Pathways to neurodegeneration

Thomas, Julia; Brier, Matthew R.; Snyder, Abraham Z.; Vaida, Florin; Ances, Beau M.

doi:10.1212/wnl.0b013e318288792b

Cited by 156 publications

(183 citation statements)

References 40 publications

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“…However, there are occurrences of PD without Lewy bodies called secondary Parkinsonism that are thought to involve viral infections. A large subset of HIV-infected patients present akinetic Parkinsonian syndromes at the early stage of disease onset, but PD-like syndromes are mostly reversed by HAART depending on the age and genetic predisposition of the patient [227, 228]. Patients who survive beyond 50 years of age most often exhibit accelerated degradation of neural networks compared with age-matched controls, mostly in the basal ganglia and hippocampal regions, due to the synergistic effects of immune-senescence and sustained viral load, despite beingundercontrol[229].…”

Section: Other Neurodegenerative Diseases Linked To Hiv Infectionmentioning

confidence: 99%

An Overview of Human Immunodeficiency Virus Type 1-Associated Common Neurological Complications: Does Aging Pose a Challenge?

Nookala

Mitra

Chaudhari

et al. 2017

JAD

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With increasing survival of patients infected with human immunodeficiency virus type 1 (HIV-1), the manifestation of heterogeneous neurological complications is also increasing alarmingly in these patients. Currently, more than 30% of about 40 million HIV-1 infected people worldwide develop central nervous system (CNS)-associated dysfunction, including dementia, sensory, and motor neuropathy. Furthermore, the highly effective antiretroviral therapy has been shown to increase the prevalence of mild cognitive functions while reducing other HIV-1-associated neurological complications. On the contrary, the presence of neurological disorder frequently affects the outcome of conventional HIV-1 therapy. Although, both the children and adults suffer from the post-HIV treatment-associated cognitive impairment, adults, especially depending on the age of disease onset, are more prone to CNS dysfunction. Thus, addressing neurological complications in an HIV-1-infected patient is a delicate balance of several factors and requires characterization of the molecular signature of associated CNS disorders involving intricate cross-talk with HIV-1-derived neurotoxins and other cellular factors. In this review, we summarize some of the current data supporting both the direct and indirect mechanisms, including neuro-inflammation and genome instability in association with aging, leading to CNS dysfunction after HIV-1 infection, and discuss the potential strategies addressing the treatment or prevention of HIV-1-mediated neurotoxicity.

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Section: Other Neurodegenerative Diseases Linked To Hiv Infectionmentioning

confidence: 99%

An Overview of Human Immunodeficiency Virus Type 1-Associated Common Neurological Complications: Does Aging Pose a Challenge?

Nookala

Mitra

Chaudhari

et al. 2017

JAD

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“…In particular, functional correlations between brain networks are significantly reduced in HIV+ patients and a signature of the disease may be present that is different than other neurodegenerative disorders. The effects of HIV and aging on BOLD resting state functional correlations were shown to be independent of each other [75]*. However, the effects of cART have not been assessed using BOLD imaging.…”

Section: Functional Magnetic Resonance Imaging (Fmri)mentioning

confidence: 99%

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

Ances

Hammoud

2014

Current Opinion in HIV and AIDS

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Purpose of review HIV enters the brain after initial infection, and with time can lead to HIV associated neurocognitive disorders (HAND). While the introduction of combination antiretroviral therapy (cART) has reduced the more severe forms of HAND, milder forms are still highly prevalent. The “gold standard” for HAND diagnosis remains detailed neuropsychological performance (NP) testing but additional biomarkers (including neuroimaging) may assist in early detection of HAND. Recent findings We review the application of recently developed non-invasive magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques in HIV+ individuals. In particular, magnetic resonance spectroscopy (MRS) may be more sensitive than conventional MRI alone in detecting HIV associated changes. Diffusion tensor imaging (DTI) has become increasingly popular for assessing changes in white matter structural integrity due to HIV. Both functional MRI and PET have been limitedly performed but could provide keys for characterizing neuropathophysiologic changes due to HIV. Summary It is hoped that continued progress will allow novel neuroimaging methods to be included in future HAND management guidelines.

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“…Age differences in functional connectivity have been examined extensively for the default network (e.g., Andrews-Hanna et al, 2007;Damoiseaux et al, 2008;Grady et al, 2012), and to some extent for other brain networks (Allen et al, 2011;Campbell et al, 2012;Onoda et al, 2012;Rieckmann et al, 2011;Thomas et al, 2013;Tomasi and Volkow, 2012;Voss et al, 2010). Weaker functional connectivity has been reported specifically within the SLN or in SLN nodes in older adults (Allen et al, 2011;Geerligs et al, in press;He et al, 2014;Meier et al, 2012;Onoda et al, 2012;Tomasi and Volkow, 2012), leading us to predict age-related reductions in SLN functional connectivity in our results, although connectivity within the striatum, a node of the SLN, has been shown to increase with age (Allen et al, 2011;Tomasi and Volkow, 2012;Wang et al, 2012).…”

Section: The Current Studymentioning

confidence: 99%

Age differences in brain activity related to unsuccessful declarative memory retrieval

2015

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Although memory recall is known to be reduced with normal aging, little is known about the patterns of brain activity that accompany these recall failures. By assessing faulty memory, we can identify the brain regions engaged during retrieval attempts in the absence of successful memory and determine the impact of aging on this functional activity. We used functional magnetic resonance imaging to examine age differences in brain activity associated with memory failure in three memory retrieval tasks: autobiographical (AM), episodic (EM) and semantic (SM). Compared to successful memory retrieval, both age groups showed more activity when they failed to recall a memory in regions consistent with the salience network (SLN), a brain network also associated with non-memory errors. Both groups also showed strong functional coupling among SLN regions during incorrect trials and in intrinsic patterns of functional connectivity. In comparison to young adults, older adults demonstrated (1) less activity within the SLN during unsuccessful AM trials; (2) weaker intrinsic functional connectivity between SLN nodes and dorsolateral prefrontal cortex; and (3) less differentiation of SLN functional connectivity during incorrect trials across memory conditions. These results suggest that the SLN is engaged during recall failures, as it is for non-memory errors, which may be because errors in general have particular salience for adapting behavior. In older adults, the dedifferentiation of functional connectivity within the SLN across memory conditions and the reduction of functional coupling between it and prefrontal cortex may indicate poorer internetwork communication and less flexible use of cognitive control processes, either while retrieval is attempted or when monitoring takes place after retrieval has failed. Keywords fMRI; aging; episodic memory; salience network; frontal lobe IntroductionA number of studies have provided extensive evidence of the neural circuitry that supports memory retrieval (e.g., Cabeza and Nyberg, 2000;Spaniol et al., 2009 CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscript2008), as well as evidence of how aging influences this circuitry (e.g., Cabeza et al., 2005;Grady, 2012;Rajah and D'Esposito, 2005). However, most research has investigated how the brain supports successful memory performance (Addis and McAndrews, 2006;Brewer et al., 1998;Morcom et al., 2003;Wagner et al., 1998), and limited attention has been paid to brain networks involved in faulty memory retrieval, most notably faulty long-term memory recall. A number of processes may be engaged during recall, including goal setting, memory search, accessing (hopefully correct) stored memories, and evaluating retrieval success (Henson et al., 1999;Moscovitch, 1992;Rugg et al., 2002). The assessment of faulty memory retrieval can be used to identify brain regions whose activity reflects processes engaged when retrieval fails. Such processes can include cognitive control processes involved regardless of retrieval succes...

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Pathways to neurodegeneration

Cited by 156 publications

References 40 publications

An Overview of Human Immunodeficiency Virus Type 1-Associated Common Neurological Complications: Does Aging Pose a Challenge?

An Overview of Human Immunodeficiency Virus Type 1-Associated Common Neurological Complications: Does Aging Pose a Challenge?

Neuroimaging of HIV-associated neurocognitive disorders (HAND)

Age differences in brain activity related to unsuccessful declarative memory retrieval

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