Predicting neurocognitive function with hippocampal volumes and <scp>DTI</scp> metrics in patients with Alzheimer's dementia and mild cognitive impairment

Shim, Geumsook; Choi, Kwang Yeon; Kim, Dohyun; Suh, Sang Il; Lee, Suji; Jeong, Hyun Chul; Jeong, Bumseok

doi:10.1002/brb3.766

Cited by 38 publications

(25 citation statements)

References 57 publications

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“…To increase the predictive validity of SMI as a marker of pre‐clinical AD, numerous studies have focused on the biomarkers of AD‐related neurodegeneration in SMI and provided evidence of amyloidosis and neurodegeneration of grey matter in SMI . Microstructural changes in WM have been reported to occur prior to hippocampal atrophy and could be helpful in predicting neurocognitive function during the AD neurodegenerative process . However, relatively little evidence has been reported on the degeneration of WM in SMI.…”

Section: Discussionmentioning

confidence: 99%

White matter integrity disruption in the pre‐dementia stages of Alzheimer's disease: from subjective memory impairment to amnestic mild cognitive impairment

Shao

Zhang

et al. 2019

Euro J of Neurology

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Background and purpose Subjective memory impairment (SMI) and amnestic mild cognitive impairment (aMCI) are thought to represent the pre‐dementia stages of Alzheimer's disease (AD). SMI is considered a more advanced pre‐clinical status prior to aMCI. Understanding the neuromechanism of SMI will have great benefits for monitoring the disease progression of AD. The study aims to explore whether SMI shows alterations of white matter (WM) integrity similar to the patterns of aMCI. Methods The atlas‐based analyses were performed to investigate the diffusion changes in the major WM tracts amongst 22 individuals with normal cognition (NC), 22 SMI patients and 25 aMCI patients. The correlations between the altered diffusion metrics and cognitive performance in the SMI and aMCI groups were assessed. Results The diffusion tensor metrics of SMI were intermediate between the NC and aMCI groups. The aMCI group presented disrupted integrity in multiple WM tracts, including the left anterior thalamic radiation, right corticospinal tract and left cingulum of the hippocampus (CgH), compared to the NC group. The left CgH showed diffusion alterations in the SMI group. In the aMCI group, the mean diffusivity of the left CgH was negatively correlated with episodic memory, whilst the radial diffusivity of the right corticospinal tract was negatively correlated with executive function. No significant relationship was found in the SMI group. Conclusion The study suggested that SMI patients might present detectable WM integrity changes in the left CgH before exhibiting objective cognitive dysfunction, which may provide novel insights into the pathological mechanisms of AD.

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Section: Discussionmentioning

confidence: 99%

White matter integrity disruption in the pre‐dementia stages of Alzheimer's disease: from subjective memory impairment to amnestic mild cognitive impairment

Shao

Zhang

et al. 2019

Euro J of Neurology

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“…Alterations in white matter microstructure are thought to contribute to cognitive decline due to progressive “disconnection” between cortical regions (O’Sullivan et al, 2001). Some investigators have found a relationship between DTI indices and more global measures of cognitive function in individuals with AD (e.g., Bozzali et al, 2002; Lee et al, 2002; Shim et al, 2017). For example, Nir et al (2013) found that FA, MD, AxD, and RD in the left hippocampal cingulum and left fornix were strongly associated with MMSE scores, while FA, MD, AxD, and RD in the left cingulum, bilateral sagittal stratum, and bilateral inferior fronto-occipital fasciculus were related to Clinical Dementia Rating scores, and FA and MD in the left hippocampal cingulum were related to AD Assessment Scale (ADAS) cognitive scores.…”

Section: Introductionmentioning

confidence: 99%

Relationship Between DTI Metrics and Cognitive Function in Alzheimer’s Disease

Mayo

Garcia‐Barrera

Mazerolle

et al. 2019

Front. Aging Neurosci.

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Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder with a clinical presentation characterized by memory impairment and executive dysfunction. Our group previously demonstrated significant alterations in white matter microstructural metrics in AD compared to healthy older adults. We aimed to further investigate the relationship between white matter microstructure in AD and cognitive function, including memory and executive function.Methods: Diffusion tensor imaging (DTI) and neuropsychological data were downloaded from the AD Neuroimaging Initiative database for 49 individuals with AD and 48 matched healthy older adults. The relationship between whole-brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and composite scores of memory and executive function was examined. We also considered voxel-wise relationships using Tract-Based Spatial Statistics.Results: As expected, individuals with AD had lower composite scores on tests of memory and executive function, as well as disrupted white matter integrity (low FA, high MD, AxD, and RD) relative to healthy older adults in widespread regions, including the hippocampus. When the AD and healthy older adult groups were combined, we found significant relationships between DTI metrics (FA/MD/AxD/RD) and memory scores across widespread regions of the brain, including the medial temporal regions. We also found significant relationships between DTI metrics (FA/MD/AxD/RD) and executive function in widespread regions, including the frontal areas in the combined group. However, when the groups were examined separately, no significant relationships were found between DTI metrics (FA/MD/AxD/RD) and memory performance for either group. Further, we did not find any significant relationships between DTI metrics (FA/MD/AxD/RD) and executive function in the AD group, but we did observe significant relationships between FA/RD, and executive function in healthy older adults.Conclusion: White matter integrity is disrupted in AD. In a mixed sample of AD and healthy elderly persons, associations between measures of white matter microstructure and memory and executive cognitive test performance were evident. However, no significant linear relationship between the degree of white matter disruption and level of cognitive functioning (memory and executive abilities) was found in those with AD. Future longitudinal studies of the relations between DTI metrics and cognitive function in AD are required to determine whether DTI has potential to measure progression of AD and/or treatment efficacy.

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“…Thus, improved in vivo MRI-based delineation of hippocampal subregions may permit selective differentiation of hippocampal-based neurocognitive processes in health ( Middlebrooks et al, 2017 ) and disease ( Small, 2014 ). Available evidence suggests that different neurodegenerative disorders affect selective hippocampal subfield volumes: CA1 is frequently reported as atrophied in Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) ( Braak and Braak, 1997 ; Khan et al, 2015 ; Saito and Murayama, 2007 ; Shim et al, 2017 ; West et al, 2004 ), but not in other forms of dementia (e.g., Dementia with Lewy Bodies) ( Li et al, 2016 ; Mak et al, 2016 ). Relative to controls: CA4/dentate gyrus volume is compromised in trauma and post-traumatic stress disorder ( Aas et al, 2014 ; Boen et al, 2014 ; Hayes et al, 2017 ; Teicher et al, 2012 ); significant volume deficits are observed in subfields CA1 and CA4/dentate in patients with hippocampal sclerosis due to temporal lobe epilepsy ( Sone et al, 2016 ); presubiculum is smaller in patients with schizophrenia ( Haukvik et al, 2015 ); and smaller volumes of CA2+3 are reported in Parkinson's disease (PD), prior to treatment ( Gyorfi et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal subfield CA2+3 exhibits accelerated aging in Alcohol Use Disorder: A preliminary study

Zahr

Pohl

Saranathan

et al. 2019

NeuroImage: Clinical

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The profile of brain structural dysmorphology of individuals with Alcohol Use Disorders (AUD) involves disruption of the limbic system. In vivo imaging studies report hippocampal volume loss in AUD relative to controls, but only recently has it been possible to articulate different regions of this complex structure. Volumetric analysis of hippocampal regions rather than total hippocampal volume may augment differentiation of disease processes. For example, damage to hippocampal subfield cornu ammonis 1 (CA1) is often reported in Alzheimer's disease (AD), whereas deficits in CA4/dentate gyrus are described in response to stress and trauma. Two previous studies explored the effects of chronic alcohol use on hippocampal subfields: one reported smaller volume of the CA2+3 in alcohol-dependent subjects relative to controls, associated with years of alcohol consumption; the other, smaller volumes of presubiculum, subiculum, and fimbria in alcohol-dependent relative to control men.The current study, conducted in 24 adults with DSM5-diagnosed AUD (7 women, 53.7 ± 8.8) and 20 controls (7 women, 54.1 ± 9.3), is the first to use FreeSurfer 6.0, which provides state-of-the art hippocampal parcellation, to explore the sensitivity of hippocampal sufields to alcoholism. T1- and T2- images were collected on a GE MR750 system with a 32-channel Nova head coil. FreeSurfer 6.0 hippocampal subfield analysis produced 12 subfields: parasubiculum; presubiculum; subiculum; CA1; CA2+3; CA4; GC-ML-DG (Granule Cell (GC) and Molecular Layer (ML) of the Dentate Gyrus (DG)); molecular layer; hippocampus-amygdala-transition-area (HATA); fimbria; hippocampal tail; hippocampal fissure; and whole volume for left and right hippocampi. A comprehensive battery of neuropsychological tests comprising attention, memory and learning, visuospatial abilities, and executive functions was administered.Multiple regression analyses of raw volumetric data for each subfields by group, age, sex, hemisphere, and supratentorial volume (svol) showed significant effects of svol (p < .04) on nearly all structures (excluding tail and fissure). Volumes corrected for svol showed effects of age (fimbria, fissure) and group (subiculum, CA1, CA4, GC-ML-DG, HATA, fimbria); CA2+3 showed a diagnosis-by-age interaction indicating older AUD individuals had a smaller volume than would be expected for their age. There were no selective relations between hippocampal subfields and performance on neuropsychological tests, likely due to lack of statistical power.The current results concur with the previous study identifying CA2+3 as sensitive to alcoholism, extend them by identifying an alcoholism-age interaction, and suggest an imaging phenotype distinguishing AUD from AD and stress/trauma.

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Predicting neurocognitive function with hippocampal volumes and DTI metrics in patients with Alzheimer's dementia and mild cognitive impairment

Cited by 38 publications

References 57 publications

White matter integrity disruption in the pre‐dementia stages of Alzheimer's disease: from subjective memory impairment to amnestic mild cognitive impairment

White matter integrity disruption in the pre‐dementia stages of Alzheimer's disease: from subjective memory impairment to amnestic mild cognitive impairment

Relationship Between DTI Metrics and Cognitive Function in Alzheimer’s Disease

Hippocampal subfield CA2+3 exhibits accelerated aging in Alcohol Use Disorder: A preliminary study

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