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The human hippocampus is difficult to image given its small size, location, shape, and complex internal architecture. Structural magnetic resonance imaging (MRI) has shown age-related hippocampal volume changes that vary along the anterior-posterior axis. Diffusion tensor imaging (DTI) provides complementary measures related to microstructure, but there are few hippocampus DTI studies investigating change with age in healthy participants, and all have been limited by low spatial resolution. The current study uses high resolution 1 mm isotropic DTI of 153 healthy volunteers aged 5-74 years to investigate diffusion and volume trajectories of the hippocampus (whole, head, body, and tail) and correlations with memory. Hippocampal volume showed age-related changes that differed between head (peaking at midlife), body (no changes), and tail (decreasing across the age span). Fractional anisotropy (FA) and mean, axial, and radial diffusivities (MD, AD, RD) yielded peaks or minima, respectively, at ~30-35 years in all three subregions of the hippocampus. Greater magnitude changes were observed during development than in aging. Age trajectories for both volume and DTI were similar between males and females. Correlations between tests of memory and FA and/or volume were significant in younger subjects (5-17 years), but not in 18-49 year olds or 50-74 year olds. MD was significantly correlated with memory performance in 18-49 year olds, but not in other age groups. Given the diffusion-weighted image contrast and resolution, head digitations could be examined revealing that the majority of subjects had 3-4 (48%) or 2 (32%) bilaterally with no effect of age. One millimeter isotropic DTI yielded high quality diffusion-weighted maps of the human hippocampus that showed regionally specific age effects and cognitive correlations along the anterior-posterior axis from 5 to 74 years.

Depressive symptoms are more prevalent in persons with HIV (PWH) than HIV‐uninfected individuals. In HIV‐uninfected individuals, depression has been associated with atrophy in the hippocampus and other brain regions. In the present study, we investigated the impact of depression on brain structure in PWH. One hundred PWH participated in a cross‐sectional study (56.6 ± 6.4 yrs, range 41–70 yrs, 24 females, 63 African Americans). The Beck's Depression Inventory‐II (BDI‐II) was used to assess depressive symptoms. Structural MRI images were collected. Both the voxel‐based morphometry (VBM) technique and a region of interest (ROI) based approach were used to examine the relationship between hippocampal gray matter volume (GMv) and depressive symptoms. The impact of HIV CD4 nadir and antidepressants was also investigated. Both VBM and ROI approaches revealed that higher BDI‐II scores (implicating more severe depressive symptoms) were associated with loss of hippocampal GMv, especially in the right hippocampus and the right entorhinal cortex. Low CD4 nadir predicted additional hippocampal volume loss independent of depressive symptoms. Taking antidepressants did not have a detectable effect on hippocampal volume. In summary, having more depressive symptoms is associated with smaller hippocampal volume in PWH, and a history of severe immunosuppression (i.e., low CD4 nadir) correlates with additional hippocampal volume reduction. However, the impact of depression on hippocampal volume may be independent of HIV‐disease severity such as low CD4 nadir., In people with HIV infection, having more depressive symptoms is associated with smaller hippocampal volume. A history of severe immunosuppression (i.e., low CD4 nadir) correlates with additional hippocampal volume reduction. However, the impact of depression on hippocampal volume may be independent of HIV‐disease severity such as low CD4 nadir.

Early childhood is characterized by vast changes in behaviors supported by the hippocampus and an increased susceptibility of the hippocampus to environmental influences. Thus, it is an important time to investigate the development of the hippocampus. Existing research suggests subregions of the hippocampus (i.e., head, body, tail) have dissociable functions and that the relations between subregions and cognitive abilities vary across development. However, longitudinal research examining age-related changes in subregions in humans, particularly during early childhood (i.e., 4–6 years), is limited. Using a large sample of 184 healthy 4- to 8-year-old children, the present study is the first to characterize developmental changes in hippocampal subregion volume from early- to mid-childhood. Results reveal differential developmental trajectories in hippocampal head, body, and tail during this period. Specifically, head volume showed a quadratic pattern of change, and both body and tail showed linear increases, resulting in a pattern of cubic change for total hippocampal volume. Further, main effects of sex on hippocampal volume (males > females) and hemispheric differences in developmental trajectories were observed. These findings provide an improved understanding of the development of the hippocampus and have important implications for research investigating a range of cognitive abilities and behaviors.

Objective Several studies have found an increase in hippocampal volume following electroconvulsive therapy (ECT), but the effect on cortical thickness has been less investigated. We aimed to examine the effects of ECT on cortical thickness and their associations with clinical outcome. Method Using 3 Tesla MRI scanner, we obtained T1-weighted brain images of 18 severely depressed patients at three time points: before, right after and 6 months after a series of ECT. The thickness of 68 cortical regions was extracted using Free Surfer, and Linear Mixed Model was used to analyze the longitudinal changes. Results We found significant increases in cortical thickness of 26 regions right after a series of ECT, mainly within the frontal, temporal and insular cortex. The thickness returned to the baseline values at 6-month follow-up. We detected no significant decreases in cortical thickness. The increase in the thickness of the right lateral orbitofrontal cortex was associated with a greater antidepressant effect, r = 0.75, P = 0.0005. None of the cortical regions showed any associations with cognitive side effects. Conclusion The increases in cortical thickness induced by ECT are transient. Further multimodal MRI studies should examine the neural correlates of these increases and their relationship with the antidepressant effect.

Background and purpose This study evaluates the contribution of an automated amygdalar fluid-attenuated inversion recovery (FLAIR) signal analysis for the lateralization of mesial temporal lobe epilepsy (mTLE). Methods Sixty-nine patients (27 M, 42 F) who had undergone surgery and achieved an Engel class Ia postoperative outcome were identified as a pure cohort of mTLE cases. Forty-six nonepileptic subjects comprised the control group. The amygdala was segmented in T1-weighted images using an atlas-based segmentation. The right/left ratios of amygdalar FLAIR mean and standard deviation were calculated for each subject. A linear classifier (ie, discriminator line) was designed for lateralization using the FLAIR features and a boundary domain, within which lateralization was assumed to be less definitive, was established using the same features from control subjects. Hippocampal FLAIR and volume analysis was performed for comparison. Results With the boundary domain in place, lateralization accuracy was found to be 70% with hippocampal FLAIR and 67% with hippocampal volume. Taking amygdalar analysis into account, 22% of cases that were found to have uncertain lateralization by hippocampal FLAIR analysis were confidently lateralized by amygdalar FLAIR. No misclassified case was found outside the amygdalar FLAIR boundary domain. Conclusions Amygdalar FLAIR analysis provides an additional metric by which to establish mTLE in those cases where hippocampal FLAIR and volume analysis have failed to provide lateralizing information.

OBJECTIVES: MRI has become an indispensable tool for brain volumetric studies, with the hippocampus an important region of interest. Automation of the MRI segmentation process has helped advance the field by facilitating the volumetric analysis of larger cohorts and more studies. FreeSurfer has emerged as the de facto standard tool for these analyses, but studies validating its output are all based on older versions. To characterize FreeSurfer’s validity, we compare several versions of FreeSurfer software with traditional hand-tracing. EXPERIMENTAL DESIGN: Using MRI images of 262 males and 402 females aged 38 to 84, we directly compare estimates of hippocampal volume from multiple versions of FreeSurfer, its hippocampal subfield routines, and our manual tracing protocol. We then use those estimates to assess asymmetry and atrophy, comparing performance of different estimators with each other and with brain atrophy measures. PRINCIPAL OBSERVATIONS: FreeSurfer consistently reports larger volumes than manual tracing. This difference is smaller in larger hippocampi or older people, with these biases weaker in version 6.0.0 than prior versions. All methods tested agree qualitatively on rightward asymmetry and increasing atrophy in older people. CONCLUSIONS: FreeSurfer saves time and money, and approximates the same atrophy measures as manual tracing, but it introduces biases that could require statistical adjustments in some studies.

Introduction Apolipoproteins of demonstrated importance to brain cholesterol and s-amyloid metabolism may serve as novel risk markers for Alzheimer's pathology. Methods We measured apolipoproteins (apoE, apoJ, apoA-I, and apoC-III and their uniquely defined subspecies) by enzyme-linked immunosorbent assay in plasma collected in 2000 and 2008 from 176 dementia-free participants of the Ginkgo Evaluation of Memory Study and related these to s-amyloid on positron emission tomography scans, hippocampal volume, and white matter lesion volume in 2009. Results Higher apoE was associated with lower s-amyloid deposition. Despite apoA-I being unrelated to hippocampal volume, subspecies of apoA-I containing or lacking apoJ or apoC-III showed opposite associations with hippocampal volume. Higher apoJ and apoE lacking apoJ were associated with higher hippocampal volume and higher white matter lesion volume, respectively. Associations were similar in participants without cognitive impairment or APOE e4 noncarrier and when analyzing apolipoproteins in 2000–2002. Discussion Apolipoproteins may be important minimally invasive biomarkers indicative of Alzheimer's pathology.

Dual-process theories posit that two separate processes are involved in recognition, namely recollection and familiarity. Studies investigating the neuroanatomical substrates of these two processes have frequently revealed that, while recollection is functionally linked with the hippocampus, familiarity appears to be associated with perirhinal and/or entorhinal cortices integrity. Interestingly these regions are known to be sensitive to normal and neuropathological aging processes. The objective of this study was to examine the effects of aging on recollection and familiarity performance, as well as to investigate associations with the rate of false alarms. In older individuals, we further aimed to explore relationships between these recognition variables and structural integrity of the hippocampus and the entorhinal and perirhinal cortices. Younger (N = 56) and older (N = 59) adults were tested on a computerized recollection and familiarity task. In a separate session, older adults (N = 56) underwent a structural MRI. Hippocampal, entorhinal and perihinal cortices volumes were automatically segmented and then manually corrected to ensure validity of the volumetric assessment. Regional volumes were normalized for total intracranial volume. While the overall recognition performance did not significantly differ across groups, our results reveal a decrease in recollection, together with an increase in familiarity in older adults. The increase reliance on familiarity was significantly and positively associated with the rate of false alarms. In the older adult sample, significant positive associations were found between recollection estimates and normalized hippocampal volumes. The normalized total hippocampal volume accounted for 25% of the variance in recollection performance. No correlation was found between any recognition variables and perirhinal or entorhinal cortices volumes. Overall, our results suggest that the age-related impairment in recollection is linked with reduced hippocampal structural integrity.

Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.

Introduction Animal studies have shown that male but not female offspring exposed to maternal obesity have abnormal hippocampal development. Similar sex differences were observed in animal models of developmental programming by prenatal stress or maternal diabetes. We aimed to translate this work into humans by examining sex‐specific effects of exposure to maternal obesity on hippocampal volume in children. Methods Eighty‐eight children (37 boys and 51 girls) aged 7–11 years completed the study. Maternal prepregnancy body mass index (BMI) was obtained from electronic medical records. A high‐resolution anatomical scan was performed using a 3‐Tesla magnetic resonance imaging (MRI) scanner. Total hippocampal volume and hippocampal subfield volumes were analyzed using FreeSurfer 6.0. Linear regression was used to investigate sex differences in relationships between maternal prepregnancy BMI and child hippocampal volume. Results Maternal prepregnancy BMI ranged from 19.0 to 50.4 kg/m2. We observed a significant interaction between maternal prepregnancy BMI and sex on total hippocampal volume (p, We provide novel evidence in support of findings in rodent models suggesting that in utero exposure to maternal obesity differentially impacts the hippocampus of boys compared to girls during childhood. This is the first study in humans to show changes to the hippocampus in association with in utero exposure to maternal obesity.

Aim We determined if differences in renal function, even within normal levels, influenced hippocampal volume (HCV) and cognition. Methods Cognitively normal (CN) and mild cognitive impairment (MCI) subjects with eGFR ≥ 60 ml/min/1.73m2 were selected from the ADNI database (N = 1,269) and divided into three groups (eGFR 60-75, 75-90 and ≥90). Associations between eGFR, HCV and cognition scores were examined using regression methods, and random-coefficient models. The relationship between various factors, such as vascular burden and brain amyloid deposition, were investigated using path analysis. Results Higher eGFR was associated with larger HCVs and better cognition in all subjects at baseline. In MCI subjects, hippocampal atrophy in the eGFR ≥ 90 group progressed at just half the rate of the eGFR 75-90 group (P = .006), and was also somewhat slower than the eGFR 60-75 group (P = .08). A comprehensive path model linking eGFR, HCV and cognition, and integrating vascular burden and amyloid deposition, is proposed. Conclusions Higher renal function was associated with slower hippocampal atrophy and cognitive decline even within normal levels of renal function. This relationship was mediated mainly through cardiovascular risk burden and amyloid deposition. Further studies examining neuroinflammation are needed. Geriatr Gerontol Int 2017; 17: 1899-1906.

Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc.

Objectives: Depression is associated with an increased risk of cognitive decline. The present study compared two-year change in cognitive performance between depressed older persons and a non-depressed control group, between remitted and non-remitted patients, and evaluated whether vascular burden at baseline was associated with more cognitive decline in depressed older persons.Methods: Depressed patients (n = 378) aged >= 60 were recruited from mental healthcare institutes and general practices, and a non-depressed control group (n = 132) was recruited from general practices. A DSM-IV depressive episode was established with the Composite International Diagnostic Interview, and processing speed, working memory, verbal memory and interference control were evaluated with three neurocognitive tasks at baseline and 2 years later. A modified Framingham Risk Score, anklebrachial index, and history of a vascular event defined vascular burden at baseline.Results: After adjusting for baseline cognitive performance, age, sex, and education level, depressed older persons had worse processing speed and verbal memory scores at follow-up than controls (regression coefficients: -0.172; p = 0.042 and -0.309; p = 0.001, respectively) but did not differ in the other two-cognitive outcomes. In the sample of depressed patients, remission status at 2 years follow-up and baseline vascular burden did not predict cognitive performance at follow-up, after adjustment for baseline cognitive performance, age, sex and education level.Conclusions: Our findings suggest that cognitive deficits in depressed older persons are not just a manifestation of depression. In addition, vascular burden was not associated with worse cognitive decline in a sample of depressed older persons. Copyright (C) 2016 John Wiley & Sons, Ltd.

Objectives To quantify associations between inflammatory biomarkers and hippocampal volume (HV) and to examine effect modification according to sex, race, and age. Design Cross-sectional analyses using generalized estimating equations to account for familial clustering; standardized β-coefficients adjusted for age, sex, race, and education. Setting Community cohorts in Jackson, Mississippi and Rochester, Minnesota. Participants The Genetic Epidemiology Network of Arteriopathy study. Measurements C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors 1 (sTNFR-1) and 2 (sTNFR-2) from peripheral blood were measured in a sample of 773 non-Hispanic whites (61% women, aged 60.2 ± 9.8) and 514 African Americans (70% women, aged 63.9 ± 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV. Results In the full sample, higher sTNFR-1 and sTNFR-2 were associated with smaller HV. Each standard deviation (SD) increase in sTNFR-1 was associated with 59.1 mm3 (95% confidence interval (CI) = −101.4 to −16.7 mm3) smaller HV and each SD increase in sTNFR-2 associated with 48.8 mm3 (95% CI = −92.2 to −5.3 mm3) smaller HV. Relationships were stronger for sTNFR-2 in men (HV = −116.6 mm3 for each SD increase, 95% CI = −201.0 to −32.1) than women (HV = −26.0 per SD increase, 95% CI = −72.4–20.5) and sTNFR-1 in non-Hispanic whites (HV = −84.7 mm3 per SD increase, 95% CI = −142.2 to −27.1) than African Americans (HV = −14.1 mm3 per SD increase, 95% CI = −78.3–50.1). Associations between IL-6 or CRP and HV were not supported. Conclusion Higher levels of sTNFRs were associated cross-sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late-life cognitive impairment.

Exposure to stress has been causally linked to changes in hippocampal volume (HV). Given that the hippocampus undergoes rapid changes in the first years of life, stressful experiences during this period may be particularly important in understanding individual differences in the development of the hippocampus. One hundred seventy-eight early adolescents (ages 9-13 years; 43% male) were interviewed regarding exposure to and age of onset of experiences of stress; the severity of each stressful event was rated by an objective panel. All participants underwent structural magnetic resonance imaging, from which HVs were automatically segmented. Without considering the age of onset for stressful experiences, there was a small but statistically significant negative association of stress severity with bilateral HV. When considering the age of onset, there was a moderate and significant negative association between stress severity during early childhood (through 5 years of age) and HV; there was no association between stress severity during later childhood (age 6 years and older) and HV. We provide evidence of a sensitive period through 5 years of age for the effects of life stress on HV in adolescence. It will be important in future research to elucidate how reduced HV stemming from early life stress may contribute to stress-related health outcomes.