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Background: Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients. Methods: This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment. Results: The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients. Conclusion: Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.

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Sleep apnea, affecting an estimated 1 in 4 American adults, has been reported to be associated with both brain structural abnormality and impaired cognitive function. Obstructive sleep apnea is known to be affected by upper airway anatomy. To better understand the contribution of upper airway anatomy to pathways linking sleep apnea with impaired cognitive function, we investigated the association of upper airway anatomy with structural brain abnormalities. Based in the Multi-Ethnic Study of Atherosclerosis, a longitudinal cohort study of community-dwelling adults, a comprehensive sleep study and an MRI of the upper airway and brain were performed on 578 participants. Machine learning models were used to select from 74 upper airway measures those measures most associated with selected regional brain volumes and white matter hyperintensity volume. Linear regression assessed associations between the selected upper airway measures, sleep measures, and brain structure. Maxillary divergence was positively associated with hippocampus volume, and mandible length was negatively associated with total white and gray matter volume. Both coefficients were small (coefficients per standard deviation 0.063 mL, p = 0.04, and - 7.0 mL, p < 0.001 respectively), and not affected by adjustment for sleep study measures. Self-reported snoring >2 times per week was associated with larger hippocampus volume (coefficient 0.164 mL, p = 0.007), and higher percentage of time in the N3 sleep stage was associated with larger total white and gray matter volume (4.8 mL, p = 0.004). Despite associations of two upper airway anatomy measures with brain volume, the evidence did not suggest that these upper airway and brain structure associations were acting primarily through the pathway of sleep disturbance.

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BACKGROUND: Evidence of type 2 diabetes mellitus (T2DM) associated with hippocampal atrophy is reported by researchers all around the globe. The majority of such studies were conducted among the geriatric and elderly populations with other substantial co-morbid diseases. Hence, the present study aims to evaluate the hippocampal volume of T2DM subjects below 60 years without any concomitant disorders and assess the declarative memory. MATERIALS AND METHODS: The cross-sectional observational study was conducted among the ethnic population of Manipur. A total of 17 T2DM subjects and 17 healthy controls, who are apparently healthy, matched by age, sex, and comparable education, were enrolled in the study. Magnetic Resonance Imaging (MRI) of high-resolution sagittal structural T1-weighted anatomical sequence was acquired using a three-dimension magnetization-prepared rapid-acquisition gradient echo (MPRAGE). The hippocampus volume was measured using the volBrain Automated MRI Brain Volumetry System. Declarative memory was estimated by the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: No statistically significant differences were found in hippocampal volume, and RAVLT scores between T2DM subjects, and healthy controls group (P > 0.05). CONCLUSIONS: The study data indicates that there is no particular hippocampal volume vulnerability in T2DM participants within the ethnic population of Manipur.

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Introduction: Stroke has been considered to raise the risk of dementia in several studies, but the relationship between brain structural changes and poststroke cognitive impairment (PSCI) is unclear. Methods: In this study, 23 PSCI patients with basal ganglia infarcts after 2 weeks and 29 age-matched controls underwent magnetic resonance imaging measuring cortical thickness and volume changes, as well as neuropsychological tests. CI was derived from a performance score <1.5 standard deviations for normally distributed scores. We compared Z scores in different cognitive domains and cortical thickness and volumes in two groups. Multiple linear regressions were used to investigate the relationship between cortical thickness and volumes and neuropsychological tests. Results: A majority of PSCI patients were in their 50s (55.19±8.52 years). PSCI patients exhibited significantly decreased Z scores in multiple domains, such as memory, language, visuomotor speed, and attention/executive function. The volumes of the middle posterior corpus callosum, middle anterior corpus callosum, and hippocampus in PSCI patients were markedly lower than controls. The thickness of the right inferior temporal cortex and insula were significantly smaller than controls. It found that the reduced right hippocampus was related to executive dysfunction. Hippocampus dysfunction may be involved in language impairment (p<0.05) in PSCI patients with basal ganglia infarcts. Conclusion: These findings demonstrated that brain structure changed after ischemic stroke, and different gray-matter structural changes could lead to specific cognitive decline in PSCI patients with basal ganglia infarcts. Atrophy of the right hippocampus potentially serves as an imaging marker of early executive function of PSCI.

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White matter (WM) degeneration is suggested to predict the early signs of Alzheimer's disease (AD). The exact structural regions of brain circuitry involved are not known. This study aims to examine the associations between WM tract integrity, represented by the diffusion tensor imaging (DTI) measures, and AD diagnosis and to denote the key substrates in predicting AD. It included DTI measures of mean diffusivity (MD), fractional anisotropy, radial diffusivity and axial diffusivity of 18 main WM tracts in 84 non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative dataset. The multivariable general linear model was used to examine the association of AD diagnosis with each DTI measure adjusting for age, gender and education. The corpus callosum, fornix, cingulum hippocampus, uncinate fasciculus, sagittal striatum, left posterior thalamic radiation and fornix-stria terminalis showed significant increases in MD, radial and axial diffusivity, whereas the splenium of corpus callosum and the fornix showed significant decreases in fractional anisotropy among AD patients. Variable cluster analysis identified that hippocampus volume, mini-mental state examination (MMSE), cingulate gyrus/hippocampus, inferior fronto-occipital fasciculus and uncinate fasciculus are highly correlated in one cluster with MD measures. In conclusion, there were significant differences in DTI measures between the brain WM of AD patients and controls. Age is the risk factor associated with AD, not gender or education. Right cingulum gyrus and right uncinate fasciculus are particularly affected, correlating well with a cognitive test MMSE and MD measures for dementia in AD patients and could be a region of focus for AD staging.

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BACKGROUND: Magnetic resonance imaging (MRI) studies of prenatal alcohol exposure (PAE) commonly report reduced hippocampal volumes, which animal models suggest may result from microstructural changes that include cell loss and altered myelination. Diffusion tensor imaging (DTI) is sensitive to microstructural changes but has not yet been used to study the hippocampus in PAE. METHODS: Thirty-six healthy controls (19 females; 8 to 24 years) and 19 participants with PAE (8 females; 8 to 23 years) underwent high-resolution (1 mm isotropic) DTI, anatomical T1-weighted imaging, and cognitive testing. Whole-hippocampus, head, body, and tail subregions were manually segmented to yield DTI metrics (mean, axial, and radial diffusivities-MD, AD, and RD; fractional anisotropy-FA), volumes, and qualitative assessments of hippocampal morphology and digitations. Automated segmentation of T1-weighted images was used to corroborate manual whole-hippocampus volumes. RESULTS: Gross morphology and digitation counts were similar in both groups. Whole-hippocampus volumes were 18% smaller in the PAE than the control group on manually traced diffusion images, but automated T1-weighted image segmentations were not significantly different. Subregion segmentation on DTI revealed reduced volumes of the body and tail, but not the head. There were no significant differences in diffusion metrics between groups for any hippocampal region. Correlations between age and volume were not significant in either group, whereas negative correlations between age and whole-hippocampus MD/AD/RD, and head/body (but not tail) MD/AD/RD were significant in both groups. There were no significant effects of sex, group by age, or group by sex for any hippocampal metric. In controls, seven positive linear correlations were found between hippocampal volume and cognition; five of these were left lateralized and included episodic and working memory, and two were right lateralized and included working memory and processing speed. In PAE, left tail MD positively correlated with executive functioning, and right head MD negatively correlated with episodic memory. CONCLUSIONS: Reductions of hippocampal volumes and altered relationships with memory suggest disrupted hippocampal development in PAE.

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BACKGROUND: The choroid is involved directly or indirectly in many pathological conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). OBJECTIVE: The objective of this study was to investigate the association between retinal choroidal properties and the pathology of AD by determining choroidal thickness, hippocampus volume, cognitive functions, and plasma BACE1 activity. METHODS: In this cross-sectional study, 37 patients with AD and 34 age-matched controls were included. Retinal choroidal thickness was measured via enhanced depth imaging optical coherence tomography. Hippocampal volume was measured via 3.0T MRI. Cognitive functions were evaluated using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog). Plasma BACE1 activity was analyzed using a fluorescence substrate-based plasma assay, and regression model were to analyze the data. RESULTS: Retinal choroidal thickness was significantly thinner in the AD group than in the control group [(114.81±81.30) µm versus (233.79±38.29) µm, p < 0.05]. Multivariable regression analysis indicated that the ADAS-cog scores (ß=-0.772, p = 0.000) and age (ß=-0.176, p = 0.015) were independently associated with choroidal thickness. The logistic regression model revealed that the subfoveal choroidal thickness was a significant predictor for AD (OR = 0.984, 95% CI: 0.972-0.997). CONCLUSION: There was a general tendency of choroid thinning as the cognitive function declined. Although choroidal thickness was not a potential indicator for early stage AD, it was valuable in monitoring AD progression.

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Differences in hippocampus volume have been identified in adult patients with obsessive-compulsive disorder (OCD). However, the role of this limbic structure in pediatric patients is unclear. This study aimed to investigate the hippocampus and its subregions in a sample of 29 children and adolescents with OCD compared to 28 healthy controls, matched for age, sex, education, and IQ. Volumetric segmentation was performed using the Freesurfer software to calculate the volumes of the subregions that reflect the hippocampal cytoarchitecture. The volumes of three anatomic subregions (tail, body, and head) were also calculated. ANCOVA was performed to investigate differences of these volumes between patients and controls, controlling for total gray matter volume. After Bonferroni correction for multiple comparisons (p-value < 0.00556 for the body and < 0.00625 for the head structures), patients presented statistically significant larger volumes of the following structures: left subiculum body; left CA4 body; left GC-DG body; left molecular layer body; right parasubiculum; left CA4 head; left molecular layer head; right subiculum head and right molecular layer head. These enlarged volumes resulted in larger left and right whole hippocampi in patients, as well as bilateral hippocampal heads and left hippocampal body (all p-values < 0.00625). There were no associations between OCD severity and hippocampal volumes. These findings diverge from previous reports on adults and may indicate that larger hippocampal volumes could reflect an early marker of OCD, not present in adults.

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BACKGROUND: Muscle mass, strength and function declines with advancing age. Strength training (ST) improves these parameters in older adults, but the gains often disappear after completion of a short-term intervention. The purpose of the present study was to investigate muscle mass, -strength and -function one year after the completion of a successful long-term (12 months) supervised ST program in older adults. METHOD: Men and women (n = 419, age: 62-70 years) completed one year of supervised heavy resistance training (HRT, n = 143) or moderate intensity resistance training (MIT, n = 144) and were compared to a non-exercising control group (CON, n = 132). At 1-year follow-up, 398 participants returned for measurements of muscle power, -strength and -mass, physical function, body composition, hippocampus volume and physical/mental well-being. The results were compared to pre-training (baseline) and post-training (1-year) values. Further, the participants from the two previous training groups (HRT + MIT, n = 265) were divided into 1) those who on their own continued the ST program (>9 months) the year after completion of the supervised ST program (CONTIN, n = 65) and 2) those who stopped during the follow-up year (<9 months) (STOP, n = 200). RESULTS: Out of all the improvements obtained after the 1-year training intervention, only knee extensor muscle strength in HRT was preserved at 1-year follow-up (p < 0.0001), where muscle strength was 7% higher than baseline. Additionally, the decrease in muscle strength over the second year was lower in CONTIN than in STOP with decreases of 1% and 6%, respectively (p < 0.05). Only in CONTIN was the muscle strength still higher at 1-year follow-up compared with baseline with a 14% increase (p < 0.0001). The heavy strength training induced increase in whole-body lean mass was erased at 1-year follow-up. However, there was a tendency for maintenance of the cross-sectional area of m. vastus lateralis from baseline to 1-year follow-up in HRT compared with CON (p = 0.06). Waist circumference decreased further over the second year in CONTIN, whereas it increased in STOP (p < 0.05). CONCLUSION: Even though long-term strength training effectively improved muscle function and other health parameters in older adults, only knee extensor muscle strength was preserved one year after completion of heavy (but not moderate intensity) resistance training. Continuation of strength training resulted in better maintenance of muscle strength and health, which indicates that it is required to continue with physical activity to benefit from the long-term effects of strength training upon muscle function and health in older men and women.

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BACKGROUND: Many research papers claim that patients with specific psychiatric disorders (major depressive disorder, posttraumatic stress disorder, borderline personality disorder, alcohol use disorder, and others) have smaller hippocampi, but most of those reports compared patients to healthy controls. We hypothesized that if psychiatrically matched controls (psychiatric control, matched for demographics and psychiatric comorbidities) were used, much of the biomarker literature in psychiatric research would not replicate. We used hippocampus and amygdala volume only as examples, as these are very commonly replicated results in psychiatry biomarker research. We propose that psychiatry biomarker research could benefit from using psychiatric controls, as the use of healthy controls results in data that are not disorder-specific. METHOD: Hippocampus/amygdala volumes were compared between major depressive disorder, sex-/age-/race-matched healthy control, and psychiatric control (N = 126/group). Similar comparisons were performed for posttraumatic stress disorder (N = 67), borderline personality disorder (N = 111), and alcohol use disorder (N = 136). RESULTS: Major depressive disorder patients had smaller left (p = 8.79 × 10-3) and right (p = 3.13 × 10-3) hippocampal volumes than healthy control. Posttraumatic stress disorder had smaller left (p = 0.018) and right (p = 8.64 × 10-4) hippocampi than healthy control. Borderline personality disorder had smaller right hippocampus (p = 7.90 × 10-3) and amygdala (p = 1.49 × 10-3) than healthy control. Alcohol use disorder had smaller right hippocampus (p = 0.034) and amygdala (p = .024) than healthy control. No differences were found between any of the four diagnostic groups and psychiatric control. CONCLUSION: When psychiatric controls were used, there was no difference in hippocampal or amygdalar volume between any of the diagnoses studied and controls. This strategy (keeping all possible relevant variables matched between experimental groups) has been used to advance science for hundreds of years, and we propose should also be used in biomarker psychiatry research.

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BACKGROUND: Physical muscle function and brain hippocampus size declines with age, accelerating after the age of 60. Strength training over a few months improves physical function, but less is known about how long-term strength training affects physical function and hippocampus volume. Therefore, we aimed to investigate the effect of 1-year strength training of two different intensities upon muscle mass, function, and hippocampus volume in retirement-age individuals. METHODS: In this multidisciplinary randomized controlled trial (clinicaltrials.gov: NCT02123641), participants were allocated to either a) supervised, heavy resistance training (HRT, n = 149, 3/wk), b) moderate intensity resistance training (MIT, n = 154, 3/wk) or c) non-exercise activities (CON, n = 148). 451 participants were randomized (62-70 yrs., women 61%, ≈80% with a chronic medical disease) and 419 were included in the intention-to-treat analysis (n = 143, 144 and 132; HRT, MIT and CON). Changes in muscle power (primary outcome), strength and size, physical function, body composition, hippocampus volume and physical/mental well-being were analyzed. FINDINGS: Of the participants (HRT + MIT), 83% completed training at least 2/week. Leg extensor power was unchanged in all groups, but strength training had a positive effect on isometric knee extensor strength in both groups, whereas an increased muscle mass, cross-sectional area of vastus lateralis muscle, a decreased whole-body fat percentage, visceral fat content and an improved mental health (SF-36) occurred in HRT only. Further, chair-stand performance improved in all groups, whereas hippocampus volume decreased in all groups over time with no influence of strength training. INTERPRETATION: Together, the results indicate that leg extensor power did not respond to long-term supervised strength training, but this type of training in a mixed group of healthy and chronically diseased elderly individuals can be implemented with good compliance and induces consistent changes in physiological parameters of muscle strength, muscle mass and abdominal fat.

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OBJECTIVES: The aim of the study was to compare the hippocampus sizes of healthy medical faculty students, who were exposed to an intense data input and who underwent serious learning activity and those of healthy sport faculty students who did sports regularly by using MR images and to examine the relationship between a hippocampus size and intelligence. METHODS: We made the study with 58 healthy young males (27 sport sciences faculty students and 31 medical faculty students). R. B. Cattell 3A Culture Fair Intelligence Test was administered to the volunteers. Following this, we got MR images of our volunteers. RESULTS: We could not find a statistically significant difference between medical faculty students and sport sciences faculty students in terms of hippocampus volumes. We could not find a correlation between IQ values and hippocampus volumes. Also, we could not find a significant difference between a right and left hippocampus. CONCLUSION: While doing sport, blood flow increases in the hippocampus, as in all areas of the body. This increased blood flow creates a stimulating effect on neurogenesis. Neurons, which develop as the result of neurogenesis, mean an increase in volume (Tab. 4, Ref. 54).

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The hippocampus and amygdala have been proposed as key neural structures related to anxiety. A more active hippocampus/amygdala system has been related to greater anxious responses in situations involving conflict/novelty. The Roman Low- (RLA) and High-avoidance (RHA) rat lines/strains constitute a genetic model of differential anxiety. Relative to RHA rats, RLA rats exhibit enhanced anxiety/fearfulness, augmented hippocampal/amygdala c-Fos expression following exposure to novelty/conflict, increased hippocampal neuronal density and higher endocrine responses to stress. Neonatal handling (NH) is an environmental treatment with long-lasting anxiety/stress-reducing effects in rodents. Since hippocampus and amygdala volume are supposed to be related to anxiety/fear, we hypothesized a greater volume of both areas in RLA than in RHA rats, as well as that NH treatment would reduce anxiety and the volume of both structures, in particular in the RLA strain. Adult untreated and NH-treated RHA and RLA rats were tested for anxiety, sensorimotor gating (PPI), stress-induced corticosterone and prolactin responses, two-way active avoidance acquisition and in vivo 7 T 1H-Magnetic resonance image. As expected, untreated RLA rats showed higher anxiety and post-stress hormone responses, as well as greater hippocampus and amygdala volumes than untreated RHA rats. NH decreased anxiety/stress responses, especially in RLA rats, and significantly reduced hippocampus and amygdala volumes in this strain. Dorsal striatum volume was not different between the strains nor it was affected by NH. Finally, there were positive associations (as shown by correlations, factor analysis and multiple regression) between anxiety and PPI and hippocampus/amygdala volumes.

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INTRODUCTION: For early detection of Alzheimer's disease (AD), the field needs biomarkers that can be used to detect disease status with high sensitivity and specificity. Apolipoprotein J (ApoJ, also known as clusterin) has long been associated with AD pathogenesis through various pathways. The aim of this study was to investigate the potential of plasma apoJ as a blood biomarker for AD. METHODS: Using the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the present study assayed plasma apoJ levels over baseline and 18 months in 833 individuals. Plasma ApoJ levels were analyzed with respect to clinical classification, age, gender, apolipoprotein E (APOE) ε4 allele status, mini-mental state examination score, plasma amyloid beta (Aß), neocortical Aß burden (as measured by Pittsburgh compound B-positron emission tomography), and total adjusted hippocampus volume. RESULTS: ApoJ was significantly higher in both mild cognitive impairment (MCI) and AD groups as compared with healthy controls (HC; P < .0001). ApoJ significantly correlated with both "standardized uptake value ratio" (SUVR) and hippocampus volume and weakly correlated with the plasma Aß1-42/Aß1-40 ratio. Plasma apoJ predicted both MCI and AD from HC with greater than 80% accuracy for AD and greater than 75% accuracy for MCI at both baseline and 18-month time points. DISCUSSION: Mean apoJ levels were significantly higher in both MCI and AD groups. ApoJ was able to differentiate between HC with high SUVR and HC with low SUVR via APOE ε4 allele status, indicating that it may be included in a biomarker panel to identify AD before the onset of clinical symptoms.

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A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippocampal volume and white matter lesions. Among depressed individuals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings.

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BACKGROUND: We performed the current study to test the hypothesis that the aggregation of cardiovascular risk factors in patients with Alzheimer's disease (AD) was associated with a higher rate of volume loss in the hippocampus and progression of cognitive deficits. METHODS: A total of 103 persons with AD were included (65 men and 38 women, average age of 74.5 ± 0.8 years). All participants underwent 1.5 T structural magnetic resonance imaging (MRI), at specified intervals (6 or 12 months) for 2-3 years. We determined the rates of hippocampus, whole brain, ventricle, middle temporal lobe, fusiform, and entorhinal volume loss (in cubic millimeter/year) for all patients with AD, separately for 0-6 months, 6-12 months and 0-12, 12-18 and 18-24 months scan intervals. RESULTS: There were significant differences in Mini-Mental State Examination (MMSE) (p = 0.001) and Alzheimer's disease Assessment Scale (ADAS) (p = 0.01) scale scores between persons with and without hypertension and in MMSE (p = 0.04) and Clinical Dementia Rating (CDR) (p = 0.008) scale scores between persons with and without hyperlipidemia. There were no significant differences in MMSE, ADAS, and CDR scales scores between persons with and without diabetes mellitus and cigarette smoking. There were no significant differences in regional brain volume loss in those with or without cardiovascular risk factors. CONCLUSIONS: Cardiovascular risk factors have a significant influence on the progression of cognitive deficits in patients with AD. The progression of cognitive deficits in patients with AD is not mediated by progressive hippocampal volume loss.