Subcortical Brain Atrophy Research Articles

Cortical lobar volume reductions associated with homocysteine-related subcortical brain atrophy and poorer cognition in healthy aging.

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.

First seizure in elderly patients: Need to treat? Evidence from a retrospective study

BackgroundThe risk of seizure recurrence after a first unprovoked epileptic seizure is reported to be approximately 40%. Little is known about the recurrence risk after a first seizure in elderly patients, who may be at higher risk due to an increased rate of structural lesions, encephalopathy, subcortical arteriosclerotic encephalopathy or brain atrophy.MethodsIn a retrospective approach, the recurrence rate in 304 patients aged 60 years and above who presented with a first seizure between 2004 and 2017 was analyzed. Hierarchical Cox regression was used to investigate the impact of EEG and neuroimaging results, age or the prescription of anti-seizure medication (ASM) on seizure recurrence.ResultsSeizure recurrence rates were 24.5% and 34.4% after one and two years, respectively. Anti-seizure medication was started in 87.8% of patients, in 28.8% despite the absence of clear epileptogenic lesions on neuroimaging or epileptiform potentials in the EEG. Medical treatment significantly reduced the risk of recurrence (hazard ratio = 0.47). Epileptiform potentials in the EEG, epileptogenic lesions in neuroimaging and age had no significant effect on seizure recurrence. Age and the presence of neurodegenerative and psychiatric comorbidities showed a significant association with ASM prescription.ConclusionsThe present data show a strong protective effect of ASM on seizure recurrence in patients above the age of 60, even in the absence of pathologic neuroimaging or EEG results needed for the diagnosis of epilepsy. Treatment with ASM therefore seems beneficial for reducing the recurrence risk in elderly patients. The lack of a significant association between seizure recurrence and epileptogenic lesions might be related to other confounding factors like encephalopathy, subcortical arteriosclerotic encephalopathy, neurodegenerative diseases or brain atrophy.

Cortical and Subcortical Brain Atrophy Assessment Using Simple Measures on NCCT Compared with MRI in Acute Stroke.

Brain atrophy is an important surrogate for brain reserve, the capacity of the brain to cope with acquired injuries such as acute stroke. It is unclear how well atrophy measurements on MR imaging can be reproduced using NCCT imaging. We aimed to compare pragmatic atrophy measures on NCCT with MR imaging in patients with acute ischemic stroke. This is a post hoc analysis, including baseline NCCT and 24-hour follow-up MR imaging data from the Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Cortical atrophy was measured using the global cortical atrophy scale, and subcortical atrophy was measured using the intercaudate distance-to-inner-table width (CC/IT) ratio. Agreement and correlation between these measures on NCCT and MR imaging were calculated using the Gwet agreement coefficient 1 and Pearson correlation coefficients, respectively. Among 1105 participants in the ESCAPE-NA1 trial, interpretable NCCT and 24-hour MR imaging were available in 558 (50.5%) patients (mean age, 67.2 [SD, 13.7] years; 282 women). Cortical atrophy assessments performed on NCCT underestimated atrophy severity compared with MR imaging (eg, patients with global cortical atrophy of ≥1 assessed on NCCT = 133/558 [23.8%] and on MR imaging = 247/558 [44.3%]; a 20.5% difference). Overall, cortical (ie, global cortical atrophy) atrophy assessments on NCCT had substantial or better agreement with MR imaging (Gwet agreement coefficient 1 of > 0.784; P < .001). Subcortical atrophy measures (CC/IT ratio) showed strong correlations between NCCT and MR imaging (Pearson correlation = 0.746, P < .001). Brain atrophy can be evaluated using simple measures in emergently acquired NCCT. Subcortical atrophy assessments on NCCT show strong correlations with MR imaging. Although cortical atrophy assessments on NCCT are strongly correlated with MR imaging ratings, there is a general underestimation of atrophy severity on NCCT.

Sclerostin, vascular risk factors, and brain atrophy in excessive drinkers.

Heavy alcohol consumption causes several organic complications, including vessel wall calcification. Vascular damage may be involved in the development of brain atrophy and cognitive impairment. Recently, sclerostin (whose levels may be altered in alcoholics) has emerged as a major vascular risk factor. The objective of the present study is to analyze the prevalence of vascular calcifications in alcoholics, and the relationships of these lesions with brain atrophy, as well as the role of sclerostin on these alterations. A total of 299 heavy drinkers and 32 controls were included. Patients underwent cranial computed tomography, and several indices related to brain atrophy were calculated. In addition, patients and controls underwent plain radiography and were evaluated for the presence or absence of vascular calcium deposits, cardiovascular risk factors, liver function, alcohol intake, serum sclerostin, and routine laboratory variables. A total of 145 (48.47%) patients showed vascular calcium deposits, a proportion significantly higher than that observed in controls (χ2 = 16.31; p < 0.001). Vascular calcium deposits were associated with age (t = 6.57; p < 0.001), hypertension (t = 5.49; p < 0.001), daily ethanol ingestion (Z = 2.18; p = 0.029), duration of alcohol consumption (Z = 3.03; p = 0.002), obesity (χ2 = 4.65; p = 0.031), total cholesterol (Z = 2.04; p = 0.041), triglycerides (Z = 2.05; p = 0.04), and sclerostin levels (Z = 2.64; p = 0.008). Calcium deposits were significantly related to Bifrontal index (Z = 2.20; p = 0.028) and Evans index (Z = 2.25; p = 0.025). Serum sclerostin levels were related to subcortical brain atrophy, assessed by cella media index (Z = 2.43; p = 0.015) and Huckmann index (ρ = 0.204; p = 0.024). Logistic regression analyses disclosed that sclerostin was the only variable independently related to brain atrophy assessed by altered cella media index. Sclerostin was also related to the presence of vascular calcifications, although this relationship was displaced by age if this variable was also included. Prevalence of vascular calcification in alcoholics is very high. Vascular calcium deposits are related to brain atrophy. Serum sclerostin is strongly related to brain shrinkage and also shows a significant relationship with vascular calcifications, only displaced by advanced age.

Association of homocysteine-related subcortical brain atrophy with white matter lesion volume and cognition in healthy aging

Homocysteine (Hcy) is a vascular risk factor associated with cognitive impairment and cerebrovascular disease but has also been implicated in Alzheimer's disease (AD). Using multivariate Scaled Subprofile Model (SSM) analysis, we sought to identify a network pattern in structural neuroimaging reflecting the regionally distributed association of plasma Hcy with subcortical gray matter (SGM) volumes and its relation to other health risk factors and cognition in 160 healthy older adults, ages 50–89. We identified an SSM Hcy-SGM pattern that was characterized by bilateral hippocampal and nucleus accumbens volume reductions with relative volume increases in bilateral caudate, pallidum, and putamen. Greater Hcy-SGM pattern expression was associated with greater white matter hyperintensity (WMH) volume, older age, and male sex, but not with other vascular and AD-related risk factors. Mediation analyses revealed that age predicted WMH volume, which predicted Hcy-SGM pattern expression, which, in turn, predicted cognitive processing speed performance. These findings suggest that the multivariate SSM Hcy-SGM pattern may be indicative of cognitive aging, reflecting a potential link between vascular health and cognitive dysfunction in healthy older adults.

Brain aging and cardiovascular factors in HIV: a longitudinal volume and shape MRI study.

We aimed to examine the relative contributions of HIV infection, age, and cardiovascular risk factors to subcortical brain atrophy in people with HIV (PWH). Longitudinal observational study. Virally suppressed PWH with low neuropsychological confounds (n = 75) and demographically matched HIV-negative controls (n = 31) completed baseline and 18-month follow-up MRI scans, neuropsychological evaluation, cardiovascular assessments, and HIV laboratory tests. PWH were evaluated for HIV-associated neurocognitive disorder (HAND). Subcortical volumes were extracted with Freesurfer after removal of white matter hyperintensities. Volumetric and shape analyses were conducted using linear mixed-effect models incorporating interactions between age, time, and each of HIV status, HAND status, HIV disease factors, and cardiovascular markers. Across baseline and follow-up PWH had smaller volumes of most subcortical structures compared with HIV-negative participants. In addition, over time older PWH had a more rapid decline in caudate volumes (P = 0.041), predominantly in the more severe HAND subgroups (P = 0.042). Higher CD4+ cell counts had a protective effect over time on subcortical structures for older participants with HIV. Increased cardiovascular risk factors were associated with smaller volumes across baseline and follow-up for most structures, although a more rapid decline over time was observed for striatal volumes. There were no significant shape analyses findings. The study demonstrates a three-hit model of general (as opposed to localized) subcortical injury in PWH: HIV infection associated with smaller volumes of most subcortical structures, HIV infection and aging synergy in the striatum, and cardiovascular-related injury linked to early and more rapid striatal atrophy.

Symptomatic C9ORF72 mutation in non-fluent aphasia without neuroimaging signs of cerebral atrophy: A case study

Expansion mutations in the C9orf72 gene may cause familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Diffuse subcortical brain atrophy, while absent in asymptomatic patients, is frequent in symptomatic C9orf72 subjects, suggesting a direct association with active disease. Therefore, neuroimaging studies may be used as follow-up biomarker in patients carrying the mutation. Here, we describe a case of initial non-fluent aphasia in a C9orf72 patient.

APOE Genotypes and Brain Imaging Classes in Normal Cognition, Mild Cognitive Impairment, and Alzheimer's Disease: A Longitudinal Study.

To evaluate in 419 stroke-free cognitively normal subjects (CN) aged 45-82 years covering during a long prospective study (11.54 ± 1.47 years) the preclinical to dementia spectrum: 1) the distribution of small vessel disease (V) and brain atrophy (A) aggregated as following: V-/A-, V-/A+, V+/A-, V+/A+; 2) the relationship of these imaging classes with individual apolipoprotein E (APOE) genotypes; 3) the risk of progression to Alzheimer Disease (AD) of the individual APOE genotypes. Participants underwent one baseline (t0), and 4 clinical and neuropsychological assessments (t1,t2,t3, and t4). Brain MRI was performed in all subjects at t0, t2, t3 and t4.. White matter hyperintensities were assessed through two visual rating scales. Lacunes were also rated. Subcortical and global brain atrophy were determined through the bicaudate ratio and the lateral ventricle to brain ratio, respectively. APOE genotypes were determined at t0 in all subjects. Cox proportional hazard model was used to evaluate the risk of progression to AD. The imaging class of mixed type was very common in AD, and in non amnestic mild cognitive impaired APOE ε4 non carriers. In these subjects, frontal and parieto-occipital regions were most affected by small vessel disease. Our findings suggest that the APOE ε3 allele is probably linked to the brain vascular pathology.

Brain Atrophy and the Risk of Futile Endovascular Reperfusion in Acute Ischemic Stroke

Background and Purpose- We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion. Methods- We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models. Results- From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002-1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001-1.002], P<0.001) in determining the risk of futile reperfusion. Conclusions- A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.

Stereological Investigation of Regional Brain Volumes after Acute and Chronic Cuprizone-Induced Demyelination.

Brain volume measurement is one of the most frequently used biomarkers to establish neuroprotective effects during pre-clinical multiple sclerosis (MS) studies. Furthermore, whole-brain atrophy estimates in MS correlate more robustly with clinical disability than traditional, lesion-based metrics. However, the underlying mechanisms leading to brain atrophy are poorly understood, partly due to the lack of appropriate animal models to study this aspect of the disease. The purpose of this study was to assess brain volumes and neuro-axonal degeneration after acute and chronic cuprizone-induced demyelination. C57BL/6 male mice were intoxicated with cuprizone for up to 12 weeks. Brain volume, as well as total numbers and densities of neurons, were determined using design-based stereology. After five weeks of cuprizone intoxication, despite severe demyelination, brain volumes were not altered at this time point. After 12 weeks of cuprizone intoxication, a significant volume reduction was found in the corpus callosum and diverse subcortical areas, particularly the internal capsule and the thalamus. Thalamic volume loss was accompanied by glucose hypermetabolism, analyzed by [18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography. This study demonstrates region-specific brain atrophy of different subcortical brain regions after chronic cuprizone-induced demyelination. The chronic cuprizone demyelination model in male mice is, thus, a useful tool to study the underlying mechanisms of subcortical brain atrophy and to investigate the effectiveness of therapeutic interventions.

Facial expressiveness and physiological arousal in frontotemporal dementia: Phenotypic clinical profiles and neural correlates.

Early theories of emotion processing propose an interplay between autonomic function and cognitive appraisal of emotions. Patients with frontotemporal dementia show profound social cognition deficits and atrophy in regions implicated in autonomic emotional responses (insula, amygdala, prefrontal cortex), yet objective measures of facial expressiveness and physiological arousal have been relatively unexplored. We investigated psychophysiological responses (surface facial electromyography (EMG); skin conductance level (SCL)) to emotional stimuli in 25 behavioural-variant frontotemporal dementia (bvFTD) patients, 14 semantic dementia (SD) patients, and 24 healthy older controls, while viewing emotionally positive, neutral, or negative video clips. Voxel-based morphometry was conducted to identify neural correlates of responses. Unlike controls, patients with bvFTD did not show differential facial EMG responses according to emotion condition, whereas SD patients showed increased zygomaticus responses to both positive and neutral videos. Controls showed greater arousal (SCL) when viewing positive and negative videos; however, both bvFTD and SD groups showed no change in SCL across conditions. Regardless of group membership, right insula damage was associated with dampened zygomaticus responses to positive film stimuli. Change in arousal (SCL) was associated with lower integrity of the caudate, amygdala, and temporal pole. Our results demonstrate that while bvFTD patients show an overall dampening of responses, SD patients appear to show incongruous facial emotional expressions. Abnormal responding is related to cortical and subcortical brain atrophy. These results identify potential mechanisms for the abnormal social behaviour in bvFTD and SD and demonstrate that psychophysiological responses are an important mechanism underpinning normal socioemotional functioning.

Cerebral Small Vessel Disease: A Review Focusing on Pathophysiology, Biomarkers, and Machine Learning Strategies

Cerebral small vessel disease (cSVD) has a crucial role in lacunar stroke and brain hemorrhages and is a leading cause of cognitive decline and functional loss in elderly patients. Based on underlying pathophysiology, cSVD can be subdivided into amyloidal and non-amyloidal subtypes. Genetic factors of cSVD play a pivotal role in terms of unraveling molecular mechanism. An important pathophysiological mechanism of cSVD is blood-brain barrier leakage and endothelium dysfunction which gives a clue in identification of the disease through circulating biological markers. Detection of cSVD is routinely carried out by key neuroimaging markers including white matter hyperintensities, lacunes, small subcortical infarcts, perivascular spaces, cerebral microbleeds, and brain atrophy. Application of neural networking, machine learning and deep learning in image processing have increased significantly for correct severity of cSVD. A linkage between cSVD and other neurological disorder, such as Alzheimer’s and Parkinson’s disease and non-cerebral disease, has also been investigated recently. This review draws a broad picture of cSVD, aiming to inculcate new insights into its pathogenesis and biomarkers. It also focuses on the role of deep machine strategies and other dimensions of cSVD by linking it with several cerebral and non-cerebral diseases as well as recent advances in the field to achieve sensitive detection, effective prevention and disease management.

Prediction of white matter lesions and subcortical atrophy for cognitive impairment in patients with ischemic stroke

Objective To investigate the predictive role of cerebral white matter lesions (WML) and subcortical atrophy on cognitive function in patients with acute ischemic stroke (AIS) after 3 months. Methods 233 cases of AIS patients admitted to hospital continuously from September 2016 to March 2018 were enrolled and all of them underwent brain MRI.The degree of WML on FLAIR was evaluated according to the Fazekas grading standard.The linear measurement of subcortical atrophy on T1WI was carried out on the subcortical brain atrophy index, including EVANS ratio (ER), inverse cella media index (iCMI), caudate head index (CHI) and basal cistern index (BCI). Demographic, clinical and imaging data of all patients were also recorded.Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were conducted at 3 months after AIS.The patients were divided into normal cognitive function (NCI) group and post stroke cognitive impairment (PSCI) group according to evaluation results of MMSE and MoCA.Multivariate logistic regression analysis was used to screen the independent risk factors of cognitive impairment. Results Univariate analysis showed that age (t=-4.233, P=0.000), sex (χ2=7.501, P=0.006), education (H=21.188, P=0.000), NHISS score (H=5.791, P=0.016), history of atrial fibrillation (χ2=6.484, P=0.011), TIA (χ2= 9.015, P=0.003), smoking history (χ2=6.943, P=0.008), Fazekas WML score (χ2=27.885, P=0.000), EVANS ratio (H=31.129, P=0.000), inverse cella media index (H=9.434, P=0.002), caudate head index (H=15.148, P=0.000), basal cistern index (t=-1.979, P=0.049) and baseline cognitive function (χ2=136.994, P=0.000) were related to cognitive impairment in patients with AIS after 3 months (P<0.05). Multivariate logistic regression analysis showed that WML score (OR=3.416, P=0.047, 95%CI: 1.017-11.482), EVANS ratio (OR=1.245, P=0.038, 95%CI: 1.012-1.531) and caudate head index (OR=1.187, P=0.040, 95%CI: 1.008-1.397) were risk factors for cognitive impairment in AIS patients after 3 months adjusting for age, education, disease severity and baseline cognitive function. Conclusion WML, EVANS ratio and caudate head index can predict short-term cognitive function in patients with AIS. Key words: White matter lesions; Subcortical atrophy; Acute ischemic stroke; Cognitive impairment

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

Objective: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly understood. Damage within the CNS is driven by the autoimmune response; however, immunopathophysiology of neuropsychiatric (NP) SLE is multifactorial. Immune cell neurotrophin production could be neuroprotective against autoimmunity-driven CNS damage, as has been shown in multiple sclerosis. The aim of this study was to establish whether immune cell neurotrophin production is associated with damage severity in NPSLE. Methods: Selected neurotrophins (BDNF, NGF, NT-3, and NT-4/5) were measured with ELISA within peripheral blood mononuclear cells (PBMCs) isolated from 38 NPSLE patients matched with 39 healthy controls. Subcortical and cortical structure volumes were segmented with the Freesurfer 5.3 pipeline on T1-weighted isotropic images acquired on a 1.5-T MRI scanner. Results: BDNF and NGF levels in PBMCs were reduced in NPSLE compared to the healthy population. The PBMC BDNF level was associated with reduced thalamus, caudate, and putamen volumes. The NGF level correlated with lateral ventricles enlargement and thalamic volume loss. Conclusions: In NPSLE, immune cell BDNF and NGF levels are linked with subcortical atrophy. Higher BDNF levels are associated with higher midsagittal atrophy, which may reflect compensatory mechanisms, upregulating BDNF when neuroprotection is needed. These data require further confirmation.

Human Leukocyte Antigen (HLA) and Gulf War Illness (GWI): HLA-DRB1*13:02 Spares Subcortical Atrophy in Gulf War Veterans

BackgroundGulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990–91 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. We reported previously on the protective role of six Human Leukocyte Antigen (HLA) alleles in GWI (Georgopoulos et al., 2016) and their association with regional brain function (James et al., 2016). More recently, we reported on the presence of subcortical brain atrophy in GWI (Christova et al., 2017) and discussed its possible relation to immune mechanisms. Here we focused on one of the six HLA GWI-protective HLA alleles, DRB1*13:02, which has been found to have a protective role in a broad range of autoimmune diseases (Furukawa et al., 2017), and tested its effects on brain volumes. MethodsSeventy-six Gulf War veterans (55 with GWI and 21 healthy controls) underwent a structural Magnetic Resonance Imaging (sMRI) scan to measure the volumes of 9 subcortical brain regions to assess differences between participants with (N=11) and without (N=65) HLA class II allele DRB1*13:02. FindingsWe found that DRB1*13:02 spared subcortical brain atrophy in Gulf War veterans; overall subcortical volume was 6.6% higher in carriers of DRB1*13:02 (P=0.007). The strongest effect was observed in the volume of cerebellar gray matter which was 9.6% higher (P=0.007) in carriers of DRB1*13:02 than in non-carriers. By contrast, DRB1*13:01 had no effect. InterpretationThese findings document the protective effect of DRB1*13:02 on brain atrophy in Gulf War veterans and are in keeping with recent results documenting sharing of brain mechanisms between GWI and other immune-related diseases (Georgopoulos et al., 2017). We hypothesize that the protective role of DRB1*13:02 is due to its successful elimination of external antigens to which Gulf War veterans were exposed, antigens that otherwise would persist causing low-grade inflammation and possibly leading to autoimmunity. Funding sourceU.S. Department of Defense (W81XWH-15-1-0520), Department of Veterans Affairs, American Legion Brain Sciences Chair, and University of Minnesota.

Subcortical brain atrophy in Gulf War Illness.

Gulf War Illness (GWI) is a multisystem disorder that has affected a substantial number of veterans who served in the 1990-1991 Gulf War. The brain is prominently affected, as manifested by the presence of neurological, cognitive and mood symptoms. Although brain dysfunction in GWI has been well documented (EBioMedicine 12:127-32, 2016), abnormalities in brain structure have been debated. Here we report a substantial (~10%) subcortical brain atrophy in GWI comprising mainly the brainstem, cerebellum and thalamus, and, to a lesser extent, basal ganglia, amygdala and diencephalon. The highest atrophy was observed in the brainstem, followed by left cerebellum and right thalamus, then by right cerebellum and left thalamus. These findings indicate graded atrophy of regions anatomically connected through the brainstem via the crossed superior cerebellar peduncle (left cerebellum→right thalamus, right cerebellum→left thalamus). This distribution of atrophy, together with the observed systematic reduction in volume of other subcortical areas (basal ganglia, amygdala and diencephalon), resemble the distribution of atrophy seen in toxic encephalopathy (Am J Neuroradiol 13:747-760, 1992) caused by a variety of substances, including organic solvents. Given the potential exposure of Gulf War veterans to "a wide range of biological and chemical agents including sand, smoke from oil-well fires, paints, solvents, insecticides, petroleum fuels and their combustion products, organophosphate nerve agents, pyridostigmine bromide, …" (Institute of Medicine National Research Council. Gulf War and Health: Volume 1. Depleted uranium, pyridostigmine bromide, sarin, and vaccines. National Academies Press, Washington DC, 2000), it is reasonable to suppose that such exposures, alone or in combination, could underlie the subcortical atrophy observed.

Frontal Cortical Atrophy as a Predictor of Poststroke Apathy.

The aim of the study was to identify associations between the symptoms of poststroke apathy and sociodemographic, stroke-related (severity of stroke, degree of disability, and performance in activities of daily living), and radiological correlates. We determined the degree of cortical and subcortical brain atrophy, the severity of white matter and basal ganglia lesions on baseline computed tomography (CT) scans, and the localization of acute ischemia on control CT or magnetic resonance imaging scans in subacute stages of stroke. During follow-up examinations, in addition to the assessment of apathy symptoms using the Apathy Scale, we also evaluated symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale. The study included 47 consecutive patients with acute ischemic stroke. Correlates significantly associated with apathy, determined at baseline and during follow-up, were entered into the "predictive" and "associative" multiple regression models, respectively. Frontal cortical atrophy and symptoms of depression were most strongly associated with poststroke apathy symptoms. In order to model an interrelation between both cortical atrophy and white matter lesions and aging, we supplemented 2 additional "predictive" models using interaction variables, whereby we confirmed the role of frontal cortical atrophy as a predictor of poststroke apathy also as a function of the increasing age of patients.

Subcortical volume changes in dementia with Lewy bodies and Alzheimer's disease. A comparison with healthy aging.

Differentiating Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), two of the commonest forms of dementia in older age, remains a diagnostic challenge. To assist with better understanding of the differences between the conditions during life, we assessed limbic and subcortical brain volumes in AD, DLB, and healthy older individuals using magnetic resonance imaging (MRI), with the hypothesis that when compared with controls, subcortical volumes would be reduced to a greater extent in DLB than in AD. One hundred participants (35 healthy controls, 32 AD, and 33 DLB) underwent 3 Tesla T1 weighted MR scanning. Volumes were automatically segmented for each participant using FreeSurfer, then expressed as a percentage of their total intracranial volumes. Group effects were assessed using multivariate analysis of covariance, controlling for age and gender. Significant group effects were apparent among subcortical brain volumes (F 28,162 = 4.8, p < 0.001; Wilk's Λ = 0.30, partial η 2 = 0.45), while univariate tests showed differences in all volumetric measures (p AD, p < 0.008). For similar levels of dementia severity, DLB appears to have greater involvement of subcortical brain atrophy than AD. Further investigation of the subcortical brain structures in DLB is warranted to fully understand their neurobiological role in this disease.

Brain volume and white matter in youth with type 2 diabetes compared to obese and normal weight, non-diabetic peers: A pilot study

Type 2 Diabetes Mellitus (T2DM) and obesity are linked to specific patterns of subcortical brain atrophy and decreased microstructural integrity of white matter. Fifteen adolescents (12–21-years-old, 80% Caucasian, 15% African American, mean BMI=32)–five with T2DM confirmed by oral glucose tolerance test, five matched obese adolescent controls without diabetes (OBCN), and five matched (race, sex) normal-weight controls (NWCN)–underwent Magnetic Resonance Imaging (MRI) for the collection of gray matter volume and white matter integrity. Analyses of Variance (ANOVAs) of the neuroimaging data revealed significant differences in caudate nucleus volume [F(2,12)=7.79, p<0.05] such that the normal-weight group had significantly greater volume than the obese and T2DM groups (NWCN>OBCN, p=0.020; OBCN>T2DM, p=0.042; and NWCN>T2DM; p=0.003) after controlling for participant Body Mass Index (BMI). Similarly, there was a main effect for the volume of the thalamus [F(2,12)=4.39, p<0.05] with greater volume for both the NWC and the OBC groups in comparison to the T2DM group (NWC>T2DM, p=0.020; OBC>T2DM; p=0.040). Finally, an examination of white matter integrity among the three groups illustrated a pattern of white matter integrity reduction between normal-weight participants and both obese controls and T2DM participants, with T2DM demonstrating the greatest deficit in functional anisotropy (FA) volume, but these results were not significant after further controlling for BMI. Results from the current pilot study illuminate a host of brain morphology differences between youth with T2DM, obese youth, and normal-weight controls; future research with a larger sample size is critical.

Isolated, subtle, neurological abnormalities in neurologically and cognitively healthy aging subjects.

The aim of this study is to describe the frequency of isolated, subtle, neurological abnormalities (ISNAs) in a large population of neurologically and cognitively healthy subjects and to compare ISNAs to various types of MRI-detected cerebrovascular lesions and subcortical brain atrophy in different age classes. 907 subjects were selected from a large, prospective hospital-based study. At baseline neurological examination, 17 ISNAs were selected. Primitive reflexes were the most common ISNAs (35.8%), while dysphagia was the most rarely encountered (0.3%). Measures of small vessel disease, i.e., deep and subcortical white matter hyperintensity and lacunar infarcts as well as subcortical atrophy, were variously associated with ISNAs. In the adult group, the ISNAs were associated with hypertriglyceridemia, TIA, and subcortical lacunar infarcts, while in the elderly-old group they were associated with arterial hypertension, subcortical white matter hyperintensity, and subcortical atrophy. An increased risk of ISNAs was associated with lacunae and white matter hyperintensity in the parietal region. This study shows that white matter hyperintensity, lacunae, and subcortical atrophy are associated with an increased risk of ISNAs in cognitively and neurologically healthy aging subjects. ISNAs are not benign signs. Therefore, adults and elderly people presenting with ISNAs should have access to accurate history and diagnosis to prevent progression of small vessel disease and future neurological and cognitive disabilities.