Frontiers in aging neuroscience
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Front Aging Neurosci · Jan 2017
Disrupted Thalamus White Matter Anatomy and Posterior Default Mode Network Effective Connectivity in Amnestic Mild Cognitive Impairment.
Alzheimer's disease (AD) and its prodromal state amnestic mild cognitive impairment (aMCI) are characterized by widespread abnormalities in inter-areal white matter fiber pathways and parallel disruption of default mode network (DMN) resting state functional and effective connectivity. In healthy subjects, DMN and task positive network interaction are modulated by the thalamus suggesting that abnormal task-based DMN deactivation in aMCI may be a consequence of impaired thalamo-cortical white matter circuitry. Thus, this article uses a multimodal approach to assess white matter integrity between thalamus and DMN components and associated effective connectivity in healthy controls (HCs) relative to aMCI patients. ⋯ No structural deficits were found between DMN nodes. Abnormal posterior DMN activity may be driven by changes in thalamic white matter connectivity; a view supported by the close anatomical and functional association of thalamic nuclei effected by AD pathology and the posterior DMN nodes. We conclude that dysfunctional posterior DMN activity in aMCI is consistent with disrupted cortico-thalamo-cortical processing and thalamic-based dissemination of hippocampal disease agents to cortical hubs.
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Front Aging Neurosci · Jan 2017
ReviewInsulin Resistance and Alzheimer's Disease: Bioenergetic Linkages.
Metabolic dysfunction is a well-established feature of Alzheimer's disease (AD), evidenced by brain glucose hypometabolism that can be observed potentially decades prior to the development of AD symptoms. Furthermore, there is mounting support for an association between metabolic disease and the development of AD and related dementias. Individuals with insulin resistance, type 2 diabetes mellitus (T2D), hyperlipidemia, obesity, or other metabolic disease may have increased risk for the development of AD and similar conditions, such as vascular dementia. ⋯ Despite the progress made in understanding the pathogenesis of AD and in the development of potential therapies, at present we remain without a disease-modifying treatment. In this review, we will discuss insulin resistance as a contributing factor to the pathogenesis of AD, as well as the metabolic and bioenergetic disruptions linking insulin resistance and AD. We will also focus on potential neuroimaging tools for the study of the metabolic dysfunction commonly seen in AD with hopes of developing therapeutic and preventative targets.
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Front Aging Neurosci · Jan 2017
Cortical Surface Thickness in the Middle-Aged Brain with White Matter Hyperintense Lesions.
Background and purpose: Previous voxel-based morphometry (VBM) studies have suggested that cortical atrophy is regionally distributed in middle-aged subjects with white matter hyperintense (WMH) lesions. However, few studies have assessed cortical thickness in middle-aged WMH subjects. In this study, we examined cortical thickness as well as cortical morphometry associated with the presence of WMH lesion load in middle-aged subjects. ⋯ A voxel-wise negative correlation was found between cortical thickness and WMH lesion loads in the right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), and right subcallosal cortex (P < 0.01, FWE-corrected). Conclusion: The main findings of this study suggest that middle-aged WMH subjects are more likely to exhibit cortical thinning, especially in multimodal integration and recognition- and motor-related regions. The current morphometry data provide further evidence for WMH-associated structural plasticity.
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Despite varied etiologies and symptoms, several neurodegenerative diseases-specifically, Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HDs)-share the common feature of abnormal circadian rhythms, such as those in behavior (e.g., disrupted sleep/wake cycles), physiological processes (e.g., diminished hormone release) and biochemical activities (e.g., antioxidant production). Circadian disturbances are among the earliest symptoms of these diseases, and the molecular mechanisms of the circadian system are suspected to play a pivotal, and possibly causal, role in their natural histories. Here, we review the common circadian abnormalities observed in ADs, PDs and HDs, and summarize the evidence that the molecular circadian clockwork directly influences the course of these disease states. On the basis of this research, we explore several circadian-oriented interventions proposed as treatments for these neurological disorders.
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Front Aging Neurosci · Jan 2017
Functional Connectivity Disruption in Subjective Cognitive Decline and Mild Cognitive Impairment: A Common Pattern of Alterations.
Functional connectivity (FC) alterations represent a key feature in Alzheimer's Disease (AD) and provide a useful tool to characterize and predict the course of the disease. Those alterations have been also described in Mild Cognitive Impairment (MCI), a prodromal stage of AD. There is a growing interest in detecting AD pathology in the brain in the very early stages of the disorder. ⋯ These results highlight that elders with SCD present FC alterations. More importantly, those disruptions affected AD typically related areas and showed great overlap with the alterations exhibited by MCI patients. These results support the consideration of SCD as a preclinical stage of AD and may indicate that FC alterations appear very early in the course of the disease.