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.

Theory of Mind in Mild Cognitive Impairment – Relationship with Limbic Structures and Behavioural Change

2019 ◽  
Vol 25 (10) ◽  
pp. 1023-1034 ◽  
Author(s):  
Johannes C. Michaelian ◽  
Loren Mowszowski ◽  
Adam J. Guastella ◽  
Julie D. Henry ◽  
Shantel Duffy ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Theory Of Mind ◽  
Social Cognitive ◽  
Behavioural Change ◽  
Hippocampal Volume ◽  
Control Group ◽  
Social Cognitive Deficits ◽  
Magnetic Resonance Imaging Mri ◽  
The Mind

AbstractObjectives:Older adults presenting with mild cognitive impairment (MCI) have a higher risk of developing dementia and also demonstrate impairments in social cognition. This study sought to establish whether in people with MCI, poorer theory of mind (ToM) was associated with volumetric changes in the amygdala and hippocampus, as well as early changes in behaviour.Methods:One hundred and fourteen people with MCI and fifty-two older adult controls completed the Reading the Mind in the Eyes Test (RMET), while close informants (e.g., spouse/family member/friend/carer) described any current behavioural changes using the Revised Cambridge Behavioural Inventory (CBI-R). A subsample of participants completed structural magnetic resonance imaging (MRI).Results:The MCI group showed poorer performance on all neuropsychological tests administered, and moderate reductions on the RMET compared to the control group (d = .44), with greater reduction observed in those with amnestic compared to non-amnestic MCI (p = .03). While a robust correlation was identified between poorer RMET performance and smaller hippocampal volume in the control group (ρ = .53, p = .01), this relationship was not apparent in the MCI group (ρ = .21, p = .11). In the MCI group, poorer RMET performance was associated with poorer everyday skills (ρ = −.26, p = .01) assessed by the CBI-R.Conclusions:Our findings cross-validate previous reports that social cognitive deficits in ToM are a feature of MCI and also suggest that disruptions to broader neural networks are likely to be implicated. Furthermore, ToM deficits in MCI are associated with a decline in everyday skills such as writing or paying bills.

scholarly journals Visceral adiposity links cerebrovascular dysfunction to cognitive impairment in middle-aged mice

2019 ◽  
Vol 130 ◽  
pp. 104536 ◽  
Author(s):  
Olivier Pétrault ◽  
Maud Pétrault ◽  
Thavarak Ouk ◽  
Régis Bordet ◽  
Vincent Bérézowski ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Visceral Adiposity ◽  
Middle Aged ◽  
Aged Mice ◽  
Cerebrovascular Dysfunction

scholarly journals Hippocampal volume change in depression: Late- and early-onset illness compared

2004 ◽  
Vol 184 (6) ◽  
pp. 488-495 ◽  
Author(s):  
Adrian J. Lloyd ◽  
I. Nicol Ferrier ◽  
Robert Barber ◽  
Anil Gholkar ◽  
Allan H. Young ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Early Onset ◽  
Late Onset ◽  
Neuronal Damage ◽  
Hippocampal Volume ◽  
Vascular Pathology ◽  
Hippocampal Atrophy ◽  
Resonance Imaging ◽  
Biological Factors ◽  
Magnetic Resonance Imaging Mri

BackgroundEvidence for structural hippocampal change in depression is limited despite reports of neuronal damage due to hypercortisolaemia and vascular pathology.AimsTo compare hippocampal and white matter structural change in demographically matched controls and participants with early-onset and late-onset depression.MethodHigh-resolution volumetric magnetic resonance imaging (MRI) and rating of MRI hyperintensities.ResultsA total of 51 people with depression and 39 control participants were included. Participants with late-onset depression had bilateral hippocampal atrophy compared with those with early-onset depression and controls. Hippocampal volumes did not differ between control participants and those with early-onset depression. Age of depression onset correlated (negatively) with hippocampal volume but lifetime duration of depression did not. Hyperintensity ratings did not differ between groups.ConclusionsResults suggest that acquired biological factors are of greater importance in late-than in early-onset illness and that pathological processes other than exposure to hypercortisolaemia of depression underlie hippocampal atrophy in depression of late life.

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 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.

scholarly journals Impaired Spatial Learning and Memory in Middle-Aged Mice with Kindling-Induced Spontaneous Recurrent Seizures

2019 ◽  
Vol 10 ◽  
Author(s):  
Haiyu Liu ◽  
Kurt R. Stover ◽  
Nila Sivanenthiran ◽  
Jonathan Chow ◽  
Chloe Cheng ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Spatial Learning And Memory ◽  
Middle Aged ◽  
Aged Mice ◽  
Spontaneous Recurrent Seizures

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.

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.

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.

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.

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