Elderly people with human T-cell leukemia virus type 1-associated myelopathy present an early impairment in cognitive skillsAbstract
Background Cerebral changes occur in individuals with human T-cell leukemia virus type 1 (HTLV-1 )-associated myelopathy (HAM) and seem to predominate in subcortical areas. Little is known about the cognitive decline in the elderly living with HTLV-1.
Objective To evaluate the cognitive aging of individuals infected with HTLV-1 aged ≥ 50 years.
Methods This is a cross-sectional study of former blood donors infected with HTLV-1 who have been followed in the cohort of the Interdisciplinary Research Group on HTLV-1 since 1997. The groups of study consisted of 79 HTLV-1 infected individuals aged ≥ 50 years, with 41 of them presenting symptomatic HAM and 38 being asymptomatic carriers, and 59 seronegative individuals (controls) aged ≥ 60 years. All were submitted to the P300 electrophysiological test and neuropsychological tests.
Results Individuals with HAM presented delayed P300 latency in relation to the other groups, and this latency delay increased progressively with aging. The performance of this group in the neuropsychological tests was also the worst. The HTLV-1- asymptomatic group performance was similar to that of the control group.
Conclusions Individuals with HAM presented cognitive decline that progressed with aging and, although HTLV-1-asymptomatic carriers appear to present cognitive aging similar to that of healthy elderly people, concern about a subclinical cognitive impairment is warranted in this population.
Keywords: Aged; Human T-lymphotropic Virus 1; Paraparesis, Tropical Spastic; Event-Related Potentials, P300; Neuropsychological Tests; Cognition
Resumo
Antecedentes Alterações cerebrais ocorrem em indivíduos com mielopatia associada ao vírus da leucemia de células T humanas tipo 1 (HTLV-1) (HAM) e parecem predominar em áreas subcorticais. Pouco se sabe sobre o declínio cognitivo em idosos vivendo com HTLV-1.
Objetivo Avaliar o envelhecimento cognitivo de indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos.
Métodos Trata-se de um estudo transversal com ex-doadores de sangue infectados pelo HTLV-1 acompanhados na coorte do Grupo Interdisciplinar de Pesquisa em HTLV-1 há 20 anos. Os grupos de estudo foram compostos por 79 indivíduos infectados pelo HTLV-1 com idade ≥ 50 anos, sendo que 41 apresentavam HAM e 38 eram portadores assintomáticos, e 59 indivíduos soronegativos (controles) com idade ≥ 60 anos. Todos foram submetidos ao teste eletrofisiológico P300 e testes neuropsicológicos.
Resultados Indivíduos com HAM apresentaram atraso na latência do P300 em relação aos demais grupos, e esse atraso de latência aumentou progressivamente com o envelhecimento. O desempenho desse grupo nos testes neuropsicológicos também foi o pior. O desempenho do grupo HTLV-1- assintomático foi semelhante ao do grupo controle.
Conclusão Indivíduos com HAM apresentaram declínio cognitivo que progrediu com o envelhecimento e, embora os portadores assintomáticos do HTLV-1 pareçam apresentar envelhecimento cognitivo semelhante ao dos idosos saudáveis, justificase a preocupação com um comprometimento cognitivo subclínico nessa população.
Palavras-chave: Idoso; Vírus Linfotrópico T Tipo 1 Humano; Paraparesia Espástica Tropica l; Potenciais Evocados P300; Testes Neuropsicológicos; Cognição
INTRODUCTION
The human T-cell leukemia virus type 1 (HTLV-1) is endemic in some regions of the world, and Japan, Africa,theCaribbean islands, and South America are the areas of greatest circulation of this virus. In these areas, the prevalence gradually increases with age, especially among women.1,2 The prevalence analysis of HTLV-1 infection in Brazil’s blood bank in 2016 indicates that every 1,008 in 100,000 blood-donor candidates have HTLV-1 infection, and 354 (35%) are older than 50-year-old.2 Thus, a higher prevalence of HTLV-1 infection is expected in the elderly population compared with the younger.
Human T-cell leukemia virus type 1 can cause HTLV-1-associated myelopathy (HAM), a neurological disease in which diffuse loss of myelin and axons occurs in the medulla, especially in the thoraco-lumbar region.3 The spinal cord damage leads to changes in motor and autonomic function that impair functionality and activities of daily living. Bladder dysfunction, constipation, and gait changes are the most common alterations.4 Consequently, the studies about the neurological manifestations associated with HTLV-1 have been focused on the spinal cord disease and, comparatively, fewer studies have considered the brain changes associated with HTLV-1 infection, al- though brain changes in the asymptomatic phase of the infection have already been found.5 In HAM, the magnetic resonance imaging (MRI) showed lesions similar to the ones found in the human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs).6 Therefore, cognitive impairment can be a neurological manifestation associated with HTLV-1 infection.7,8,9,10,11
The literature is scarce regarding the cognitive performance of HTLV-1-infected people over 50 years of age, and, then, we aimed at evaluating the performance of people living with HTLV-1 over 50 years of age in terms of attention, memory, general cognitive ability, executive functions, motor and psychomotor speed, and manual dexterity. Our hypothesis is that HTLV-1-infected people, especially those who develop HAM, present cognitive impairment parallel to the spinal cord damage.
METHODS
Ethical aspects
This research was conducted in accordance with the principles expressed in the Declaration of Helsinki and was approved by the research ethics committee from Universidade FederaldeMinas Gerais (COEPUFMG), logged under protocol CAAE 92928518.3.0000.5149 and number 2898825. All participants provided voluntary written consent and declared that they were aware of the study procedures and their choice to participate.
Participants
All participants in this study take part in the cohort of the Interdisciplinary Research Group on HTLV-1 (GIPH). They are seronegative blood donors and former blood donors infected with HTLV-1 from the state of Minas Gerais, Brazil, who have been followed up since 1997. In this study, 138 individuals from this cohort were included and distributed into the groups with and without HTLV-1 infection.
The study groups consisted of 59 HTLV-1-seronegative blood donors (controls), as assessed by enzyme-linked immune sorbent assay (ELISA), and 79 HTLV-1-infected ex-blood donors, diagnosed by ELISA and confirmed by Western blot analysis (WB HTLV 2.4, Genelabs Diagnostics, Singapore Science Park 1, Singapore) or by real-time polymerase chain reaction (RTPCR). The HTLV-1 group was divided into 41 HAM and 38 HTLV-1-asymptomatic carriers, according to the neurological assessment.12 The score on the Osame motor disability score (OMDS) scale was ≥ 1 for individuals with HAM and 0 for HTLV-1-asymptomatic carriers.13
Study design
A cross-sectional, comparative study was carried out, nested to an open cohort, in which HTLV-1 seropositive adults ≥ 50 years of age were compared to HTLV-1 seronegative adults ≥ 60 years of age in relation to cognitive abilities that were assessed using the P300 electrophysiological test and neuropsychological tests. The decision to evaluate individuals infected with HTLV-1 who were 10 years younger than the seronegative controls was based on the comparison of the aging of these patients with the pattern of premature aging that occurs in HIV infection, in which individuals above 50 years of age are classified as elderly people.14 Human T-cell leukemia virus type 1 and HIV cause structural brain changes seen in MRI that seem to be similar.6
The individuals recruited for this research were initially submitted to a clinical and neurological evaluation and, later, to an audiological evaluation that consisted of tonal and vocal audiometry, imitanciometry with 226 Hz probe (Interacoustics, Middelfart, Denmark), and brainstem auditory evoked potential (BAEP) at 90 dB hearing level (dB HL) (model MASBE/ATCPlus, Contronic Ltda., Pelotas, RS, Brazil). Finally, the participants included in this study were submitted to cognitive assessment.
The exclusion criteria were coinfection with HIV and/or HTLV-2, patients with diagnoses of dementia, alcoholism, or drug addiction, mental illness, sequelae due to opportunistic infections in the central nervous system (CNS), hearing loss greater than 40 dB HL at frequencies from 500 Hz to 4,000 Hz, any alteration in the middle ear or deformities in the external auditory canal, alteration of the auditory pathways to the brainstem, and patients with depressive symptoms scored above 5 on the geriatric depression scale of 15 items.15
Neurocognitive tests
Electrophysiological test – Auditory P300 Test
The event-related potential (ERP) is an electrophysiological method that allows the capture of human neuroelectric activities when the individual is subjectedto a specific event, such as an auditory stimulus. The P300 complex of the ERP consists of a large positive waveform whose peak occurs around 300 milliseconds (ms) after the stimulus presentation. The P300 is generated by a complex neural network, in which connections occur involving the thalamus, temporalparietal cortex, prefrontal cortex, hippocampus and limbic region, being closely related to short-term memory and attention.16 The P300 latency increases with aging, and latency prolongation beyond the accepted limits considered as normal for a determined age group indicates the occurrence of a cognitive dysfunction.16,17,18 Sleep deprivation can interfere with the generation of P300.19 So, the participants were instructed to sleep at least 6hours on the night before the auditory P300 test. Drugs that act on the CNS, such as benzodiazepines, neuroleptics, and anticonvulsants, can delay P300. So, these drugs were controlled in the statistical analysis.
The auditory P300 test was performed with the individual in a seated and comfortable position, with their eyes open, in an electric and acoustically treated room with dim light, using the MASBE/ACTPlus equipment (Contronic Ltda. The participants’ skin was cleaned with abrasive paste, and the electrodes were fixed according to the international electrode system (IES) 10-20 standard, with the negative electrodes placed on theleft (A1)andright (A2) earlobes, the ground electrode on the forehead (Fp1), and the active electrode on the forehead (Fz).20 Studies have already shown that obtaining P300 latency is not affected by the location chosen for fixing the active electrode, whether in Fz, Cz or Pz.7,21,22 In relation to the electrode impedance, the maximum accepted value for each electrode was 3 kΩ, and the difference in impedance between the electrodes was, at most, 1 kΩ. The stimulus used was the tone burst with binaural presentation with TDH-39 phone (Huntington, NY, United States) and intensity of 90dB HL. For the generation of P300, the auditory oddball paradigm was used, in which 2 stimuli were presented randomly, with one of them occurring frequently and the other in a rare way (target). The individuals were instructed to identify and mentally count the number of rare stimuli (target). The parameters defined for the stimulus characterized as frequent were a tone burst soundinthefrequencyof1,000 Hz, 50 cycles ofduration, 20% rise and decay time, 60% plateau, trapezoidal envelope, and alternating polarity. For the tone burst stimulus characterized as rare, the parameters were a frequency of 2,000 Hz, 100 cycles of duration, 20% rise and decay time, 60% plateau, trapezoidal envelop and alternating polarity. For each exam, 300 stimuli were presented, with a rate of 0.8 stimuli per second, with 80% of frequent stimuli and 20% rare. The amplifiers were configured with the 200 µV full scale, the 01 Hz high-pass filter, the 20Hz low-pass filter and the 60Hz notch filter. The time window was 1,000ms and the electroencephalogram was enlarged 50,000 times. Before starting the exam, the stimuli were presented so that the participants became familiar with the test. The procedure was repeated once more to guarantee the replication of the tracing. P300 analysis was performed separately by two independent examiners who were experienced in electrophysiological examinations. The analysis was masked in relation to the group.
The P300 component is the largest positive peak between 250 and 500ms following the presentation of the stimulus, and it occurs after the N100, P160, and N200 components. The study of the P300 can regard its amplitude or latency. Amplitude can be interpreted as the number of cognitive resources that an individual allocates in a cognitive task and, therefore, refers to mental effort.16 Latency, on the other hand, allows inference regarding performance in specific cognitive skills, especially attention and working memory. Thus, the P300 latency (P3b) is more commonly used to diagnose and monitor cognitive impairment and, for this reason, was the variable considered in the present research.23
Neuropsychological tests
After being submitted to the auditory P300 test, the participants underwent neuropsychological tests to assess specific cognitive domains. The tests applied were Raven colored progressive matrices (RAVEN), which assesses general cognitive ability24; Rey auditory-verbal learning test (RAVLT) adapted for the Brazilian elderly population, which evaluates recent memory, verbal learning, susceptibility to interference, retention of information after a certain period of time in which other activities are performed, and memory recognition25; frontal assessment battery (FAB), which evaluates executive functions26; international HIV dementia scale (IHDS), which identifies individuals at risk of developing HIV-associated neurocognitive disorders (HANDs),27 and Nine-hole peg test (NHPT) dominant hand (DH) and nondominant hand (NDH), which assesses manual dexterity.28 Higher score as a result on the NHPT indicates worse performance because it shows that the individual spent more time to complete the test. Lower scores for the other tests indicate poorer performance.
Statistical analysis
The measurement of interrater agreement of the P300 result was applied using the intraclass correlation coefficient (ICC), in which a value ≥ 0.70 indicates good reliability.29 Descriptive analysis was performed using measures of central tendency and variability for continuous variables and analysis of frequency for categorical variables. The pattern of distribution of the continuous variables was performed using the Shapiro-Wilk and Kolmogorov-Smirnov tests. The comparison of continuous variables between groups was performed using the analysis of variance (ANOVA) with Bonferroni, Kruskal-Wallis, and Mann-Whitney tests. Spearman correlation coefficients were calculated to find correlation between variables. To compare categorical variables between groups, the Chi-squared test was used. For statistical significance, an alpha error of 0.05 was considered. The analyses were performed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, NY, USA).
RESULTS
Characteristics of the participants
The groups were similar regarding educational level (p = 0.224) and gender (p = 0.895). As expected, the average age of the control group was higher than the one of the HTLV-1-infected groups (p < 0.001). These data are summarized in Table 1.
Some patients used medications with possible potential deleterious effects on the cognition: 7 (5%) clonazepam, 4 (3%) baclofen, 3 (2%), gabapentin, and less than 1% reported oxcarbazepine, carbamazepine, pregabaline, or phenobarbital. No association was found between cognitive performance and the use of these medications.
Electrophysiological test - Auditory P300 Test
In the P300 interrater analysis, a good reliability was found in the double masking analysis of the P300 latency (ICC = 0.984, p < 0.001). So, the P300 measures were shown to be adequate. The P300 latency was delayed in the HAM group when compared with the HTLV-1-asymptomatic and control groups (Figure 1).
Between-groups comparison of P300 latency obtained from the seronegative group (n = 59), human T-cell lymphotropic virus type 1 (HTLV-1)-asymptomatic group (n =38) and HTLV-1 associated myelopathy (HAM) group (n = 41). Note: The boxes denote the P300 latency in each of the three groups. The horizontal line in the box represents the median; the box hinges represent the first (Q1) and third quartiles (Q3). Upper and lower whiskers extend from the hinge to the highest/lowest value that lies within the 1.5 interquartile range (IQR) of the hinge. Notes: *p < 0.001; p, significance probability (independent-samples Kruskal-Wallis test for specific comparisons).
The difference was clarified in the stratified analysis by age group. Comparisons were made in groups and between groups for the ranges of 50 to 59, 60 to 69, and 70 to 79 years of age. The HAM group had the most delayed latency compared with the HTLV-1-asymptomatic and control groups (Table 2).
Comparison of P300 latency stratified by the age ranges 50 to 59, 60 to 69, and 70 to 79 in the asymptomatic and HTLV-1-infected groups and between them
A regular and progressive P300 delay was observed from the ranges of 50 to 59, 60 to 69, and 70 to 79 years of age in the HAM group (Figure 2 and Table 2). The HTLV-1-asymptomatic group presented a different P300 pattern. In this group, the latency, although slightly delayed, was considered similar to the one found in the control group for all the age ranges (Table 2). In addition, a stable P300 latency with aging was observed, as it occurred in the control group (Figure 2 and Table 2).
Scatter graph showing the correlation between P300 latency and the aging of (A) individuals with HTLV-1-associated myelopathy (HAM), (B) HTLV-1-asymptomatic carriers, and (C) seronegative controls distributed by age. Note: A positive correlation between increasing age and prolongation of P300 latency was detected only for the HAM group.Notes: p, significance probability; r, correlation coefficient; Spearman rho test.
In order to characterize thetrend of P300 latency with the aging in the groups with and without the HTLV-1 infection, a correlation between P300 latency and age was performed, and a positive correlation was found between an increasing age and P300 latency prolongation only for the HAM group (Figure 2).
Neuropsychological tests
The performance of the individuals in neuropsychological tests can be seen in Table 3. The general cognitive ability (RAVEN) was found to be similar among the groups. The analysis of the RAVLT test, including all the scales, was found to be different in the A5 subscale, which evaluates verbal learning, and in A7, which evaluates verbal recall related to long-term memory, indicating worse performance of the HAM group compared to the control group, but not to the HTLV-1-asymptomatic group. The test of executive functions using FAB and motor skills using IHDS, which are more specific for HAND, found a worse performance in theHAM group, compared with the HTLV-1-asymptomatic and control groups. In addition, in the analysis of the time spent performing the NHPT, the HAM group presented a worse result using either the dominant or non-dominant hand when compared with the other two groups.
Comparative analysis between the seronegative (n = 59), HTLV-1-asymptomatic carriers (n = 38), and HAM (n = 41) groups regarding performance in neuropsychological tests
DISCUSSION
The understanding of the cognitive aging process that occurs in individuals living with HTLV-1 can contribute to early therapeutic decisions that favor the maintenance of the cognitive skills. This research discusses HTLV-1 infection andaging. Cognitive changes were moresevere inindividuals with HAM compared to the findings of the other groups. Human T-cell leukemia virus type 1-asymptomatic carriers presented a performance closer to that observed in the control group, except for the findings in the RAVLT test (Table 2 and Table 3).
The P300 latency was delayed in the HAM group in comparison to the seronegative controls. Even when comparing participants in the older age group among the seronegative controls (70–79) and in the younger age group among those with HAM (50–59), the difference remained (Table 2). In fact, a delayed P300 latency in individuals with HAM has already been noted.7 Considering that only the HAM group showed a consistent P300 latency prolongation in comparison to the seronegative controls (Figure 1 and Table 2) and that this delay was correlated with aging (Figure 2), it was assumed that individuals with HAM presented an early cognitive decline that could not be explained by aging alone, as this same trend did not occur in the HTLV-1-asymptomatic group. The results of the neuropsychological tests support this hypothesis. The HAM group had greater difficulty to perform such tests compared with the other groups, especially the tests that are more related to subcortical changes – FAB, IHDS, and NHPT (Table 3). A study on P300 in elderly people living with HIV, usingasimilar methodologytothatof thepresent study, observed similar changes inthe HAM grouptotheones found by us.30 In fact, the HIV-positive individuals over 50 years of age have an increased risk of cognitive impairment, with changes that are found mainly in attention, memory, fluency and executive functions.12 These findings reinforce the suspicion that HIVand HTLV-1 may cause lesions in the CNS that are similar in terms of location and pathophysiology.31 The HTLV-1 virus causes an uncontrolled inflammation in the CNS, leading to a progressive demyelination, which seems to occur in HAND.32,33 The predominance of an inflammatory profile in the CNS of individuals with HAM is well established.34
The P300 latency maintained a pattern related to the aging that varied according to the HTLV-1 group. Differently from the results presented by the individuals with HAM, the P300 latency remained stable with the aging in HTLV-1 asymptomatic carriers, similar to what was observed in the control group (Table 2 and Figure 2). A progressive P300 latency delay is expected to occur with aging.17,35 On the other hand, studies about this subject have been scarce, and aging without a concomitant P300 latency delay has also been published.30
When a comparison was made between the HAM and HTLV-1 asymptomatic groups, an unexpected P300 latency similarity appeared in the comparison between the HAM youngest age group and the eldest HTLV-1-asymptomatic age group (Table 2). This is consistent with the absence of difference between the HTLV-1-asymptomatic and HAM groups in terms of episodic memory (RAVLT A5 and A7) (Table 3). Possibly, some of the HTLV-1-asymptomatic carriers presented a memory impairment that characterized an intermediate clinical syndrome between the asymptomatic phase and HAM and may have already developed neurological manifestations,both medullaryand subcortical, but in a subclinical form.8,9,11,36,37,38,39 Therefore, in spite of the HTLV-1-asymptomatic group having shown a good performance in most neuropsychological tests, we cannot rule out the possibility of the virus action in the CNS of this population. Some studies have demonstrated that HTLV-1-asymptomatic individuals presented a worse performance in episodic memory and also in other subcortical cognitive skills when compared with controls.8 In the GIPH cohort, a previous study has demonstrated neurophysiological changes associated with cognitive dysfunction in HAM, which was also found in the asymptomatic phase of the infection.10
Regarding the predominance of the female gender in the GIPH cohort, which was represented by the predominance of women in the present work, this reflects the epidemiologyof HTLV-1 in Brazil and in the world.1,2 This bias did not interfere in the findings of the present work, since it has already been demonstrated in the elderly population that there is no difference in P300 latency between genders.17 Medications such as benzodiazepines and anticonvulsants can affect P300 amplitude.40 In our study, only 10% of patients used at least one of these drugs for symptomatic mitigation, and in the data analysis, no association was found between cognitive performance and the use of these medications.
The limitation of the present study was the selection of neuropsychological tests that focused on subcortical dementia and not on a global cognitive evaluation. The reason was that the studied population included fragile HAM elderly people who would not tolerate a long-time test. So, the time taken to run the entire battery of cognitive tests was a limiting factor. The inclusion of P300 was important because this test is easy to apply, it is not tiring and, finally, changes in the electrophysiological tests precede changes observed in the neuropsychological tests.
In conclusion, HAM was associated with a cognitive decline, possibly of subcortical onset, that seems to worsen with aging. Those infected with HTLV-1, classified as asymptomaticcarriers, did not appear to exhibit a cognitive decline that was different from healthy seronegative elderly. However, HTLV-1-asymptomatic individuals with any cognitive complaint, especially regarding memory, should be submitted to a battery of neurocognitive tests in order to investigate cases of possible subclinical manifestation of the disease.
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SupportConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Acknowledgements
We are grateful to the Interdisciplinary HTLV Research Group (GIPH) participants. We are also grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for their support. We alsothank the personnel of Hospital das Clínicas and Pró-reitoria de pesquisas da Universidade Federal de Minas Gerais for their collaboration during the study.
References
-
1 Gessain A, Cassar O. Epidemiological Aspects and World Distribution of HTLV-1 Infection. Front Microbiol 2012;3:388. Doi: 10.3389/fmicb.2012.00388
» https://doi.org/10.3389/fmicb.2012.00388 -
2 Miranda C, Utsch-Gonçalves D, Piassi FCC, et al. Prevalence and Risk Factors for HumanT-Cell Lymphotropic Virus (HTLV) in Blood Donors in Brazil-A 10-Year Study (2007-2016). Front Med (Lausanne) 2022;9:844265. Doi: 10.3389/fmed.2022.844265
» https://doi.org/10.3389/fmed.2022.844265 -
3 Gao H, Ye X, Cai R, et al. Multiple spotty lesions of the spinal cord in a Chinese patient with human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. Int J Infect Dis 2018;68:1–3. Doi: 10.1016/j.ijid.2017.12.022
» https://doi.org/10.1016/j.ijid.2017.12.022 -
4 Tanajura D, Castro N, Oliveira P, et al. Neurological Manifestations in Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)-Infected Individuals Without HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Longitudinal Cohort Study. Clin Infect Dis 2015;61(01):49–56. Doi: 10.1093/cid/civ229
» https://doi.org/10.1093/cid/civ229 -
5 Silva TR, Rocha Santos MA, Macedo de Resende L, et al. Vestibular Evoked Myogenic Potential on Ocular, Cervical, and Soleus Muscles to Assess the Extent of Neurological Impairment in HTLV-1 Infection. Front Neurol 2020;11:433. Doi: 10.3389/fneur.2020.00433
» https://doi.org/10.3389/fneur.2020.00433 -
6 Araújo AQ, Leite AC, Lima MA, Silva MT. HTLV-1 and neurological conditions: when to suspect and when to order a diagnostic test for HTLV-1 infection? Arq Neuropsiquiatr 2009;67(01):132–138. Doi: 10.1590/s0004-282X2009000100036
» https://doi.org/10.1590/s0004-282X2009000100036 -
7 Fukushima T, Ikeda T, Uyama E, Uchino M, Okabe H, Ando M. Cognitive event-related potentials and brain magnetic resonance imaging in HTLV-1 associated myelopathy (HAM). J Neurol Sci 1994;126(01):30–39. Doi: 10.1016/0022-510x(94)90091-4
» https://doi.org/10.1016/0022-510x(94)90091-4 -
8 Gascon MR, Haziot ME, Assone T, et al. Memory impairment: an intermediate clinical syndrome symptom in HTLV-1-infected patients? Arq Neuropsiquiatr 2019;77(06):429–435. Doi: 10.1590/0004-282X20190062
» https://doi.org/10.1590/0004-282X20190062 -
9 de Castro ARR, Labanca L, de Resende LM, de Sousa MR, Dias RTS, de Morais Caporali JF, Utsch-Gonçalves D. Cognitive screening in HTLV-1-infected people using a self-perceived memory score and auditory P300. J Neurovirol. 2022 Feb-28(1):123-132. Doi: 10.1007/s13365-021-01044-1
» https://doi.org/10.1007/s13365-021-01044-1 -
10 Castro ARR, Labanca L, Resende LM, Utsch-Gonçalves D. Case Report: Cognitive Impairment without Clinical Spinal Disease May Be the First Sign of HTLV-1 Neurological Alteration. Am J Trop Med Hyg 2020;102(02):366–369. Doi: 10.4269/ajtmh.19-0218
» https://doi.org/10.4269/ajtmh.19-0218 -
11 de Paula JJ, Romanelli LC, de Faria RCV, et al. Cognitive impairment in the HTLV-1 infection: a comparative study associated with functional performance. J Neurovirol 2021;27(06):849–856. Doi: 10.1007/s13365-020-00905-5
» https://doi.org/10.1007/s13365-020-00905-5 -
12 De Castro-Costa CM, Araújo AQ, Barreto MM, et al. Proposal for diagnostic criteria of tropical spastic paraparesis/HTLV-I-associated myelopathy(TSP/HAM).AIDSRes Hum Retroviruses2006;22 (10):931–935. Doi: 10.1089/aid.2006.22.931
» https://doi.org/10.1089/aid.2006.22.931 - 13 Osame M. Review of WHO Kagoshima meeting and diagnostic guidelines for HAM/TSP. In: Blattner W, (Ed). Human Retrovirology: HTLV. 1990Raven Inc., New-York; 191–197
- 14 Becker JT, Lopez OL, Dew MA, Aizenstein HJ. Prevalence of cognitive disorders differs as a function of age in HIV virus infection. AIDS 2004; 18(Suppl 1):S11–S18
-
15 Almeida OP, Almeida SA. Confiabilidade da versão brasileira da escala de depressão em geriatria (GDS) versão reduzida[Reliability of the Brazilian version of the ++abbreviated form of Geriatric Depression Scale (GDS) short form]. Arq Neuropsiquiatr 1999 Jun 57 (2B):421–6. Portuguese Doi: 10.1590/s0004-282X1999000300013
» https://doi.org/10.1590/s0004-282X1999000300013 -
16 Polich J. Updating P300: an integrative theory of P3a and P3b. Clin Neurophysiol 2007;118(10):2128–2148. Doi: 10.1016/j.clinph.2007.04.019
» https://doi.org/10.1016/j.clinph.2007.04.019 -
17 Stenklev NC, Laukli E. Cortical cognitive potentials in elderly persons. J Am Acad Audiol 2004;15(06):401–413. Doi: 10.3766/jaaa.15.6.2
» https://doi.org/10.3766/jaaa.15.6.2 -
18 Braverman ER, Blum K. P300 (latency) event-related potential: an accurate predictor of memory impairment. Clin Electroencephalogr 2003;34(03):124–139. Doi: 10.1177/155005940303400306
» https://doi.org/10.1177/155005940303400306 -
19 Muller-Gass A, Campbell K. Sleep deprivation moderates neural processes associated with passive auditory capture. Brain Cogn 2019;132:89–97. Doi: 10.1016/j.bandc.2019.03.004
» https://doi.org/10.1016/j.bandc.2019.03.004 - 20 Klem GH, Lüders HO, Jasper HH, Elger C. The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 1999;52:3–6. PMID: 10590970
-
21 Gongora M, Nicoliche E, Magalhães J, et al. Event-related potential (P300): the effects of levetiracetam in cognitive performance. Neurol Sci 2021;42(06):2309–2316. Doi: 10.1007/s10072-020-04786-8
» https://doi.org/10.1007/s10072-020-04786-8 -
22 Yilmaz FT, Özkaynak SS, Barçin E. Contribution of auditory P300 test to the diagnosis of mild cognitive impairment in Parkinson’s disease. Neurol Sci 2017;38(12):2103–2109. Doi: 10.1007/s10072-017-3106-3
» https://doi.org/10.1007/s10072-017-3106-3 -
23 Gironell A, García-Sánchez C, Estévez-González A, Boltes A, Kulisevsky J. Usefulness of p300 in subjective memory complaints: a prospective study. J Clin Neurophysiol 2005;22(04): 279–284. Doi: 10.1097/01.wnp.0000173559.60113.ab
» https://doi.org/10.1097/01.wnp.0000173559.60113.ab - 24 Angelini AL, Alves ICB, Custódio EM, Duarte WF, Duarte JLM. Matrizes Progressivas Coloridas de Raven: Escala Especial. Manual. 1999. FALTA O DOI
-
25 Malloy-Diniz LF, Lasmar VA, Gazinelli Lde S, Fuentes D, Salgado JV. The Rey Auditory-Verbal Learning Test: applicability for the Brazilian elderly population. Braz J Psychiatry. 2007;Dec29(04): 324–9. Doi: 10.1590/s1516-44462006005000053
» https://doi.org/10.1590/s1516-44462006005000053 -
26 Beato RG, Nitrini R, Formigoni AP, Caramelli P. Brazilian version of the Frontal Assessment Battery (FAB): Preliminary data on administration to healthy elderly. Dement Neuropsychol 2007;1 (01):59–65. Doi: 10.1590/S1980-57642008DN10100010
» https://doi.org/10.1590/S1980-57642008DN10100010 -
27 Rodrigues RA, Oliveira RL, Grinsztejn B, Silva MT. Validity of the International HIV dementia scale in Brazil. Arq Neuropsiquiatr 2013;71(06):376–379. Doi: 10.1590/0004-282X20130042
» https://doi.org/10.1590/0004-282X20130042 -
28 Oxford Grice K, Vogel KA, Le V, Mitchell A, Muniz S, Vollmer MA. Adult norms for a commercially available Nine Hole Peg Test for finger dexterity. Am J Occup Ther 2003;57(05):570–573. Doi: 10.5014/ajot.57.5.570
» https://doi.org/10.5014/ajot.57.5.570 -
29 de Vet HC, Terwee CB, Knol DL, Bouter LM. When to use agreement versus reliability measures. J Clin Epidemiol 2006;59(10):1033-–1039. Doi: 10.1016/j.jclinepi.2005.10.015
» https://doi.org/10.1016/j.jclinepi.2005.10.015 -
30 Pereira Diniz JLC, Tupinambas U, Labanca L, Barbara SM, Souza O, Utsch-Gonçalves D. The Cognitive Impairment of Elderly Living with Human Immunodeficiency Virus (HIV): A Cross-Sectional Study about the Role of Viral Neurotoxicity. J Neuroinfect Dis 2016;7(03):1–7. Doi: 10.4172/2314-7326.1000224
» https://doi.org/10.4172/2314-7326.1000224 -
31 Winston A, Spudich S. Cognitive disorders in people living with HIV. Lancet HIV 2020;7(07):e504–e513. Doi: 10.1016/S2352-3018(20)30107-7
» https://doi.org/10.1016/S2352-3018(20)30107-7 -
32 Mackiewicz MM, Overk C, Achim CL, Masliah E. Pathogenesis of age-related HIV neurodegeneration. J Neurovirol 2019;25(05): 622–633. Doi: 10.1007/s13365-019-00728-z
» https://doi.org/10.1007/s13365-019-00728-z -
33 Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 2002;202 (1-2):13–23. Doi: 10.1016/s0022-510x(02)00207-1
» https://doi.org/10.1016/s0022-510x(02)00207-1 -
34 Champs APS, de Azeredo Passos VM, Carvalho G, Barreto SM, Meirelles C, Caramelli P. Cognitive impairment in HTLV-1-associated myelopathy, proviral load and inflammatory markers. Int J Infect Dis 2019;84:121–126. Doi: 10.1016/j.ijid.2019.05.010
» https://doi.org/10.1016/j.ijid.2019.05.010 -
35 Fjell AM, Walhovd KB. P300 and neuropsychological tests as measures of aging: scalp topography and cognitive changes. Brain Topogr 2001;14(01):25–40. Doi: 10.1023/a:1012563605837
» https://doi.org/10.1023/a:1012563605837 -
36 Caporali JFM, Labanca L, Florentino KR, Souza BO, Utsch Gonçalves D. Intrarater and interrater agreement and reliability of vestibular evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) for HTLV-1 associated myelopathy testing. PLoS One 2018;13(09):e0204449. Doi: 10.1371/journal.pone.0204449
» https://doi.org/10.1371/journal.pone.0204449 -
37 Labanca L, Starling AL, de Sousa-Pereira SR, et al. Electrophysio-logical analysis shows dizziness as the first symptom in human T cell lymphotropic virus type-associated myelopathy/tropical spastic paraparesis. AIDS Res Hum Retroviruses 2015;31(06): 649–654. Doi: 10.1089/AID.2014.0153
» https://doi.org/10.1089/AID.2014.0153 -
38 Labanca L, de Morais Caporali JF, da Silva Carvalho SA, et al. Vestibular-evoked myogenic potential triggered by galvanic vestibular stimulation may reveal subclinical alterations in human T-cell lymphotropic virus type 1-associated myelopathy. PLoS One 2018;13(07):e0200536. Doi: 10.1371/journal.pone.0200536
» https://doi.org/10.1371/journal.pone.0200536 -
39 Silva TR, Labanca L, Caporali JFM, et al. Ocular vestibular evoked myogenic potential (VEMP) reveals mesencephalic HTLV-1-associated neurological disease. PLoS One 2019;14(12):e0217327. Doi: 10.1371/journal.pone.0217327
» https://doi.org/10.1371/journal.pone.0217327 -
40 Gonul AS, Suer C, Coburn K, Ozesmi C, Oguz A, Yilmaz A. Effects of olanzapine on auditory P300 in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2003;27(01):173–177. Doi: 10.1016/s0278-5846(02)00349-4
» https://doi.org/10.1016/s0278-5846(02)00349-4
Publication Dates
-
Publication in this collection
19 May 2023 -
Date of issue
Mar 2023
History
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Received
17 Aug 2022 -
Reviewed
18 Oct 2022 -
Accepted
03 Nov 2022
