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Neuroimaging predictors of brain amyloidosis in mild cognitive impairment.

ABSTRACT: OBJECTIVE:To identify a neuroimaging signature predictive of brain amyloidosis as a screening tool to identify individuals with mild cognitive impairment (MCI) that are most likely to have high levels of brain amyloidosis or to be amyloid-free. METHODS:The prediction model cohort included 62 MCI subjects screened with structural magnetic resonance imaging (MRI) and (11) C-labeled Pittsburgh compound B positron emission tomography (PET). We identified an anatomical shape variation-based neuroimaging predictor of brain amyloidosis and defined a structural MRI-based brain amyloidosis score (sMRI-BAS). Amyloid beta positivity (A?(+) ) predictive power of sMRI-BAS was validated on an independent cohort of 153 MCI patients with cerebrospinal fluid A?1-42 biomarker data but no amyloid PET scans. We compared the A?(+) predictive power of sMRI-BAS to those of apolipoprotein E (ApoE) genotype and hippocampal volume, the 2 most relevant candidate biomarkers for the prediction of brain amyloidosis. RESULTS:Anatomical shape variations predictive of brain amyloidosis in MCI embraced a characteristic spatial pattern known for high vulnerability to Alzheimer disease pathology, including the medial temporal lobe, temporal-parietal association cortices, posterior cingulate, precuneus, hippocampus, amygdala, caudate, and fornix/stria terminals. A?(+) prediction performance of sMRI-BAS and ApoE genotype jointly was significantly better than the performance of each predictor separately (area under the curve [AUC] = 0.88 vs AUC = 0.70 and AUC = 0.81, respectively) with >90% sensitivity and specificity at 20% false-positive rate and false-negative rate thresholds. Performance of hippocampal volume as an independent predictor of brain amyloidosis in MCI was only marginally better than random chance (AUC = 0.56). INTERPRETATION:As one of the first attempts to use an imaging technique that does not require amyloid-specific radioligands for identification of individuals with brain amyloidosis, our findings could lead to development of multidisciplinary/multimodality brain amyloidosis biomarkers that are reliable, minimally invasive, and widely available.

SUBMITTER: Tosun D

PROVIDER: S-EPMC4603555 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Neuroimaging predictors of brain amyloidosis in mild cognitive impairment.

Tosun Duygu D Joshi Sarang S Weiner Michael W MW

Annals of neurology 20130801 2

<h4>Objective</h4>To identify a neuroimaging signature predictive of brain amyloidosis as a screening tool to identify individuals with mild cognitive impairment (MCI) that are most likely to have high levels of brain amyloidosis or to be amyloid-free.<h4>Methods</h4>The prediction model cohort included 62 MCI subjects screened with structural magnetic resonance imaging (MRI) and (11) C-labeled Pittsburgh compound B positron emission tomography (PET). We identified an anatomical shape variation- ...[more]

PMID: 23686534

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Project description:Traumatic brain injury (TBI) can be serious partly due to the challenges of assessing and treating its neurocognitive and affective sequelae. The effects of a single TBI may persist for years and can limit patients' activities due to somatic complaints (headaches, vertigo, sleep disturbances, nausea, light or sound sensitivity), affective sequelae (post-traumatic depressive symptoms, anxiety, irritability, emotional instability) and mild cognitive impairment (MCI, including social cognition disturbances, attention deficits, information processing speed decreases, memory degradation and executive dysfunction). Despite a growing amount of research, study comparison and knowledge synthesis in this field are problematic due to TBI heterogeneity and factors like injury mechanism, age at or time since injury. The relative lack of standardization in neuropsychological assessment strategies for quantifying sequelae adds to these challenges, and the proper administration of neuropsychological testing relative to the relationship between TBI, MCI and neuroimaging has not been reviewed satisfactorily. Social cognition impairments after TBI (e.g., disturbed emotion recognition, theory of mind impairment, altered self-awareness) and their neuroimaging correlates have not been explored thoroughly. This review consolidates recent findings on the cognitive and affective consequences of TBI in relation to neuropsychological testing strategies, to neurobiological and neuroimaging correlates, and to patient age at and assessment time after injury. All cognitive domains recognized by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are reviewed, including social cognition, complex attention, learning and memory, executive function, language and perceptual-motor function. Affect and effort are additionally discussed owing to their relationships to cognition and to their potentially confounding effects. Our findings highlight non-negligible cognitive and affective impairments following TBI, their gravity often increasing with injury severity. Future research should study (A) language, executive and perceptual-motor function (whose evolution post-TBI remains under-explored), (B) the effects of age at and time since injury, and (C) cognitive impairment severity as a function of injury severity. Such efforts should aim to develop and standardize batteries for cognitive subdomains-rather than only domains-with high ecological validity. Additionally, they should utilize multivariate techniques like factor analysis and related methods to clarify which cognitive subdomains or components are indeed measured by standardized tests.

Project description:Mild cognitive impairment (MCI) is a multifactorial and complex central neurodegenerative disease. Acupuncture appears to be an effective method for cognitive function improvement in MCI patients. Neural plasticity remaining in the MCI brain implies that acupuncture-associated benefits may not be limited to the cognitive function. Instead, neurological alternations in the brain play a vital role in corresponding to the cognitive improvement. However, previous studies have mainly focused on the effects of cognitive function, leaving neurological findings relatively unclear. This systematic review summarized existing studies that used various brain imaging techniques to explore the neurological effect regarding acupuncture use for MCI treatment. Potential neuroimaging trials were searched, collected, and identified independently by two researchers. Four Chinese databases, four English databases, and additional sources were searched to identify studies reporting the use of acupuncture for MCI from the inception of databases until 1 June 2022. Methodological quality was appraised using the Cochrane risk-of-bias tool. In addition, general, methodological, and brain neuroimaging information was extracted and summarized to investigate the potential neural mechanisms by which acupuncture affects patients with MCI. In total, 22 studies involving 647 participants were included. The methodological quality of the included studies was moderate to high. The methods used included functional magnetic resonance imaging, diffusion tensor imaging, functional near-infrared spectroscopy, and magnetic resonance spectroscopy. Acupuncture-induced brain alterations observed in those patients with MCI tended to be observable in the cingulate cortex, prefrontal cortex, and hippocampus. The effect of acupuncture on MCI may play a role in regulating the default mode network, central executive network, and salience network. Based on these studies, researchers could extend the recent research focus from the cognitive domain to the neurological level. Future researches should develop additional relevant, well-designed, high-quality, and multimodal neuroimaging researches to detect the effects of acupuncture on the brains of MCI patients.

Project description:IntroductionWhile Alzheimer's disease (AD) is divided into severity stages, mild cognitive impairment (MCI) remains a solitary construct despite clinical and prognostic heterogeneity. This study aimed to characterize differences in genetic, cerebrospinal fluid (CSF), neuroimaging, and neuropsychological markers across clinician-derived MCI stages.MethodsVanderbilt Memory & Aging Project participants with MCI were categorized into 3 severity subtypes at screening based on neuropsychological assessment, functional assessment, and Clinical Dementia Rating interview, including mild (n = 18, 75 ± 8 years), moderate (n = 89 72 ± 7 years), and severe subtypes (n = 18, 78 ± 8 years). At enrollment, participants underwent neuropsychological testing, 3T brain magnetic resonance imaging (MRI), and optional fasting lumbar puncture to obtain CSF. Neuropsychological testing and MRI were repeated at 18-months, 3-years, and 5-years with a mean follow-up time of 3.3 years. Ordinary least square regressions examined cross-sectional associations between MCI severity and apolipoprotein E (APOE)-ε4 status, CSF biomarkers of amyloid beta (Aβ), phosphorylated tau, total tau, and synaptic dysfunction (neurogranin), baseline neuroimaging biomarkers, and baseline neuropsychological performance. Longitudinal associations between baseline MCI severity and neuroimaging and neuropsychological trajectory were assessed using linear mixed effects models with random intercepts and slopes and a follow-up time interaction. Analyses adjusted for baseline age, sex, race/ethnicity, education, and intracranial volume for MRI models.ResultsStages differed at baseline on APOE-ε4 status (early < middle = late; p-values < 0.03) and CSF Aβ (early > middle = late), phosphorylated and total tau (early = middle < late; p-values < 0.05), and neurogranin concentrations (early = middle < late; p-values < 0.05). MCI stage related to greater longitudinal cognitive decline, hippocampal atrophy, and inferior lateral ventricle dilation (early < late; p-values < 0.03).DiscussionClinician staging of MCI severity yielded longitudinal cognitive trajectory and structural neuroimaging differences in regions susceptible to AD neuropathology and neurodegeneration. As expected, participants with more severe MCI symptoms at study entry had greater cognitive decline and gray matter atrophy over time. Differences are likely attributable to baseline differences in amyloidosis, tau, and synaptic dysfunction. MCI staging may provide insight into underlying pathology, prognosis, and therapeutic targets.

Project description:To understand how a model of Alzheimer disease pathophysiology based on ?-amyloidosis and neurodegeneration predicts the regional anatomic expansion of hypometabolism and atrophy in persons with mild cognitive impairment (MCI).To define the role of ?-amyloidosis and neurodegeneration in the subsequent progression of topographic cortical structural and metabolic changes in MCI.Longitudinal, observational study with serial brain imaging conducted from March 28, 2006, to January 6, 2015, using a population-based cohort. A total of 96 participants with MCI (all aged >70 years) with serial imaging biomarkers from the Mayo Clinic Study of Aging or Mayo Alzheimer's Disease Research Center were included. Participants were characterized initially as having elevated or not elevated brain ?-amyloidosis (A+ or A-) based on 11C-Pittsburgh compound B positron emission tomography. They were further characterized initially by the presence or absence of neurodegeneration (N+ or N-), where the presence of neurodegeneration was defined by abnormally low hippocampal volume or hypometabolism in an Alzheimer disease-like pattern on 18fluorodeoxyglucose (FDG)-positron emission tomography.Regional FDG standardized uptake value ratio (SUVR) and gray matter volumes in medial temporal, lateral temporal, lateral parietal, and medial parietal regions.In the primary regions of interest (ROI), the A+N+ group (n = 45) had lower FDG SUVR at baseline compared with the A+N- group (n = 17) (all 4 ROIs; P <?.001). The A+N+ group also had lower FDG SUVR at baseline (all 4 ROIs; P <?.01) compared with the A-N- group (n = 12). The A+N+ group had lower medial temporal gray matter volume at baseline (P <?.001) compared with either the A+N- group or A-N- group. The A+N+ group showed large longitudinal declines in FDG SUVR (P <?.05 for medial temporal, lateral temporal, and medial parietal regions) and gray matter volumes (P <?.05 for medial temporal and lateral temporal regions) compared with the A-N+ group (n = 22). The A+N+ group also showed large longitudinal declines compared with the A-N- group on FDG SUVR (P <?.05 for medial temporal and lateral parietal regions) and gray matter volumes (all 4 ROIs; P <?.05) compared with the A+N- group. The A-N+ group did not show declines in FDG SUVR or gray matter volume compared with the A+N- or A-N- groups.Persons with MCI who were A+N+ demonstrated volumetric and metabolic worsening in temporal and parietal association areas, consistent with the expectation that the MCI stage in the Alzheimer pathway heralds incipient isocortical involvement. The A-N+ group, those with suspected non-Alzheimer pathophysiology, lacked a distinctive longitudinal volumetric or metabolic profile.

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Neuroimaging predictors of brain amyloidosis in mild cognitive impairment.

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Neuroimaging predictors of brain amyloidosis in mild cognitive impairment.

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