Regional White Matter Hyperintensity Influences Grey Matter Atrophy in Mild Cognitive Impairment
TL;DR: Although WMH volume was highest in AD subjects, it had a more pervasive influence on brain structure and cognitive impairment in MCI, highlighting the importance of early detection of cerebrovascular disease, as its intervention at the MCI stage might potentially slow down neurodegeneration.
Abstract: The association between cerebrovascular disease pathology (measured by white matter hyperintensities, WMH) and brain atrophy in early Alzheimer's disease (AD) remain to be elucidated. Thus, we investigated how WMH influence neurodegeneration and cognition in prodromal and clinical AD. We examined 51 healthy controls, 35 subjects with mild cognitive impairment (MCI), and 30 AD patients. We tested how total and regional WMH is related to specific grey matter volume (GMV) reductions in MCI and AD compared to controls. Stepwise regression analysis was further performed to investigate the association of GMV and regional WMH volume with global cognition. We found that total WMH volume was highest in AD but showed the strongest association with lower GMV in MCI. Frontal and parietal WMH had the most extensive influence on GMV loss in MCI. Additionally, parietal lobe WMH volume (but not hippocampal atrophy) was significantly associated with global cognition in MCI while smaller hippocampal volume (but not WMH volume) was associated with lower global cognition in AD. Thus, although WMH volume was highest in AD subjects, it had a more pervasive influence on brain structure and cognitive impairment in MCI. Our study thus highlights the importance of early detection of cerebrovascular disease, as its intervention at the MCI stage might potentially slow down neurodegeneration.
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TL;DR: The results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD.
Abstract: White matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI-2 dataset from August 2010 to May 2017. Cross-sectional and longitudinal associations of WMHs with 8 cognitive domains were explored, using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog13), Rey Auditory Verbal Learning Test (RAVLT), Functional Assessment Questionnaire (FAQ), executive function (ADNI-EF), and memory function (ADNI-Mem). The association analyses were performed using multiple linear regression models, linear mixed models, Spearman rank correlation, and Kaplan-Meier survival curves. The volumes of WMHs were greater in patients with Alzheimer's disease (AD) dementia compared with controls (p < 0.001) and mild cognitive impairment (p = 0.006) patients at baseline. The bigger volumes of WMHs correlated with worse performances on ADAS-Cog13 and ADNI-EF (p = 0.029; p = 0.003) at baseline and MMSE, MoCA, CDRSB, ADAS-Cog13, FAQ, and ADNI-Mem (overall p < 0.05) longitudinally, after adjusting for age, sex, educational level, apolipoprotein E ɛ4 genotype, hypertension, hyperlipidemia, diabetes, smoking, infarction, and diagnosis. Additionally, the correlations between the change rate of WMHs and change rates of MMSE, MoCA, CDRSB, FAQ, ADNI-EF, and ADNI-Mem were statistically significant. Furthermore, patients with high WMH volumes showed an increased likelihood of dementia. The results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD.
45 citations
TL;DR: In this article, a cross-sectional association between regional WMH volume and cognition was assessed within each group, controlling for cerebral amyloid burden, global cortical atrophy, and hippocampal atrophy.
Abstract: Introduction White matter hyperintensities (WMH) are often described in Alzheimer's disease (AD), but their topography and specific relationships with cognition remain unclear. Methods Regional WMH were estimated in 54 cognitively impaired amyloid beta-positive AD (Aβpos-AD), compared to 40 cognitively unimpaired amyloid beta-negative older controls (Aβneg-controls) matched for vascular risk factors. The cross-sectional association between regional WMH volume and cognition was assessed within each group, controlling for cerebral amyloid burden, global cortical atrophy, and hippocampal atrophy. Results WMH volume was larger in Aβpos-AD compared to Aβneg-controls in all regions, with the greatest changes in the splenium of the corpus callosum (S-CC). In Aβpos-AD patients, larger total and regional WMH volume, especially in the S-CC, was strongly associated with decreased cognition. Discussion WMH specifically contribute to lower cognition in AD, independently from amyloid deposition and atrophy. This study emphasizes the clinical relevance of WMH in AD, especially posterior WMH, and most notably S-CC WMH.
37 citations
TL;DR: In this article, the authors applied graph theoretical analysis to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in Alzheimer's disease, bvFTD, and healthy participants.
Abstract: Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social–emotional functional deficits. In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled. Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes. Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.
25 citations
TL;DR: It is suggested that patients with SIVD show abnormal neurovascular coupling at the early stage of the disease and during disease development, which might be associated with disease severity and cognitive impairment.
Abstract: Patients with subcortical ischemic vascular disease (SIVD) exhibit a high risk of cognitive impairment that might be caused by neurologic deficits and vascular injuries. However, the mechanism remains unknown. In current study, 24 normal controls (NC) and 54 SIVD patients, including 26 SIVD patients with no cognitive impairment (SIVD-NCI) and 28 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the resting-state functional MRI (rs-fMRI) and neuropsychological assessments. We combined regional homogeneity (ReHo) and cerebral blood flow (CBF) by using the global ReHo-CBF correlations coefficient and the ReHo/CBF ratio to detect the inner link between neuronal activity and vascular responses. Correlations between the ReHo/CBF ratio and neuropsychological assessments were explored in patients with SIVD. As a result, we identified significantly decreased global ReHo-CBF coupling in the SIVD-NCI group and SIVD- MCI group with respect to the NC. The SIVD-MCI group showed more serious decoupling of the global ReHo-CBF correlation. We also found a significantly abnormal ReHo/CBF ratio predominantly located in cognitive-related brain regions, including the left insula, right middle temporal gyrus, right precuneus, left precentral gyrus, and left inferior parietal lobule but not the supramarginal and angular gyri. The SIVD-MCI group showed more severe disorders of neurovascular coupling than the other two groups. Moreover, the ReHo/CBF ratio in the left precentral gyrus of the SIVD-NCI group exhibited a positive correlation with the MMSE scores. These findings suggested that patients with SIVD show abnormal neurovascular coupling at the early stage of the disease and during disease development. It might be associated with disease severity and cognitive impairment. Neurovascular decoupling in brain may be a possible neuropathological mechanism of SIVD.
18 citations
Cites result from "Regional White Matter Hyperintensit..."
...This finding is consistent with the previous studies showing that the precentral gyrus is susceptible to cerebral vascular diseases, which may lead to cognitive injuries (Vipin et al., 2018; Caruso et al., 2019)....
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TL;DR: In this paper , the impact of WMHs on grey matter atrophy and cognition in normal aging (n = 571), mild cognitive impairment (MCI, n = 551), Alzheimer's dementia (AD, N = 212), fronto-temporal dementia (FTD, N= 125), and Parkinson's disease (PD, n= 271).
13 citations
References
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TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
76,181 citations
01 Jan 2002
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Abstract: EXAMINATION of the mental state is essential in evaluating psychiatric patients.1 Many investigators have added quantitative assessment of cognitive performance to the standard examination, and have documented reliability and validity of the several “clinical tests of the sensorium”.2*3 The available batteries are lengthy. For example, WITHERS and HINTON’S test includes 33 questions and requires about 30 min to administer and score. The standard WAIS requires even more time. However, elderly patients, particularly those with delirium or dementia syndromes, cooperate well only for short periods.4 Therefore, we devised a simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely. It is “mini” because it concentrates only on the cognitive aspects of mental functions, and excludes questions concerning mood, abnormal mental experiences and the form of thinking. But within the cognitive realm it is thorough. We have documented the validity and reliability of the MMS when given to 206 patients with dementia syndromes, affective disorder, affective disorder with cognitive impairment “pseudodementia”5T6), mania, schizophrenia, personality disorders, and in 63 normal subjects.
70,887 citations
TL;DR: A 10‐minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first‐line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia.
Abstract: Objectives: To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia.
Design: Validation study.
Setting: A community clinic and an academic center.
Participants: Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score≥17), and 90 healthy elderly controls (NC).
Measurements: The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD.
Results: Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively).
Conclusion: MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
16,037 citations
Johns Hopkins University1, Johns Hopkins University School of Medicine2, Mayo Clinic3, McGill University4, Harvard University5, University of California, Irvine6, University of Pittsburgh7, Columbia University Medical Center8, Eli Lilly and Company9, Washington University in St. Louis10, UCL Institute of Neurology11, VU University Medical Center12, Alzheimer's Association13, Northwestern University14, National Institutes of Health15
TL;DR: The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available.
Abstract: The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.
13,710 citations
TL;DR: In this paper, the authors describe the steps involved in VBM, with particular emphasis on segmenting gray matter from MR images with non-uniformity artifact and provide evaluations of the assumptions that underpin the method, including the accuracy of the segmentation and the assumptions made about the statistical distribution of the data.
8,049 citations