Keywords:
Epilepsy - Memory - Aged
Palavras-chave:
Epilepsia - Memoria - Idoso
INTRODUCTION
Memory complaints are frequent in the older population and may be associated with
emotional aspects and cognitive deficits in neuropsychological tests[1]. Studies suggest that these complaints may be predictors of cognitive decline in
highly educated older adults[2].
Cognitive impairment in epilepsy is common, associated with clinical variables and
repercussions on the quality of life (QoL), suggesting a complex relationship between
cognition and pathophysiological mechanisms, as well as biological and psychosocial
factors[3],[4],[5],[6],[7],[8],[9],[10],[11].
In adults with epilepsy, some clinical variables, such as early age of onset and depressive
symptoms, are associated with greater cognitive complaints[12],[13]. However, the relationship between objective and subjective cognitive performance
is sometimes inconsistent, or the correlation is weak[6],[7],[8].
The literature has described cognitive deficits in older adults with epilepsy (OAE)[10],[11]; nonetheless, the presence of subjective complaints and their relationship with
impairment in neuropsychological tests is little known, and the literature still has
gaps regarding whether these variables are associated with subjective cognitive impairment
in OAE.
Thus, this research is justified by the need to expand the knowledge of memory complaints
in OAE and the associated neurophysiopathological, clinical, and emotional aspects,
since the clinical valuation of cognitive complaints can contribute to a better understanding
of the interface between cognition and epilepsy.
This study aimed to assess the occurrence of memory complaints and whether there is
an association between objective cognitive performance, clinical characteristics of
epilepsy, depression, and perceived QoL in OAE.
METHODS
Participants
This study included 83 consecutive outpatients (age≥60 years) diagnosed with epilepsy
(OAE), treated at the neurology outpatient clinic at the Hospital of the Pontifícia
Universidade Católica de Campinas, São Paulo, Brazil. The inclusion criteria were:
(1) diagnosis of epilepsy according to the International League Against Epilepsy (ILAE)
Classification of Epilepsies and Epileptic Syndromes criteria[14]; (2) signing an informed consent form to undergo the procedures.
Based on the ILAE criteria, 61 (73.4%) cases presented focal structural epilepsy,
and 22 had epilepsy of unknown etiology. In 18 (21.6%) cases, the individuals were
diagnosed with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), not submitted
to surgery. At the time of the survey, 48 (57.8%) OAE were taking a single antiepileptic
drug (AED), and 35 (42.1%) were on 2 or more AEDs. A total of 45 (54.2%) participants
reported having no seizures in the previous year. The electroencephalogram (EEG) revealed
epileptiform activity (EA) laterality in the right cerebral hemisphere in 35 cases,
in the left hemisphere in 31 cases, and no EA in 17 cases.
The exclusion criteria were: difficulties in understanding the instrument questions
due to a lower educational level or mental disability; history of neurosurgery, neurological
and psychiatric diseases, or any other progressive chronic diseases.
The control group (CG) consisted of individuals who did not have neurological or psychiatric
diseases or other progressive chronic diseases, preferentially recruited from family
members. The individuals who agreed to participate in the research were interviewed
to collect their sociodemographic and clinical data, and then submitted to the specific
protocol. Thus, the CG comprised 40 individuals similar to the patients in age, gender,
and socioeconomic conditions.
The study was approved by the Human Research Ethics Committee of the Pontifícia Universidade
Católica de Campinas, protocol number 73249517300005481. All participants were informed
of the research protocol and signed the consent form.
The OAE who agreed to participate in the study were submitted to a clinical assessment
and to the research instruments, presented individually, in a quiet and well-lit room,
in the neurological clinic of the hospital. This assessment was performed in a single
session on the day the person had a medical appointment.
Procedures
The OAE were submitted to:
-
A questionnaire on sociodemographic data (age, gender, educational level).
-
A neurological investigation, including the individual's detailed medical history
and the collection of clinical data on epilepsy (age of onset, seizure type and frequency,
duration of epilepsy, and number of AEDs taken).
-
Digital EEG to assess the location and the EA laterality.
-
Memory Complaint Questionnaire (MAC-Q)[15]: consisting of 5 questions that assessed the individual's current performance in
daily activities and 1 question that compared their perceived current memory to how
it was when they were 18–20 years old (better, worse, or much worse). The cut-off
score established to indicate a memory complaint was >25.
-
Mini-Mental State Examination (MMSE)[16] as a brief screening measure of cognition. The maximum score was 30 points. The
cut-off scores for the Brazilian population were established by Bruck et al.: 23 for
1–4 years of schooling; 26 for 5–9 years; and 27 for 10 years or more[17].
-
Brief Cognitive Battery-Education (BCB-Edu)[18] to assess cognitive performance, encompassing the identification of ten common pictures
(naming) and immediate recollection (incidental memory). Subsequently, the pictures
were presented again, and the subject was asked to memorize them for 30 seconds and
then recall them (immediate memory). This procedure was repeated one more time (learning).
Next, the participants completed the semantic verbal fluency (SVF) test (animal pictures
in one minute) and the clock drawing test[19]. After, they were asked to recall the pictures presented earlier (delayed recall).
Finally, those ten pictures were presented alongside ten distracting pictures, and
the participant had to identify the ones originally presented (recognition). For immediate
memory, learning, delayed recall, and recognition, the cut-off scores were respectively
<5, <7, <6, and <9. For the SVF test, the cut-off score was 9 for illiterate individuals
and individuals with <8 years of schooling; and 13 for individuals with more than
8 years of formal education[20].
-
Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)[21]. The NDDI-E is an epilepsy-specific self-rating questionnaire developed to rapidly
screen the symptoms of depression in the two weeks prior to a medical appointment
at epilepsy clinics. It consists of six items reflecting depressive symptoms. Each
item is assigned a score of 1–4, from “never” to “always/often”. The total score ranges
from 6 to 24, and higher scores correspond to greater depression severity. In Brazil,
the cut-off score for more severe depressive symptoms was set at >15.
-
Quality of Life in Epilepsy Inventory (QOLIE-31)[22], an epilepsy-specific QoL inventory. This inventory includes the total score and
the following dimensions: seizure worry, overall QoL, emotional well-being, energy/fatigue,
cognitive functioning, medication effects, social functioning. The overall score ranges
from 1 to 100. Higher scores indicate higher levels of QoL.
The CG individuals were submitted to a questionnaire on sociodemographic data, an
EEG, the MMSE, and the BCB-Edu.
Data analysis
MAC-Q scores of the OAE were compared to those of the CG. Data obtained from the MAC-Q
were compared with the objective cognitive performance. In the OAE group, we assessed
the association between memory complaints (MAC-Q>25), objective cognitive performance,
clinical variables (age of onset, number of AEDs taken, seizure frequency and type),
sociodemographic aspects (age, educational level), and the NDDI-E and QOLIE-31 scores.
Based on the cognitive performance in the MMSE and the BCB-Edu, OAE were categorized
into: 1): subjects with intact cognition and minimally impaired when compared to individuals
in the CG; and 2): subjects with impairment in multiple cognitive domains (changes
in memory, language, and attention in the BCB-Edu and scores below the cut-off point
in the MMSE, according to their educational level)[16],[17],[18],[19],[20].
Categorical variables were expressed as absolute values and percentages, and continuous
variables as mean and standard deviations. Student's t-test, analysis of variance (ANOVA), and Pearson's chi-square test were used to compare
continuous and categorical variables. Pearson's correlation coefficient measured the
degree of association among quantitative variables.
The influence of sociodemographic and clinical variables (age, educational level,
age of onset, number of AEDs taken — 1 or ≥2), cognitive aspects (impairment in multiple
cognitive domains — yes or no), and NDDI-E scores regarding subjective memory loss
(MAC-Q>25) was assessed using logistic regression, with stepwise selection criteria.
A logistic regression analysis was also performed to identify which factors influence
impairment in multiple cognitive domains (no or yes).
We used the Statistical Package for the Social Sciences, version 22, for statistical
analysis. Statistical significance was set at p<0.05 in all tests.
RESULTS
MAC-Q: OAE, CG
No significant differences were found in terms of gender, educational level, and age
between OAE and individuals in the CG. OAE had lower cognitive performance scores
and higher MAC-Q scores compared to the CG ([Table 1]).
Table 1
Sociodemographic, clinical, and cognitive aspects and Memory Complaint Questionnaire,
Neurological Disorders Depression Inventory for Epilepsy, and Quality of Life in Epilepsy
Inventory scores of older adults with epilepsy and individuals in the control group.
|
OAE (n=83)
|
CG (n=40)
|
p-value
|
|
Gender: female/male
|
39/44
|
23/17
|
0.275a
|
|
Age (years)
|
68.4 (±7.0)
|
68.5 (±4.1)
|
0.974b
|
|
Educational level (years)
|
3.9 (±3.3)
|
4.2 (±2.3)
|
0.534b
|
|
MMSE (total score)
|
22.7 (±4.1)
|
24.9 (±3.0)
|
0.004b
*
|
|
BCB-Edu
|
|
|
|
|
Identification
|
9.6 (±1.0)
|
9.9 (±0.1)
|
0.050b
|
|
Naming
|
9.4 (±1.5)
|
9.8 (±0.4)
|
0.029b
*
|
|
Incidental memory
|
5.2 (±1.5)
|
5.9 (±1.5)
|
0.022b
*
|
|
Immediate memory
|
6.6 (±1.7)
|
7.7 (±1.6)
|
0.001b
*
|
|
Learning test
|
7.1 (±1.8)
|
8.0 (±1.3)
|
0.010b
*
|
|
Delayed recall
|
6.4 (±1.3)
|
7.6 (±2.0)
|
0.001b
*
|
|
Recognition
|
8.1 (±2.5)
|
9.2 (±2.2)
|
0.017b
*
|
|
Clock drawing test
|
4.7 (±2.8)
|
6.3 (±2.6)
|
0.003b
*
|
|
SVF test
|
10.4 (±4.6)
|
12.9 (±5.1)
|
0.010b
*
|
|
MAC-Q
|
25.9 (±5.4)
|
24.0 (±3.9)
|
0.034b
*
|
|
Age at first seizure (years)
|
46.8 (±23.4)
|
|
|
|
Average epilepsy duration (years)
|
21.7 (±20.9)
|
|
|
|
Seizure onset: <60/≥60 years
|
54/ 29
|
|
|
|
QOLIE-31 (total score)
|
67.7 (±16.8)
|
|
|
|
NDDI-E
|
10.9 (±4.6)
|
|
|
|
NDDI-E>15
|
13 (15.6%)
|
|
|
OAE: older adults with epilepsy; CG: control group; MAC-Q: Memory Complaint Questionnaire;
MMSE: Mini-Mental State Examination; BCB-Edu: Brief Cognitive Battery-Education; SVF
test: semantic verbal fluency test; QOLIE-31: Quality of Life in Epilepsy Inventory;
NDDI-E: Neurological Disorders Depression Inventory for Epilepsy;
achi-square test;
bStudent's t-test;
*p<0.05.
Subjective memory loss (MAC-Q>25) was higher in OAE than in individuals of the CG
— chi-square test; 54 (65%) vs. 18 (45%); p=0.034. Controls showed no difference regarding
the occurrence of MAC-Q>25 according to gender, age, and education level.
MAC-Q: clinical variables and cognitive performance
[Table 2] shows the values of the correlations between age, age at first seizure, MAC-Q and
NDDI-E scores, and cognitive tests of OAE.
Table 2
Correlation between clinical and sociodemographic data, Memory Complaint Questionnaire
and Neurological Disorders Depression Inventory for Epilepsy scores, and objective
cognitive performance.
|
Age
|
Age at first seizure
|
MAC-Q
|
NDDI-E
|
|
MAC-Q
|
0.331*
|
0.260*
|
|
|
|
NDDI-E
|
0.284*
|
0.141
|
0.268*
|
|
|
MMSE
|
-0.224*
|
-0.086
|
-0.316*
|
-0.219*
|
|
Clock drawing test
|
-0.218*
|
0.064
|
-0.140
|
-0.141
|
|
SVF test
|
-0.054
|
-0.113
|
-0.212
|
-0.137
|
|
Identification
|
-0.343*
|
-0.233*
|
-0.102
|
-0.335*
|
|
Naming
|
-0.228*
|
0.083
|
0.039
|
-0.395*
|
|
Incidental memory
|
-0.432**
|
-0.256*
|
-0.312*
|
-0.240*
|
|
Immediate memory
|
-0.530*
|
-0.189
|
-0.280*
|
-0.295*
|
|
Learning test
|
-0.440*
|
-0.267*
|
-0.290*
|
-0.332*
|
|
Delayed recall
|
-0.305*
|
-0.102
|
-0.205
|
-0.181
|
|
Recognition
|
-0.426*
|
-0.156
|
-0.244*
|
-0.186
|
MAC-Q: Memory Complaint Questionnaire; NDDI-E: Neurological Disorders Depression Inventory
for Epilepsy; MMSE: Mini-Mental State Examination; SVF test: semantic verbal fluency
test; Pearson's correlation;
*p<0.05;
**p<0.001.
Subjective memory loss (MAC-Q>25) was identified in 45 (54.2%) cases. Higher age,
lower educational level, onset of seizures after 60 years of age, greater NDDI-E scores,
lower QOLIE-31 scores, and impairment in multiple cognitive domains were associated
with a MAC-Q>25 score. We found no significant association between memory complaints
and other clinical and electroencephalographic aspects ([Table 3]).
Table 3
Sociodemographic and clinical aspects, Neurological Disorders Depression Inventory
for Epilepsy and Quality of Life in Epilepsy Inventory scores according to the Memory
Complaint Questionnaire, and the occurrence of impairment in multiple cognitive domains.
|
MAC-Q
|
Cognitive impairment
|
|
≤25 (n=38)
|
>25 (n=45)
|
p-value
|
No (n=49)
|
Yes (n=34)
|
p-value
|
|
Gender: female/male
|
14/24
|
25/20
|
0.089a
|
23/26
|
16/18
|
0.991a
|
|
Age (years)
|
65.8 (±4.9)
|
70.5 (±7.8)
|
0.002b
*
|
66.2 (±5.2)
|
71.5 (±8.0)
|
0.001b
*
|
|
Educational level (years)
|
4.6 (±3.1)
|
2.9 (±2.5)
|
0.013b
|
4.6 (±3.1)
|
2.4 (±2.0)
|
<0.000b
*
|
|
Age at first seizure (years)
|
40.2 (±22.7)
|
52.3 (±22.7)
|
0.018b
*
|
42.8 (±20.8)
|
52.5 (±25.9)
|
0.077b
|
|
Seizure onset: <60/ ≥60
|
29/9
|
25/20
|
0.048a
|
36/13
|
18/16
|
0.054a
|
|
Epilepsy duration (years)
|
25.6 (±21.8)
|
18.4 (±19.8)
|
0.120b
|
23.5 (±20.4)
|
19.0 (±21.8)
|
0.345b
|
|
Seizures in the previous year: yes/no
|
20/18
|
18/27
|
0.205a
|
24/25
|
14/20
|
0.510c
|
|
EA laterality: right/left
|
16/15
|
19/16
|
0.828a
|
23/18
|
12/13
|
0.614a
|
|
Number of AEDs taken: 1/≥2
|
19/19
|
29/16
|
0.265c
|
25/24
|
23/11
|
0.176c
|
|
Structural epilepsy/unknown etiology
|
27/11
|
34/11
|
0.803a
|
32/17
|
29/5
|
0.048a
*
|
|
QOLIE-31
|
|
|
|
|
|
|
|
Emotional well-being
|
76.8 (±16.7)
|
62.3 (±26.3)
|
0.010b
*
|
64.0 (±24.7)
|
74.6 (±21.6)
|
0.080b
|
|
Cognitive functioning
|
79.0 (±19.4)
|
61.1 (±25.2)
|
0.002b
*
|
65.6 (±26.9)
|
72.4 (±20.0)
|
0.259b
|
|
Total score
|
74.1 (±11.7)
|
63.6 (±18.4)
|
0.007*
|
65.7 (±17.1)
|
70.9 (±16.1)
|
0.219b
|
|
NDDI-E
|
9.5 (±4.4)
|
12.1 (±4.8)
|
0.013b
*
|
9.8 (±4.2)
|
12.5 (±5.2)
|
0.014b
*
|
|
Cognitive impairment: no/yes
|
27/11
|
22/23
|
0.047a
*
|
|
|
|
MAC-Q: Memory Complaint Questionnaire; EA: epileptiform activity; AED: antiepileptic
drug; NDDI-E: Neurological Disorders Depression Inventory for Epilepsy;
achi-square test;
b
t-test;
cFisher's exact test;
*p<0.05.
Some impairment was detected in multiple cognitive domains of 34 (41%) OAE. [Table 3] presents sociodemographic aspects and clinical variables, as well as NDDI-E and
QOLIE-31 scores, according to MAC-Q.
In the logistic regression analysis, the only predictive factor for a MAC-Q>25 score
was age, while age and education were predictive factors for impairment in multiple
cognitive domains. Other clinical aspects were excluded from the equation ([Table 4]).
Table 4
Logistic regression to determine the factors that contribute to impairment in multiple
cognitive domains and a Memory Complaint Questionnaire score >25 in 83 older adults
with epilepsy.
|
Predictor
|
Odds ratio
|
95%CI
|
p-value
|
|
Impairment in multiple cognitive domains
|
Age
|
1.11
|
1.10 1.22
|
0.016*
|
|
Educational level
|
0.78
|
0.62 0.64
|
0.016*
|
|
MAC-Q
|
Age
|
1.12
|
1.04 1.23
|
0.005*
|
MAC-Q: Memory Complaint Questionnaire; OAE: older adults with epilepsy; 95%CI: 95%
confidence interval;
*p<0.05.
DISCUSSION
The results of this study provide evidence that OAE have significantly more complaints
of memory loss and cognitive impairment than individuals in the CG.
Cognitive deficit in OAE was associated with clinical aspects, similar to other studies[10],[11]; however, little is understood about the impact of chronic epilepsy or early onset
of seizures on the cognition of older adults.
An association between impairment in multiple cognitive domains and subjective memory
complaints was identified, revealing a complex mechanism involving different anatomical-pathophysiological
aspects and neuropsychological factors in the perceived cognition of OAE. In contrast,
other studies of OAE do not describe these findings[10]. The association between objective and subjective cognitive impairment has been
reported in several cases of adults with epilepsy, using different cognitive tests[8],[13],[23],[24].
This study found an association of subjective complaints with sociodemographic aspects
(age and education), onset of seizures after 60 years of age, and other aspects of
epilepsy. Other studies of OAE did not find associations between cognitive complaints
and clinical aspects of epilepsy[10].
Depressive symptoms were associated with subjective memory complaints, suggesting
that depressive symptoms can manifest as poor perceived health, multiple somatic complaints,
and an exacerbated perception of cognitive impairments. Recent studies have indicated
that the affective status contributes to subjective memory complaints in adults with
different types of epilepsies[6],[7],[9],[13],[23],[24],[25],[26],[27], OAE[10], and healthy adults[3].
Memory complaints, but not the objective cognitive deficit, were related to worse
QoL (emotional well-being, cognitive functioning, and total score), suggesting that
QoL is a complex, subjective perception of multiple abilities[28].
This study has some limitations. The epilepsy clinic used in this article is in a
university hospital but not a tertiary epilepsy center. This is a cross-sectional
study with a relatively small sample, and the instruments used are mostly cognitive
screening tests and depression in epilepsy screening test. The sample size of the
control group is small. The groups were formed by individuals with lower educational
levels, which can make cognitive assessment difficult and limit the generalization
of the findings.
In summary, OAE reported more memory complaints and had worse cognitive performance
levels than individuals in the CG. Memory complaints were associated with sociodemographic
and clinical variables, depression, and lower cognitive performance. A better perception
of QoL was related to lower memory complaints.
