, 2006; Li, et al, 2013b). Brueggen et al (Brueggen, et al, 2015) have recently shown that hippocampus volume is superior to MD when predicting individuals who convert from MCI to AD.…”

Section: Discussionmentioning

confidence: 99%

“…Li et al (Li, et al, 2013a; Li, et al, 2013b) have shown that a combination of volume and MD assessed across subcortical gray matter structures, including the hippocampus, can better discriminate early-stage AD from normal subjects. Future analyses may include latent class analysis (Lazarsfeld and Henry, 1968), or factor mixture models (Everitt, 1988) that integrate individual differences in both volume and MD across all seven subcortical ROIs.…”

Section: Discussionmentioning

confidence: 99%

“…MD in subcortical ROIs is also increasingly used to investigate biomedical (Craiu, 2013; Kregel, et al., 2015; Simo, et al, 2013), psychiatric (Buhler and Mann, 2011; Peng, et al, 2012; Rosenbloom, et al, 2003; Serafini, et al, 2014; Wen, et al, 2011), as well as cognitive (Stigler, et al., 2011) and age-related (Carlesimo, et al., 2010; Cherubini, et al, 2010; Fellgiebel, et al, 2006; Fellgiebel and Yakushev, 2011; Holtzer, et al, 2014; Li, et al, 2013b; Muller, et al, 2007; Teipel, et al, 2013) traits. For example, variation in hippocampus MD has been linked to cognitive decline (den Heijer, et al, 2012; Piras, et al, 2010), mild cognitive impairment (MCI), and Alzheimer’s Disease (AD) (Cherubini, et al, 2010; Fellgiebel, et al., 2006; Kantarci, et al, 2005; Li, et al, 2013b). …”

Section: Introductionmentioning

confidence: 99%

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Genetic and environmental influences on mean diffusivity and volume in subcortical brain regions

Gillespie

Neale

Hagler

et al. 2017

Human Brain Mapping

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Increased mean diffusivity (MD) is hypothesized to reflect tissue degeneration and may provide subtle indicators of neuropathology as well as age-related brain changes in the absence of volumetric differences. Our aim was to determine the degree to which genetic and environmental variation in subcortical MD is distinct from variation in subcortical volume. Data were derived from a sample of 387 male twins (83 MZ twin pairs, 55 DZ twin pairs, and 111 incomplete twin pairs) who were MRI scanned as part of the Vietnam Era Twin Study of Aging (VETSA). Quantitative estimates of mean diffusivity and volume for 7 subcortical regions were obtained: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens. After adjusting for covariates, bivariate twin models were fitted to estimate the size and significance of phenotypic, genotypic, and environmental correlations between MD and volume at each subcortical region. With the exception of the amygdala, familial aggregation in MD was entirely explained by additive genetic factors across all subcortical regions with estimates ranging from 46% to 84%. Based on bivariate twin modeling, variation in subcortical MD appears to be both genetically and environmentally unrelated to individual differences in subcortical volume. Therefore, subcortical MD may be an alternative biomarker of brain morphology for complex traits worthy of future investigation.

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Discriminative analysis of early-stage Alzheimer’s disease and normal aging with automatic segmentation technique in subcortical gray matter structures: a multicenter in vivo MRI volumetric and DTI study

Cited by 22 publications

References 37 publications

Neural substrates of verbal memory impairments in adults with type 2 diabetes mellitus

Neural substrates of verbal memory impairments in adults with type 2 diabetes mellitus

GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimerâ€™s disease

Genetic and environmental influences on mean diffusivity and volume in subcortical brain regions

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