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INTRODUCTION: Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co‐exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS: In a unique cohort of mixed Alzheimer's disease and moderate–severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aβ, as assessed by 18F‐AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape. RESULTS: Frontal WMH, occipital WMH, and Aβ were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aβ. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aβ‐vulnerable subregions. DISCUSSION: Hippocampal degeneration is differentially sensitive to SVD and Aβ pathology. The pattern of hippocampal atrophy could serve as a disease‐specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5-15 years prior. Methods: This study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C-), and healthy controls (HC). The participants were recruited 5-15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests. Results: At TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = -0.585, p = 0.007). Conclusion: The observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment. [ABSTRACT FROM AUTHOR]

PurposeThe objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5–15 years prior.MethodsThis study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C−), and healthy controls (HC). The participants were recruited 5–15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests.ResultsAt TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = −0.585, p = 0.007).ConclusionThe observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment.

Background and purposeThe progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized.MethodsForty-five patients with svMCI and 46 patients with SVaD who were negative on Pittsburgh compound B (PiB) positron emission tomography imaging and 75 individuals with normal cognition (NC) were recruited.ResultsCompared with NC, patients with PiB(-) svMCI exhibited frontal, language and retrieval type memory dysfunctions, which in patients with PiB(-) SVaD were further impaired and accompanied by visuospatial and recognition memory dysfunctions. Compared with NC, patients with PiB(-) svMCI exhibited cortical thinning in the frontal, perisylvian, basal temporal and posterior cingulate regions. This atrophy was more prominent and extended further toward the lateral parietal and medial temporal regions in patients with PiB(-) SVaD. Compared with NC subjects, patients with PiB(-) svMCI exhibited hippocampal shape deformities in the lateral body, whilst patients with PiB(-) SVaD exhibited additional deformities within the lateral head and inferior body.ConclusionsOur findings suggest that patients with CVD in the absence of Alzheimer's disease pathology can be demented, showing cognitive impairment in multiple domains, which is consistent with the topography of cortical thinning and hippocampal shape deformity.

Introduction: Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood., Methods: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aβ, as assessed by 18 F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape., Results: Frontal WMH, occipital WMH, and Aβ were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aβ. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aβ-vulnerable subregions., Discussion: Hippocampal degeneration is differentially sensitive to SVD and Aβ pathology. The pattern of hippocampal atrophy could serve as a disease-specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Hippocampal damage and associated cognitive deficits are frequently observed in neuroimmunological disorders, but comparative analyses to identify shared hippocampal damage patterns are missing. Here, we adopted a transdiagnostic analytical approach and investigated hippocampal shape deformations and associated cognitive deficits in four neuroimmunological diseases.We studied 120 patients (n = 30 in each group), including patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), anti-NMDAR and anti-LGI1 encephalitis. A control group was matched to each patient sample from a pool of 79 healthy participants. We performed an MRI-based vertex-wise hippocampal shape analysis, extracted hippocampal volume estimates and scalar projection values as a measure of surface displacement. Cognitive testing included assessment of verbal memory and semantic fluency performance.Our cross-sectional analyses revealed characteristic patterns of bilateral inward deformations covering up to 32% of the hippocampal surface in MS, anti-NMDAR encephalitis, and anti-LGI1 encephalitis, whereas NMOSD patients showed no deformations compared to controls. Significant inversions were noted mainly on the hippocampal head, were accompanied by volume loss, and correlated with semantic fluency scores and verbal episodic memory in autoimmune encephalitis and MS. A deformation overlap analysis across disorders revealed a convergence zone on the left anterior hippocampus that corresponds to the CA1 subfield.This convergence zone indicates a shared downstream substrate of immune-mediated damage that appears to be particularly vulnerable to neuroinflammatory processes. Our transdiagnostic morphological view sheds light on mutual pathophysiologic pathways of cognitive deficits in neuroimmunological diseases and stimulates further research into the mechanisms of increased susceptibility of the hippocampus to autoimmunity.

Hippocampal volume and shape are known magnetic resonance imaging biomarkers of neurodegeneration. Recently, hippocampal texture has been shown to improve prediction of dementia in patients with mild cognitive impairment, but it is unknown whether texture adds prognostic information beyond volume and shape and whether the predictive value extends to cognitively healthy individuals. Using 510 subjects from the Rotterdam Study, a prospective, population-based cohort study, we investigated if hippocampal volume, shape, texture, and their combination were predictive of dementia and determined how predictive performance varied with time to diagnosis and presence of early clinical symptoms of dementia. All features showed significant predictive performance with the area under the receiver operating characteristic curve ranging from 0.700 for texture alone to 0.788 for the combination of volume and texture. Although predictive performance extended to those without objective cognitive complaints or mild cognitive impairment, performance decreased with increasing follow-up time. We conclude that a combination of multiple hippocampal features on magnetic resonance imaging performs better in predicting dementia in the general population than any feature by itself. • Investigated magnetic resonance imaging–based dementia prediction in a population setting. • Hippocampal volume, shape, and texture are predictive for dementia in this setting. • The combination of different magnetic resonance imaging–based features improves predictive value. • All features are predictive in subjects without objective cognitive complaints. • Volume and texture combined are predictive up to 6 years before diagnosis. [ABSTRACT FROM AUTHOR]

Aβ deposition is a driving force of Alzheimer's disease pathology and can be detected early by amyloid positron emission tomography. Identifying presymptomatic structural brain changes associated with Aβ deposition might lead to a better understanding of its consequences and provide early diagnostic information. In this respect we analyzed measures of cortical thickness and subcortical volumes along with hippocampal, thalamic and striatal shape and surface area by applying novel analysis strategies for structural magnetic resonance imaging. We included 69 cognitively normal elderly subjects after careful clinical and neuropsychological workup. Standardized uptake value ratios (cerebellar reference) for uptake of 11-C-Pittsburgh Compound B (PiB) were calculated from positron emission tomographic data for a cortical measurement and for bilateral hippocampus, thalamus and striatum. Associations to shape, surface area, volume and cortical thickness were tested using regression models that included significant predictors as covariates. Left anterior hippocampal shape was associated with regional PiB uptake ( P < 0.05, FDR corrected), whereas volumes of the hippocampi and their subregions were not associated with cortical or regional PiB uptake (all P > 0.05, FDR corrected). Within the entorhinal cortical region of both hemispheres, thickness was negatively associated with cortical PiB uptake ( P < 0.05, FDR corrected). Hence, localized shape measures and cortical thickness may be potential biomarkers of presymptomatic Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Several anatomical MRI markers for Alzheimer's disease (AD) have been identified. Hippocampal volume, cortical thickness, and grey matter density have been used successfully to discriminate AD patients from controls. These anatomical MRI measures have so far mainly been used separately. The full potential of anatomical MRI scans for AD diagnosis might thus not yet have been used optimally. In this study, we therefore combined multiple anatomical MRI measures to improve diagnostic classification of AD. For 21 clinically diagnosed AD patients and 21 cognitively normal controls, we calculated (i) cortical thickness, (ii) cortical area, (iii) cortical curvature, (iv) grey matter density, (v) subcortical volumes, and (vi) hippocampal shape. These six measures were used separately and combined as predictors in an elastic net logistic regression. We made receiver operating curve plots and calculated the area under the curve (AUC) to determine classification performance. AUC values for the single measures ranged from 0.67 (cortical thickness) to 0.94 (grey matter density). The combination of all six measures resulted in an AUC of 0.98. Our results demonstrate that the different anatomical MRI measures contain complementary information. A combination of these measures may therefore improve accuracy of AD diagnosis in clinical practice. Hum Brain Mapp 37:1920-1929, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: Hippocampal malrotation (HIMAL) has been increasingly reported in patients with prolonged febrile seizures and temporal lobe epilepsy (TLE). We investigated Magnetic resonance imaging (MRI) findings of HIMAL and the relationship between HIMAL and epilepsy. Method: We retrospectively reviewed the brain MRI of children who visited Ajou University Hospital for seizures or other neurological symptoms from January 2013 to September 2014. We analyzed MRI findings of HIMAL, type of seizures and epilepsy, age, history of febrile seizures and electroencephalogram. Results: A total of 710 brain MRI cases were reviewed. HIMAL was not found in 421 patients with neurological symptoms such as headache and syncope. Among the 289 patients with seizures, 213 patients with idiopathic epilepsy underwent MRI using routine protocol and 76 patients with focal epilepsy, complex febrile seizures (CFS) and febrile status epilepticus underwent MRI using epilepsy protocol. HIMAL was not found in 213 patients and found in 12 (15.8%) of 76 patients; eight (67%) were TLE, three (25%) CFS, and one (8%) was frontal lobe epilepsy. On the brain MRI findings of HIMAL, it was always on the left side and four (33.3%) were total HIMAL and eight (67.7%) were partial HIMAL. All patients with HIMAL presented with a rounded shape and vertical orientation of the hippocampus. Conclusion: HIMAL is found only in patients with TLE and CFS. Three of the patients with TLE had a past history of prolonged febrile seizures. These data suggest that HIMAL may play a role in temporal lobe epileptogenesis from febrile seizures. [ABSTRACT FROM AUTHOR]

Aberrant hippocampal morphology plays an important role in the pathophysiology of aging. Volumetric analysis of the hippocampus has been performed in aging studies; however, the shape morphometry-which is potentially more informative in terms of related cognition-has yet to be examined. In this paper, we employed an advanced brain mapping technique, large deformation diffeomorphic metric mapping (LDDMM), and a dimensionality reduction approach, locally linear diffeomorphic metric embedding (LLDME), to explore age-related changes in hippocampal shape as delineated from magnetic resonance (MR) images of 302 healthy adults aged from 18 to 94 years. Compared with the hippocampal volumes, the hippocampal shapes clearly showed the nonlinear trajectory of biological aging across the human lifespan, where the variation of hippocampal shapes by age was characterized by a cubic polynomial. By integrating of LDDMM and LLDME, we were also able to illustrate the average hippocampal shapes in each individual decade. In addition, LDDMM and LLDME facilitated the identification of 63 years as a threshold beyond which hippocampal morphological changes were accelerated. Adults over 63 years of age showed the inward-deformation bilaterally in the head of the hippocampi and the left subiculum regardless of hippocampal volume reduction when compared to adults younger than 63. Hence, we demonstrated that the shape of anatomical structures added another dimension of structural morphological quantification beyond the volume in understanding aging. Hum Brain Mapp 34:3075-3085, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Studying the distribution and chronological sequence of brain morphological changes that occur in normal aging is crucial for understanding the mechanisms underlying these alterations and for distinguishing them from pathological processes. Whether the hippocampal formation is subjected to or spared from age-related shrinkage still remains controversial. We used magnetic resonance imaging (MRI) in order to assess hippocampal and entorhinal morphology in two population-based cognitively unimpaired cohorts (aged 53–55 years and 73–75 years, respectively) matched for gender, education, handedness, and apolipoprotein E status. Voxel-based morphometry (VBM-DARTEL) and shape analysis (FSL-FIRST) revealed significant bihemispheric age-related shrinkage of subiculum and cornu ammonis as well as of the entorhinal cortex (investigated with VBM only). The results lend further support to an effect of aging on medial temporal lobe morphology and thus may be of importance for the interpretation of structural imaging findings, especially in those diseases that are typically related to advancing age, as well as for the interpretation of functional imaging studies, where age-related differences in hippocampal activation may—to a locally varying degree—be explained by morphometric alterations. [Copyright &y& Elsevier]

Abstract: Previous studies provided hippocampal shape analysis of Alzheimer''s disease (AD) patients using automated segmentation techniques. However, the relationships between the hippocampal deformations and various cognitive impairments were not clear. The aim of this study was to investigate hippocampal shape changes and their relationship to cognitive impairments. Fifty-one drug-naïve patients with AD and 50 group-matched healthy control subjects underwent 3T MRI scanning, and the hippocampal volumes and deformations were compared between the groups. Additionally, we explored the correlation pattern between the hippocampal deformations and the cognitive dysfunctions in AD using the Korean version of the Consortium to Establish a Registry for Alzheimer''s Disease (CERAD-K). AD subjects exhibited significant hippocampal deformations in the cornu ammnonis (CA1) and subiculum areas compared to those in healthy subjects (p <0.05, false discovery rate (FDR) corrected). Significant correlations were observed between hippocampal deformations in CA1 and subiculum areas and verbal immediate recall, verbal delayed recall, verbal recognition memory, and constructional recall scores (p <0.05, FDR corrected). This study was the first to explore the relationships between hippocampal deformations and various cognitive impairments of drug-naïve patients with AD. These structural changes in hippocampal CA1 and subiculum areas might be the core of the underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to the various cognitive dysfunctions in AD. [Copyright &y& Elsevier]

Abstract: Late-onset depression often precedes the onset of dementia associated with the hippocampal degeneration. Using large deformation diffeomorphic metric mapping (LDDMM), we evaluated apolipoprotein E epsilon-4 allele (apoE E4) effects on hippocampal volume and shape in 38 depressed patients without the apoE E4, 14 depressed patients with one apoE E4, and 31 healthy comparison subjects without the apoE E4. The hippocampal volumes were manually assessed. We applied a diffeomorphic template generation procedure for creating the hippocampal templates based on a subset of the population. The LDDMM mappings were used to generate the hippocampal shape of each subject and characterize the surface deformation of each hippocampus relative to the template. Such deformation was modeled as random field characterized by the Laplace–Beltrami basis functions in the template coordinates. Linear regression was used to examine group differences in the hippocampal volume and shape. We found that there were significant hippocampal shape alternations in both depressed groups while the groups of depressed patients and the group of healthy subjects did not differ in the hippocampal volume. The depressed patients with one apoE E4 show more pronounced shape inward-compression in the anterior CA1 than the depressed patients without the apoE E4 when compared with the healthy controls without the apoE E4. Thus, hippocampal shape abnormalities in late-onset depressed patients with one apoE E4 may indicate future conversion of this group to AD at higher risk than depressed patients without the apoE E4. [Copyright &y& Elsevier]

: BackgroundNeuroanatomical abnormalities have been reported in schizophrenia subjects and their relatives and may be related to genetic vulnerability. The objective of this study was to further elucidate hippocampal deformities as a marker of genetic vulnerability for schizophrenia.: MethodsMagnetic resonance scans were collected in 13 pairs of schizophrenics and their unaffected siblings from families with multiple affected members, in 12 schizophrenics from families without another affected member, and in 10 healthy controls. Hippocampal volume and shape were compared using large-deformation high-dimensional brain mapping.: ResultsDecreases in hippocampal volume, covaried for total cerebral volume, were observed in the schizophrenia subjects from families with multiple affected members, as well as in their unaffected siblings. Shape analysis demonstrated that both groups of schizophrenia subjects, as well as the unaffected siblings, could be distinguished from the controls; however, no significant difference in hippocampal shape was found between the schizophrenia subjects and their unaffected siblings. Visualization of the pattern of hippocampal shape deformity in both groups of schizophrenia subjects and in the unaffected siblings showed inward deformities of the head of the hippocampus.: ConclusionsDeformations of hippocampal anatomy may be related to the genetic vulnerability of acquiring schizophrenia. [Copyright &y& Elsevier]

Hippocampal damage and associated cognitive deficits are frequently observed in neuroimmunological disorders, but comparative analyses to identify shared hippocampal damage patterns are missing. Here, we adopted a transdiagnostic analytical approach and investigated hippocampal shape deformations and associated cognitive deficits in four neuroimmunological diseases. We studied 120 patients (n = 30 in each group), including patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), anti-NMDAR and anti-LGI1 encephalitis. A control group was matched to each patient sample from a pool of 79 healthy participants. We performed an MRI-based vertex-wise hippocampal shape analysis, extracted hippocampal volume estimates and scalar projection values as a measure of surface displacement. Cognitive testing included assessment of verbal memory and semantic fluency performance. Our cross-sectional analyses revealed characteristic patterns of bilateral inward deformations covering up to 32% of the hippocampal surface in MS, anti-NMDAR encephalitis, and anti-LGI1 encephalitis, whereas NMOSD patients showed no deformations compared to controls. Significant inversions were noted mainly on the hippocampal head, were accompanied by volume loss, and correlated with semantic fluency scores and verbal episodic memory in autoimmune encephalitis and MS. A deformation overlap analysis across disorders revealed a convergence zone on the left anterior hippocampus that corresponds to the CA1 subfield. This convergence zone indicates a shared downstream substrate of immune-mediated damage that appears to be particularly vulnerable to neuroinflammatory processes. Our transdiagnostic morphological view sheds light on mutual pathophysiologic pathways of cognitive deficits in neuroimmunological diseases and stimulates further research into the mechanisms of increased susceptibility of the hippocampus to autoimmunity., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have made it possible to identify specific locations of subtle morphometric changes within a structure of interest., Methods: In this cross-sectional study, we used high-resolution magnetic resonance imaging to examine the relationship between PTSD symptomatology, as measured using the Clinician Administered PTSD Scale for the DSM-IV (CAPS), and structural shape of the hippocampus and amygdala using vertex-wise shape analyses in a group of combat-exposed US Veterans (N = 69)., Results: Following correction for multiple comparisons and controlling for age and cranial volume, we found that participants with more severe PTSD symptoms showed an indentation in the anterior half of the right hippocampus and an indentation in the dorsal region of the right amygdala (corresponding to the centromedial amygdala). Post hoc analysis using stepwise regression suggest that among PTSD symptom clusters, arousal symptoms explain most of the variance in the hippocampal abnormality, whereas re-experiencing symptoms explain most of the variance in the amygdala abnormality., Conclusion: The results provide evidence of localized abnormalities in the anterior hippocampus and centromedial amygdala in combat-exposed US Veterans suffering from PTSD symptoms. This novel finding provides a more fine-grained analysis of structural abnormalities in PTSD and may be informative for understanding the neurobiology of the disorder., Competing Interests: Declaration of Conflicting Interests Dr. Abdallah has served as a consultant or on advisory boards for Genentech and Janssen. He also serves as editor for the journal Chronic Stress published by SAGE Publications, Inc. Dr. Krystal is a consultant for AbbVie, Inc., Amgen, Astellas Pharma Global Development, Inc., AstraZeneca Pharmaceuticals, Biomedisyn Corporation, Bristol-Myers Squibb, Eli Lilly and Company, Euthymics Bioscience, Inc., Neurovance, Inc., FORUM Pharmaceuticals, Janssen Research & Development, Lundbeck Research USA, Novartis Pharma AG, Otsuka America Pharmaceutical, Inc., Sage Therapeutics, Inc., Sunovion Pharmaceuticals, Inc., and Takeda Industries; is on the Scientific Advisory Board for Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Inc., Naurex, Inc., and Pfizer; serves as the Associate Editor for the journal Chronic Stress; is a stockholder in Biohaven Medical Sciences; holds stock options in Mnemosyne Pharmaceuticals, Inc.; holds patents for Dopamine and Noradrenergic Reuptake Inhibitors in Treatment of Schizophrenia, U.S. Patent No. 5,447,948 (issued Sep 5, 1995), and Glutamate Modulating Agents in the Treatment of Mental Disorders, U.S. Patent No. 8,778,979 (issued Jul 15, 2014); and filed a patent for Intranasal Administration of Ketamine to Treat Depression. U.S. Application No. 14/197,767 (filed on Mar 5, 2014); U.S. application or Patent Cooperation Treaty international application No. 14/306,382 (filed on Jun 17, 2014). Dr. L. A. Averill serves as the Managing Editor for Chronic Stress. All other authors report no competing interests.

The hippocampus is one of the earliest affected brain regions in Alzheimer's disease (AD) and its dysfunction is believed to underlie the core feature of the disease-memory impairment. Given that hippocampal volume is one of the best AD biomarkers, our review focuses on distinct subfields within the hippocampus, pinpointing regions that might enhance the predictive value of current diagnostic methods. Our review presents how changes in hippocampal volume, shape, symmetry and activation are reflected by cognitive impairment and how they are linked with neurogenesis alterations. Moreover, we revisit the functional differentiation along the anteroposterior longitudinal axis of the hippocampus and discuss its relevance for AD diagnosis. Finally, we indicate that apart from hippocampal subfield volumetry, the characteristic pattern of hippocampal hyperactivation associated with seizures and neurogenesis changes is another promising candidate for an early AD biomarker that could become also a target for early interventions.