Percentage Of Intracranial Volume Research Articles

Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.

Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk. We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) as a percentage of intracranial volume, a general cognitive composite derived from neuropsychological testing (SD units [SDU]), and the risk of incident dementia. We sought to replicate associations with dementia in the clinic-based ACE csf cohort, which also had YKL-40 measured from the CSF. Meta-analyses of MRI outcomes included 6,558 dementia-free participants, and for analysis of cognition, 6,670. The blood draw preceded MRI/cognitive assessment by up to 10.6 years across cohorts. The mean ages ranged from 50 to 76 years, with 39%-48% male individuals. In random-effects meta-analysis of study estimates, each SDU increase in log-transformed YKL-40 levels was associated with smaller total brain volume (β = -0.33; 95% CI -0.45 to -0.22; p < 0.0001) and poorer cognition (β = -0.04; 95% CI -0.07 to -0.02; p < 0.01), following adjustments for demographic variables. YKL-40 levels did not associate with hippocampal volume or WMHV. In the FHS, each SDU increase in log YKL-40 levels was associated with a 64% increase in incident dementia risk over a median of 5.8 years of follow-up, following adjustments for demographic variables (hazard ratio 1.64; 95% CI 1.25-2.16; p < 0.001). In the ACE csf cohort, plasma and CSF YKL-40 were correlated (r = 0.31), and both were associated with conversion from mild cognitive impairment to dementia, independent of amyloid, tau, and neurodegeneration status. Higher plasma YKL-40 levels were associated with lower brain volume, poorer cognition, and incident dementia. Plasma YKL-40 may be useful for studying the association of inflammation and its treatment on dementia risk.

Validation of QyScore’s® fully automated quantitative image segmentation tools against expert manual gold‐standards

AbstractBackgroundQuantitative imaging provides valuable information for early detection, disease progression and treatment response monitoring. Manual segmentation is the current gold‐standard, but is prohibitively labour‐intensive for large scale use, such as in clinical routine, and suffers from individual variability. Thus, there is a substantial unmet need for validation of automatic segmentation techniques that perform as accurately as this labour‐intensive manual gold‐standard.MethodThe validation cohort consisted of 50 individuals with multiple diagnoses, wide age range (18‐86 yrs), balanced for sex and acquired on multiple scanners for improved generalizability of quantification results (Table 1). Three expert neuroradiologists each manually segmented the caudate, putamen, globus pallidus, thalamus, cerebellum, brainstem, and lateral ventricles on 3DT1 images using itk‐SNAP (http://www.itksnap.org/) software. A consensus expert segmentation was then derived using the STAPLE (Simultaneous Truth and Performance Level Estimation) algorithm (Wakefield et al., (2004)) for each region and compared with the fully automated segmentations produced using QyScore®, a CE‐marked and FDA‐cleared neuroimaging medical device. Performance was investigated using the Dice Similarity Coefficient (DSC) and concordance assessed with plotted linear regression.ResultMean, standard deviation and confidence intervals of the DSC demonstrated a high degree of agreement between the consensus manual gold‐standard and QyScore®’s automated segmentations (Table 2). Importantly, this agreement remained consistent following stratification by field strength, demonstrating generalizability to most clinical imaging centres. For 1.5T scanners the mean DSC was 0.81, 0.89, 0.79, 0.86, 0.94, 0.93 and 0.91 for the caudate, putamen, globus pallidus, thalamus, cerebellum, brainstem, and lateral ventricles respectively. For the 3T scanners, this was equivalent or marginally better at 0.84, 0.89, 0.82, 0.86, 0.94, 0.94, and 0.93 respectively. In addition, strong concordance was demonstrated between the volumes, expressed as a percentage of intracranial volume (%ICV), obtained by the automated medical device QyScore® and the consensus of the manual gold‐standard segmentation (Figure 1: Table 2).ConclusionQyScore® produces fast reliable automated segmentations with comparable accuracy to expert neuroradiologists. These findings support the implementation of QyScore® in clinical trials and in clinical routine to provide quantitative image analysis in support of diagnosis and monitoring of disease progression and treatment response.

Short sleep duration and hypertension: A double hit for the brain

AbstractBackgroundThe mechanisms linking short sleep duration to increased dementia risk remain unclear. Sleep duration has a powerful influence on blood pressure (BP), with short sleep durations increasing hypertension risk. Since high BP is a dementia risk factor, short sleep may increase risk of cognitive impairment via adverse effects on vascular health. We assessed whether the association of sleep duration with cognition and vascular brain injury was moderated by hypertensive status.Method684 dementia‐free participants (mean age 62±9 years; 53.1% female) from the community‐based Framingham Heart Study Offspring and Omni 1 cohort completed assessments of cognition, office BP, and self‐reported habitual sleep duration; 637 also completed brain MRI. Hypertensive status was defined as a combination of systolic BP ≥ 140mmHg and/or diastolic BP ≥90mmHg or use of anti‐hypertensive medication. Outcomes included the Trail Making Test B minus A, Visual Reproductions, Similarities, and white matter hyperintensity volume (WMHV) expressed as a percentage of intracranial volume. Linear regressions were performed between total sleep time and cognitive domains adjusted for demographic factors, APOE e4 positivity, use of sleeping pills, and BMI. An interaction term for hypertensive status was included in regression models.ResultShort sleep durations of ≤5 hours/night occurred in 13% of participants and 35% were hypertensive. There were no direct associations between sleep duration and any of the outcomes. However, there was a significant interaction between sleep duration and hypertensive status when predicting the outcomes of executive function/processing speed (Trail Making) and WMHV. When data were stratified by hypertensive status, shorter sleep duration was associated with poorer executive function/processing speed scores in the hypertensive group (β±SE = 0.04±0.02 per hour increase in sleep duration, p = 0.02), but not in the normotensive group (β±SE = ‐0.01±0.01, p = 0.22). Similarly, shorter sleep duration was associated with higher WMHV burden in the hypertensive group (β±SE = ‐0.13±0.06, per hour decrease in sleep duration, p = 0.03), but not in the normotensive group (β±SE = 0.01±0.04, p = 0.760).ConclusionThe combination of short sleep and hypertension is associated with worse cognitive performance and brain injury. Further work will examine this interaction more completely.

T1 MRI reveals differential hippocampal atrophy in Lewy Body Disorders with and without Alzheimer’s copathology

AbstractBackgroundLewy body disorders (LBD) include Parkinson disease (PD), Parkinson disease dementia (PDD), and dementia with Lewy bodies (DLB). LBD are the second leading cause of neurodegenerative dementia after Alzheimer’s disease (AD). An estimated 50% of LBD patients have coexisting AD pathology (LBD+AD), which correlates with shorter time to dementia and death. Autopsy evidence suggests that verbal memory impairment correlates with the severity of hippocampal tau pathology in LBD. However, it is unknown whether greater hippocampal tau burden in LBD+AD causes neurodegeneration detectable by in vivo structural MRI, and whether hippocampal atrophy explains verbal memory impairment.MethodUsing a case‐control design, we studied 87 patients with clinical diagnoses of LBD (PD, n = 52; PDD, n = 12; DLB, n = 23) with available T1 MRI and AD biomarkers or, and cognitively‐normal controls (n = 131). AD copathology was defined hierarchically by: a) AD “intermediate” or “high” by ABC neuropathologic criteria; 2) positive amyloid PET; and 3) CSF total tau:β‐amyloid1‐42 ratio &gt; 0.3 (autopsy‐validated cutpoint). The Automated Segmentation of Hippocampal Subfields (ASHS) pipeline was applied to subjects’ T1 MRIs. Hippocampal volume (HV) was compared between controls, LBD‐AD, and LBD+AD, and correlated with verbal memory scores. Linear regression was used to test the association of AD copathology (independent variable) and HV (dependent variable), covarying for age, sex, education, and clinical diagnosis.ResultStatistically significant differences (ANOVA p = 0.002) in bilateral HV (expressed as percentage of intracranial volume) were seen between groups (mean 0.456for controls, 0.444±0.045 for LBD‐AD, and 0.416±0.063 for LBD+AD). Tukey’s test showed significant differences between LBD+AD vs controls (p = 0.001) and LBD+AD vs. LBD‐AD (p = 0.047). Linear regression showed statistically significant association of LBD+AD with bilateral HV (p = 0.034). Among all LBD patients, hippocampal volume positively correlated with verbal memory (immediate recall: r2 = 0.24, p = 0.033, delayed recall: r2 = 0.22, p = 0.042, recognition discrimination r2 = 0.58, p&lt;0.001).ConclusionIn patients with LBD, AD copathology is associated with increased hippocampal atrophy as measured by in vivo T1 MRI, which correlates with greater verbal memory deficits. This work supports the that AD copathology impairs cognition in LBD via hippocampal neurodegeneration.

Validation of QyScore’s® fully automated quantitative image segmentation tools against expert manual gold‐standards

AbstractBackgroundQuantitative imaging provides valuable information for early detection, disease progression and treatment response monitoring. Manual segmentation is the current gold‐standard, but is prohibitively labour‐intensive for large scale use, such as in clinical routine, and suffers from individual variability. Thus, there is a substantial unmet need for validation of automatic segmentation techniques that perform as accurately as this labour‐intensive manual gold‐standard.MethodThe validation cohort consisted of 50 individuals with multiple diagnoses, wide age range (18‐86 yrs), balanced for sex and acquired on multiple scanners for improved generalizability of quantification results (Table 1). Three expert neuroradiologists each manually segmented the caudate, putamen, globus pallidus, thalamus, cerebellum, brainstem, and lateral ventricles on 3DT1 images using itk‐SNAP (http://www.itksnap.org/) software. A consensus expert segmentation was then derived using the STAPLE (Simultaneous Truth and Performance Level Estimation) algorithm (Wakefield et al., (2004)) for each region and compared with the fully automated segmentations produced using QyScore®, a CE‐marked and FDA‐cleared neuroimaging medical device. Performance was investigated using the Dice Similarity Coefficient (DSC) and concordance assessed with plotted linear regression.ResultMean, standard deviation and confidence intervals of the DSC demonstrated a high degree of agreement between the consensus manual gold‐standard and QyScore®’s automated segmentations (Table 2). Importantly, this agreement remained consistent following stratification by field strength, demonstrating generalizability to most clinical imaging centres. For 1.5T scanners the mean DSC was 0.81, 0.89, 0.79, 0.86, 0.94, 0.93 and 0.91 for the caudate, putamen, globus pallidus, thalamus, cerebellum, brainstem, and lateral ventricles respectively. For the 3T scanners, this was equivalent or marginally better at 0.84, 0.89, 0.82, 0.86, 0.94, 0.94, and 0.93 respectively. In addition, strong concordance was demonstrated between the volumes, expressed as a percentage of intracranial volume (%ICV), obtained by the automated medical device QyScore® and the consensus of the manual gold‐standard segmentation (Figure 1: Table 2).ConclusionQyScore® produces fast reliable automated segmentations with comparable accuracy to expert neuroradiologists. These findings support the implementation of QyScore® in clinical trials and in clinical routine to provide quantitative image analysis in support of diagnosis and monitoring of disease progression and treatment response.

Longitudinal Changes of White Matter Hyperintensities in Sporadic Small Vessel Disease: A Systematic Review and Meta-analysis.

White matter hyperintensities (WMHs) are frequent imaging features of small vessel disease (SVD) and related to poor clinical outcomes. WMH progression over time is well described, but regression was also noted recently, although the frequency and associated factors are unknown. This systematic review and meta-analysis aims to assess longitudinal intraindividual WMH volume changes in sporadic SVD. We searched EMBASE and MEDLINE for articles up to 28 January 2022 on WMH volume changes using MRI on ≥2 time points in adults with sporadic SVD. We classified populations (healthy/community-dwelling, stroke, cognitive, other vascular risk factors, and depression) based on study characteristics. We performed random-effects meta-analyses with Knapp-Hartung adjustment to determine mean WMH volume change (change in milliliters, percentage of intracranial volume [%ICV], or milliliters per year), 95% CI, and prediction intervals (PIs, limits of increase and decrease) using unadjusted data. Risk of bias assessment tool for nonrandomized studies was used to assess risk of bias. We followed Preferred Reporting in Systematic Review and Meta-Analysis guidelines. Forty-one articles, 12,284 participants, met the inclusion criteria. Thirteen articles had low risk of bias across all domains. Mean WMH volume increased over time by 1.74 mL (95% CI 1.23-2.26; PI -1.24 to 4.73 mL; 27 articles, N = 7,411, mean time interval 2.7 years, SD = 1.65); 0.25 %ICV (95% CI 0.14-0.36; PI -0.06 to 0.56; 6 articles, N = 1,071, mean time interval 3.5 years, SD = 1.54); or 0.58 mL/y (95% CI 0.35-0.81; PI -0.26 to 1.41; 8 articles, N = 3,802). In addition, 13 articles specifically mentioned and/or provided data on WMH regression, which occurred in asymptomatic, stroke, and cognitive disorders related to SVD. Net mean WMH volume increases over time mask wide-ranging change (e.g., mean increase of 1.75 mL ranging from 1.25 mL decrease to 4.75 mL increase), with regression documented explicitly in up to one-third of participants. More knowledge on underlying mechanisms, associated factors, and clinical correlates is needed, as WMH regression could be an important intervention target.

Exercise Capacity and Frailty Are Associated with Cerebral White Matter Hyperintensity in Older Adults with Cardiovascular Disease.

Cerebral white matter hyperintensity (WMH) is highly prevalent among older adults. There is little information about the relationship among WMH extent, frailty status, and exercise capacity in older adults with cardiovascular disease (CVD). We assessed the association of WMH with frailty and exercise capacity in CVD patients.Seventy-eight stable older adults with CVD were evaluated for WMH, the Kihon Checklist (KCL), short physical performance battery score (SPPB), and cardiopulmonary exercise testing. WMH volume was quantified on brain magnetic resonance imaging. Patients were classified into 3 groups (using tertiles of 0.52% and 1.05%) according to WMH as a percentage of intracranial volume (ICV), and their KCL scores and exercise capacities were compared. The 3 WMH/ICV groups were mild (n = 26, 0.26% ± 0.14% of intracranial volume), moderate (n = 26, 0.70% ± 0.15%), and severe (n = 26, 1.75% ± 0.67%). Peak VO2 was 15.2 ± 3.7 mL kg-1 minute-1 (mild group), 12.9 ± 3.5 mL kg-1 min-1 (moderate), and 11.4 ± 2.3 mL kg-1 minute-1 (severe) (mild versus moderate, P = 0.049; mild versus severe, P = 0.001). Multivariate regression analysis showed significant associations of severe WMH/ICV with peak VO2 and SPPB. Cerebral WMH was strongly negatively associated with SPPB and peak VO2. WMH volume may be related to exercise capacity and frailty in stable older adult patients with CVD.

Consistency of associations of systolic and diastolic blood pressure with white matter hyperintensities: A meta-analysis.

BackgroundWhite matter hyperintensities are the commonest manifestation of cerebral small vessel disease, associated with stroke, functional impairment, and cognitive decline. They are commonly preceded by hypertension, but the magnitude and clinical importance of this association is unclear.AimsQuantify the relationship between blood pressure and white matter hyperintensities across studies.MethodsPubMed and EMBASE were searched for studies reporting associations between concurrent or historic blood pressure and white matter hyperintensities. Beta coefficients from linear models were extracted, whether standardized, unstandardized, unadjusted or adjusted for age, sex, and cardiovascular risk factors. Beta-coefficients were combined by fixed and random effects meta-analysis, combining standardized beta-coefficients or unstandardized coefficients measured by consistent methods.ResultsTwenty-five of 3230 papers were eligible, including 53,392 participants. Systolic blood pressure was significantly associated with white matter hyperintensity volume (WMHV) after maximal adjustment (standardized beta 0.096, 95%CI 0.06–0.133, p < 0.001, I2 = 65%), including for concurrent readings (b = 0.106, p < 0.001) or readings five years previously (b = 0.077, p < 0.001), and for younger or older populations (mean age < 65: b = 0.114; >65 b = 0.069). Unstandardized, adjusted associations were similar for raw WMHV, log-transformed WMHV, or WMHV as percentage of intracranial volume. Unadjusted associations with systolic blood pressure (SBP) were greater (standardized beta = 0.273, 0.262–0.284, p < 0.0001). However, while associations with DBP were weaker than SBP (standardized beta = 0.065, p < 0.001), they were minimally affected by adjustment for age.ConclusionsA standard deviation increase in SBP is associated with 10% of a standard deviation increase in WMHV, providing the current best estimate of the potential reduction in progression of white matter hyperintensities expected with good control of blood pressure.

The Indigenous South American Tsimane Exhibit Relatively Modest Decrease in Brain Volume With Age Despite High Systemic Inflammation.

Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40-94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate β^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. β^T was compared to the corresponding regression coefficient estimate β^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis β T = β R was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.

Slow-Wave Sleep and MRI Markers of Brain Aging in a Community-Based Sample.

To test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI. We studied 492 participants (age 58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume, and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE ε4 carrier status, stroke risk factors, sleeping pill use, body mass index, and depression. Less slow-wave sleep was associated with lower cortical brain volume (absolute duration, β [standard error] = 0.20 [0.08], p = 0.015; percentage, 0.16 [0.08], p = 0.044), lower subcortical brain volume (percentage, 0.03 [0.02], p = 0.034), and higher white matter hyperintensities volume (absolute duration, -0.12 [0.05], p = 0.010; percentage, -0.10 [0.04], p = 0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts. Loss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.

Comparison of brain atrophy and cognitive performance in individuals with low and high cardiovascular risk: Data from the Diabetes and Dementia (D2) Study

AbstractBackgroundGrowing evidence suggests that increased cardiovascular risk might accelerate brain atrophy and cognitive decline. The aim of this analysis was to investigate associations between the Framingham Risk Score (FRS), brain volume and cognitive function in individuals with type 2 diabetes (T2DM) participating in the Diabetes‐and‐Dementia (D2) study.MethodNinety cognitively‐normal participants with T2DM completed neuropsychological assessments, health‐and‐lifestyle questionnaires, 24‐hour ambulatory blood pressure monitoring and a 3T‐MRI scan. FreeSurfer (version 6.0) was used to estimate total brain volume (TBV), mean cortical thickness and subcortical volumes, including the thalami and caudate nuclei. TBV was expressed as a percentage of intracranial volume. Averages between left and right volumes were calculated for subcortical structures. The sample was divided into low (n=45) and high (n=45) FRS groups based on the median score (X=39.7). Differences in volumes were compared between groups. Four cognitive domains, including visuospatial skills, verbal memory, language, and executive functions &amp; speed of processing information, were derived using a factor analysis. These domains were used to compare cognitive performance between individuals with low and high FRS.ResultParticipants in the high FRS group were significantly older and had a lower percentage of women: age (F (1, 89)=26.6; p&lt;0.000); sex (x2=10.07, p=0.01). The high FRS group, after correcting for age and sex, had significantly smaller TBV (F (1, 86)=60.6; p=0.023) and reduced cortical thickness (F (1, 82)=9.93; p=0.002). No difference was found in other subcortical structures. Multivariate analysis revealed a statistically significant difference in cognition between individuals with low and high FRS (F (1, 85)=4.46, p=0.003). Univariate analyses showed statistically significant differences in executive function &amp; processing speed (F (1, 81) = 5.69; p=0.019), with the low FRS group outperforming the high FRS group.ConclusionHigh cardiovascular risk in T2DM is associated with accelerated structural brain aging, manifesting as cerebral atrophy and poorer cognitive function, particularly in processing speed and executive function.

Cognitive and imaging impacts of left ventricular hypertrophy in people with type 2 diabetes

AbstractBackgroundOlder adults with type 2 diabetes mellitus (T2DM) are at an increased risk of cognitive decline and dementia. Left ventricular hypertrophy (LVH) is prevalent in T2DM and is independently associated with cognitive decline. We conducted a study to establish whether T2DM patients with LVH have increased rates of brain atrophy and cognitive impairment.MethodsThirty‐seven cognitively healthy adults (50 years and older) with T2DM were divided into those with (n=13) and without (n=24) LVH. All participants completed neuropsychological assessments, health‐and‐lifestyle questionnaires, 24‐hour ambulatory blood pressure monitoring, an echocardiogram and a 3T‐MRI scan. FreeSurfer (version 6.0) was used to estimate total brain volume (TBV), mean cortical thickness and subcortical volumes, including the thalami and caudate nuclei. TBV was expressed as a percentage of intracranial volume. Averages between left and right volumes were calculated for subcortical structures. Left ventricular mass was indexed to height2.7 using the American Society of Echocardiography criteria. LVH was defined as &gt;49g/m2.7 for males and &gt;45g/m2.7 for females. Three cognitive domains (visuospatial skills, verbal memory and executive functions) were derived through factor analysis. These variables were used to compare cognitive performance between individuals with and without LVH.ResultsThere was a higher percentage of women (x2=11.01, df=1, p&lt;0.01) in the LVH group. No differences in cortical thickness and TBV were found between groups. The LVH group showed significantly lower volume in the cerebellar cortex (F(1, 32)=5.25 p=0.029) and in the amygdala (F(1, 32)=6.24 p=0.018) after correcting for sex, age, blood pressure and BMI when compared to the no LVH group. Significant differences were found in the visuospatial skills factor (F(1, 43)=4.09; p = 0.049), with the LVH group performing worse than the no LVH group.ConclusionsThe presence of LVH in individuals with T2DM was associated with atrophy in the cerebellar cortex and in the amygdala, as well as with poorer visuospatial function.

Perivascular spaces in the centrum semiovale at the beginning of the 8th decade of life: effect on cognition and associations with mineral deposition

Brain iron deposits (IDs) are indicative of microvessel dysfunction which may predispose to small vessel disease (SVD) brain damage and worsen cognition later in life. Visible perivascular spaces in the centrum semiovale (CSO-PVS) are SVD features linked with microvessel dysfunction. We examined possible associations of CSO-PVS volume and count with brain IDs and cognitive abilities in 700 community-dwelling individuals from the Lothian Birth Cohort 1936 who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years. Brain IDs were assessed automatically followed by manual editing. PVS were automatically assessed in the centrum semiovale and deep corona radiata supraventricular. General factors of overall cognitive function (g), processing speed (g-speed) and memory (g-memory) were used in the analyses. Median (IQR) volumes of IDs and CSO-PVS expressed as a percentage of intracranial volume were 0.0021 (0.011) and 0.22 (0.13)% respectively. Median count of CSO-PVS was 410 (IQR = 201). Total volumes of CSO-PVS and ID, adjusted for head size, were correlated (Spearman ρ = 0.13, p < 0.001). CSO-PVS volume, despite being correlated with all three cognitive measures, was only associated with g-memory (B = -114.5, SE = 48.35, p = 0.018) in general linear models, adjusting for age, sex, vascular risk factors, childhood intelligence and white matter hyperintensity volume. The interaction of CSO-PVS count with diabetes (B = -0.0019, SE = 0.00093, p = 0.041) and volume with age (B = 1.57, SE = 0.67, p = 0.019) were also associated with g-memory. Linear regression models did not replicate these associations. Therefore, it does not seem that CSO-PVS burden is directly associated with general cognitive ability in older age.

The long-term effect of perinatal asphyxia on hippocampal volumes.

Hypoxic-ischemic encephalopathy (HIE) in term-born infants can lead to memory problems. The hippocampus is important for long-term episodic memory. The primary aim was to investigate the effect of HIE on hippocampal volumes in 9- to 10-year-old children. The secondary aim was to investigate the association between hippocampal volumes and previously found impaired memory and cognitive functions in the current cohort. In total 26 children with mild HIE, 26 with moderate HIE, and 37 controls were included. The intelligence quotient (IQ) and memory were tested. A 3D-volumetric MRI was obtained. Brain segmentation was performed for hippocampal volumes and intracranial volume. The differences in hippocampal volumes, memory, and IQ between the groups were determined. Multivariable linear regression analyses were performed, including hippocampal volume as a percentage of intracranial volume as a dependent variable. Smaller hippocampal volumes were found in moderate HIE (p < 0.001), with a trend toward smaller volumes in mild HIE, compared to controls. In multivariable linear regression analysis, hippocampal volume as a percentage of intracranial volume was significantly associated with long-term visuospatial memory. Children with moderate HIE had smaller hippocampal volumes than controls, with a trend toward smaller volumes following mild HIE. Reduced hippocampal volumes were associated with poorer long-term visuospatial memory.

Abstract WP344: Basal Ganglia Atrophy in Cerebral Amyloid Angiopathy

Background/Purpose: Cerebral Amyloid Angiopathy (CAA) is associated with cortical and white matter atrophy. We hypothesized that atrophy in CAA extended into the subcortical gray matter as well and might explain previously observed alterations in subcortical gray matter diffusion-tensor properties. Methods: We compared multimodal MRIs from 80 prospectively enrolled non-demented patients with probable CAA, to two other cohorts: 80 Healthy Controls (HC) and 80 patients with Alzheimer’s Disease (AD) from the AD Neuroimaging Initiative. Validated FreeSurfer algorithms were used to calculate Gray Matter (GMV) and Basal Ganglia Volumes (BGV), expressed as percentage of intracranial volume (ICV). High-resolution diffusion scans were used to calculate the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) within the basal ganglia. A visual basal ganglia atrophy scale was also developed to compare atrophy between 93 patients with CAA-related intracerebral hemorrhage (CAA-ICH) and 93 age-matched patients diagnosed with Hypertensive Arteriopathy and ICH (HTN-ICH). Results: CAA patients (mean age: 70.3 ± 8.5) were age-matched to HC (71.8 ± 3.7) and AD patients (70.4 ± 6.8). Patients with CAA had significantly lower BGV (1.16% ± 0.14) when compared to both HC (1.30% ± 0.13, p&lt;0.0001) and AD (1.23% ± 0.12, p=0.003). Within the CAA cohort, there was a positive association between BGV and GMV (r=0.45, p&lt;0.0001) and negative association between BGV and FA (r=-0.36, p=0.001). All associations remained independent after correcting for age, sex, and presence of hypertension. For the clinical ICH cohorts, patients diagnosed with CAA-ICH displayed significantly lower visually rated BGV when compared to similar aged patients with HTN-ICH (mean age: 68.5 for both groups, basal ganglia atrophy scale: 7.31 ± 1.03 vs 8.24 ± 1.14, p&lt;0.0001). Conclusions: Patients with CAA displayed substantial atrophy in the basal ganglia when compared to HC, AD, and HTN-ICH patients. Within the CAA cohort, greater basal ganglia atrophy was independently correlated with greater cortical atrophy and previously observed increases in basal ganglia anisotropy. The mechanisms for and clinical manifestations of CAA-related basal ganglia atrophy remain to be determined.

Abstract TP413: Longitudinal Structural Brain Alterations in Cerebral Amyloid Angiopathy

Background/Purpose: Cross-sectional studies show associations between cerebral amyloid angiopathy (CAA) and cortical as well as white matter atrophy. We hypothesized that CAA patients also have hastened gray and white matter atrophy in longitudinal follow up. Methods: We compared multimodal MRIs from 49 prospectively enrolled non-demented patients with probable CAA (per Boston criteria) scanned at two different time points, to two other longitudinal cohorts: 49 Healthy Controls (HC) and 49 patients with Alzheimer’s Disease (AD) from the AD Neuroimaging Initiative. Validated FreeSurfer algorithms were used to calculate Gray Matter (GMV) and White Matter Volumes (WMV), expressed as percentage of intracranial volume (ICV). Cognitive assessments were done for 34 CAA patients during their baseline and follow up visits, and z scores for executive function, processing speed and memory were calculated. Multivariable models were adjusted for age, sex, presence of hypertension, and baseline variable of interest. Results: Patients with CAA were of similar age (baseline mean age: 71.1) to HC (72.8, p=0.183) but younger than patients with AD (77.3, p&lt;0.001). In all cohorts, the follow up scans were performed 1.1 years after the initial MRIs. The GMV percent decrease was significantly larger in CAA than HC (1.21%, p=0.030), but significantly worse in AD than CAA (1.52%, p=0.029). The WMV percent decrease was significantly higher in patients with CAA when compared to both HC (1.82%, p=0.006) and patients with AD (1.69%, p=0.016). All of these associations remained significant in multivariable models. The WMV percent decrease within the CAA cohort correlated strongly with the longitudinal percent decrease in executive cognitive scores both in univariable (r=0.58, p=0.0003) and multivariable regression models (p=0.0006). Conclusions: Patients with CAA have worse gray matter atrophy than HC as well as worse white matter atrophy than both HC and AD longitudinally, results in line with previous cross-sectional work. The rates of atrophy in CAA also correlated strongly with measures of worsening cognitive function. Our findings support the projected cause-effect relationship between CAA and global brain atrophy leading to cognitive impairment.

Coupled changes in hippocampal structure and cognitive ability in later life.

IntroductionThe hippocampus plays an important role in cognitive abilities which often decline with advancing age.MethodsIn a longitudinal study of community‐dwelling adults, we investigated whether there were coupled changes in hippocampal structure and verbal memory, working memory, and processing speed between the ages of 73 (N = 655) and 76 years (N = 469). Hippocampal structure was indexed by hippocampal volume, hippocampal volume as a percentage of intracranial volume (H_ICV), fractional anisotropy (FA), mean diffusivity (MD), and longitudinal relaxation time (T1).ResultsMean levels of hippocampal volume, H_ICV, FA, T1, and all three cognitive abilities domains decreased, whereas MD increased, from age 73 to 76. At baseline, higher hippocampal volume was associated with better working memory and verbal memory, but none of these correlations survived correction for multiple comparisons. Higher FA, lower MD, and lower T1 at baseline were associated with better cognitive abilities in all three domains; only the correlation between baseline hippocampal MD and T1, and change in the three cognitive domains, survived correction for multiple comparisons. Individuals with higher hippocampal MD at age 73 experienced a greater decline in all three cognitive abilities between ages 73 and 76. However, no significant associations with changes in cognitive abilities were found with hippocampal volume, FA, and T1 measures at baseline. Similarly, no significant associations were found between cognitive abilities at age 73 and changes in the hippocampal MRI biomarkers between ages 73 and 76.ConclusionOur results provide evidence to better understand how the hippocampus ages in healthy adults in relation to the cognitive domains in which it is involved, suggesting that better hippocampal MD at age 73 predicts less relative decline in three important cognitive domains across the next 3 years. It can potentially assist in diagnosing early stages of aging‐related neuropathologies, because in some cases, accelerated decline could predict pathologies.

Comparision between Brain Atrophy and Subdural Volume to Predict Chronic Subdural Hematoma: Volumetric CT Imaging Analysis.

ObjectiveBrain atrophy and subdural hygroma were well known factors that enlarge the subdural space, which induced formation of chronic subdural hematoma (CSDH). Thus, we identified the subdural volume that could be used to predict the rate of future CSDH after head trauma using a computed tomography (CT) volumetric analysis.MethodsA single institution case-control study was conducted involving 1,186 patients who visited our hospital after head trauma from January 1, 2010 to December 31, 2014. Fifty-one patients with delayed CSDH were identified, and 50 patients with age and sex matched for control. Intracranial volume (ICV), the brain parenchyme, and the subdural space were segmented using CT image-based software. To adjust for variations in head size, volume ratios were assessed as a percentage of ICV [brain volume index (BVI), subdural volume index (SVI)]. The maximum depth of the subdural space on both sides was used to estimate the SVI.ResultsBefore adjusting for cranium size, brain volume tended to be smaller, and subdural space volume was significantly larger in the CSDH group (p=0.138, p=0.021, respectively). The BVI and SVI were significantly different (p=0.003, p=0.001, respectively). SVI [area under the curve (AUC), 77.3%; p=0.008] was a more reliable technique for predicting CSDH than BVI (AUC, 68.1%; p=0.001). Bilateral subdural depth (sum of subdural depth on both sides) increased linearly with SVI (p<0.0001).ConclusionSubdural space volume was significantly larger in CSDH groups. SVI was a more reliable technique for predicting CSDH. Bilateral subdural depth was useful to measure SVI.

Association of homocysteine with ventricular dilatation and brain atrophy in Parkinson's disease

Parkinson's disease (PD) patients are treated with levodopa (L-dopa) to help stabilize their impaired motor abilities; however, L-dopa leads to increased homocysteine (Hcy) levels, which may have a deleterious effect on brain structure and function. The purpose of this study was to examine the impact of increased Hcy concentration on global brain atrophy as determined by magnetic resonance imaging in PD patients and controls. The effect of high Hcy level on ventricular dilatation (percentage of intracranial volume [%ICV]) and total tissue volume (%ICV) was examined at baseline and longitudinally at 36 months. Age, sex, education, and L-dopa duration (in PD patients) were included as covariates. Elevated Hcy levels correlated positively with ventricular dilatation (%ICV) in the whole sample (P = 0.004) and in the PD group (P = 0.008). At baseline, adults with a high Hcy level (>14 μmol/L) had higher ventricular volume (%ICV) than adults with a low Hcy level (≤ 14 μmol/L) in the whole sample (P = 0.006) and in the PD group (P = 0.03), which persisted over 36 months in both the whole sample (P = 0.004) and the PD group (P = 0.03). PD patients with high Hcy concentrations had a greater rate of ventricular enlargement (%ICV) over time compared with those with low Hcy concentration (P = 0.02). Elevated Hcy concentration was associated with increased ventricular dilatation (%ICV) in PD patients. A larger sample with a broader age range and longer follow-up is needed to establish the consequences of high Hcy level, including interactions with genetic and environmental risk factors, in PD.

Diabetes mellitus and progression of vascular brain lesions and brain atrophy in patients with symptomatic atherosclerotic disease. The SMART-MR study

AimDiabetes mellitus (DM) is associated with brain atrophy and vascular brain lesions. Cardiovascular disease is a key determinant in this association. We assessed whether DM increased the rate of progression of brain atrophy, vascular brain lesions, and cognitive decline in patients with symptomatic atherosclerotic disease. MethodsIn 663 patients (58±10years) from the SMART-MR study (n=89 with DM), 1.5T MRI and neuropsychological examination were performed at baseline and after 3.9±0.4years follow-up. ResultsRepeated measures ANCOVA (adjusted for age, sex, and vascular risk factors) showed that patients with DM had smaller total brain volume (mean differences as percentage of intracranial volume (ICV) [95% CI]: −1.36% [−1.81; −0.91]), smaller gray matter volume (−1.23% [−1.85; −0.61]), larger ventricular volume (0.32% [0.14; 0.49]), and larger white matter lesion volume (0.31% [0.09; 0.53]) than patients without DM. Patients with DM had accelerated increase in ventricular volume over time compared with patients without DM (mean differences ventricular volume as percentage of ICV: 0.32% [0.25; 0.39] vs. 0.17% [0.15; 0.19]; p-interaction DM×time<0.01). Poisson regression showed that patients with DM had an increased risk for incident brain infarcts (relative risk [95% CI]: 1.62 [1.04; 2.53]). Patients with and without DM had similar performance on cognition. ConclusionsDM on top of existing symptomatic atherosclerotic disease is associated with increased brain atrophy and vascular brain lesion load that proceed at a slightly higher rate than in patients without DM.