scholarly journals Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease

Neurology ◽  
2019 ◽  
Vol 92 (6) ◽  
pp. e601-e612 ◽  
Author(s):  
Rik Ossenkoppele ◽  
Ruben Smith ◽  
Tomas Ohlsson ◽  
Olof Strandberg ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Cortical Thickness ◽  
Neuropsychological Tests ◽  
Temporal Cortex ◽  
Memory Task ◽  
Multiple Comparisons ◽  
Regions Of Interest ◽  
Cognitive Changes ◽  
Preclinical Ad ◽  
Prodromal Ad

ObjectiveTo examine the cross-sectional associations between regional tau, β-amyloid (Aβ), and cortical thickness and neuropsychological function across the preclinical and clinical spectrum of Alzheimer disease (AD).MethodsWe included 106 participants from the Swedish Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study, of whom 33 had preclinical AD (Aβ-positive cognitively normal individuals), 25 had prodromal AD (Aβ-positive mild cognitive impairment), and 48 had probable AD dementia. All underwent [18F]flortaucipir (tau) and structural MRI (cortical thickness), and 88 of 106 underwent [18F]flutemetamol (Aβ) PET. Linear regression models adjusted for age, sex, and education were performed to examine associations between 7 regions of interest and 7 neuropsychological tests for all 3 imaging modalities.ResultsIn preclinical AD, [18F]flortaucipir, but not [18F]flutemetamol or cortical thickness, was associated with decreased global cognition, memory, and processing speed (range standardized β = 0.35–0.52,p< 0.05 uncorrected for multiple comparisons). In the combined prodromal AD and AD dementia group, both increased [18F]flortaucipir uptake and reduced cortical thickness were associated with worse performance on a variety of neuropsychological tests (most regions of interest survived correction for multiple comparisons atp< 0.05), while increased [18F]flutemetamol uptake was specifically associated with lower scores on a delayed recall memory task (p< 0.05 uncorrected for multiple comparisons). The strongest effects for both [18F]flortaucipir and cortical thickness on cognition were found in the lateral and medial parietal cortex and lateral temporal cortex. The effect of [18F]flutemetamol on cognition was generally weaker and less region specific.ConclusionOur findings suggest that tau PET is more sensitive than Aβ PET and measures of cortical thickness for detecting early cognitive changes in preclinical AD. Furthermore, both [18F]flortaucipir PET and cortical thickness show strong cognitive correlates at the clinical stages of AD.

scholarly journals Cognitive Phenotypes, Brain Morphometry and the Detection of Cognitive Decline in Preclinical AD

2009 ◽  
Vol 21 (1-2) ◽  
pp. 29-37 ◽  
Author(s):  
Mark W. Jacobson ◽  
Linda K. McEvoy ◽  
Anders Dale ◽  
Christine Fennema-Notestine
Keyword(s):  
Test Performance ◽  
Neuropsychological Tests ◽  
Healthy Aging ◽  
Structural Changes ◽  
Cognitive Test ◽  
Cognitive Changes ◽  
Brain Morphometry ◽  
Preclinical Phase ◽  
Preclinical Ad ◽  
Cognitive Test Performance

Identifying a preclinical phase of Alzheimer’s Disease (PCAD) that is distinct from cognitive changes in healthy aging continues to be a major research focus. Combining neuropsychological and neuroimaging methodologies should improve our ability to differentiate healthy from pathological aging, although studies that utilize both methods often result in equivocal findings, possibly due to variability in cognitive test performance that may be capturing distinct phenotypes. One method of capturing this cognitive variability is to utilize contrasting neuropsychological tests to identify subgroups representative of distinct cognitive phenotypes, and determine whether differences in brain morphometry support these classifications. We review several approaches to defining cognitive subgroups, and we consider the possibility that cognitive asymmetry might provide one means of identifying both functional and structural changes associated with aging and dementia.

scholarly journals Association of β-Amyloid Accumulation With Executive Function in Adults With Unimpaired Cognition

Neurology ◽  
2022 ◽  
pp. 10.1212/WNL.0000000000013299
Author(s):  
Pontus Tideman ◽  
Erik Stomrud ◽  
Antoine Leuzy ◽  
Niklas Mattsson-Carlgren ◽  
Sebastian Palmqvist ◽  
...  
Keyword(s):  
Executive Function ◽  
Cortical Thickness ◽  
Cognitive Test ◽  
Csf Biomarkers ◽  
Cognitive Changes ◽  
Cognitive Domains ◽  
Preclinical Ad ◽  
Β Amyloid ◽  
Tau Pet ◽  
With Memory

Background and Objectives:The neuropathological changes underlying Alzheimer´s disease (AD) start before overt cognitive symptoms arise, but it is not well-known how they relate to the first subtle cognitive changes. The objective for this study was to examine the independent associations of the AD hallmarks β-amyloid (Aβ), tau, and neurodegeneration with different cognitive domains in cognitively unimpaired (CU) individuals.Methods:In this cross-sectional study, CU participants from the prospective BioFINDER-2 study were included. All had CSF biomarkers (Aβ42 and P-tau181), MRI (cortical thickness of AD-susceptible regions), Aβ-PET (neocortical uptake), tau-PET (entorhinal uptake), and cognitive test data for i) memory, ii) executive function, iii) verbal function, iv), and visuospatial function. Multivariable linear regression models were performed, using either CSF Aβ42, P-tau181 and cortical thickness or Aβ-PET, tau-PET, and cortical thickness, as predictors of cognitive function. The results were validated in an independent cohort (ADNI).Results:316 CU participants were included from the BioFINDER-2 study. Abnormal Aβ-status was independently associated with the executive measure, regardless of modality (CSF Aβ42 β=0.128, p=0.024; Aβ-PET β=0.124, p=0.049), while tau was independently associated with memory (CSF P-tau181 β=0.132, p=0.018; tau-PET β=0.189, p=0.002). Cortical thickness was independently associated with the executive measure and verbal fluency in both models (p=0.005-0.018). To examine the relationships in the earliest stage of preclinical AD, only participants with normal biomarkers of tau and neurodegeneration were included (n=217 CSF-based; n=246 PET-based). Again, Aβ-status was associated with executive function (CSF Aβ42, β=0.189, p=0.005; Aβ-PET, β=0.146, p=0.023), but not with other cognitive domains. The results were overall replicated in the ADNI cohort (n=361).Discussion:These findings suggest that Aβ is independently associated with worse performance on an executive measure but not with memory performance, which instead is associated with tau pathology. This may have implications for early preclinical AD screening and outcome measures in AD trials targeting Aβ pathology.

scholarly journals Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 13 ◽  
Author(s):  
Federica Cacciamani ◽  
Marion Houot ◽  
Geoffroy Gagliardi ◽  
Bruno Dubois ◽  
Sietske Sikkes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Meta Analysis ◽  
Self Report ◽  
Original Research ◽  
Cognitive Changes ◽  
Amnestic Mci ◽  
Preclinical Ad ◽  
Prodromal Ad

Background: Identifying a poor degree of awareness of cognitive decline (ACD) could represent an early indicator of Alzheimer's disease (AD).Objectives: (1) to understand whether there is evidence of poor ACD in the pre-dementia stages of AD; (2) to summarize the main findings obtained investigating ACD in AD; (3) to propose a conceptual framework.Data Sources: We searched Scopus, Pubmed, and the reference lists for studies published up to August 2020. Original research articles must report a measure of ACD and included individuals with AD dementia, or prodromal AD (or MCI), or being at risk for AD.Data Synthesis: All studies covering preclinical, prodromal, and AD dementia were systematically reviewed. We intended to perform a meta-analysis of empirical studies on preclinical AD or prodromal AD (or MCI), to compare ACD between clinical groups. Due to the paucity of literature on preclinical AD, meta-analysis was only possible for prodromal AD (or MCI) studies.Results: We systematically reviewed 283 articles, and conducted a meta-analysis of 18 articles on prodromal AD (or MCI), showing that ACD was not significantly different between patients with amnestic and non-amnestic MCI (SMD = 0.09, p = 0.574); ACD was significantly poorer in amnestic MCI (SMD = −0.56, p = 0.001) and mild AD (SMD = −1.39, p &lt; 0.001) than in controls; ACD was also significantly poorer in mild AD than in amnestic MCI (SMD = −0.75, p &lt; 0.001), as well as poorer than in non-amnestic MCI (SMD = −1.00, p &lt; 0.001). We also discuss key findings on ACD in AD, such as its neural and cognitive correlates.Conclusions and Implications: We propose that patients may be complaining of their initial subtle cognitive changes, but ACD would soon start to decrease. The individual would show mild anosognosia in the MCI stage, and severe anosognosia in dementia. The evaluation of ACD (comparing self-report to cognitive scores or to informant-report) could be useful to guide the clinician toward a timely diagnosis, and in trials targeting early-stage AD.

scholarly journals Lipid Peroxidation Assessment in Preclinical Alzheimer Disease Diagnosis

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1043
Author(s):  
Carmen Peña-Bautista ◽  
Lourdes Álvarez-Sánchez ◽  
Inés Ferrer ◽  
Marina López-Nogueroles ◽  
Antonio José Cañada-Martínez ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Area Under Curve ◽  
Disease Diagnosis ◽  
Csf Biomarkers ◽  
Preclinical Ad ◽  
Aging Populations ◽  
Advanced Stages ◽  
Preclinical Diagnosis ◽  
T Tau ◽  
And Oxidative Stress

Background: Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the earliest stages. A diagnosis in the initial or preclinical stages of the disease could help in a more effective action of the treatments. Methods: Isoprostanoid biomarkers were determined in plasma samples from preclinical AD participants (n = 12) and healthy controls (n = 31) by chromatography and mass spectrometry (UPLC-MS/MS). Participants were accurately classified according to cerebrospinal fluid (CSF) biomarkers and neuropsychological examination. Results: Isoprostanoid levels did not show differences between groups. However, some of them correlated with CSF biomarkers (t-tau, p-tau) and with cognitive decline. In addition, a panel including 10 biomarkers showed an area under curve (AUC) of 0.96 (0.903–1) and a validation AUC of 0.90 in preclinical AD prediction. Conclusions: Plasma isoprostanoids could be useful biomarkers in preclinical diagnosis for AD. However, these results would require a further validation with an external cohort.

scholarly journals Online Learning for Classification of Alzheimer Disease based on Cortical Thickness and Hippocampal Shape Analysis

2014 ◽  
Vol 20 (1) ◽  
pp. 61 ◽  
Author(s):  
Ga-Young Lee ◽  
Jeonghun Kim ◽  
Ju Han Kim ◽  
Kiwoong Kim ◽  
Joon-Kyung Seong
Keyword(s):  
Online Learning ◽  
Alzheimer Disease ◽  
Cortical Thickness ◽  
Shape Analysis

scholarly journals Changes in thalamocortical connectivity as a potential mechanism of cross-modal plasticity in congenitally blind individuals

2018 ◽  
Author(s):  
Theo Marins ◽  
Maite Russo ◽  
Erika Rodrigues ◽  
jorge Moll ◽  
Daniel Felix ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Cortical Thickness ◽  
Visual Information ◽  
Brain Plasticity ◽  
Temporal Cortex ◽  
Occipital Cortex ◽  
Brain Structures ◽  
Congenitally Blind ◽  
Blind Individuals ◽  
Neuroimaging Techniques

ABSTRACTEvidence of cross-modal plasticity in blind individuals has been reported over the past decades showing that non-visual information is carried and processed by classical “visual” brain structures. This feature of the blind brain makes it a pivotal model to explore the limits and mechanisms of brain plasticity. However, despite recent efforts, the structural underpinnings that could explain cross-modal plasticity in congenitally blind individuals remain unclear. Using advanced neuroimaging techniques, we mapped the thalamocortical connectivity and assessed cortical thickness and integrity of white matter of congenitally blind individuals and sighted controls to test the hypothesis that aberrant thalamocortical pattern of connectivity can pave the way for cross-modal plasticity. We described a direct occipital takeover by the temporal projections from the thalamus, which would carry non-visual information (e.g. auditory) to the visual cortex in congenitally blinds. In addition, the amount of thalamo-occipital connectivity correlated with the cortical thickness of primary visual cortex (V1), supporting a probably common (or related) reorganization phenomena. Our results suggest that aberrant thalamocortical connectivity as one possible mechanism of cross-modal plasticity in blinds, with potential impact on cortical thickness of V1.SIGNIFICANT STATEMENTCongenitally blind individuals often develop greater abilities on spared sensory modalities, such as increased acuity in auditory discrimination and voice recognition, when compared to sighted controls. These functional gains have been shown to rely on ‘visual’ cortical areas of the blind brain, characterizing the phenomenon of cross-modal plasticity. However, its anatomical underpinnings in humans have been unsuccessfully pursued for decades. Recent advances of non-invasive neuroimaging techniques allowed us to test the hypothesis of abnormal thalamocortical connectivity in congenitally blinds. Our results showed an expansion of the thalamic connections to the temporal cortex over those that project to the occipital cortex, which may explain, the cross-talk between the visual and auditory systems in congenitally blind individuals.

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