Keywords Aged - Human T-lymphotropic Virus 1 - Paraparesis, Tropical Spastic - Event-Related
Potentials, P300 - Neuropsychological Tests - Cognition
Palavras-chave Idoso - Vírus Linfotrópico T Tipo 1 Humano - Paraparesia Espástica Tropical - 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, the Caribbean 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, although 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 Federal
de Minas Gerais (COEP UFMG), 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 (RT-PCR).
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 subjected to 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, temporal-parietal 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 6 hours 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 the
left (A1) and right (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 90 dB 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 sound in the frequency
of 1,000 Hz, 50 cycles of duration, 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 20 Hz low-pass filter and the 60 Hz notch filter. The
time window was 1,000 ms 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 500 ms 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 ability[24 ]; 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 recognition[25 ]; frontal assessment battery (FAB), which evaluates executive functions[26 ]; 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 non-dominant 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 ].
Table 1
General characteristics of the asymptomatic and HTLV-1-infected groups (n = 138)
Variables
Seronegative
HTLV-1-asymptomatic
HAM
p -value
(n = 59)
(n = 38)
(n = 41)
Age (years old)
66 ± 3.6
61 ± 6.8
61 ± 8.3
< 0.001
a
0.001 (G1 > G2)
a
0.002 (G1 > G3)
a
Education (years of schooling)
5 (4/10)
7 (4/10)
5 (3/8)
0.224b
−
Female
40 [68]
24 [63]
27 [66]
0.895c
−
OMDS
0
0
4 (1/5)
< 0.001
b
0.001 (G1 > G3)
b
0.001 (G2 > G3)
b
Abbreviations: G1, seronegative group; G2, HTLV-1-asymptomatic group; G3, HAM group;
HAM, HTLV-1 associated myelopathy; HTLV-1, human T-cell lymphotropic virus type 1;
OMDS, Osame motor disability score; p , significance probability.
Notes: Data are expressed as mean ± standard deviation for continuous variables with
normal distribution, median (Quartil Q1/Quartil Q3) for continuous variables with
non-normal distribution or absolute numbers [percentage] for categorical variables.
a ANOVA test – Bonferroni; b Kruskal-Wallis test; c Chi-Square test.
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 ]).
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 ]).
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
P300 latency (ms)
G1 (seronegative) - n = 59
G2 (HTLV-1-asymptomatic) - n = 38
G3 (HAM) - n = 41
p -value
General comparison
331.33 (316.19/346.47)
343.95 (329.44/359.02)
−
0.142
331.33 (316.19/346.47)
−
369.18 (346.61/386.84)
< 0.001
a
−
343.95 (329.44/359.02)
369.18 (346.61/386.84)
< 0.001
a
Comparison by age group
[60-69]
[70-79]
[50-59]
[60-69]
[70-79]
[50-59]
[60-69]
[70-79]
P-Value
n = 46
n = 13
n = 18
n = 13
n = 7
n = 18
n = 13
n = 10
G1 [60-69] x
332.59
330.92
−
−
−
−
−
−
0.862
G1 [70-79]
(317.14/346.47)
(314.93/345.21)
G2 [50-59] x
−
−
345.21
343.95
−
−
−
−
0.795
G2 [60-69]
(329.44/357.19)
(314.93/361.56)
G2 [50-59] x
−
−
345.21
−
344.00
−
−
−
0.739
G2 [70-79]
(329.44/357.19)
(336.00/364.13)
G2 [60-69] x
−
−
−
343.95
344.00
−
−
−
0.968
G2 [70-79]
(314.93/361.56)
(336.00/364.13)
G3 [50-59] x
−
−
−
−
−
365.65
366.65
−
0.298
G3 [60-69]
(340.79/377.86)
(348.99/389.36)
G3 [50-59] x
−
−
−
−
−
365.65
−
398.19
0.003
b
G3 [70-79]
(340.79/377.86)
(378.64/419.64)
G3 [60-69] x
−
−
−
−
−
−
366.65
398.19
0.040
b
G3 [70-79]
(348.99/389.36)
(378.64/419.64)
G1 [60-69] x
332.59
−
345.21
−
−
−
−
−
0.099
G2 [50-59]
(317.14/346.47)
(329.44/357.19)
G1 [60-69] x
332.59
−
−
343.95
−
−
−
−
0.167
G2 [60-69]
(317.14/346.47)
(314.93/361.56)
G1 [70-79] x
−
330.92
345.21
−
−
−
−
−
0.128
G2 [50-59]
(314.93/345.21)
(329.44/357.19)
G1 [70-79] x
−
330.92
−
343.95
−
−
−
−
0.227
G2 [60-69]
(314.93/345.21)
(314.93/361.56)
G1 [70-79] x
−
330.92
−
−
344.00
−
−
−
0.191
G2 [70-79]
(314.93/345.21)
(336.00/364.13)
G1 [60-69] x
332.59
−
−
−
−
365.65
−
−
< 0.001
b
G3 [50-59]
(317.14/346.47)
(340.79/377.86)
G1 [60-69] x
332.59
−
−
−
−
−
366.65
−
< 0.001
b
G3 [60-69]
(317.14/346.47)
(348.99/389.36)
G1 [70-79] x
330.92
365.65
0.005
b
G3 [50-59]
(314.93/345.21)
(340.79/377.86)
G1 [70-79] x
−
330.92
−
−
−
−
366.65
−
0.002
b
G3 [60-69]
(314.93/345.21)
(348.99/389.36)
G1 [70-79] x
−
330.92
−
−
−
−
−
398.19
< 0.001
b
G3 [70-79]
(314.93/345.21)
(378.64/419.64)
G2 [50-59] x
−
−
345.21
−
−
365.65
−
−
0.025
b
G3 [50-59]
(329.44/357.19)
(340.79/377.86)
G2 [60-69] x
−
−
−
343.95
−
−
366.65
−
0.024
b
G3 [60-69]
(314.93/361.56)
(348.99/389.36)
G2 [70-79] x
−
−
−
−
344.00
−
−
398.19
0.008
b
G3 [70-79]
(336.00/364.13)
(378.64/419.64)
G2 [60-69] x
−
−
−
343.95
−
365.65
−
−
0.072
G3 [50-59]
(314.93/361.56)
(340.79/377.86)
G2 [70-79] x
−
−
−
−
344.00
365.65
−
−
0.146
G3 [50-59]
(336.00/364.13)
(340.79/377.86)
G2 [70-79] x
−
−
−
−
344.00
−
366.65
−
0.103
G3 [60-69]
(336.00/364.13)
(348.99/389.36)
Abbreviations: G1, Seronegative group; G2, HTLV-1-asymptomatic group; G3, HAM group;
HAM, HTLV-1 associated myelopathy; HTLV-1, human T-cell lymphotropic virus type 1;
ms, milliseconds; p, significance probability.
Notes: Data are expressed as median (Q1 quartile/Q3 quartile). a Kruskal-Wallis test; b Mann-Whitney test.
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 ]).
Figure 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 the trend 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.
Table 3
Comparative analysis between the seronegative (n = 59), HTLV-1-asymptomatic carriers
(n = 38), and HAM (n = 41) groups regarding performance in neuropsychological tests
Variable
Seronegative
HTLV-1-asymptomatic
HAM
P -value
General intelligence
RAVEN(total)
23 (17/27)
25 (19/30)
23 (19/28)
0.275a
−
Screening tests
FAB (total)
17 (14/17)
17 (15/18)
14 (13/16)
0.003
a
0.023 (G1 > G3)
a
0.003 (G2 > G3)
a
IHDS (total)
11 (9/12)
11 (9/12)
10 (9/11)
0.020
a
0.044 (G1 > G3)
a
0.041 (G2 > G3)
a
Episodic memory
RAVLT A5 (total)
11 (10/13)
11 (10/13)
9 (8/12)
0.010
a
0.008 (G1 > G3)
a
RAVLT A7 (total)
8 (7/11)
7 (6/10)
7 (5/10)
0.040
a
0.046 (G1 > G3)
a
Motor processing and attention
NHPT - DH (time - seconds)
20 (19/24)
21 (20/26)
25 (22/28)
<0.001
a
< 0.001 (G1 < G3)
a
0.019 (G2 < G3)
a
NHPT - NDH (time - seconds)
22 (20/24)
22 (21/25)
25 (24/30)
< 0.001
a
<0.001 (G1 < G3)
a
0.006 (G2 < G3)
a
Abbreviations: DH, dominant hand; FAB, frontal assessment battery; G1, seronegative
group; G2, HTLV-1-asymptomatic group; G3, HAM group; HAM, HTLV-1 associated myelopathy;
HTLV-1, human T-cell lymphotropic virus type 1; IHDS, international HIV dementia scale;
NDH, non-dominant hand; NHPT, nine-hole peg test; p , significance probability; RAVLT, Rey auditory-verballearning test.
Notes: Data are expressed in median (Q1 quartile/Q3 quartile). a Kruskal-Wallis test.
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 and aging. Cognitive
changes were more severe in individuals 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 ([Figure1 ] 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, using a similar methodology
to that of the present study, observed similar changes in the HAM group to the ones
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 HIV and 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 medullary
and 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 epidemiology of
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
asymptomatic carriers, 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.
