Mean Hippocampal Volume Research Articles

Abstract P420: Alcohol Consumption and Longitudinal Changes in Magnetic Resonance Imaging-defined Brain Abnormalities: The Cardiovascular Health Study

Introduction: Alcohol intake has been related with a complex group of associations with brain structure in cross-sectional analyses, but to our knowledge, its prospective relationship with structural brain abnormalities detected by MRI has never been reported. Hypothesis: We hypothesized that consumers of 1-<7 drinks/week would have slower progression of leukoaraiosis (white matter abnormalities) but more rapid progression of brain atrophy than longer-term abstainers. Methods: As part of the Cardiovascular Health Study, 1 996 adults aged ≥65 years underwent MRI scanning in 1991-94 and again in 1997-99, having excluded 120 participants with a history of cerebrovascular disease before the initial scan. Alcohol consumption was assessed at each annual visit by self-reported intake of wine, beer and liquor. A 10-point white matter grade (WMG) and ventricular grade (VG) were assessed in a standardized and blinded manner in both scans; hippocampal and total brain volumes were also quantified on the second scan. We estimated the associations of alcohol intake in categories (as reported closest to the date of initial scan), with MRI findings at follow-up with multinomial ordered logistic regression (WMG ≤ 3 ref and ≥ 4; VG ≤ 3 ref , =4 and ≥5) using inverse probability weighting to account for attrition. Results: We observed a U-shaped association with WMG, with significantly lower risk among participants consuming 1-<7 drinks/week (OR 0.38; 95% CI 0.17-0.82, table) than long-term abstainers (P quadtrend = 0.01). For VG, the association was inverse (P trend = 0.06), with significantly less progression among drinkers of 1-<7 drinks/week than long-term abstainers (OR 0.62; 95% CI 0.40-0.97). We identified no significant associations of alcohol intake with quantitative mean hippocampal or total brain volumes at the second scan. Conclusions: Compared with long-term abstention, consumption of 1-<7 drinks/week of alcohol was generally associated with less progression of leukoaraiosis and some measures of brain atrophy in older adults.

Normative hippocampal volumetric measurements using magnetic resonance imaging

Background/aimA wide variety of neurological and psychiatric disorders have been shown to be closely related to changes in hippocampal volume (HV). It appears that hippocampal volumetry will be an indispensable part of clinical practice for a number of neuropsychiatric disorders in the near future. The aim of this study was to establish a normative data set for HV according to age and sex in the general population.Materials and methods Hippocampal magnetic resonance imaging scans of 302 healthy volunteers were obtained using a 1.5 T unit with a 20-channel head coil. The hippocampal volumetric assessment was conducted using the volBrain fully automated segmentation algorithm on coronal oblique T1-weighted magnetization prepared rapid gradient-echo (MP-RAGE) images obtained perpendicular to the long axis of the hippocampus. The mean values of HV of groups according to age and sex were calculated. The associations between HV and age and sex were analyzed.ResultsThe mean HV of the study group was found to be 3.81 ± 0.46 cm3. We found that the mean HV of males (3.94 ± 0.49 cm3) was significantly higher than that of females (3.74 ± 0.42 cm3), and the mean right HV (3.86 ± 0.48 cm3) was significantly higher than that of the left HV (3.78 ± 0.49 cm3) (P = 0.001). Among both females and males, there were statistically significant but poor negative correlations between age and volumetric measurements of both the right and the left hippocampi (P < 0.05).ConclusionThe normative hippocampal volumetric data obtained in this study may be beneficial in clinical applications for many neuropsychiatric diseases, especially for mesial temporal sclerosis and cognitive disorders.

Abnormal hippocampal structure and function in juvenile myoclonic epilepsy and unaffected siblings.

Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy syndrome, characterized by a complex polygenetic aetiology. Structural and functional MRI studies demonstrated mesial or lateral frontal cortical derangements and impaired fronto-cortico-subcortical connectivity in patients and their unaffected siblings. The presence of hippocampal abnormalities and associated memory deficits is controversial, and functional MRI studies in juvenile myoclonic epilepsy have not tested hippocampal activation. In this observational study, we implemented multi-modal MRI and neuropsychological data to investigate hippocampal structure and function in 37 patients with juvenile myoclonic epilepsy, 16 unaffected siblings and 20 healthy controls, comparable for age, gender, handedness and hemispheric dominance as assessed with language laterality indices. Automated hippocampal volumetry was complemented by validated qualitative and quantitative morphological criteria to detect hippocampal malrotation, assumed to represent a neurodevelopmental marker. Neuropsychological measures of verbal and visuo-spatial learning and an event-related verbal and visual memory functional MRI paradigm addressed mesiotemporal function. We detected a reduction of mean left hippocampal volume in patients and their siblings compared with controls (P < 0.01). Unilateral or bilateral hippocampal malrotation was identified in 51% of patients and 50% of siblings, against 15% of controls (P < 0.05). For bilateral hippocampi, quantitative markers of verticalization had significantly larger values in patients and siblings compared with controls (P < 0.05). In the patient subgroup, there was no relationship between structural measures and age at disease onset or degree of seizure control. No overt impairment of verbal and visual memory was identified with neuropsychological tests. Functional mapping highlighted atypical patterns of hippocampal activation, pointing to abnormal recruitment during verbal encoding in patients and their siblings [P < 0.05, familywise error (FWE)-corrected]. Subgroup analyses indicated distinct profiles of hypoactivation along the hippocampal long axis in juvenile myoclonic epilepsy patients with and without malrotation; patients with malrotation also exhibited reduced frontal recruitment for verbal memory, and more pronounced left posterior hippocampal involvement for visual memory. Linear models across the entire study cohort indicated significant associations between morphological markers of hippocampal positioning and hippocampal activation for verbal items (all P < 0.05, FWE-corrected). We demonstrate abnormalities of hippocampal volume, shape and positioning in patients with juvenile myoclonic epilepsy and their siblings, which are associated with reorganization of function and imply an underlying neurodevelopmental mechanism with expression during the prenatal stage. Co-segregation of abnormal hippocampal morphology in patients and their siblings is suggestive of a genetic imaging phenotype, independent of disease activity, and can be construed as a novel endophenotype of juvenile myoclonic epilepsy.

Dentate gyrus volume deficit in schizophrenia.

Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined. Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed. This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = -0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = -0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10-8, 95% CI 7.0-14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume. This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.

Post-mortem MRI-based volumetry of the hippocampus in forensic cases of decedents with severe mental illness.

A decrease in the volume of the hippocampus is associated with severe mental illness, especially schizophrenia, and has been studied extensively in the living using magnetic resonance imaging. Autopsy cohorts also represent a valuable data source for imaging studies. However, post-mortem magnetic resonance imaging (PMMRI) is subject to unique challenges, such as the lower core temperature of scanned subjects and the influence of decomposition processes. This study aimed to determine if results from in vivo studies could be replicated on a post-mortem cohort of decedents who suffered from severe mental illness. We included 96 decedents with either schizophrenia (n = 34), depressive disorder (n = 17), or no known psychiatric diagnosis (n = 45) from April 2015 to January 2017. All cases underwent a T2-weighted cerebral MRI less than 24h before autopsy. We used a manual segmentation algorithm to define the hippocampus on coronal images and subsequently estimate the volume of the region. The group with schizophrenia had a statistically significant 9.5% decrease in mean hippocampal volume compared with control subjects, while the group with depression trended towards a reduced volume, but this difference was not statistically significant. Thus we were able to replicate previous results from in vivo studies. PMMRI has unique potential for research in that it can be combined with procedures possible only in the research fields of clinical pathology and forensic science, e.g. histopathological sampling.

Differences in hippocampal subfield volume are seen in phenotypic variants of early onset Alzheimer's disease.

The most common presentation of early onset Alzheimer's disease (EOAD – defined as symptom onset <65 years) is with progressive episodic memory impairment – amnestic or typical Alzheimer's disease (tAD). However, EOAD is notable for its phenotypic heterogeneity, with posterior cortical atrophy (PCA) – characterised by prominent higher-order visual processing deficits and relative sparing of episodic memory – the second most common canonical phenotype. The hippocampus, which comprises a number of interconnected anatomically and functionally distinct subfields, is centrally involved in Alzheimer's disease and is a crucial mediator of episodic memory. The extent to which volumes of individual hippocampal subfields differ between different phenotypes in EOAD is unclear. The aim of this analysis was to investigate the hypothesis that patients with a PCA phenotype will exhibit differences in specific hippocampal subfield volumes compared to tAD. We studied 63 participants with volumetric T1-weighted MRI performed on the same 3T scanner: 39 EOAD patients [27 with tAD and 12 with PCA] and 24 age-matched controls. Volumetric estimates of the following hippocampal subfields for each participant were obtained using Freesurfer version 6.0: CA1, CA2/3, CA4, presubiculum, subiculum, hippocampal tail, parasubiculum, the molecular and granule cell layers of the dentate gryus (GCMLDG), the molecular layer, and the hippocampal amygdala transition area (HATA). Linear regression analyses comparing mean hippocampal subfield volumes between groups, adjusting for age, sex and head size, were performed. Using a Bonferonni-corrected p-value of p < 0.0025, compared to controls, tAD was associated with atrophy in all hippocampal regions, except the parasubiculum. In PCA patients compared to controls, the strongest evidence for volume loss was in the left presubiclum, right subiculum, right GCMLDG, right molecular layer and the right HATA. Compared to PCA, patients with tAD had strong evidence for smaller volumes in left CA1 and left hippocampal tail. In conclusion, these data provide evidence that hippocampal subfield volumes differ in different phenotypes of EOAD.

Efeitos da exposição repetida a diferentes concentrações de sevoflurano sobre o hipocampo de ratos neonatos

Background and objectivesDeveloping brain is more vulnerable to environmental risk than is the developed brain. We evaluated the effects of repeated exposure to different concentrations of sevoflurane on the neonatal mouse hippocampus using stereological methods. MethodsEighteen neonatal male mice were randomly divided into three groups. Group A, inhaled sevoflurane at a concentration of 1.5%; Group B, inhaled sevoflurane at a concentration of 3%; and Group C (control group), inhaled only 100% oxygen. Treatments were applied for 30min a day for 7 consecutive days. The hippocampal volume, dendrite length, number of neurons, and number of glial cells were evaluated in each group using stereological estimations. ResultsWe identified a ∼2% reduction in the volume of the hippocampus in Group A compared to Group C. Mean hippocampal volume was ∼11% smaller in Group B than it was in Group C. However, these differences in hippocampal volume between the groups were not statistically significant (p>0.05 for all). As for the number of neurons, we found significantly fewer neurons in Group A (∼29% less) and Group B (∼43% less) than we did in Group C (p<0.05 for both). The dendrite length was ∼8% shorter in Group A and ∼11% shorter in Group B than it was in Group C. ConclusionsRepeated exposure to sevoflurane, regardless of the concentration, reduced the volume of the neonatal mouse hippocampus, as well as the number of neurons and dendrite length.

Effects of repeated exposure to different concentrations of sevoflurane on the neonatal mouse hippocampus

Background and objectivesDeveloping brain is more vulnerable to environmental risk than is the developed brain. We evaluated the effects of repeated exposure to different concentrations of sevoflurane on the neonatal mouse hippocampus using stereological methods. MethodsEighteen neonatal male mice were randomly divided into three groups. Group A, inhaled sevoflurane at a concentration of 1.5%; Group B, inhaled sevoflurane at a concentration of 3%; and Group C (control group), inhaled only 100% oxygen. Treatments were applied for 30min a day for 7 consecutive days. The hippocampal volume, dendrite length, number of neurons, and number of glial cells were evaluated in each group using stereological estimations. ResultsWe identified a ∼2% reduction in the volume of the hippocampus in Group A compared to Group C. Mean hippocampal volume was ∼11% smaller in Group B than it was in Group C. However, these differences in hippocampal volume between the groups were not statistically significant (p>0.05 for all). As for the number of neurons, we found significantly fewer neurons in Group A (∼29% less) and Group B (∼43% less) than we did in Group C (p<0.05 for both). The dendrite length was ∼8% shorter in Group A and ∼11% shorter in Group B than it was in Group C. ConclusionsRepeated exposure to sevoflurane, regardless of the concentration, reduced the volume of the neonatal mouse hippocampus, as well as the number of neurons and dendrite length.

Vestibular Function and Hippocampal Volume in the Baltimore Longitudinal Study of Aging (BLSA).

This study evaluated whether reduced vestibular function in aging adults is associated with lower hippocampal volume. Cross-sectional study. Baltimore Longitudinal Study of Aging, a long-running longitudinal cohort study of healthy aging. Eligible participants were aged ≥ 60 years and had both vestibular physiological testing and brain magnetic resonance imaging at the same visit. Vestibular function testing consisted of the cervical vestibular-evoked myogenic potential (cVEMP) to assess saccular function, ocular VEMP to assess utricular function, and video head-impulse testing to assess the horizontal semicircular canal vestibulo-ocular reflex. Hippocampal volume calculated using diffeomorphometry. The study sample included 103 participants (range of 35-90 participants in subanalyses) with mean (±SD) age 77.2 years (±8.71). Multivariate linear models including age, intracranial volume, sex, and race showed that 1 μV amplitude increase of cVEMP was associated with an increase of 319.1 mm (p = 0.003) in mean hippocampal volume. We did not observe a significant relationship between ocular VEMP amplitude or vestibulo-ocular reflex gain and mean hippocampal volume. Lower cVEMP amplitude (i.e., reduced saccular function) was significantly associated with lower mean hippocampal volume. This is in line with previous work demonstrating a link between saccular function and spatial cognition. Hippocampal atrophy may be a mechanism by which vestibular loss contributes to impaired spatial cognition in older adults. Future work using longitudinal data will be needed to evaluate the causal nature of the association between vestibular loss and hippocampal atrophy.

DIFFERENTIAL HIPPOCAMPAL SUBFIELD LOSS IN DIFFERENT PHENOTYPES OF YOUNG ONSET ALZHEIMER’S DISEASE

Young onset Alzheimer's disease (YOAD - defined as symptom onset < 65 years) is notable for its degree of phenotypic heterogeneity. Total hippocampal volume is a key biomarker of Alzheimer's disease, and automated methods are now able to provide volumetric estimates of the histologically distinct subfields that contribute to total hippocampal volume. To what extent the volumes of individual hippocampal subfields change in YOAD and how this contributes to phenotypic heterogeneity is unclear. The aim of this analysis is to investigate the extent of hippocampal subfield loss in YOAD and how this relates to disease phenotype. 63 participants with volumetric T1-weighted MRI performed on the same 3T scanner were included in the analysis. This comprised 27 YOAD patients with a typical amnestic presentation; 12 patients with a visual symptom-led posterior cortical atrophy presentation; and 24 age-matched healthy controls. Volumetric estimates of hippocampal subfields for each participant were performed using Freesurfer version 6. This algorithm is based on a computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI and includes: CA1, CA2/3, CA4, fimbria, hippocampal fissure, presubiculum, subiculum, hippocampal tail, parasubiculum, the dentate gyrus, the molecular layer and the hippocampal amygdala transition area. Linear regression analyses comparing mean hippocampal subfield volumes between groups after adjustment for age, gender and total intracranial volume were performed. A threshold of p<0.004 for formal statistical significance was used following Bonferroni correction for comparison across the multiple regions of interest. Compared to healthy controls, amnestic YOAD patients showed strong evidence of widespread volume loss in all hippocampal subfields (p=<0.001), except the parasubiculum. In posterior cortical atrophy patients the strongest evidence for volume loss compared to controls was in: the fimbria (p<0.001), presubiculum (p=0.001), subiculum (p=0.001), dentate gyrus (p=0.001), molecular layer (p=0.001) and the hippocampal amygdala transition area (p=0.002). Comparing YOAD phenotypes, there was evidence of decreased volume in patients with an amnestic presentation compared to a posterior cortical atrophy presentation in CA1 (p=0.004) and the hippocampal tail (p=0.003). These data demonstrate evidence for differential hippocampal subfield loss in patients with YOAD relating to phenotypic presentation . Hippocampal formation subfields. Panel A: Diagram adapted from original drawing by Golgi(Golgi, 1903) depicting the hippocampal formation subfields (NB. does not include hippocampal amygdala transition area and hippocampal tail). Panel B: Example of segmentation of the left hippocampal formation into constituent subfields in the sagittal, axial, and coronal planes (NB. selected slices do not show the relatively smaller hippocampal amygdala transition area and parasubiculum.)

Effects of amyloid pathology and neurodegeneration on cognitive change in cognitively normal adults.

Understanding short-term cognitive decline in relation to Alzheimer's neuroimaging biomarkers in early stages of the development of neuropathology and neurodegeneration will inform participant recruitment and monitoring strategies in clinical trials aimed at prevention of cognitive impairment and dementia. We assessed associations among neuroimaging measures of cerebral amyloid pathology, a hallmark Alzheimer's neuropathology, hippocampal atrophy, and prospective cognition among 171 cognitively normal Baltimore Longitudinal Study of Aging participants (baseline age 56-95 years, 48% female, 562 cognitive assessments, 3.7 years follow-up). We categorized each individual based on dichotomous amyloid pathology (A) and hippocampal neurodegeneration (N) status at baseline: A-N-, A+N-, A-N+, A+N+. We conducted linear mixed effects analyses to assess cross-sectional and longitudinal trends in cognitive test z-scores by amyloid and neurodegeneration group. To investigate the effects of amyloid dose and degree of hippocampal atrophy, we assessed the associations of continuous mean cortical amyloid level and hippocampal volume with cognitive performance among individuals with detectable amyloid pathology at baseline. Individuals with amyloidosis or hippocampal atrophy had steeper longitudinal declines in verbal episodic memory and learning compared to those with neither condition (A+N- versus A-N-: β = - 0.069, P = 0.017; A-N+ versus A-N-: β = - 0.081, P = 0.025). Among individuals with hippocampal atrophy, amyloid positivity was associated with steeper declines in verbal memory (β = - 0.123, P = 0.015), visual memory (β = - 0.121, P = 0.036), language (β = - 0.144, P = 0.0004), and mental status (β = - 0.242, P = 0.002). Similarly, among individuals with amyloidosis, hippocampal atrophy was associated with steeper declines in verbal memory (β = - 0.135, P = 0.004), visual memory (β = - 0.141, P = 0.010), language (β = - 0.108, P = 0.006), and mental status (β = - 0.165, P = 0.022). Presence of both amyloidosis and hippocampal atrophy was associated with greater declines than would be expected by their additive contributions in visual memory (β = - 0.139, P = 0.036), language (β = - 0.132, P = 0.005), and mental status (β = - 0.170, P = 0.049). Neither amyloidosis nor hippocampal atrophy was predictive of declines in executive function, processing speed, or visuospatial ability. Among individuals with amyloidosis, higher baseline amyloid level was associated with lower concurrent visual memory, steeper declines in language, visuospatial ability, and mental status, whereas greater hippocampal atrophy was associated with steeper declines in category fluency. Our results suggest that both amyloid pathology and neurodegeneration have disadvantageous, in part synergistic, effects on prospective cognition. These cognitive effects are detectable early among cognitively normal individuals with amyloidosis, who are in preclinical stages of Alzheimer's disease according to research criteria. Our findings highlight the importance of early intervention to target both amyloidosis and atrophy to preserve cognitive function before further damage occurs.

Abstract 92: Detection of Radiologic and Laboratory Features of Cerebral Amyloid Angiopathy in Patients with Alzheimer’s Disease

Background: Patients with Cerebral Amyloid Angiopathy (CAA) have posterior vascular amyloid deposition and lower Amyloid Beta (Aβ) levels when compared to Alzheimer’s Disease (AD). We hypothesized that similar findings would be observed in AD patients with strictly lobar microbleeds (LMB) and/or cortical superficial siderosis (cSS) attributable to CAA [CAA-AD], when compared to AD with no hemorrhagic lesion [NH-AD]. Methods: We reviewed brain MRIs of patients with AD who had T2*-, FLAIR and 3D T1-weighted MRI as well as Florbetapir PET, CSF Aβ-42 and tau levels, and APOE status within the ADNI database. We compared the demographics, quantitative imaging and lab findings of CAA-AD to NH-AD. Results: The CAA-AD (n=51) and NH-AD (n=85) groups were balanced for age, gender and history of hypertension (all p&gt;0.2). The APOE4 was more frequently present in the CAA-AD group (78% vs 60%, p=0.038), no difference for APOE2 (p=0.41). Patients with CAA-AD had higher WMH volume (0.73 vs 0.49 % intracranial volume [ICV], p=0.035) and higher occipital-to-global Florbetapir ratio (0.98 vs 0.94, p=0.02) but similar mean cortical Florbetapir uptake (1.38 vs 1.36, p=0.57), cortical thickness (2.22 vs 2.20 mm, p=0.38), and hippocampal volume (0.37 vs 0.38 % of ICV, p=0.24) when compared to NH-AD. In a multivariable regression model that included all variables above, higher occipital-to-global Florbetapir ratio (p=0.009) and presence of APOE4 (p=0.002) were associated with CAA-AD, higher WMH (p=0.097) showed a trend. In 117 patients with CSF data, CAA-AD (n=46) had lower Aβ-42 (127 vs 140 pg/ml, p=0.038) but similar tau levels (131 vs 136 pg/ml, p=0.68) when compared to NH-AD. Lower Aβ-42 was associated with CAA-AD (p=0.024) in the relevant multivariate regression model. Conclusions: Over one-third of patients with AD displayed subtle hemorrhagic lesions in a CAA-pattern on MRI. When compared to NH-AD, they have higher occipital Florbetapir uptake suggesting vascular amyloid binding and lower CSF Aβ-42 levels that might be related to sequestering of amyloid in cortical vessel walls. These results support the possibility that advanced CAA commonly accompanies clinically diagnosed AD, contributing to dementia pathogenesis and potentially affecting clinical treatment decisions.

Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved byefficient invivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI before and 1year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40Gy) or low (<10Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α=0.05. Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=-0.24, P=.03). Mean hippocampal volume was significantly reduced 1year after high-dose RT (mean -6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). The hippocampus demonstrates radiation dose-dependent atrophy after treatment for brain tumors. Quantitative MRI is a noninvasive imaging technique capable of measuring radiation effects on intracranial structures. This technique could be investigated as a potential biomarker for development of reliable dose constraints for improved cognitive outcomes.

Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer's disease patients at an early disease stage.

To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer’s disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes.

Analysis of the Metabolic and Structural Brain Changes in Patients With Torture-Related Post-Traumatic Stress Disorder (TR-PTSD) Using ¹⁸F-FDG PET and MRI.

Many people exposed to torture later suffer from torture-related post-traumatic stress disorder (TR-PTSD). The aim of this study was to analyze the morphologic and functional brain changes in patients with TR-PTSD using magnetic resonance imaging (MRI) and positron emission tomography (PET).This study evaluated 19 subjects. Thirteen subcortical brain structures were evaluated using FSL software. On the T1-weighted images, normalized brain volumes were measured using SIENAX software. The study compared the volume of the brain and 13 subcortical structures in 9 patients suffering from TR-PTSD after torture and 10 healthy volunteers (HV). Diffusion-weighted imaging (DWI) was performed in the transverse plane. In addition, the 18F-FDG PET data were evaluated to identify the activity of the elected regions.The mean left hippocampal volume for the TR-PTSD group was significantly lower than in the HV group (post hoc test (Bonferroni) P < 0.001). There was a significant difference between the gray matter volume of the patients with TR-PTSD and the HV group (post hoc test (Bonferroni) P < 0.001). The TR-PTSD group showed low significant expansion of the ventricles in contrast to the HV group (post hoc test (Bonferroni) P < 0.001). Diffusion-weighted imaging revealed significant differences in the right frontal lobe and the left occipital lobe between the TR-PTSD and HV group (post hoc test (Bonferroni) P < 0.001).Moderate hypometabolism was noted in the occipital lobe in 6 of the 9 patients with TR-PTSD, in the temporal lobe in 1 of the 9 patients, and in the caudate nucleus in 5 of the 9 patients. In 2 cases, additional hypometabolism was observed in the posterior cingulate cortex and in the parietal and frontal lobes.The findings from this study show that TR-PTSD might have a deleterious influence on a set of specific brain structures. This study also demonstrated that PET combined with MRI is sensitive in detecting possible metabolic and structural brain changes in TR-PTSD.

The change of hippocampal volume and its relevance with inner ear function in Meniere's disease patients.

To reveal the relationship between the disease progression and the hippocampal volume in Meniere's disease, which may indirectly reflect the degree of patients' chronic exposure to stress. Retrospective review of medical records and brain magnetic resonance image (MRI) of Meniere's disease patients and healthy controls from 2008 to 2013. Age- and sex-matched consecutive 38 definite Meniere's disease patients and 76 healthy controls where brain MRIs, hearing, and vestibular function tests were available. We divided the patients into normal and abnormal groups according to the results functional tests such as pure tone audiometry (PTA), vestibular evoked myogenic potential (VEMP), and bithermal caloric test. Absolute hippocampal volume of Meniere's disease patients was significantly smaller than that of controls (3.33±0.84cm(3) for left side vs. 3.82±0.37cm(3) for right side, p<0.001). Mean left hippocampal volume of patients with abnormal VEMP and bithermal caloric test on lesion side was significantly smaller than that of the patients with the normal test result (all p<0.05). Average hearing thresholds of the patients showed strong correlation with left hippocampal volumes (p-value<0.001). Those with decreased left hippocampal volume were also more likely to experience augmented emotional stress reactivity. Meniere's disease patients had significantly decreased hippocampal volume and the volume was significantly correlated with severity of hearing and vestibular function of affected side. This may represent that Meniere's disease patients are exposed to chronic stress for unpredictable vertigo and hearing fluctuation, which finally cause hippocampus atrophy.

Imaging Correlates of Memory and Concussion History in Retired National Football League Athletes.

To our knowledge, this is the first study to show an association between concussion, cognition, and anatomical structural brain changes across the age spectrum in former National Football League athletes. To assess the relationship of hippocampal volume, memory performance, and the influence of concussion history in retired National Football League athletes with and without mild cognitive impairment (MCI). This retrospective cohort study assessed differences between groups, mean hippocampal volumes, and memory performance by computing age quintiles based on group-specific linear regression models corrected for multiple comparisons for both athletes and control participants. The study was conducted starting in November 2010 and is ongoing at a research center in the northern region of Texas. This current analysis was conducted from October 9, 2013, to August 21, 2014. Participants included 28 retired National Football League athletes, 8 of whom had MCI and a history of concussion, 21 cognitively healthy control participants, and 6 control participants with MCI without concussion. Hippocampal volume, age, California Verbal Learning Test scores, and the number of grade 3 (G3) concussions. In addition, the number of games played was examined as an objective variable pertaining to football history. The mean (SD) age was 58.1 (13) years for the 28 former athletes and 59.0 (12) years for the 27 control participants. Retired athletes with concussion history but without cognitive impairment had normal but significantly lower California Verbal Learning Test scores compared with control participants (mean [SD], 52.5 [8] vs 60.24 [7]; P = .002); those with a concussion history and MCI performed worse (mean [SD], 37 [8.62]) compared with both control participants (P < .001) and athletes without memory impairment (P < .001). Among the athletes, 17 had a G3 concussion and 11 did not. Older retired athletes with at least 1 G3 concussion had significantly smaller bilateral hippocampal volumes compared with control participants at the 40th age percentile (left, P = .04; right, P = .03), 60th percentile (left, P = .009; right, P = .01), and 80th percentile (left, P = .001; right, P = .002) and a smaller right hippocampal volume compared with athletes without a G3 concussion at the 40th percentile (P = .03), 60th percentile (P = .02), and 80th percentile (P = .02). Athletes with a history of G3 concussion were more likely to have MCI (7 of 7) compared with retired athletes without a history of G3 concussion (1 of 5) older than 63 years (P = .01). In addition, the left hippocampal volume in retired athletes with MCI and concussion was significantly smaller compared with control participants with MCI (P = .03). Prior concussion that results in loss of consciousness is a risk factor for increased hippocampal atrophy and the development of MCI. In individuals with MCI, hippocampal volume loss appears greater among those with a history of concussion.

Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder.

Pediatric bipolar disorder (PBD) is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF) is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder). We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

Hippocampal volume and hippocampal angle (a more practical marker) in mild cognitive impairment: A case-control magnetic resonance imaging study.

Background:Mild cognitive impairment (MCI) accompanies brain atrophy in neuroimaging investigations. The aim of this study was to compare MCI patients with the normal population for hippocampal volume (HV) and hippocampal angle (HA), and to assess the correlation between HV and HA.Materials and Methods:In a case-control study on 2014, in Kashani Hospital (Isfahan, Iran), 20 MCI patients were compared with 20 normal controls for HV and HA. Subjects were diagnosed with MCI or normal control, based on neuropsychiatry interview, which was confirmed by neuropsychiatry unit cognitive assessment tool (NUCOG). All magnetic resonance imaging scans were processed using the Free-Surfer software package for HV assessment. The HA was measured on the most rostral slice in which the uncal sulcus could be identified on a coronal plane. The data were analyzed using multiple analysis of co-variance and Pearson correlation.Results:The mean (standard deviation [SD]) score of NUCOG in control and case group were 91.05 (3.01) and 82.42 (3.57), respectively. Comparison of HV and HA scores in two groups, showed that mean (SD) HV and HA were not different between control and case groups, significantly, (P = 0.094 and P = 0.394, respectively). There was a negative correlation between the adjusted HV and the HA in case (r = −0.642, P = 0.004), and control groups (r = −0.654, P = 0.003).Conclusion:HV and HA were not different between MCI patients and normal controls; however, HA is correlated with HV negatively and may be used as an alternative factor because of more feasibility and availability in clinical settings in compared to HV.

Classification of non-demented patients attending a memory clinic using the new diagnostic criteria for Alzheimer's disease with disease-related biomarkers.

New diagnostic criteria for predemential Alzheimer's disease (AD) advocate the use of biomarkers. However, the benefit of using biomarkers has not been clearly demonstrated in clinical practice. To investigate whether a combination of biomarkers may be helpful in classifying a population of non-demented patients attending a Memory Clinic. Sixty non-demented patients were compared with 31 healthy elderly subjects. All subjects underwent a neuropsychological examination, brain 3T magnetic resonance imaging, [F18]-fluorodeoxyglucose and [F18]-flutemetamol positron emission tomography. According to their performance on memory, language, executive, and visuo-spatial domains, the patients were classified as mild cognitive impairment (amnestic, non-amnestic, single, or multiple domain) or subjective cognitive impairment. Patients were then classified according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, using the normalized mean hippocampal volume (Freesurfer), [F18]-FDG PALZAD, and [F18]-flutemetamol standard uptake value ratio (SUVr) (cut-off at the 10th percentile of controls). The standard of truth was the clinical status at study entry (patient versus control). The sensitivity/specificity of the clinical classification was 65/84%. The NIA-AA criteria were applicable in 85% of patients and 87% of controls. For biomarkers the best sensitivity (72%) at a fixed specificity of 84% was achieved by a combination of the three biomarkers. The clinical diagnosis was reconsidered in more than one third of the patients (42%) as a result of including the biomarker results. Application of the new NIA-AA AD diagnostic criteria based on biomarkers in an unselected sample of non-demented patients attending a Memory Clinic was useful in allowing for a better classification of the subjects.