Cognitive dysfunction in chronic Chagas disease cardiomyopathy

Dias, Jesângeli Sousa; Lacerda, Amanda Mota; Vieira-de-Melo, Rodrigo M.; Viana, Leila C.; Jesus, Pedro A. P.; Reis, Francisco José Farias Borges dos; Nitrini, Ricardo; Charchat‐Fichman, Helenice; Lopes, Antônio Alberto; Oliveira‐Filho, Jamary

doi:10.1590/s1980-57642009dn30100006

Cited by 12 publications

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References 29 publications

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“…Importantly, cognitive and memory impairments have been described in chronic CD patients, mainly detected as disturbs of comprehension and perception, orientation and attention loss, as well as impaired capacity to answer to visual-paired comparison tests [ 11 – 15 ]. However, it is a controversial matter as immediate and delayed memory impairment were not detected in patients with Chagas’ heart disease, the main clinical form of CD [ 7 ]. Herein, we questioned whether T .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies described CNS impairment and behavioral alterations in chronic CD patients, attributed to left ventricular heart dysfunction, resulting in brain ischemia by hypoperfusion and/or embolic events [ 6 ]. A higher frequency of cognitive changes has been observed in patients with Chagas’ heart disease, when compared to patients with other cardiac diseases [ 7 ]. Post-mortem analysis of the CNS of CD patients showed cerebral and cerebellar atrophy without neuroinflammation [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Memory impairment in chronic experimental Chagas disease: Benznidazole therapy reversed cognitive deficit in association with reduction of parasite load and oxidative stress in the nervous tissue

et al. 2021

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Memory impairment has been associated with chronic Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. In degenerative diseases, memory loss has been associated with increased oxidative stress, revealed as enhanced lipid peroxidation, in the cerebral cortex. Benznidazole (Bz), a trypanocidal drug efficient to reduce blood parasite load in the acute and chronic phases of infection, showed controversial effects on heart disease progression, the main clinical manifestation of CD. Here, we evaluated whether C57BL/6 mice infected with the Colombian type I T. cruzi strain present memory deficit assessed by (i) the novel object recognition task, (ii) the open field test and (iii) the aversive shock evoked test, at 120 days post infection (dpi). Next, we tested the effects of Bz therapy (25mg/Kg/day, for 30 consecutive days) on memory evocation, and tried to establish a relation between memory loss, parasite load and oxidative stress in the central nervous system (CNS). At 120 dpi, T. cruzi-infected mice showed memory impairment, compared with age-matched non-infected controls. Bz therapy (from 120 to 150 dpi) hampered the progression of habituation and aversive memory loss and, moreover, reversed memory impairment in object recognition. In vehicle-administered infected mice, neuroinflammation was absent albeit rare perivascular mononuclear cells were found in meninges and choroid plexus. Bz therapy abrogated the infiltration of the CNS by inflammatory cells, and reduced parasite load in hippocampus and cerebral cortex. At 120 and 150 dpi, lipid peroxidation was increased in the hippocampus and cortex tissue extracts. Notably, Bz therapy reduced levels of lipid peroxidation in the cerebral cortex. Therefore, in experimental chronic T. cruzi infection Bz therapy improved memory loss, in association with reduction of parasite load and oxidative stress in the CNS, providing a new perspective to improve the quality of life of Chagas disease patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Memory impairment in chronic experimental Chagas disease: Benznidazole therapy reversed cognitive deficit in association with reduction of parasite load and oxidative stress in the nervous tissue

et al. 2021

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“…In the present volume of Dementia & Neuropsychologia , we have published the first formal cognitive evaluation of Chagas disease patients controlling for the presence of cardiac disease, with the disease being the same in cases and controls alike. 34 Subtle abnormalities of visuo-spatial and visual memory deficits were detected. We have recently expanded the cognitive battery to include the clock drawing test and Luria’s sequence and have found both to be more frequently abnormal in Chagas disease patients clinically unaffected by stroke (unpublished observation).…”

Section: Cognitive Dysfunctionmentioning

confidence: 99%

Stroke and brain atrophy in chronic Chagas disease patients: A new theory proposition

Oliveira‐Filho

2009

Dement. neuropsychol.

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Chagas disease (CD) remains a major cause of cardiomyopathy and stroke in developing countries. Brain damage in CD has been attributed exclusively to the effects of structural heart disease on the brain, including cardioembolism and low cardiac output symptoms. However, CD patients also develop stroke and brain atrophy independently of cardiac disease severity. Chronic inflammation directed against T. cruzi may act as a trigger for endothelial damage, platelet activation, acceleration of atherosclerosis and apoptosis, all of which lead to stroke and brain atrophy. In the present article, evidence supporting this new theory is presented, along with considerations towards mechanistically-based targeted treatment.

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“…Dias et al. 22 studied 37 patients with CCC and 42 patients with other cardiomyopathies (OC) matched for gender, educational level and cardiac systolic function, comparing them using the following tests: Mini-Mental State Examination (MMSE), Brief Cognitive Screening Battery, Digit Span Test (forward and backward sequences), Rey Auditory-Verbal Learning Test, Rey Osterreith Complex Figure test (ROCF) and the Hospital Anxiety and Depression Scale. Overall, cognitive performance of the two groups was similar, except for the late recall of the Rey Osterreith Complex figure, where even after correcting for potential confounders (age, education, functional class of HF, use of medications), the performance of the Chagas disease group was significantly worse.…”

Section: Introductionmentioning

confidence: 99%

Clinical assessment, neuroimaging and immunomarkers in Chagas disease study (CLINICS): rationale, study design and preliminary findings

Oliveira‐Filho

Dias

Jesus

et al. 2012

Dement. neuropsychol.

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Chagas disease (CD) is an important cause of cardiomyopathy and stroke in Brazil. Brain infarcts and atrophy seem to occur independently of cardiomyopathy severity and cognitive impairment is understudied.ObjectiveCompare the prevalence of brain magnetic resonance imaging abnormalities between patients with or without CD; determine if inflammatory biomarkers are increased in CD; and determine the efficacy of aspirin in reducing the rate of microembolization in these patients.Methods500 consecutive patients with heart failure will undergo a structured cognitive evaluation, biomarker collection and search for microembolic signals on transcranial Doppler. The first 90 patients are described, evaluated with cognitive tests and brain magnetic resonance imaging to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (MI) and creatine (Cr).ResultsMean age was 55±11 years, 51% female, 38 (42%) with CD. Mean NAA/Cr ratio was lower in patients with CD as compared to other cardiomyopathies. Long-term memory and clock-drawing test were also significantly worse in CD patients. In the multivariable analysis correcting for ejection fraction, age, sex and educational level, reduced NAA/Cr (p=0.006) and cognitive dysfunction (long-term memory, p=0.023; clock-drawing test, p=0.015) remained associated with CD.ConclusionIn this preliminary sample, CD was associated with cognitive impairment and decreased NAA/Cr independently of cardiac function or educational level.

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Cognitive dysfunction in chronic Chagas disease cardiomyopathy

Cited by 12 publications

References 29 publications

Memory impairment in chronic experimental Chagas disease: Benznidazole therapy reversed cognitive deficit in association with reduction of parasite load and oxidative stress in the nervous tissue

Memory impairment in chronic experimental Chagas disease: Benznidazole therapy reversed cognitive deficit in association with reduction of parasite load and oxidative stress in the nervous tissue

Stroke and brain atrophy in chronic Chagas disease patients: A new theory proposition

Clinical assessment, neuroimaging and immunomarkers in Chagas disease study (CLINICS): rationale, study design and preliminary findings

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