Gray Matter Volume Loss Research Articles

Early regional cerebral grey matter damage predicts long-term cognitive impairment phenotypes in multiple sclerosis: a 20-year study.

Despite grey matter atrophy in cortical and subcortical regions has been related to cognitive impairment in multiple sclerosis, only a few studies evaluated its predictive value for alterations in the long-term. We aimed to determine early predictors of cognitive status after 20 years of multiple sclerosis. In this longitudinal retrospective study, participants underwent a 1.5 T MRI scanning at diagnosis (T0) and after two years (T2), which included the evaluation of regional grey matter volume loss patterns. All individuals with multiple sclerosis underwent a comprehensive neuropsychological assessment at the end of the study and were classified considering their global and specific cognitive domains status (memory, attention/information processing speed, executive functioning). Clinical and MRI characteristics were assessed as predictors of long-term cognitive impairment. Analysis of covariance, t-test, unadjusted and adjusted (for age, sex, disease duration, volume of white matter lesions, volume of cortical lesions) logistic regression were conducted. One hundred seventy-five people with multiple sclerosis (118 females; mean ± SD age at the end of study = 47.7 ± 9.4 years) clinically followed for 20 years from onset (mean ± SD = 19.9 ± 5.1) were evaluated. At the end of the study, 81 (47%) were classified as cognitively impaired: 38 as mildly impaired (22%), and 43 as severely impaired (25%). In particular, 46 were impaired in memory (27%), 66 were impaired in attention/information processing speed (38%), and 71 were impaired in executive functioning (41%). Regression models identified precuneus (adjusted odds ratio = 3.37; P < 0.001), insula (adjusted odds ratio = 2.33; P = 0.036), parahippocampal gyrus (adjusted odds ratio = 2.07; P < 0.001) and cingulate (adjusted odds ratio = 1.81; P = 0.009) as the most associated regions with global cognitive impairment and domains-specific cognitive alterations after a mean of 20 years of multiple sclerosis, after adjusting for demographic and clinical variables as well as for focal white matter and grey matter damage. Early grey matter volume loss of specific cortical and deep grey matter regions predicts global and domain cognitive alterations after 20 years from multiple sclerosis diagnosis.

Cardiovascular Disease, Brain Glucose Metabolism, and Neurocognitive Decline in People With Human Immunodeficiency Virus.

Cardiovascular disease (CVD) and neuroinflammation are thought to exacerbate neurocognitive dysfunction in treated people with human immunodeficiency virus (PWH). Here, we longitudinally measured brain glucose metabolism as a measure of neuronal integrity in treated PWH using [18F]Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in correlation with atherosclerotic cardiovascular disease (ASCVD) scores, cerebrospinal fluid (CSF) neuroinflammatory markers, neurocognitive outcomes, and other clinical and laboratory variables (CLVs). Well-controlled PWH (n = 36) underwent baseline and follow-up FDG PET/CT obtained 3.5 years apart on average. Longitudinal changes in whole brain and regional relative FDG uptake, brain volumes, CLVs, CSF cytokines, and neuropsychological measures were measured. A variable selection model identified baseline variables related to future brain metabolic changes while multivariable models explored neuropsychological implications of brain metabolism and volumetrics. High ASCVD scores predicted future decreased thalamic uptake (slope = -0.0068, P = .027) and decreasing thalamic uptake correlated with worsening cognition (slope = 15.80, P = .020). Despite longitudinal greater than expected gray matter loss, whole brain FDG uptake did not change over the follow-up period. Most CSF cytokines decreased longitudinally but were not predictive of FDG changes. We found that high ASCVD scores in a group of treated PWH were related to thalamic hypometabolism, which in turn correlated with neurocognitive decline. Our findings support the contribution of CVD to neurocognitive dysfunction. More proactive CVD management may have a role in mitigating progression of cognitive impairment. Lack of change in global brain glucose metabolism despite documented accelerated gray matter volume loss over the same period suggests that FDG PET might underestimate neuronal injury in PWH compared to structural magnetic resonance imaging.

Correlation of MRI brain findings with executive dysfunction and vascular risk factors in elderly patients with cognitive impairment

Objectives: The primary objective of the present study was to investigate the relationship between gray matter changes, white matter changes and executive function among older Indian adults with vascular risk factors. Methods: This hospital based observational analytical study was conducted in a tertiary care health facility located in the north-western region of India for a duration of one year between October 2021 and September 2022 among patients between 60 and 90 years of age presenting to the outpatient sections of Department of Neurology with executive dysfunction. We assessed the vascular risk factors, evaluated executive function, and then the patients underwent brain MRI on a 1.5T MRI scanner. Results: The proportion of patients with dorsolateral atrophy was significantly higher (p&lt;0.001) among patients with executive dysfunction (83.10%). Hypertension significantly contributed to predict the atrophy of temporal lobe and parietal lobe (p&lt;0.05). Hyperintensity of periventricular area was found significantly higher among executive dysfunction patients (85.92%). Elevated HbA1c levels and smoking significantly contributed to predict the white matter hyperintensity of basal ganglia (p&lt;0.05). The present study also found that hypertension and alcohol use significantly predicted white matter hyperintensity in the frontal area (p&lt;0.05). Conclusion: Specific white matter hyperintensity loci and grey matter volume loss were closely associated with executive dysfunction in elderly. It is understood that modifying and treating vascular risk factors can prevent progression of executive dysfunction and these findings emphasize the complex nature of the relationship between vascular risk factors, cognitive impairment, and brain structure.

Impact of Sleeve Gastrectomy on Brain Structural Integrity.

Potential brain structural differences in people with obesity (PwO) who achieve over or less than 50% excess weight loss (EWL) after sleeve gastrectomy (SG) are currently unknown. We compared measures of gray matter volume (GMV) and white matter (WM) microstructural integrity of PwO who achieved over or less than 50% EWL after SG with a group of controls with obesity (CwO) without a past history of metabolic bariatric surgery. Sixty-two PwO underwent 1.5T MRI scanning: 24 who achieved more than 50% of EWL after SG ("group a"), 18 who achieved less than 50% EWL after SG ("group b"), and 20 CwO ("group c"). Voxel-based morphometry and tract-based spatial Statistics analyses were performed to investigate GMV and WM differences among groups. Multiple regression analyses were performed to investigate relationships between structural and psychological measures. Group a demonstrated significantly lower GMV loss and higher WM microstructural integrity with respect to group b and c in some cortical regions and several WM tracts. Positive correlations were observed in group a between WM integrity and several psychological measures; the lower the WM integrity, the higher the mental distress, emotional dysregulation, and binge eating behavior. The present results gain a new understanding of the neural mechanisms of outcome in patients who undergo SG. We found limited GMV changes and extensive WM microstructural differences between PwO who achieved over or less than 50% EWL after SG, which may be due to higher vulnerability of WM to the metabolic dysfunction present in PwO.

Association of sarcopenia with regional brain atrophy and white matter lesions in a general older population: the Hisayama Study.

Sarcopenia has been reported to be associated with cognitive decline and the risk of dementia. However, few studies have addressed the association between sarcopenia and brain morphological changes in the general population. A total of 1373 community-dwelling participants aged ≥ 65years underwent brain MRI. Sarcopenia was defined based on the Asian Working Group for Sarcopenia's criteria. The pattern of regional gray matter volume loss associated with sarcopenia were assessed using a voxel-based morphometry (VBM) analysis. Regional brain volumes, intracranial volumes (ICV), and white matter lesions volumes (WMLV) were also measured using FreeSurfer. An analysis of covariance was used to examine the associations of sarcopenia with regional brain volumes in proportion to ICV. Of the participants, 112 had sarcopenia. The participants with sarcopenia had significantly lower total brain volume/ICV and total gray matter volume/ICV and higher WMLV/ICV than those without sarcopenia after adjusting for confounders. In VBM, sarcopenia was associated with lower gray matter volume in the frontal lobe, insula, cingulate gyrus, hippocampus, amygdala, and basal ganglia. Using FreeSurfer, we confirmed that the participants with sarcopenia had significantly lower frontal, insular, cingulate, and hippocampal volumes than those without sarcopenia. The current study showed that participants with sarcopenia had significantly lower volume in the frontal lobe, insula, cingulate, and hippocampus and higher WMLV than participants without sarcopenia. As these brain regions are likely to play an important role in cognitive function, these changes may suggest a shared underlying mechanism for the progression of sarcopenia and cognitive decline.

Beyond Hypertension: Examining Variable Blood Pressure's Role in Cognition and Brain Structure.

Hypertension or high blood pressure (BP) is one of the 12 modifiable risk factors that contribute to 40% of dementia cases that could be delayed or prevented. Although hypertension is associated with cognitive decline and structural brain changes, less is known about the long-term association between variable BP and cognitive/brain changes. This study examined the relationship between variable BP and longitudinal cognitive, white matter hyperintensity (WMH), gray matter (GM), and white matter (WM) volume change over time and postmortem neuropathology. A total of 4,606 participants (32,776 follow-ups) from RADC Research Resource Sharing Hub (RUSH) and 2,114 participants (9,827 follow-ups) fromtheAlzheimer's Disease Neuroimaging Initiative (ADNI) were included. Participants were divided into 1 of 3 groups: normal, high, or variable BP. Linear-mixed models investigated the relationship between BP and cognition, brain structure, and neuropathology. Older adults with variable BP exhibited the highest rate of cognitive decline followed by high and then normal BP. Increased GM volume loss and WMH burden were also observed in variable compared to high and normal BP. In postmortem neuropathology, both variable and high BP had increased rates compared to normal BP. Results were consistent across the RUSH and ADNI participants, supporting the generalizability of the findings. Damages potentially associated with variable BP may reduce resilience to future dementia-related pathology and increased the risk of dementia more than that caused by high BP. Improved treatment and management of variable BP may help reduce cognitive decline in the older adult population.

Impairments in knowledge of social norms in presymptomatic, prodromal, and symptomatic frontotemporal dementia.

We aimed to assess the knowledge of social norms in patients with behavioral variant frontotemporal dementia (bvFTD) with the Dutch version of the Social Norms Questionnaire (SNQ-NL). The SNQ-NL was administered in 34 patients with bvFTD, 20 prodromal mutation carriers, 76 presymptomatic mutation carriers, and 56 controls. Group differences and correlations with other neuropsychological tests and gray matter volume were examined. Patients with bvFTD had lower total SNQ-NL scores and more over-adherence errors than presymptomatic mutation carriers and controls (P<0.001). SNQ-NL performance correlated with tests for executive functioning and social cognition, and with gray matter volume in bilateral frontal and unilateral temporal regions. The SNQ-NL can identify impairments in knowledge of social norms in bvFTD, highlighting its significance in clinical diagnosis and upcoming clinical trials. The SNQ-NL currently fails to differentiate presymptomatic mutation carriers from controls; to this end, larger sample sizes from larger cohorts and longitudinal follow-up are warranted. The Dutch version of the Social Norms Questionnaire (SNQ-NL) is able to detect impairment in social cognition in symptomatic bvFTD patients.A trend towards a lower performance in prodromal mutation carriers was found.Performance on the SNQ-NL is related to other measures of social cognition, executive functioning, and language.Lower SNQ-NL performance is related to gray matter volume loss in bilateral frontal and temporal regions.The SNQ-NL provides insight into the underlying cause of deficits in social cognition in bvFTD.

Can gray matter loss in early adolescence be explained by white matter growth?

AbstractA fundamental puzzle about brain development is why the volume of gray matter (GM) apparently declines as white matter (WM) grows when children enter adolescence. Since pruned synapses are too small to affect GM volume, a prevailing theory posits that an expanded distribution of myelin causes the inner edge of the GM to “whiten” while total brain volume remains steady, shifting the MRI‐measured WM:GM boundary closer to the brain's outer surface. This theory inherently predicts that GM volume loss is concurrent with WM volume growth across regions, within sexes and over time, although these predictions have yet to be explicitly tested. In this study, we test these predictions by mapping regional GM and WM volumetric changes in 2333 participants of the Adolescent Brain Cognitive Development study aged 9–14 years who each received three MRI scans 2 years apart. We show that average GM and WM volume changes follow distinct spatial, temporal, and sex‐specific patterns, indicating that GM volume loss is not balanced by WM volume growth, although cortical GM thinning is weakly correlated with WM growth in some regions. We conclude that myelin is not the main source of measured GM volume loss, and we propose alternative candidates.

Assessment of Gray Matter Microstructural Alterations in Alzheimer's Disease by Free Water Imaging.

Cortical neurodegenerative processes may precede the emergence of disease symptoms in patients with Alzheimer's disease (AD) by many years. No study has evaluated the free water of patients with AD using gray matter-based spatial statistics. The aim of this study was to explore cortical microstructural changes within the gray matter in AD by using free water imaging with gray matter-based spatial statistics. Seventy-one participants underwent multi-shell diffusion magnetic resonance imaging, 11C-Pittsburgh compound B positron emission tomography, and neuropsychological evaluations. The patients were divided into two groups: healthy controls (n = 40) and the AD spectrum group (n = 31). Differences between the groups were analyzed using voxel-based morphometry, diffusion tensor imaging, and free water imaging with gray matter-based spatial statistics. Voxel-based morphometry analysis revealed gray matter volume loss in the hippocampus of patients with AD spectrum compared to that in controls. Furthermore, patients with AD spectrum exhibited significantly greater free water, mean diffusivity, and radial diffusivity in the limbic areas, precuneus, frontal lobe, temporal lobe, right putamen, and cerebellum than did the healthy controls. Overall, the effect sizes of free water were greater than those of mean diffusivity and radial diffusivity, and the larger effect sizes of free water were thought to be strongly correlated with AD pathology. This study demonstrates the utility of applying voxel-based morphometry, gray matter-based spatial statistics, free water imaging and diffusion tensor imaging to assess AD pathology and detect changes in gray matter.

Comparing classic-onset corticobasal syndrome to speech/language-onset corticobasal syndrome

IntroductionPatients with classic-onset corticobasal syndrome (CBS) present with asymmetric limb apraxia and parkinsonism. We have, however, observed patients who initially present with speech and/or language (SL) problems and several years later develop CBS (i.e., SL-onset CBS). We aimed to compare clinical, neuroimaging and pathological characteristics of classic-onset CBS with SL-onset CBS. MethodsWe conducted a retrospective cohort study of 62 patients who met criteria for CBS (17 presented with classic-onset CBS and 45 had SL-onset CBS). We compared demographics, clinical characteristics, and grey and white matter volume loss with SPM12 between groups and assessed pathology and corticobasal degeneration (CBD) pathological lesion counts in patients who had died and undergone autopsy. ResultsMedian age at CBS diagnosis was 66.4 years in classic-onset CBS and 73.6 years in SL-onset CBS. Classic-onset CBS had higher frequencies of dystonia, myoclonus, and alien limb phenomenon, while SL-onset CBS had a higher frequency of vertical supranuclear gaze palsy. Both groups showed smaller frontoparietal volumes than controls, with SL-onset CBS having greater volume loss in the left supplementary motor area than classic-onset CBS. All three classic-onset CBS cases with autopsy (100 %) had CBD pathology while 8/21 of SL-onset CBS cases (38 %) had CBD. Pathological lesion burden (including astrocytic plaques) did not differ between classic-onset and SL-onset CBS. ConclusionClassic-onset and SL-onset CBS appear to be different syndromes, with the former being a more profuse motor syndrome. The more widespread volume loss in SL-onset CBS likely reflects longer disease course.

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

Neuroanatomical substrates of depression in dementia with Lewy bodies and Alzheimer's disease.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are often associated with depressive symptoms from the prodromal stage. The aim of the present study was to investigate the neuroanatomical correlates of depression in prodromal to mild DLB patients compared with AD patients. Eighty-three DLB patients, 37 AD patients, and 18 healthy volunteers were enrolled in this study. Depression was evaluated with the Mini International Neuropsychiatric Interview (MINI), French version 5.0.0. T1-weighted three-dimensional anatomical images were acquired for all participants. Regression and comparison analyses were conducted using a whole-brain voxel-based morphometry (VBM) approach on the grey matter volume (GMV). DLB patients presented a significantly higher mean MINI score than AD patients (p = 0.004), 30.1% of DLB patients had clinical depression, and 56.6% had a history of depression, while 0% of AD patients had clinical depression and 29.7% had a history of depression. VBM regression analyses revealed negative correlations between the MINI score and the GMV of right prefrontal regions in DLB patients (p < 0.001, uncorrected). Comparison analyses between DLB patients taking and those not taking an antidepressant mainly highlighted a decreased GMV in the bilateral middle/inferior temporal gyrus (p < 0.001, uncorrected) in treated DLB patients. In line with the literature, our behavioral analyses revealed higher depression scores in DLB patients than in AD patients. We also showed that depressive symptoms in DLB are associated with decreased GMV in right prefrontal regions. Treated DLB patients with long-standing depression would be more likely to experience GMV loss in the bilateral middle/inferior temporal cortex. These findings should be taken into account when managing DLB patients.

Impaired Glymphatic Flow on Diffusion Tensor MRI as a Marker of Neurodegeneration in Alzheimer's Disease: Correlation with Gray Matter Volume Loss and Cognitive Decline Independent of Cerebral Amyloid Deposition.

Impaired glymphatic flow on the Alzheimer's disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum. 80 participants (mean age, 76.9±8.5 years; 57 women) with AD (n = 65) and cognitively normal (CN) (n = 15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed. The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395-1.556) than in the CN (1.784;1.615-1.952; p = 0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, p < 0.05). There was a positive correlation between the ALPS-index and MMSE score (partial r = 0.435; p < 0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, p > 0.05). Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline.

Differential Synaptic Loss in β-Amyloid Positive Versus β-Amyloid Negative Corticobasal Syndrome.

The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4-repeat-tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to β-amyloid status. Twenty-five people with CBS, and 32 age-/sex-/education-matched healthy controls participated. Regional synaptic density was estimated by [11C]UCB-J non-displaceable binding potential (BPND), AD-tau pathology by [18F]AV-1451 BPND, and gray matter volume by T1-weighted magnetic resonance imaging. Participants with CBS had β-amyloid imaging with 11C-labeled Pittsburgh Compound-B ([11C]PiB) positron emission tomography. Symptom severity was assessed with the progressive supranuclear palsy-rating-scale, the cortical basal ganglia functional scale, and the revised Addenbrooke's Cognitive Examination. Regional differences in BPND and gray matter volume between groups were assessed by ANOVA. Compared to controls, patients with CBS had higher [18F]AV-1451 uptake, gray matter volume loss, and reduced synaptic density. Synaptic loss was more severe and widespread in the β-amyloid negative group. Asymmetry of synaptic loss was in line with the clinically most affected side. Distinct patterns of [11C]UCB-J and [18F]AV-1451 binding and gray matter volume loss, indicate differences in the pathogenic mechanisms of CBS according to whether it is associated with the presence of Alzheimer's disease or not. This highlights the potential for different therapeutic strategies in CBSs. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Progression to corticobasal syndrome: a longitudinal study of patients with nonfluent primary progressive aphasia and primary progressive apraxia of speech.

Nonfluent variant primary progressive aphasia (nfvPPA) and primary progressive apraxia of speech (PPAOS) can be precursors to corticobasal syndrome (CBS). Details on their progression remain unclear. We aimed to examine the clinical and neuroimaging evolution of nfvPPA and PPAOS into CBS. We conducted a retrospective longitudinal study in 140 nfvPPA or PPAOS patients and applied the consensus criteria for possible and probable CBS for every visit, evaluating limb rigidity, akinesia, limb dystonia, myoclonus, ideomotor apraxia, alien limb phenomenon, and nonverbal oral apraxia (NVOA). Given the association of NVOA with AOS, we also modified the CBS criteria by excluding NVOA and assigned every patient to either a progressors or non-progressors group. We evaluated the frequency of every CBS feature by year from disease onset, and assessed gray and white matter volume loss using SPM12. Asymmetric akinesia, NVOA, and limb apraxia were the most common CBS features that developed; while limb dystonia, myoclonus, and alien limb were rare. Eighty-two patients progressed to possible CBS; only four to probable CBS. nfvPPA and PPAOS had a similar proportion of progressors, although nfvPPA progressed to CBS earlier (p-value = 0.046), driven by an early appearance of limb apraxia (p-value = 0.0041). The non-progressors and progressors both showed premotor/motor cortex involvement at baseline, with spread into prefrontal cortex over time. An important proportion of patients with nfvPPA and PPAOS progress to possible CBS, while they rarely develop features of probable CBS even after long follow-up.

Automatic classification of AD pathology in FTD phenotypes using natural speech.

Screening for Alzheimer's disease neuropathologic change (ADNC) in individuals with atypical presentations is challenging but essential for clinical management. We trained automatic speech-based classifiers to distinguish frontotemporal dementia (FTD) patients with ADNC from those with frontotemporal lobar degeneration (FTLD). We trained automatic classifiers with 99 speech features from 1 minute speech samples of 179 participants (ADNC=36, FTLD=60, healthy controls [HC]=89). Patients' pathology was assigned based on autopsy or cerebrospinal fluid analytes. Structural network-based magnetic resonance imaging analyses identified anatomical correlates of distinct speech features. Our classifier showed 0.88 0.03 area under the curve (AUC) for ADNC versusFTLD and 0.93 0.04 AUC for patients versusHC. Noun frequency and pause rate correlated with gray matter volume loss in the limbic and salience networks, respectively. Brief naturalistic speech samples can be used for screening FTD patients for underlying ADNC in vivo. This work supports the future development of digital assessment tools for FTD. We trained machine learning classifiers for frontotemporal dementia patients using natural speech. We grouped participants by neuropathological diagnosis (autopsy) or cerebrospinal fluid biomarkers. Classifiers well distinguished underlying pathology (Alzheimer's disease vs. frontotemporal lobar degeneration) in patients. We identified important features through an explainable artificial intelligence approach. This work lays the groundwork for a speech-based neuropathology screening tool.

Longitudinal Relationship Between Brain Atrophy Patterns, Cognitive Decline, and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease Explored by Orthonormal Projective Non-Negative Matrix Factorization.

Longitudinal magnetic resonance imaging (MRI) has been proposed for tracking the progression of Alzheimer's disease (AD) through the assessment of brain atrophy. Detection of brain atrophy patterns in patients with AD as the longitudinal disease tracker. We used a refined version of orthonormal projective non-negative matrix factorization (OPNMF) to identify six distinct spatial components of voxel-wise volume loss in the brains of 83 subjects with AD from the ADNI3 cohort relative to healthy young controls from the ABIDE study. We extracted non-negative coefficients representing subject-specific quantitative measures of regional atrophy. Coefficients of brain atrophy were compared to subjects with mild cognitive impairment and controls, to investigate the cross-sectional and longitudinal associations between AD biomarkers and regional atrophy severity in different groups. We further validated our results in an independent dataset from ADNI2. The six non-overlapping atrophy components represent symmetric gray matter volume loss primarily in frontal, temporal, parietal and cerebellar regions. Atrophy in these regions was highly correlated with cognition both cross-sectionally and longitudinally, with medial temporal atrophy showing the strongest correlations. Subjects with elevated CSF levels of TAU and PTAU and lower baseline CSF Aβ42 values, demonstrated a tendency toward a more rapid increase of atrophy. The present study has applied a transferable method to characterize the imaging changes associated with AD through six spatially distinct atrophy components and correlated these atrophy patterns with cognitive changes and CSF biomarkers cross-sectionally and longitudinally, which may help us better understand the underlying pathology of AD.

Irreversible atrophy in memory brain regions over 7 years is predicted by glycemic control in type 2 diabetes without mild cognitive impairment.

Memory-related impairments in type 2 diabetes may be mediated by insulin resistance and hyperglycemia. Previous cross-sectional studies have controversially suggested a relationship between metabolic control and a decrease in hippocampal volumes, but only longitudinal studies can test this hypothesis directly. We performed a longitudinal morphometric study to provide a direct test of a possible role of higher levels of glycated hemoglobin with long term brain structural integrity in key regions of the memory system - hippocampus, parahippocampal gyrus and fusiform gyrus. Grey matter volume was measured at two different times - baseline and after ~7 years. We found an association between higher initial levels of HbA1C and grey matter volume loss in all three core memory regions, even in the absence of mild cognitive impairment. Importantly, these neural effects persisted in spite of the fact that patients had significantly improved their glycemic control. This suggests that early high levels of HbA1c might be irreversibly associated with subsequent long-term atrophy in the medial temporal cortex and that early intensive management is critical.

Natalizumab reduces loss of gray matter and thalamic volume in patients with relapsing-remitting multiple sclerosis: A post hoc analysis from the randomized, placebo-controlled AFFIRM trial

Background: Loss of brain gray matter fractional volume predicts multiple sclerosis (MS) progression and is associated with worsening physical and cognitive symptoms. Within deep gray matter, thalamic damage is evident in early stages of MS and correlates with physical and cognitive impairment. Natalizumab is a highly effective treatment that reduces disease progression and the number of inflammatory lesions in patients with relapsing-remitting MS (RRMS). Objective: To evaluate the effect of natalizumab on gray matter and thalamic atrophy. Methods: A combination of deep learning–based image segmentation and data augmentation was applied to MRI data from the AFFIRM trial. Results: This post hoc analysis identified a reduction of 64.3% (p = 0.0044) and 64.3% (p = 0.0030) in mean percentage gray matter volume loss from baseline at treatment years 1 and 2, respectively, in patients treated with natalizumab versus placebo. The reduction in thalamic fraction volume loss from baseline with natalizumab versus placebo was 57.0% at year 2 (p < 0.0001) and 41.2% at year 1 (p = 0.0147). Similar findings resulted from analyses of absolute gray matter and thalamic fraction volume loss. Conclusion: These analyses represent the first placebo-controlled evidence supporting a role for natalizumab treatment in mitigating gray matter and thalamic fraction atrophy among patients with RRMS. ClinicalTrials.gov identifier: NCT00027300 URL: https://clinicaltrials.gov/ct2/show/NCT00027300

Neurodegeneration within the rostral spinal cord is associated with brain gray matter volume atrophy in the early stage of cervical spondylotic myelopathy.

Case-control study. Investigating the association between neurodegeneration within rostral spinal cord and brain gray matter volume (GMV) and assessing the relationship between remote neurodegenerative changes and clinical outcomes at the early phase of Cervical Spondylotic Myelopathy (CSM). University/hospital. Using Spinal Cord Toolbox, spinal cord morphometrics (cross-sectional area [CSA], gray matter area [GMA], white matter area [WMA]) of 40 patients with CSM and 28 healthy controls (HCs) were computed and compared using two-sample t test. Brain GMV of the two groups was analyzed using voxel-based morphometry approach. Pearson's correlation between spinal cord morphometrics and altered brain GMV and Spearman's relationship between remote neurodegenerations and clinical outcomes were conducted in CSM group. Compared to HCs, CSA and WMA at C2/3 and GMV in right postcentral gyrus (PoCG.R) and left supplementary motor area (SMA.L) were significantly decreased in patients with CSM. CSA and WMA at C2/3 were associated with GMV in SMA.L and MCG.R in patients with CSM. CSA at C2/3 and GMV in PoCG.R were related to modified Japanese Orthopedic Association score in patients with CSM. The associations between CSA and WMA at C2/3 and GMV in SMA.L and MCG.R suggest a concordant change pattern and adaptive mechanisms for neuronal plasticity underlying remote neurodegeneration in early CSM. The atrophy of CSA at C2/3 and GMV loss in PoCG.R can serve as potential neuroimaging biomarkers of early structural changes within spinal cord and brain preceding marked clinical disabilities in patients with CSM.