Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment

Jacquemont, Thomas; Fallani, Fabrizio De Vico; Bertrand, Anne; Epelbaum, Stéphane; Routier, Alexandre; Dubois, Bruno; Hampel, Harald; Durrleman, Stanley; Colliot, Olivier

doi:10.1016/j.neurobiolaging.2017.03.023

Cited by 20 publications

(20 citation statements)

References 90 publications

(117 reference statements)

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“…Furthermore, for individuals with both amyloid pathology and neurodegeneration (A+N+), abnormalities in structural network topology are more significant. Previous studies reported that MCI (A+N+) subjects exhibited distinct brain structural connectivity patterns which is in line with those alterations in patients with AD [35]. Similarly, employing DTI combined with graph theory, cognitively normal individuals with A+N+ showed obvious abnormalities in topological properties characterized by longer paths, lower efficiency, increased clustering and modularity compared with subjects only with neurodegenerative evidence [36].…”

Section: Diffusion Tensor Imagingsupporting

confidence: 67%

Neuroimaging Advances in Preclinical Alzheimers disease

Sheng¹,

Huang²,

Li³

et al. 2018

Neuropsychiatry

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Alzheimer's disease (AD) is considered as a continuously pathological continuum. The AD pathophysiological process begins decades before the emergence of clinical symptoms. Recently, due to the advanced neuroimaging techniques and biochemical tests, various biomarkers are gradually identified, providing the ability to detect the evidence of AD pathology in the preclinical stage and further intervene the process of disease. Multimodal magnetic resonance imaging (MRI), with relatively non-invasive and economic benefits, is of great values to promote the clinical application. Therefore, researches involving brain structural and functional alterations in preclinical AD are summarized in this review.

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Section: Diffusion Tensor Imagingsupporting

confidence: 67%

Neuroimaging Advances in Preclinical Alzheimers disease

Sheng¹,

Huang²,

Li³

et al. 2018

Neuropsychiatry

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“…It should also be acknowledged that neurodegeneration is just one of the factors that likely drives pathophysiological heterogeneity in AD risk or aMCI, with others including amyloidosis or tau pathology (Jacquemont et al . ). The observed link between neurodegeneration and PNS warrants future exploration of AD‐specific neuropathology and its effect on frontal activation and autonomic regulation.…”

Section: Discussionmentioning

confidence: 97%

“…Because aMCI can be a pathophysiologically heterogeneous group (Jacquemont et al . ), these contradictory findings may be due to the examination of HF‐HRV in the context of clinical phenotype instead of AD‐associated neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Cortical thickness is associated with altered autonomic function in cognitively impaired and non‐impaired older adults

Lin

Ren

Wang

et al. 2017

The Journal of Physiology

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The parasympathetic nervous system (PNS) is critical for adaptation to environment demands. PNS can reflect an individual's regulatory capacity of frontal brain regions and has been linked to cognitive capacity. Yet, the relationship of PNS function to cognitive decline and abnormal frontal function that characterize preclinical progression toward Alzheimer's disease (AD) is unclear. Here, we aimed to elucidate the relationship between PNS function and AD-associated neurodegeneration by testing two competing hypotheses involving frontal regions' activity (neurodegeneration vs. compensation). In 38 older human adults with amnestic mild cognitive impairment (aMCI) or normative cognition, we measured AD-associated neurodegeneration (AD signature cortical thickness; ADSCT), resting-state functional magnetic resonance imaging of frontal regions' spontaneous activation, and an electrocardiography measure of PNS (high frequency heart rate variability; HF-HRV). HF-HRV was assessed at rest and during a cognitive task protocol designed to capture HF-HRV reactivity. Higher HF-HRV at rest was significantly related to both more severe AD-associated neurodegeneration (lower ADSCT scores) and worse cognitive ability. Cognitive impairments were also related to greater suppression of HF-HRV reactivity. High activities of the anterior cingulate cortex significantly mediated relationships between ADSCT and both HF-HRV at rest and HF-HRV reactivity. Notably, these relationships were not affected by the clinical phenotype. We show that AD-associated neurodegeneration is associated with altered PNS regulation and that compensatory processes linked to frontal overactivation might be responsible for those alterations. This finding provides the first line of evidence in a new framework for understanding how early-stage AD-associated neurodegeneration affects autonomic regulation.

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“…Other limitations include the small number of studies in each diagnostic category, absence of measurement of premorbid IQ, unknown date of illness onset or character of course, minimal use of measures of adherence, and design variation between studies (Hampstead et al 2014 ). The limited number of studies in each diagnostic category is problematic as MCI subtypes may demonstrate distinct connectivity patterns (Jacquemont et al 2017 ). Improved characterization of various factors associated with baseline status and other covariates would also have aided comparability across studies.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Cognitive Intervention in Mild Cognitive Impairment (MCI): a Meta-Analysis of Outcomes on Neuropsychological Measures

et al. 2017

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Cognitive training in MCI may stimulate pre-existing neural reserves or recruit neural circuitry as “compensatory scaffolding” prompting neuroplastic reorganization to meet task demands (Reuter-Lorenz & Park, 2014). However, existing systematic reviews and meta-analytic studies exploring the benefits of cognitive interventions in MCI have been mixed. An updated examination regarding the efficacy of cognitive intervention in MCI is needed given improvements in adherence to MCI diagnostic criteria in subject selection, better defined interventions and strategies applied, increased use of neuropsychological measures pre- and post-intervention, as well as identification of moderator variables which may influence treatment. As such, this meta-analytic review was conducted to examine the efficacy of cognitive intervention in individuals diagnosed with mild cognitive impairment (MCI) versus MCI controls based on performance of neuropsychological outcome measures in randomized controlled trials (RCT). RCT studies published from January 1995 to June 2017 were obtained through source databases of MEDLINE-R, PubMed, Healthstar, Global Health, PSYCH-INFO, and Health and Psychological Instruments using search parameters for MCI diagnostic category (mild cognitive impairment, MCI, pre-Alzheimer’s disease, early cognitive decline, early onset Alzheimer’s disease, and preclinical Alzheimer’s disease) and the intervention or training conducted (intervention, training, stimulation, rehabilitation, or treatment). Other inclusion and exclusion criteria included subject selection based on established MCI criteria, RCT design in an outpatient setting, MCI controls (active or passive), and outcomes based on objective neuropsychological measures. From the 1199 abstracts identified, 26 articles met inclusion criteria for the meta-analyses completed across eleven (11) countries; 92.31% of which have been published within the past 7 years. A series of meta-analyses were performed to examine the effects of cognitive intervention by cognitive domain, type of training, and intervention content (cognitive domain targeted). We found significant, moderate effects for multicomponent training (Hedges’ g observed = 0.398; CI [0.164, 0.631]; Z = 3.337; p = 0.001; Q = 55.511; df = 15; p = 0.000; I 2 = 72.978%; τ 2 = 0.146) as well as multidomain-focused strategies (Hedges’ g = 0.230; 95% CI [0.108, 0.352]; Z = 3.692; p < 0.001; Q = 12.713; df = 12; p = 0.390; I 2 = 5.612; τ 2 = 0.003). The effects for other interventions explored by cognitive domain, training type, or intervention content were indeterminate due to concerns for heterogeneity, bias, and small cell sizes. In addition, subgroup and meta-regression analyses were conducted with the moderators of MCI category, mode of intervention, training type, intervention content, program duration (total hours), type of control group (active or passive), post-intervention follow-up assessment period, and control for repeat administration. We found significant overall effects for intervention content wi...

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Amyloidosis and neurodegeneration result in distinct structural connectivity patterns in mild cognitive impairment

Cited by 20 publications

References 90 publications

Neuroimaging Advances in Preclinical Alzheimers disease

Neuroimaging Advances in Preclinical Alzheimers disease

Cortical thickness is associated with altered autonomic function in cognitively impaired and non‐impaired older adults

The Efficacy of Cognitive Intervention in Mild Cognitive Impairment (MCI): a Meta-Analysis of Outcomes on Neuropsychological Measures

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