Hippocampal Volume and Amyloid PET Status Three Years After Ischemic Stroke: A Pilot Study

2021 ◽  
Vol 80 (2) ◽  
pp. 527-532
Author(s):  
Amy Brodtmann ◽  
Mohamed Salah Khlif ◽  
Laura J. Bird ◽  
Toby Cumming ◽  
Emilio Werden
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Pilot Study ◽  
Neurodegenerative Disorders ◽  
Hippocampal Volume ◽  
Hippocampal Atrophy ◽  
Stroke Survivors ◽  
Amyloid Pet ◽  
Recall Memory ◽  
Cardinal Feature

Hippocampal atrophy is seen in many neurodegenerative disorders and may be a cardinal feature of vascular neurodegeneration. We examined hippocampal volume (HV) in a group of ischemic stroke survivors with amyloid 18F-NAV4694 PET imaging three years after stroke. We compared HV between the amyloid-positive (n = 4) and amyloid-negative (n = 29) groups, and associations with co-morbidities using Charlson Comorbidity Indices and multi-way ANOVA. Amyloid status was not associated with verbal or visual delayed free recall memory indices or cognitive impairment. We found no association between amyloid status and HV in this group of ischemic stroke survivors.

scholarly journals Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration

Neurology ◽  
2019 ◽  
Vol 94 (4) ◽  
pp. e397-e406 ◽  
Author(s):  
Kelsey R. Thomas ◽  
Katherine J. Bangen ◽  
Alexandra J. Weigand ◽  
Emily C. Edmonds ◽  
Christina G. Wong ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Neuropsychological Testing ◽  
Selective Vulnerability ◽  
Hippocampal Volume ◽  
Rate Of Change ◽  
Hippocampal Atrophy ◽  
Amyloid Pet ◽  
Cortical Thinning ◽  
Cognitive Difficulties ◽  
Amyloid Accumulation

ObjectiveTo determine the temporal sequence of objectively defined subtle cognitive difficulties (Obj-SCD) in relation to amyloidosis and neurodegeneration, the current study examined the trajectories of amyloid PET and medial temporal neurodegeneration in participants with Obj-SCD relative to cognitively normal (CN) and mild cognitive impairment (MCI) groups.MethodA total of 747 Alzheimer's Disease Neuroimaging Initiative participants (305 CN, 153 Obj-SCD, 289 MCI) underwent neuropsychological testing and serial amyloid PET and structural MRI examinations. Linear mixed effects models examined 4-year rate of change in cortical 18F-florbetapir PET, entorhinal cortex thickness, and hippocampal volume in those classified as Obj-SCD and MCI relative to CN.ResultAmyloid accumulation was faster in the Obj-SCD group than in the CN group; the MCI and CN groups did not significantly differ from each other. The Obj-SCD and MCI groups both demonstrated faster entorhinal cortical thinning relative to the CN group; only the MCI group exhibited faster hippocampal atrophy than CN participants.ConclusionRelative to CN participants, Obj-SCD was associated with faster amyloid accumulation and selective vulnerability of entorhinal cortical thinning, whereas MCI was associated with faster entorhinal and hippocampal atrophy. Findings suggest that Obj-SCD, operationally defined using sensitive neuropsychological measures, can be identified prior to or during the preclinical stage of amyloid deposition. Further, consistent with the Braak neurofibrillary staging scheme, Obj-SCD status may track with early entorhinal pathologic changes, whereas MCI may track with more widespread medial temporal change. Thus, Obj-SCD may be a sensitive and noninvasive predictor of encroaching amyloidosis and neurodegeneration, prior to frank cognitive impairment associated with MCI.

The role of high-mobility group box protein 1 in chronic cerebral hypoperfusion-induced vascular cognitive impairment animals

2019 ◽  
Author(s):  
Amelia Nur Vidyanti ◽  
Jia-Yu Hsieh ◽  
Kun-Ju Lin ◽  
Yao-Ching Fang ◽  
Ismail Setyopranoto ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
High Mobility ◽  
Vascular Cognitive Impairment ◽  
High Mobility Group ◽  
Cerebral Hypoperfusion ◽  
Hippocampal Atrophy ◽  
Amyloid Pet ◽  
Knock Out

Abstract Background: The molecular mechanisms of vascular cognitive impairment (VCI) are diverse and still in puzzle. VCI could be attributed to chronic cerebral hypoperfusion (CCH). CCH may cause a cascade of reactions involved in ischemia and neuro-inflammation which plays important roles in the pathophysiology of VCI. High-mobility group box protein 1 (HMGB1) is a non-histone protein that serves as a damage-associated molecular signal leading to cascades of inflammation. Increased level of HMGB1 has been established in the acute phase of CCH. However, the role of HMGB1 at the chronic phase of CCH remains elucidated. Methods: We performed modified bilateral common carotid artery occlusion (BCCAO) in C57BL/6 mice to induce CCH. We examined the cerebral blood flow (CBF) reduction by laser doppler flowmetry, the protein expression of HMGB1 and its pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) by western blotting and immunohistochemistry. The brain pathology was assessed by 7T-animal MRI and amyloid-b accumulation was assessed by amyloid-PET scanning. We further evaluated the effect of HMGB1 suppression by injecting CRISPR/Cas9 knock-out plasmid intra-hippocampus bilaterally. Results: There were reduction of CBF up to 50% which persisted three months after CCH. The modified-BCCAO animals developed significant cognitive decline. The 7T-MRI image showed hippocampal atrophy, although the amyloid-PET showed no significant amyloid-beta accumulation. Increased protein levels of HMGB1, TNF-a and IL-1b were found three months after BCCAO. HMGB1 suppression by CRISPR/Cas9 knock-out plasmid restored the CBF, IL-1B, TNF-alpha, IL-6, and attenuated hippocampal atrophy and cognitive decline. Conclusion: HMGB1 plays a pivotal role in the pathophysiology of the animal model of CCH and it might be a candidate as therapeutic targets of VCI.

Hippocampal atrophy correlates with the severity of cognitive decline

2006 ◽  
Vol 19 (4) ◽  
pp. 767-777 ◽  
Author(s):  
Burcu Balam Yavuz ◽  
Servet Ariogul ◽  
Mustafa Cankurtaran ◽  
Kader Karli Oguz ◽  
Meltem Halil ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cognitive Impairment ◽  
Early Diagnosis ◽  
Cognitive Decline ◽  
Multivariate Regression Analysis ◽  
Hippocampal Volume ◽  
Cognitive Status ◽  
Hippocampal Atrophy ◽  
Covariate Effects ◽  
Left Hippocampus

Background: The aim of this study is to compare the results of magnetic resonance (MR) imaging, particularly the decline in hippocampal volume, of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) with healthy age-matched controls, to examine the reliability of hippocampal volumetry in the early diagnosis of AD and the correlation of the severity of hippocampal atrophy with the severity of cognitive decline.Methods: Twenty-six AD, 22 MCI and 15 normal cognitive status (NCS) patients were scanned with a 3 Tesla MR scanner. Hippocampus volumes were detected manually by Osiris 4.18.Results: Multivariate regression analysis, which was performed to adjust the covariate effects of education, age, gender, hypertension and diabetes mellitus, showed that hippocampal atrophy was correlated with AD and MCI for right hippocampus; AD, MCI and age for left hippocampus independent of other parameters. A second regression analysis revealed that MMSE was correlated with hippocampal volume.Conclusions: Hippocampal volumetry can be used in early diagnosis of cognitive impairment, as well as grading cognitive decline.

scholarly journals Sirt1 Protects Against Hippocampal Atrophy and its Induced Cognitive Impairment in Middle-aged Mice

2021 ◽  
Author(s):  
Zuhao Sun ◽  
Shuang Zhao ◽  
Xinjun Suo ◽  
Yan Dou
Keyword(s):  
Cognitive Impairment ◽  
Molecular Mechanisms ◽  
Hippocampal Volume ◽  
Sirtuin 1 ◽  
Spatial Learning And Memory ◽  
Hippocampal Atrophy ◽  
Middle Aged ◽  
Adeno Associated Virus ◽  
Aged Mice ◽  
Magnetic Resonance Imaging Mri

Abstract Background: Sirtuin 1 (Sirt1) is a recognized longevity gene and has been shown to be associated with aging and its related diseases. Hippocampal volume is considered to be the most sensitive brain imaging phenotype for cognition, but the effect of Sirt1 on hippocampal morphology during aging has not been reported. Results: Herein, we investigated the effect of conditional Sirt1 knockdown on hippocampal volume in middle-aged mice, as well as its cognitive function and the underlying molecular mechanisms. Brain structural magnetic resonance imaging (MRI) showed that adeno-associated virus (AAV) mediated hippocampal Sirt1 knockdown caused hippocampal atrophy in 8-month-old mice. Open field test (OFT) and Morris Water Maze (MWM) test revealed that hippocampal Sirt1 knockdown significantly weakened spatial learning and memory of mice without effect on anxiety and exploratory behavior. Western blotting analysis showed that p-tau levels were significantly increased while PSD95 levels were obviously reduced, indicating that hippocampal Sirt1 knockdown could activate tau pathology and synaptic damage.Conclusions: This work revealed that Sirt1 is an important protective gene against hippocampal atrophy and its induced cognitive impairment during aging, providing potential therapeutic targets for the prevention and intervention of aging-related neuropsychic diseases.

Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study

2010 ◽  
Vol 16 (9) ◽  
pp. 1083-1090 ◽  
Author(s):  
VM Anderson ◽  
LK Fisniku ◽  
Z. Khaleeli ◽  
MM Summers ◽  
SA Penny ◽  
...  
Keyword(s):  
Memory Performance ◽  
Memory Function ◽  
Hippocampal Volume ◽  
Hippocampal Atrophy ◽  
Primary Progressive ◽  
Recall Memory ◽  
Relapsing Remitting ◽  
The Mean ◽  
The Right ◽  
With Memory

Background: In multiple sclerosis (MS), demyelination and neuroaxonal damage are seen in the hippocampus, and MRI has revealed hippocampal atrophy. Objectives: To investigate and compare hippocampal volume loss in patients with relapsing—remitting MS (RRMS) and primary progressive MS (PPMS) using manual volumetry, and explore its association with memory dysfunction. Methods: Hippocampi were manually delineated on volumetric MRI of 34 patients with RRMS, 23 patients with PPMS and 18 controls. Patients underwent neuropsychological tests of verbal and visuospatial recall memory. Linear regression was used to compare hippocampal volumes between subject groups, and to assess the association with memory function. Results: Hippocampal volumes were smaller in MS patients compared with controls, and were similar in patients with RRMS and PPMS. The mean decrease in hippocampal volume in MS patients was 317 mm3 (9.4%; 95% CI 86 to 549; p = 0.008) on the right and 284 mm3 (8.9%; 95% CI 61 to 508; p = 0.013) on the left. A borderline association of hippocampal volume with memory performance was observed only in patients with PPMS. Conclusion: Hippocampal atrophy occurs in patients with RRMS and PPMS. Factors additional to hippocampal atrophy may impact on memory performance.

scholarly journals Altered Volume and Structural Connectivity of the Hippocampus in Alzheimer’s Disease and Amnestic Mild Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Feng Feng ◽  
Weijie Huang ◽  
Qingqing Meng ◽  
Weijun Hao ◽  
Hongxiang Yao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Diffusion Tensor ◽  
Structural Connectivity ◽  
Hippocampal Volume ◽  
Brain Regions ◽  
Amnestic Mild Cognitive Impairment ◽  
Hippocampal Atrophy

Background: Hippocampal atrophy is a characteristic of Alzheimer’s disease (AD). However, alterations in structural connectivity (number of connecting fibers) between the hippocampus and whole brain regions due to hippocampal atrophy remain largely unknown in AD and its prodromal stage, amnestic mild cognitive impairment (aMCI).Methods: We collected high-resolution structural MRI (sMRI) and diffusion tensor imaging (DTI) data from 36 AD patients, 30 aMCI patients, and 41 normal control (NC) subjects. First, the volume and structural connectivity of the bilateral hippocampi were compared among the three groups. Second, correlations between volume and structural connectivity in the ipsilateral hippocampus were further analyzed. Finally, classification ability by hippocampal volume, its structural connectivity, and their combination were evaluated.Results: Although the volume and structural connectivity of the bilateral hippocampi were decreased in patients with AD and aMCI, only hippocampal volume correlated with neuropsychological test scores. However, positive correlations between hippocampal volume and ipsilateral structural connectivity were displayed in patients with AD and aMCI. Furthermore, classification accuracy (ACC) was higher in AD vs. aMCI and aMCI vs. NC by the combination of hippocampal volume and structural connectivity than by a single parameter. The highest values of the area under the receiver operating characteristic (ROC) curve (AUC) in every two groups were all obtained by combining hippocampal volume and structural connectivity.Conclusions: Our results showed that the combination of hippocampal volume and structural connectivity (number of connecting fibers) is a new perspective for the discrimination of AD and aMCI.

006 Effect of apolipoprotein e ε4 allele on medial temporal lobe atrophy in ischaemic stroke patients

2018 ◽  
Vol 89 (6) ◽  
pp. A4.1-A4
Author(s):  
Mohamed Salah Khlif ◽  
Emilio Werden ◽  
Natalia Egorova ◽  
Wasim Khan ◽  
Amy Brodtmann
Keyword(s):  
Cognitive Impairment ◽  
Ischaemic Stroke ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Hippocampal Volume ◽  
Stroke Survivors ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
The Right ◽  
Time Point

IntroductionApolipoprotein E (APOE) ε4 allele is a known risk factor for the development of cognitive impairment. APOE ε4 carriers have been reported as having lower hippocampal volume in Alzheimer’s disease, mild cognitive impairment, and in healthy cohorts,1 but this is not well investigated in stroke. Here, we compared the regional volume in the medial temporal lobe in ischaemic stroke survivors, with and without the ε4 allele, three (time point 1, t1) and twelve (t2) months after stroke.Methods21 APOE ε4 carriers and 21 non-carriers, matched for lesion size and location and for neurological impairment as measured by NIHSS, were sampled from the CANVAS study, a longitudinal imaging study in stroke survivors.2 A mixed-effect linear model was used to analyse the effect of the ε4 allele on hippocampal, entorhinal, and para-hippocampal volumes, adjusting for age, sex, years of education, and total intracranial volume. Volumes were estimated using the longitudinal stream in FreeSurfer 5.3.ResultsThe left hippocampal (pt1=0.038, pt2=0.040) and entorhinal (pt1=0.044, pt2=0.038) volumes were significantly lower in the ε4-carrier group at each time point. The right entorhinal (pt1=pt2=0.002) and para-hippocampal (pt1=0.018, pt2=0.020) volumes were also significantly lower in the ε4-carrier group, but there was no difference in the right hippocampal volume (pt1=pt2=0.055) between the two groups. The group-time interaction was significant for the left para-hippocampal cortex (p=0.019): ε4 non-carriers showed a significant volume increase (p=0.018) between t1 and t2.ConclusionThese findings suggest that stroke survivors who carry the APOE-ε4 allele will experience greater atrophy in the medial temporal lobe in the twelve months following their stroke.References1. Manning EN, et al. e4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD. PLoS ONE2014;9(5):e97608.2. Brodtmann A, et al. Charting cognitive and volumetric trajectories after stroke: Protocol for the Cognition And Neocortical Volume After Stroke (CANVAS) study. Int J Stroke2014;9(6):824–828.

Association between executive dysfunction and hippocampal volume in Alzheimer's disease

2010 ◽  
Vol 23 (5) ◽  
pp. 764-771 ◽  
Author(s):  
Tomoyuki Nagata ◽  
Shunichiro Shinagawa ◽  
Yusuke Ochiai ◽  
Ryo Aoki ◽  
Hiroo Kasahara ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Regional Analysis ◽  
Executive Dysfunction ◽  
Hippocampal Volume ◽  
Hippocampal Atrophy ◽  
Z Score ◽  
Clinical Dementia Rating ◽  
Early Alzheimer’S Disease

ABSTRACTBackground: Some previous research has hypothesized that executive dysfunction in patients with early Alzheimer's disease (AD) occurs as a result of a disconnection between different cerebral areas. The aim of the present study was to evaluate how the hippocampal volume influences executive function as a non-memory cognitive function.Methods: From 157 consecutive patients with AD or amnestic mild cognitive impairment (A-MCI), we recruited 107 subjects who had a global Clinical Dementia Rating (CDR) of 0.5 or 1.0 and whose degree of hippocampal atrophy had been measured using magnetic resonance imaging (MRI); the severity of atrophy was assessed using the voxel-based specific regional analysis for Alzheimer's disease (VSRAD) system. We divided the subjects into three groups: mild atrophy, 0 < Z-score < 1.0 (N = 21); moderate atrophy, 1.0 ≤ Z-score < 2.0 (N = 46); or severe atrophy, 2.0 ≤ Z-score < 4.0 (N = 40) according to the Z-score and compared the Frontal Assessment Battery (FAB) and its subtest scores between each atrophy group.Results: The results demonstrated that age, sex ratio, duration of illness, education years, MMSE score, Behave-AD score, and proportion of atrophy area in total brain (%) were not significantly different among the three groups. Only the go/no-go score among the six subtests was significantly lower for increasing atrophy severity (P < 0.05). Furthermore, hippocampal atrophy significantly influenced the go/no-go score independently of interactions from whether the diagnosis was early AD or A-MCI (P < 0.05).Conclusion: These results support a significant association between hippocampal atrophy and executive dysfunction as a non-memory cognitive impairment in patients with early AD and A-MCI.

[P2-320]: RISK FACTOR PROFILES PREDICTING DELAYED VASCULAR COGNITIVE IMPAIRMENT IN YOUNG AND OLD ISCHEMIC STROKE SURVIVORS

2017 ◽  
Vol 13 (7S_Part_15) ◽  
pp. P740-P742
Author(s):  
Russell J. Chander ◽  
Bonnie Y.K. Lam ◽  
Levinia Lim ◽  
Xuling Lin ◽  
Rajinder Singh ◽  
...  
Keyword(s):  
Risk Factor ◽  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Vascular Cognitive Impairment ◽  
Stroke Survivors

scholarly journals What Determines Cognitive Functioning in the Oldest-Old? The EMIF-AD 90+ Study

2020 ◽  
Author(s):  
Nienke Legdeur ◽  
Maryam Badissi ◽  
Maqsood Yaqub ◽  
Nina Beker ◽  
Carole H Sudre ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Nutritional Status ◽  
Oldest Old ◽  
Cognitive Activity ◽  
Hippocampal Volume ◽  
Physical Parameters ◽  
Hippocampal Atrophy ◽  
Brain Pathology ◽  
The Brain

Abstract Objectives Determinants of cognitive functioning in individuals aged 90 years and older, the oldest-old, remain poorly understood. We aimed to establish the association of risk factors, white matter hyperintensities (WMHs), hippocampal atrophy, and amyloid aggregation with cognition in the oldest-old. Method We included 84 individuals without cognitive impairment and 38 individuals with cognitive impairment from the EMIF-AD 90+ Study (mean age 92.4 years) and tested cross-sectional associations between risk factors (cognitive activity, physical parameters, nutritional status, inflammatory markers, and cardiovascular risk factors), brain pathology biomarkers (WMH and hippocampal volume on magnetic resonance imaging, and amyloid binding measured with positron emission tomography), and cognition. Additionally, we tested whether the brain pathology biomarkers were independently associated with cognition. When applicable, we tested whether the effect of risk factors on cognition was mediated by brain pathology. Results Lower values for handgrip strength, Short Physical Performance Battery (SPPB), nutritional status, HbA1c, and hippocampal volume, and higher values for WMH volume and amyloid binding were associated with worse cognition. Higher past cognitive activity and lower body mass index were associated with increased amyloid binding, lower muscle mass with more WMH, and lower SPPB scores with more WMH and hippocampal atrophy. The brain pathology markers were independently associated with cognition. The association of SPPB with cognition was partially mediated by hippocampal volume. Discussion In the oldest-old, physical parameters, nutritional status, HbA1c, WMH, hippocampal atrophy, and amyloid binding are associated with cognitive impairment. Physical performance may affect cognition through hippocampal atrophy. This study highlights the importance to consider multiple factors when assessing cognition in the oldest-old.

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