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 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.

P4-122: Risk factors for prevalent cognitive impairment in chronic kidney disease: The brain in kidney disease (BRINK) study

2015 ◽  
Vol 11 (7S_Part_18) ◽  
pp. P824-P825
Author(s):  
Anne Murray ◽  
David Tupper ◽  
Sandra Savik ◽  
Elizabeth Amiot ◽  
David S. Knopman
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Cognitive Impairment ◽  
Kidney Disease ◽  
The Brain

scholarly journals Cognitive impairment and risk factors of LATE in the oldest old: The 90+ Study

2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
S. Ahmad Sajjadi ◽  
Michael Phelan ◽  
Rui Yan ◽  
Kiana Alexis Scambray ◽  
Chu‐Ching Ho ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Oldest Old

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.

Pathogenesis, Diagnosis, and Treatment of Vascular and Mixed Dementias

2013 ◽  
pp. 900-903
Author(s):  
Helena Chang Chui
Keyword(s):  
Public Health ◽  
Risk Factors ◽  
Cognitive Impairment ◽  
Mr Imaging ◽  
Early Identification ◽  
Late Life ◽  
Vascular Cognitive Impairment ◽  
Prevention And Treatment ◽  
The Brain ◽  
Alzheimer Pathology

This chapter addresses five common questions surrounding vascular cognitive impairment (VCI): pathogenesis, diagnostic accuracy, incidence and prevalence, relationship between VBI and Alzheimer disease (AD), and prevention/treatment. Although vascular cognitive impairment is considered to be the second most common form of cognitive impairment and dementia in late life, it can be argued that public health emphasis should be placed more on the prevention and treatment of vascular brain injury (VBI), which for example may be detectable by MR imaging. We review the historical syndromes and current diagnostic criteria, which have focused on defining various subtypes of VCI and have influenced estimates of incidence and prevalence. Recent neuropathological studies have highlighted the frequent concurrence of Alzheimer pathology and VBI in late life. Converging evidence suggests that AD and VBI impose differential but additive deleterious effects on cognitive function. The field is moving increasingly to earlier detection of the brain at risk using MR imaging, as well as to the early identification and treatment of vascular risk factors.

scholarly journals Magnetic Resonance Volumetry: Prediction of Subjective Memory Complaints and Mild Cognitive Impairment, and Associations with Genetic and Cardiovascular Risk Factors

2016 ◽  
Vol 6 (3) ◽  
pp. 529-540 ◽  
Author(s):  
Sigbjørn Rogne ◽  
Torgil Vangberg ◽  
Petter Eldevik ◽  
Gry Wikran ◽  
Ellisiv B. Mathiesen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cardiovascular Risk ◽  
Mild Cognitive Impairment ◽  
Cardiovascular Risk Factors ◽  
Hippocampal Volume ◽  
Subjective Memory Complaints ◽  
Subjective Memory ◽  
Memory Complaints ◽  
Mr Volumetry

Background/Aims: Subjective memory complaints (SMC) are strong predictors of mild cognitive impairment (MCI) and subsequent Alzheimer’s disease. Our aims were to see if fully automated cerebral MR volume measurements could distinguish subjects with SMC and MCI from controls, and if probable parental late-onset Alzheimer’s disease (LOAD), apolipoprotein E ε4 genotype, total plasma homocysteine, and cardiovascular risk factors were associated with MR volumetric findings. Methods: 198 stroke-free subjects comprised the control (n = 58), the SMC (n = 25) and the MCI (n = 115) groups. Analysis of covariance and receiver operating characteristic curve was used to see if MR volumetry distinguished subjects with SMC and MCI from controls. Results: Subjects with SMC and MCI had significantly larger lateral ventricles and smaller hippocampal volumes than controls. The area under the curve in subjects with SMC and MCI compared to that of controls was less than 0.68 for all volumes of intracranial structures. There was an interaction between sex and probable parental LOAD for hippocampal volume, with a significant association between probable parental LOAD and hippocampal volume in women. Conclusions: Fully automated MR volumetry can distinguish subjects with SMC and MCI from controls in a general population, but insufficiently to assume a clear clinical role. Research on sporadic LOAD might benefit from a sex-specific search for genetic risk factors.

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.

Mixed Brain Pathology Is the Most Common Cause of Cognitive Impairment in the Elderly

2020 ◽  
Vol 78 (1) ◽  
pp. 453-465
Author(s):  
Irina Alafuzoff ◽  
Sylwia Libard
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
The Elderly ◽  
Systemic Diseases ◽  
Brain Pathology ◽  
Cerebrovascular Lesions ◽  
Peripheral Organs ◽  
Age Related

Background: Systemic diseases, diabetes mellitus (DM), and cardiovascular disease (CaVD) have been suggested being risk factors for cognitive impairment (CI) and/or influence Alzheimer’s disease neuropathologic change (ADNC). Objective: The purpose was to assess the type and the extent of neuropathological alterations in the brain and to assess whether brain pathology was associated with CaVD or DM related alterations in peripheral organs, i.e., vessels, heart, and kidney. Methods: 119 subjects, 15% with DM and 24% with CI, age range 80 to 89 years, were chosen and neuropathological alterations were assessed applying immunohistochemistry. Results: Hyperphosphorylated τ (HPτ) was seen in 99%, amyloid-β (Aβ) in 71%, transactive DNA binding protein 43 (TDP43) in 62%, and α-synuclein (αS) in 21% of the subjects. Primary age related tauopathy was diagnosed in 29% (more common in females), limbic predominant age-related TDP encephalopathy in 4% (14% of subjects with CI), and dementia with Lewy bodies in 3% (14% of subjects with CI) of the subjects. High/intermediate level of ADNC was seen in 47% and the extent of HPτ increased with age. The extent of ADNC was not associated with the extent of pathology observed in peripheral organs, i.e., DM or CaVD. Contrary, brain alterations such as pTDP43 and cerebrovascular lesions (CeVL) were influenced by DM, and CeVL correlated significantly with the extent of vessel pathology. Conclusion: In most (66%) subjects with CI, the cause of impairment was “mixed pathology”, i.e., ADNC combined with TDP43, αS, or vascular brain lesions. Furthermore, our results suggest that systemic diseases, DM and CaVD, are risk factors for CI but not related to ADNC.

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