Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network

Balthazar, Márcio Luiz Figueredo; Pereira, F.; Lopes, Tátila Martins; Silva, Elvis L. da; Coan, Ana Carolina; Campos, Brunno M.; Duncan, Niall W.; Stella, Florindo; Northoff, Georg; Damasceno, Benito Pereira; Cendes, Fernando

doi:10.1002/hbm.22248

Cited by 164 publications

(153 citation statements)

References 55 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…The SN, with the anterior insula as its integral outflow hub, assists target brain regions to generate behavioral responses to salient stimuli 10 . In a previous study of our group, we showed that connectivity in the right insula of AD patients was related to symptoms of agitation, disinhibition, irritability, euphoria, and aberrant motor behavior 4 . Moreover, task-based functional MRI studies showed that hyperactivity of anterior insula has been consistently implicated with anxiety disorders 11 .…”

Section: Discussionmentioning

confidence: 67%

“…Although these networks showed alterations, some anatomical structures did not exhibit cortical atrophy, which suggests that behavioral disorders may be triggered by disruptions in functional connectivity with or without the atrophy of the structures of these networks. In addition, NPS could be related to disruptions in functional connectivity before evidence for cortical changes 4 . Voxel-based Morphometry (VBM) has recently been used in research to verify the possible correlation between GM density and NPS.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Hayata

Bergo

Rezende

et al. 2015

Arq. Neuro-Psiquiatr.

Self Cite

View full text Add to dashboard Cite

Neuropsychiatric syndromes (NPS) in dementia due to Alzheimer' s disease (AD) have received growing attention across clinical centers and research settings in the last few decades. The high prevalence of NPS and their increasing severity in AD patients aggravate the disease' s course and cause distress for caregivers. These symptoms, once considered secondary behavior due to cognitive and functional impairment in dementia, have shown patterns of temporal course, which do not necessarily follow the linear decline of cognitive impairment.Several NPS seem to be more prevalent and clinically prominent in distinct stages of the disease. Depression is the most common syndrome in mild-to-moderate AD, while delusions, hallucinations, and aggression seem to be more common as the disease progresses, whereas apathy remains across all stages of AD, worsening as the global deterioration aggravates. However, these manifestations, also detected in mild cognitive impairment (MCI), increase the risk of dementia and may occur in prodromal AD.Moreover, aberrant vocalizations commonly emerge when patients are in advanced stages of dementia. Despite the fact that NPS and cognitive alterations may considerably overlap, these findings suggest distinct etiologies for both conditions. Furthermore, over the course of the disease, the prevalence of NPS reaches 50-90% of patients with dementia AbstrACtNeuropsychiatric symptoms in Alzheimer's disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives: To compare cortical atrophy's patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method: 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results: Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion: Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices.Keywords: depression, anxiety, MRI, neurodegenerative disease, neuropsychiatry. resumo Os sintomas neuropsiquiátricos na doença de Alzheimer (DA) são prevalentes, porém suas relações com padrões de atrofia cortical não são totalmente compreendidas. Objetivos: Comparar padrões de atrofia cortical entre DA e controles; verificar se há correlações entre sintomas neuropsiquiátricos e atrofia cortical. Método: 33 pacientes com DA foram examinados pelo Inventário Neuropsiquiátrico. Os pacientes e 29 controles foram submeti...

show abstract

Section: Discussionmentioning

confidence: 67%

mentioning

confidence: 99%

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Hayata

Bergo

Rezende

et al. 2015

Arq. Neuro-Psiquiatr.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Accordingly, both inferior frontal gyrus (both sides, r3n12 and r7n12) and the frontal portion of the DMN (r1n4) proved to be positively correlated, also in contrast to controls. The relationship between DMN, salience and ECNs is under investigation, but recent studies defined that DMN and salience work oppositely, meaning that the increase of the first is followed by a decrease in the second, and vice‐versa [Balthazar, et al, 2014]. Some authors suggest that this mechanism involves a mediation of activity executed by the salience network guiding the focus on internal (DMN) or external (ECN) process and stimulus [Liang et al, 2016].…”

Section: Discussionmentioning

confidence: 99%

Large‐scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy

Campos

Coan

Yasuda

et al. 2016

Human Brain Mapping

Self Cite

108

102

View full text Add to dashboard Cite

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large‐scale RSNs is differently affected in patients with right‐ and left‐MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting‐state functional‐MRIs of 99 subjects (52 controls, 26 right‐ and 21 left‐MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF2C‐toolbox, which provided ROI‐wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right‐MTLE. Both groups showed abnormal correlation between the dorsal‐DMN and the posterior salience, as well as between the dorsal‐DMN and the executive‐control network. Patients with left‐MTLE also showed reduced correlation between the dorsal‐DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left‐MTLE expressed a low cluster coefficient, whereas the altered connections on right‐MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right‐ and left‐MTLE patients with HS have widespread abnormal interactions of large‐scale brain networks; however, all parameters evaluated indicate that left‐MTLE has a more intricate bihemispheric dysfunction compared to right‐MTLE. Hum Brain Mapp 37:3137–3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

show abstract

“…Heightened salience network connectivity in healthy individuals has been associated with negative emotional reactivity and glucocorticoid levels (e.g., cortisol), a neuroendocrine index of the stress response (30). In AD, increased salience network connectivity relates to neuropsychiatric hyperactivity symptoms (e.g., agitation, irritability, aberrant motor behavior, disinhibition, and euphoria) (31). Neurodegeneration of medial temporal structures that support emotion inhibition (27,28) and lateral temporal structures that promote socioemotional processes, including evaluation of faces (32), prosody (33), intention (34), and trustworthiness (35), may alter affective physiology, behavior, and experience in MCI and AD.…”

mentioning

confidence: 99%

Heightened emotional contagion in mild cognitive impairment and Alzheimer’s disease is associated with temporal lobe degeneration

Sturm

Yokoyama

Seeley

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

145

133

View full text Add to dashboard Cite

Emotional changes are common in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Intrinsic connectivity imaging studies suggest that default mode network degradation in AD is accompanied by the release of an emotion-relevant salience network. We investigated whether emotional contagion, an evolutionarily conserved affect-sharing mechanism, is higher in MCI and AD secondary to biological alterations in neural networks that support emotion. We measured emotional contagion in 237 participants (111 healthy controls, 62 patients with MCI, and 64 patients with AD) with the Interpersonal Reactivity Index Personal Distress subscale. Depressive symptoms were evaluated with the Geriatric Depression Scale. Participants underwent structural MRI, and voxel-based morphometry was used to relate whole-brain maps to emotional contagion. Analyses of covariance found significantly higher emotional contagion at each stage of disease progression [controls < MCI (P < 0.01) and MCI < AD (P < 0.001)]. Depressive symptoms were also higher in patients compared with controls [controls < MCI (P < 0.01) and controls < AD (P < 0.0001)]. Higher emotional contagion (but not depressive symptoms) was associated with smaller volume in right inferior, middle, and superior temporal gyri (P FWE < 0.05); right temporal pole, anterior hippocampus, parahippocampal gyrus; and left middle temporal gyrus (all P < 0.001, uncorrected). These findings suggest that in MCI and AD, neurodegeneration of temporal lobe structures important for affective signal detection and emotion inhibition are associated with up-regulation of emotion-generating mechanisms. Emotional contagion, a quantifiable index of empathic reactivity that is present in other species, may be a useful tool with which to study emotional alterations in animal models of AD.empathy | social behavior | simulation | affective resonance P rogressive deterioration of memory and other cognitive functions characterizes Alzheimer's disease (AD) (1) and its prodromal stage, mild cognitive impairment (MCI) (2). Deposition of beta-amyloid plaques and neurofibrillary tangles, the hallmark pathological changes in AD (3), is hypothesized to begin decades before the emergence of cognitive symptoms and subsequent functional decline (4). Emotional symptoms are also common and have been found in 35-85% of patients with MCI (5-7) and up to 75% of patients with AD (8), with depression and anxiety the most frequent symptoms seen. Individuals with MCI who have comorbid emotional complaints are more likely to progress to dementia than those without such symptoms (9-13). Taken together, these studies suggest that a clinical presentation that includes both cognitive decline and emotion dysregulation may point to an underlying AD process and that emotional symptoms themselves may portend or even exacerbate disease progression (9,11,14).The medial temporal lobe is among the earliest sites of disease in MCI and AD (2, 15), and hippocampal atrophy is associated with worse episodic memory performance on standardi...

show abstract

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network

Cited by 164 publications

References 55 publications

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Large‐scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy

Heightened emotional contagion in mild cognitive impairment and Alzheimer’s disease is associated with temporal lobe degeneration

Contact Info

Product

Resources

About