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The neuropsychological exam plays a central role in the assessment of elderly patients with cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological assessment protocol for this population and develop cutoff values for clinical use. A protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery, Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to 274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer`s disease) with predominantly low formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living. The study presents evidence of the construct, criteria and ecological validity for this protocol. The neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low formal education.
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Clinical Applicability and Cutoff Values for an
Unstructured Neuropsychological Assessment Protocol
for Older Adults with Low Formal Education
Jonas Jardim de Paula
*, Laiss Bertola
, Rafaela Teixeira A
, Lafaiete Moreira
Gabriel Coutinho
, Edgar Nunes de Moraes
, Maria Aparecida Camargos Bicalho
, Rodrigo Nicolato
Breno Satler Diniz
, Leandro Fernandes Malloy-Diniz
1Laboratory of Neuropsychological Investigations (LIN), Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil, 2INCT de Medicina Molecular,
Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil, 3Clinical Staff, D’Or Institute for Research and Education (ID’Or), Rio de
Janeiro, Rio de Janeiro, Brazil, 4Programa de Po
ˆncias Morfolo
´gicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil,
5Departamento de Clı
´nica Me
´dica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, 6Departamento de Sau
´de Mental, Faculdade de
Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
Background and Objectives:
The neuropsychological exam plays a central role in the assessment of elderly patients with
cognitive complaints. It is particularly relevant to differentiate patients with mild dementia from those subjects with mild
cognitive impairment. Formal education is a critical factor in neuropsychological performance; however, there are few
studies that evaluated the psychometric properties, especially criterion related validity, neuropsychological tests for patients
with low formal education. The present study aims to investigate the validity of an unstructured neuropsychological
assessment protocol for this population and develop cutoff values for clinical use.
Methods and Results:
A protocol composed by the Rey-Auditory Verbal Learning Test, Frontal Assessment Battery,
Category and Letter Fluency, Stick Design Test, Clock Drawing Test, Digit Span, Token Test and TN-LIN was administered to
274 older adults (96 normal aging, 85 mild cognitive impairment and 93 mild Alzheimer
`s disease) with predominantly low
formal education. Factor analysis showed a four factor structure related to Executive Functions, Language/Semantic
Memory, Episodic Memory and Visuospatial Abilities, accounting for 65% of explained variance. Most of the tests showed a
good sensitivity and specificity to differentiate the diagnostic groups. The neuropsychological protocol showed a significant
ecological validity as 3 of the cognitive factors explained 31% of the variance on Instrumental Activities of Daily Living.
The study presents evidence of the construct, criteria and ecological validity for this protocol. The
neuropsychological tests and the proposed cutoff values might be used for the clinical assessment of older adults with low
formal education.
Citation: de Paula JJ, Bertola L, A
´vila RT, Moreira L, Coutinho G, et al. (2013) Clinical Applicability and Cutoff Values for an Unstructured Neuropsychological
Assessment Protocol for Older Adults with Low Formal Education. PLoS ONE 8(9): e73167. doi:10.1371/journal.pone.0073167
Editor: Karl Herholz, University of Manchester, United Kingdom
Received March 31, 2013; Accepted July 17, 2013; Published September 16, 2013
Copyright: ß2013 de Paula et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the following grants: CBB-APQ-00075-09 from FAPEMIG, 573646/2008-2 from CNPq, and APQ-01972/12-10, APQ-02755-10
from FAPEMIG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail:
The neuropsychological evaluation plays an important role in
the differential diagnostic between normal and pathological aging
cognitive processes [1]. It is of particular relevance to differentiate
subjects with mild cognitive impairment (MCI) from those in the
early stages of dementia, e.g. mild Alzheimer’s disease (AD), when
cognitive screening tests are not sensitive for the differential
diagnosis [2]. The neuropsychological evaluation usually presents
similar or greater sensitivity and specificity for the identification of
AD versus MCI when compared to other diagnostic procedures.
For instance, in a recent study the neuropsychological assessment
showed higher accuracy (84%) to differentiate MCI from AD
patients, followed by structural Magnetic Resonance Imaging
(82%), PET-FDG (76%), and cerebrospinal fluid biomarkers
(73%) [3]. The combinations of different procedures increase the
diagnosis accuracy, although the estimated additional gain in effect
sizes were small.
Formal education has a major impact in the performance on
cognitive tests and can bias the interpretation of test results.
Educational level influences the performance on cognitive
screening test, such as the Mini-Mental State Examination and
the Category Fluency Test, and cut-off scores for dementia
diagnosis based on the educational level have been widely used
[4,5]. The performance on structured cognitive assessment
batteries for diagnosis of dementia, such as the Mattis Dementia
Rating Scale [6], the CERAD Battery [7], and the CAMCOG [8]
is also influenced by educational level. Educational attainment can
PLOS ONE | 1 September 2013 | Volume 8 | Issue 9 | e73167
also affect the performance on neuropsychological tests that
evaluate specific cognitive domains. Previous studies showed that
the performance on several neuropsychological tests designed to
assess language, episodic memory, and executive function is
significantly biased by education [1,9–13]. In developing coun-
tries, this is a very important issue, given the high proportion of
older adults with no or few years of formal education [14]. It is,
therefore, of utmost importance to develop and adapt neuropsy-
chological batteries taking into account the effect of formal
education to reduce the risk of bias and misclassification of
In clinical neuropsychology the use of an unstructured
assessment protocol allows the clinician to carefully choose the
neuropsychological tests according to a cognitive model and his
clinical hypothesis, mapping different cognitive domains in a
comprehensive way [1]. However, there few studies evaluating the
psychometric properties of neuropsychological instruments for
older adults with low formal education. The present study aims to
investigate the psychometric properties of a neuropsychological
assessment protocol designed for the evaluation of older adults
with low educational level. We assessed its factor structure,
criterion-related validity and ecological validity. In addition, we
proposed cut-off scores to discriminate the diagnostic groups (AD,
MCI and normal aging).
Materials and Methods
Participant’s recruitment and assessment
In the present study 274 consecutive older adults were assessed.
Participants were enrolled in an ongoing work evaluating the
relationship of depression and dementia in the elderly. The
participants or caregivers who did not show interest in joining the
study were referred and treated normally by the patient service
center, not suffering any burden with the non-participation. This
study was approved by the local Ethics Committee (registry 334/
06) and carried out in accordance with the Helsinki declaration.
All the participants (and caregivers for patients with suspected
dementia) gave written consent for the participation. Participants
with less than 60 years, previous history of neurological or
psychiatric disorders (except for depression), use of typical and
atypical antipsychotics, evidence of major vascular events on brain
computed tomography scans, severe sensorial or motor impair-
ments or other clinical conditions which may influence the
neuropsychological performance (such as hypothyroidism or B12
vitamin depletion), history of alcohol or other substance abuse and
patients which a close caregiver was not present on the assessment
were excluded from the present study.
All subjects underwent a comprehensive gerontological evalu-
ation which included the cognitive assessment with the adminis-
Table 1. Participants description, neuropsychological assessment and group comparisons for the whole sample.
Sociodemographic and
neuropsychological assessment
NA (1)
N = 96, F = 64
Dep = 34
MCI (2)
N = 85. F = 51
Dep = 22
Mild AD (3)
N = 93, F = 51
Dep = 27
Age 72.61 7.76 73.18 8.46 74.57 6.65 1.63 - -
Education 5.22 4.29 4.71 4.00 4.82 3.46 0.43 - -
Geriatric Depression Scale [Max = 15] 4.33 3.95 2.94 2.84 3.83 3.22 3.86* 0.03 1 = 3,2
Mini-Mental State Examination [Max = 30] 25.75 3.85 23.52 3.62 20.59 3.98 43.12** 0.24 1.2.3
Frontal Assessment Battery [Max = 18] 13.57 3.33 11.82 2.86 9.06 3.22 48.95** 0.27 1.2.3
Category Fluency (Animals) 13.99 4.70 11.14 3.39 8.48 3.82 44.05** 0.25 1.2.3
Category Fluency (Fruits) 11.96 3.94 9.36 2.36 7.85 2.71 42.28** 0.24 1.2.3
Letter Fluency (S) 9.99 4.32 9.15 4.00 7.11 3.44 13.28** 0.09 1 = 2.3
Digit Span Forward [Max = 144] 34.04 18.05 34.48 14.07 28.90 14.74 3.54* 0.03 1 = 2.3
Digit Span Backward [Max = 144] 15.60 9.97 12.51 10.16 8.98 7.45 12.11** 0.08 1 = 2.3
Stick Design Test [Max = 12] 11.66 0.90 11.08 1.81 10.27 2.43 13.85** 0.09 1 = 2.3
Clock Drawing Test [Max = 5] 3.53 1.78 2.66 1.74 2.01 1.60 18.69** 0.12 1.2.3
RAVLT A1 [Max = 15] 4.59 1.75 3.32 1.30 2.84 1.41 33.94** 0.20 1.2=3
RAVLT IR [Max = 15] 6.44 3.30 3.48 2.32 2.18 1.95 66.53** 0.33 1.2.3
RAVLT DR [Max = 15] 6.55 3.55 3.21 2.53 1.87 1.83 72.83** 0.35 1.2.3
RAVLT Rec [Max = 15] 7.78 4.45 0.78 6.64 21.34 6.27 63.31** 0.32 1.2.3
RAVLT Total [Max = 75] 35.07 11.81 26.32 8.72 21.40 7.47 49.66** 0.27 1.2.3
TN-LIN (Nouns) [Max = 40] 37.22 2.78 36.82 2.50 33.66 3.93 35.81** 0.21 1 = 2.3
TN-LIN (Verbs) [Max = 10] 9.57 1.03 9.66 0.72 8.92 1.46 11.70** 0.08 1 = 2.3
TN-LIN (Professions) [Max = 15] 13.38 2.56 13.08 1.85 11.28 3.13 17.90** 0.12 1 = 2.3
Token Test Attentional [Max = 15] 14.74 0.67 14.59 0.80 14.33 1.09 5.44* 0.04 1 = 2.3
Token Test Comprehension [Max = 21] 16.13 3.15 14.64 3.19 12.63 3.95 24.65** 0.16 1.2.3
*p,0.01, ** p,0.001.
Max: Maximum possible score on the test. NA: Normal Aging, MCI: Mild Cognitive Impairment, AD: Alzheimer’s dementia, F = Female, DEP = Depressed, RAVLT: Rey
Auditory-Verbal Learning Test, IR: Immediate Recall, DR: Delayed Recall, Rec: Recognition, TN-LIN: Teste de Nomeac¸a
˜o do Laborato
´rio de Investigac¸o
´gicas (Naming Test of the Laboratory of Neuropsychological Investigations).
Neuropsy Assessment of Low Educated Older Adults
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tration of the Mattis Dementia Rating Scale [6], the Mini-Mental
State Examination [4], the Verbal Learning test of the CERAD
Neuropsychological Battery [7], the Clinical Dementia Rating
[15]. Depressive symptoms were assessed by the Short-Version of
the Geriatric Depression Scale (GDS-15) [16]. Formal education
assessed in the initial clinical interview was reported in years,
discounting repetitions. Participants with less than one year and
unable to read or write simple sentences were considerate
illiterates. Participants which, do not have formal schooling, but
were able to read and write were classified with one year of formal
The performance on neuropsychological tests used for diagnosis
was interpreted based on cut-off values for the Mini-Mental State
Examination (18 points for illiterate, 23 points for participants with
1 to 7 years of formal education and 26 for participants with
8 years or more). For the Mattis Dementia Rating total score and
Subscales the ‘‘-2 Standard-Deviations’’ guideline (based on
normative values stratified by education) was used. For the
CERAD Neuropsychological Battery, we adopted as cut-off the
first quartile stratified by education, following Nitrini and
colleagues [7] recommendations. The procedure stratifies formal
education in Illiterate, Low Educated Literate (less than 4 years of
formal education) or Standard Educated Literate (4 or more years
of formal education). The lower quartile has the following values:
Immediate recall (Illiterate = 3, Low Educated Literate = 4,
Standard Educated Literate = 5), Delayed Recall (Illiterate = 3,
Low Educated Literate = 4, Standard Educated Literate = 4).
Neurocognitive status was adjudicated at expert multidisciplin-
ary meetings, taking into account all clinical, cognitive assessment,
laboratorial, and neuroimaging data when available. Functional
status was investigated based on caregiver’s reports about activities
of daily living and by the functional components of the Clinical
Dementia Rating [15]. The performance on cognitive tests was
adjusted for age and educational status, based on Brazilian norms
for each test. Alzheimer’s disease was diagnosed according to the
NINCDS-ADRDA [17] guidelines. The diagnosis of MCI was
made according to Mayo Clinic criteria [18] as follows: 1)
subjective cognitive complaint, preferably corroborated by an
informant; 2) objective impairment in the performance on
cognitive tests of the CERAD Neuropsychological Battery and
on the Mattis Dementia Rating Scale, but not severe enough to
reach dementia diagnosis; 3) preserved global cognitive function
(Mini-Mental State Examination scores above the cutoff for
dementia based on formal education); 4) preserved or minimal
impairments in activities of daily living 5) not demented.
A total of 85 subjects were identified as MCI and 93 with AD.
Ninety-six subjects with no evidence of cognitive impairment were
included as a comparison group (‘‘normal cognitive aging – NA’’
group). Normal aging and MCI participants had MMSE scores
above the cutoff for dementia according to formal education [4].
Considering the cutoff 5/6 (case/non case) on the Geriatric
Depression Scale, 35% of the NA, 26% of MCI and 29% of AD
participants has significant depressive symptoms.
Neuropsychological Assessment
The protocol used in the present study was designed to assess
episodic memory, attention, executive functions, visuospatial
abilities and language. It was designed to be fully administered
Table 2. Factor structure of the neuropsychological assessment protocol.
Neuropsychological Test
Semantic Memory
Letter Fluency (S) 0.649 0.099 20.286 20.070
Category Fluency (Animals) 0.579 0.035 20.313 20.141
Category Fluency (Fruits) 0.503 0.026 20.318 20.086
Frontal Assessment Battery 0.435 0.121 20.126 0.288
Digit Span Forward 0.426 20.018 0.064 0.115
Digit Span Backward 0.417 0.065 0.062 0.247
TN-LIN (Professions) 20.021 0.974 0.016 20.075
TN-LIN (Verbs) 20.001 0.839 0.070 20.017
TN-LIN (Nouns) 20.023 0.760 20.076 0.103
RAVLT (IR) 20.006 20.014 20.918 20.037
RAVLT (DR) 20.033 0.054 20.910 20.030
RAVLT (Total) 0.070 0.011 20.810 0.001
RAVLT (A1) 20.015 20.006 20.669 0.133
RAVLT (Rec) 0.003 0.028 20.558 0.189
Token Test – Comprehension 0.286 0.075 20.041 0.508
Token Test – Attention 20.013 0.046 20.049 0.491
Stick Design Test 0.041 0.046 20.128 0.461
Clock Drawing Test 0.304 0.135 20.119 0.318
Eigenvalue 7.901 1.969 1.325 1.085
Variance Explained 42% 10% 7% 6%
Cronbach’s Alpha 0.723 0.808 0.786 0.731
NA: Normal Aging, MCI: Mild Cognitive Impairment, AD: Alzheimer’s dementia, RAVLT: Rey Auditory-Verbal Learning Test, IR: Immediate Recall, DR: Delayed Recall, Rec:
Recognition, TN-LIN: Laboratory of neuropsychological Investigations Naming Test.
Neuropsy Assessment of Low Educated Older Adults
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in one session of 90 minutes, increasing its usefulness in the clinical
contexts where the time and human resources for the neuropsy-
chological assessment are scarce. The tests were selected based on
Brazilian studies which investigated their psychometric properties
on older adults with low formal education. Two neuropsycholo-
gists (LFM-D and JJP) searched the Brazilian and international
literature for neuropsychological tests which: 1) may be suitable for
older adults with low formal education (e.g.: avoiding reading or
calculation, complex drawing and fine motor coordination); 2)
have previous studies reporting, at least partially, validity for this
population, 3) could be all applied on a 90 minutes assessment
section, 4) tests did not have copyright agreements, with stimuli
and application procedures freely available. The following tests
were selected:
Rey Auditory Verbal Learning Test (RAVLT): a measure of episodic
memory containing five learning trials of a 15 word list followed
by a distractor, an immediate recall (RAVLT IR), a 25-minutes
delayed recall (RAVLT DR) and a recognition Trial (RAVLT
Rec). The Brazilian version of the test proposed by Malloy-Diniz
and colleagues [9] and validated for older adults [11] was chosen
for the present study. The RAVLT has good criterion validity for
the diagnosis of neurocognitive disorders in older adults, such as
AD, MCI and major depression, according to a recent review
Frontal Assessment Battery: designed as a bedside screening test for
frontal-executive impairment [20], this test is a brief and well
validated screening test for older adults, assessing different executive
components by six subtests (similarities, fluency, motor planning,
selective attention, inhibitory control and environmental autono-
my). One of the Brazilian versions was used and the total score
adopted as variable, since it was previously validated and had
adequate normative values [21]. The test performance is usually
compromised in clinical conditions related to frontostriatal
dysfunction, such as Frontotemporal dementia, Progressive Supra-
nuclear Palsy and Parkinson’s disease [20]. The battery shows
moderate correlations with classical executive-functions tests [20–
Short version of the Token Test: this language comprehension test
designed for the detection of aphasia involves verbal orders of
increasing difficulty (input) and motor sequences on colored tokens
(output). The short version (36 items) is adapted [24], validated
[10] and has adequate normative data [13] for this population.
The test was divided in two components for this study, based on
the factor structure proposed on a previous report [10]: Token
Test – Attention (items 1 to 15) and Token Test – Comprehension
(items 16 to 36).
Category Fluency and Letter Fluency: The verbal fluency tests are
classical screening tests for cognitive impairment, usually associ-
ated with the executive functions. Two categories and one letter
were chosen for the protocol, based on the normative and validity
studies for the Brazilian population: Animals [5], Fruits [12] and ‘‘S’’
[25] generated in one minute. The test is very sensitive for
cognitive impairment in different clinical conditions [2,10,12].
Digit Span: a classical measure of verbal working memory, a
cognitive process related to storage and manipulation of verbal
information. Kessels, van den Berg, Ruis and Brands [26] suggest
the use of a product score between the maximum span and the
number of correct trials (2 per span) as a more general measure of
working memory efficiency. A previous report validated this
method for older adults with low formal education [22]. In AD,
the phonological loop of the working memory (assessed by the
Digit Span Forward) is usually preserved, while the executive
Figure 1. Stepwise linear regression model for the association between cognitive and functional measures. Legend: the four
components extracted on the factor analysis (Episodic Memory, Executive Functions, Language/Semantic Memory and Visuospatial Abilities) were
used as independent predictors of older adults performance on Activities of Daily Living. Three of the four components (excluding Visuospatial
Abilities) explained about 30% of functional performance variance.
Neuropsy Assessment of Low Educated Older Adults
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components (assessed by Digit Span Backward) are slightly
impaired [27].
Clock Drawing Test: A classical drawing task designed for the
assessment of cognitive impairment in older adults and a widely
used test for cognitive screening. The Shulman’s [28] (0 to 5
points, higher scores represent better performance, pre-drawn
circle). This version was chosen for the present study, since it’s
one of the most sensitive for neurocognitive disorders in the
elderly [29].
Stick Design Test: a test used for the assessment of visuospatial
abilities consisted of four bi-dimensional models where the subject
must reproduce them using four matches [30]. The models differ
in global configuration (open and closed models), alignments,
angles and orientation of match heads. The test is a good
alternative to drawing tasks, since for very low educated or
illiterate individuals the more traditional constructional praxis tests
may cause negative emotional reactions and very low scores [31].
The Stick Design Test shows good criterion validity for dementia,
even superior to drawing tests in patients with very low formal
education [32].
The Neuropsychological Investigations Laboratory Naming Test (TN-
LIN): developed as a measure of naming abilities in children and
older adults with low formal education [33]. Based on classical
naming paradigms, the TN-LIN uses 65 black-white line drawings
divided into nouns (40), verbs (10) and professions (15). The nouns
are divided in objects (15), animals (10), food (5), transports (4), and
clothes (5). The nouns (TN-LIN Nouns), verbs (TN-LIN Verbs)
and professions (TN-LIN Professions) were used for further
Activities of Daily Living: we used the Basic Daily Life Activities
Index and the Instrumental Daily Life Activities Index, based on
the Katz [34] and Lawton [35] indexes respectively, to assess
functional performance. Each activity of daily living was scored,
based on information provided by a close caretaker, as ‘‘2’’ (no
functional impairment), ‘‘1’’ (partial dependence of human help in
performing the daily life activity) and ‘‘0’’ (complete dependence of
human help on performing the daily life activity). Scores for basic
activities range from 0–12 and instrumental activities from 0–16.
The general score (0–28 points) was used in this study. Lower
scores indicated greater impairment.
Statistical procedures
Performance on neuropsychological assessment tests and socio-
demographic characteristics were assessed by one-way ANOVA,
and the Sidak’s post hoc test was used to assess pairwise group
differences. Effect sizes for this analysis were computed by the eta-
squared. Keeping in mind the hierarchical structure of the
cognitive system [36], which leads to significant associations
among neuropsychological measures, a principal axis factoring
and an oblique (direct oblimin [37]) rotation were adopted,
allowing the encountered factors to correlate. The criteria used for
components formation include eigenvalues greater than 1 and
convergent scree-plot analysis by two independent judges. The
Keiser-Meyer-Olkim (KMO) test of sampling adequacy and the
Bartlett’s test of sphericity were used to assess the viability of the
factor extraction. Cronbach’s alpha of each factor was computed
for the assessment of reliability. These procedures aims to assess if
the proposed battery keeps its construct validity for the assessment
Table 3. NA, MCI and AD non-depressed patients’ description and ROC Curve Analysis.
Neuropsychological Tests NA x AD NA x MCI MCI x AD
AUC (SE) Cutoff Sens. Spec. AUC (SE) Cutoff Sens. Spec. AUC (SE) Cutoff Sens. Spec.
Letter Fluency (S) 0.85 (0.04)*** 10 71% 77% 0.71 (0.05)*** 11 65% 64% 0.65 (0.05)** 8 57% 41%
Category Fluency (Animals) 0.92 (0.02)*** 12 81% 86% 0.75 (0.04)*** 13 76% 67% 0.77 (0.04)*** 10 70% 35%
Category Fluency (Fruits) 0.87 (0.03)*** 11 74% 83% 0.79 (0.04)*** 12 68% 79% 0.68 (0.05)*** 9 57% 39%
Frontal Assessment Battery 0.91 (0.03)*** 12 84% 80% 0.78 (0.04)*** 14 71% 74% 0.75 (0.04)*** 11 68% 26%
Digit Span Forward 0.69 (0.05)*** 27 60% 59% - - - - 0.68 (0.05)*** 27 64% 41%
Digit Span Backward 0.82 (0.04)*** 11 76% 76% 0.67 (0.05)*** 14 60% 71% 0.65 (0.05)** 9 65% 46%
TN-LIN (Nouns) 0.84 (0.04)*** 26 74% 85% 0.62 (0.05)* 38 65% 60% 0.78 (0.04)*** 36 71% 27%
TN-LIN (Verbs) 0.70 (0.05)*** 9 86% 53% - - - - 0.67 (0.05)*** 10 78% 49%
TN-LIN (Professions) 0.78 (0.04)*** 14 79% 73% 0.67 (0.05)*** 14 79% 56% 0.68 (0.05)*** 13 73% 39%
RAVLT (IR) 0.93 (0.02)*** 5 82% 86% 0.87 (0.03)*** 6 73% 87% 0.62 (0.05)* 3 57% 42%
RAVLT (DR) 0.93 (0.02)*** 5 82% 88% 0.87 (0.03)*** 5 81% 71% 0.64 (0.05)*** 2 67% 47%
RAVLT (Total) 0.91 (0.03)*** 38 86% 82% 0.82 (0.04)*** 32 74% 75% 0.67 (0.05)*** 23 64% 41%
RAVLT (A1) 0.83 (0.04)*** 4 79% 76% 0.75 (0.04)*** 4 79% 60% 0.62 (0.05)* 4 40% 24%
RAVLT (Rec) 0.93 (0.02)*** 5 82% 85% 0.88 (0.03)*** 6 77% 81% - - - -
Token Test –
0.84 (0.04)*** 14 86% 79% 0.73 (0.05)*** 15 69% 68% 0.68 (0.05)*** 14 56% 32%
Token Test –
0.68 (0.05)*** 15 87% 49% - - - - - - - -
Stick Design Test 0.77 (0.04)*** 11 94% 59% 0.64 (0.05)** 11 94% 33% 0.64 (0.05)** 11 67% 41%
Clock Drawing Test 0.87 (0.03)*** 3 76% 85% 0.73 (0.05)*** 4 76% 60% 0.68 (0.05)*** 2 73% 46%
*p,0.05, ** p,0.01, *** p,0.001.
NA: Normal Aging, MCI: Mild Cognitive Impairment, AD: Alzheimer’s Dementia, Med: Median, AUC: Area under the Curve, SE: Standard Error, Sens.: Sensibility, Spec.:
Specificity, TN-LIN: Teste de Nomeac¸a
˜o do Laborato
´rio de Investigac¸o
˜es Neuropsicolo
´gicas (Naming Test of the Laboratory of Neuropsychological Investigations), RAVLT:
Rey Auditory-Verbal Learning Test, IR: Immediate Recall, DR: Delayed Recall, Rec: Recognition.
Neuropsy Assessment of Low Educated Older Adults
PLOS ONE | 5 September 2013 | Volume 8 | Issue 9 | e73167
of Executive Functions, Language, Memory and Visuospatial
Abilities on the studied population, assuring it’s clinical applica-
bility. Another advantage of factor analysis is the reduction of the
amount of test variables, reducing the probability of a Type 1 error
on further analysis.
The ecological validity of the neuropsychological assessment
was investigated by linear regression models, containing the ADL
measures as dependent variables and the components of the factor
analysis (extracted by the regression method and standardized
based on the non-depressed normal aging participants scores) as
predictors. We adopted stepwise procedures to reduce multi-
We carried out Receiver Operator Characteristic (ROC) curve
analyses to compare the performance of each neuropsychological
test to differentiate the diagnostic groups. Cutoffs for clinical use
considering the best ration between sensitivity and specificity were
calculated. Finally, we performed a multinomial logistic regression
analysis, with diagnosis as dependent variable and the neuropsy-
chological tests as independent variables; to evaluate which
neuropsychological tests best differentiate the diagnostic groups.
To reduce multicollinearity, we adopted a stepwise procedure
(forward entry, entering criteria: 0.05 and exclusion criteria 0.10).
For the criterion related validity procedures, only participants
with GDS-15 scores below 6 were selected. The Mini-Mental State
Examination total score was included in the models, since the
neuropsychological measures should have an addictive power with
this screening measure for the patient’s diagnosis. All the statistical
procedures were performed on SPSS 19.0 (Chicago, IL) and
statistical significance was set at a,5%.
The three groups did not differ in clinical and socio-
demographic and clinical characteristics. As expected, we found
significant differences in the scores of all neuropsychological tests
among diagnostic groups, with effect sizes ranging from small to
large (Table 1).
The Neuropsychological battery formed four related factors
(Table 2). The first factor was composed by tests related to verbal
fluency, working memory and the Frontal Assessment Battery
(Executive Functions Factor). The second component contained the
three TN-LIN variables, a test designed to assess the naming skills
(Language/Semantic Memory Factor). The third component contained
the RAVLT items (Episodic Memory Factor). The last component
contained tests designed to assess visuospatial abilities, visual
search (Visuospatial Abilities Factor). Unexpectedly, a verbal com-
prehension test was also present in this fourth factor. These four
factors explained 65% of the total variance. The internal
consistency of the individual factors and the protocol as a whole
was 0.83 satisfactory.
The ecological validity of the neuropsychological assessment
was assessed by a stepwise linear regression model. The model was
significant (F = 40.65, p,0.001, R
= 31%) and contained three
steps. The final model (third step) consisted of Executive Functions
(b= 0.27, p,0.001), Episodic Memory (b= 0.20, p = 0.002) and
Figure 2. Stepwise multinomial regression models for the classification of the participants. Legend: increase on the classification rate of
the participants by the use of different neuropsychological tests. The final model contains tests of general cognitive function (Mini-Mental State
Examination), Episodic Memory (Delayed Recall and Recognition from the Rey Auditory-Verbal Learning Test), Executive Functions (Category Fluency
Test ‘‘Animals’’ and the Frontal Assessment Battery) and Language/Semantic Memory (Laboratory of Neuropsychological Investigations Naming Test
‘‘Nouns’’). Considering its general accuracy the protocol improves the classification rate of the participant’s in 47%, starting at chance (33%). Its
accuracy is greater for the identification of normal Aging (54%) followed by AD (47%) and MCI (42%), which reflect the intermediate condition of this
last group.
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PLOS ONE | 6 September 2013 | Volume 8 | Issue 9 | e73167
Language/Semantic Memory (b= 0.23, p = 0.006), but not Visuospatial
abilities (b=20.11, p = 0.116). Figure 1 shows the relationship
between the standardized predictors and the functional measure.
Table 3 shows the cut-off values for differentiating the
diagnostic groups. All neuropsychological tests showed good
sensitivity and specificity values to discriminate between NA and
AD participants. Nonetheless, we observed that the sensitivity
and specificity of the neuropsychological tests for discriminating
NA vs. MCI, and MCI vs. AD were lower than those found for
NA vs. AD.
The multinomial logistic regression model, which seeks to
correctly classify the participants (considering the Normal Aging
group as reference), was significant (22 Log Likelihood = 198.10,
= 221.43, p,0.001, R
= 78%). Six steps were performed by
the model starting with RAVLT-DR (x
= 114.43, p,0.001), then
adding, Mini-Mental State Examination (x
= 44.02, p,0.001),
Category Fluency Animals (x
= 30.76, p,0.001), RAVLT-Rec
= 13.33, p ,0.001), TN-LIN-Nouns (x
= 12.05, p = 0.002) and
the Frontal Assessment Battery (x
= 6.83, p = 0.033). The
participant’s classification, considering chance, the final regression
model and error are shown in Figure 2.
Our results suggest that this neuropsychological protocol has
appropriate psychometric properties and can be used in the
assessment older adults with low educational level. The factor
analysis indicated a four component model related to Executive
Functions, Language/Semantic Memory, Episodic Memory and
Visuospatial Abilities, suggesting that the selected neuropsycho-
logical tests retain its construct validity for the assessment of older
adults with low formal education. The structure is very similar to
our a priori hypothesis, differing slightly on two neuropsycholog-
ical measures. The neuropsychological tests performed well to
differentiate healthy adults from MCI and AD patients and the
performance on these tests were correlated to functional perfor-
mance. These results indicate a good criterion related and ecologic
validity of this neuropsychological battery.
The factor analysis showed a four factor structure for the
neuropsychological battery (Executive Function, Language/Se-
mantic memory, Episodic memory, and Visoespacial abilities).
This is in accordance with the expected protocol structure given
the tests chosen included in the neuropsychological protocol.
Therefore, our results show that this protocol has good construct
validity and is appropriate for administration in older adults with
low educational level. This is particularly important as most of
these tests were developed in countries with population with
higher educational attainment level.
Three of the four cognitive components of our study correlated
with functional performance and only visuospatial abilities were
not correlated with functional performance. Previous studies,
nonetheless, reported significant associations between visuospatial
tests and functional measures [38,39]. We delineate three
hypotheses for the lack of significance. First, this factor has shown
relatively low variance, since more pronounced visuospatial
impairment is unlikely in normal aging, MCI and AD. The tests
related to this factor are heterogeneous, and in all of them, there
was a tendency for ceiling effects reducing the variance of this
cognitive component. Finally, the IADLs assessed in this study are
poorly related to spatial orientation, navigating, perception and
spatial processing, with only one demanding a greater loading of
spatial abilities (go out alone to distant locations using transport)
[35]. These factors might have contributed to the lack of
significant association between visoespacial abilities and functional
performance. The analysis of the protocol ecological validity
contributes for a topic usually neglected on the study of more
traditional neuropsychological measures and might be useful from
a prospective view, estimating environmental needs of the patients
and guiding rehabilitation routines [22].
This neuropsychological protocol showed good criterion related
validity, and the cutoff values found on this study could be used on
clinical setting for discriminating AD, MCI and healthy older
subjects. The best sensitivity and specificity values were observed
for AD vs. healthy controls. The sensitivity and specificity for AD
vs. MCI and MCI vs. NA was lower than those observed for AD
vs. NA, but still at an acceptable range to be used in clinical
practice. Our results are in accordance with other studies, with
minor differences in the proposed cut-off value, and differences
might be explained by sample particularities [2,5,10,12]. Interest-
ingly, our results are similar to those found in another Brazilian
study which examined an elderly population with higher
educational level and used a different neuropsychological protocol
[2]. In this study, the authors also report that the best sensitivity
and specificity values were observed for differentiating AD from
healthy controls. The sensitivity and specificity for discriminating
AD from MCI, and MCI from NA were lower. These results
suggest that the identification of MCI and its differentiation from
healthy older adults and early AD subjects are major challenges in
clinical practice. The development of novel neuropsychological
tests and protocols as well as the evaluation of combined tools and
methods specifically designed for the diagnosis of MCI is necessary
to improve our ability to make an accurate and early identification
of these subjects.
The neuropsychological assessment protocol proposed by this
study significantly improved the classification of the three groups.
A multinomial regression model included tests of delayed and
recognition memory (RAVLT), global cognitive functioning (Mini-
Mental State Examination), executive functions (Category Fluency
Animals and FAB) and language/semantic processing (TN-LIN
Nouns). These results support the hypothesis that adding cognitive
tests of different cognitive domains increase diagnostic power [40].
The accuracy, however, was lower than in other studies, such as
Schmand and colleague [3]. Our analysis involves three different
groups hypothetically defined as a continuum (NA – MCI – AD)
and the cognitive boundaries of each one are largely superim-
posed. In a previous study, we found large effect sizes when AD
patients and normal controls were compared using Token Test
raw scores, however, when scaled scores based on population
norms were adopted the effect sizes were only moderate [10]. We
believe the proposed cutoff scores of our study might improve the
clinical applicability of these measures on participants with low
formal education.
Our study was performed with a very particular and vulnerable
population, and the proposed cutoff scores might improve the
clinical use of the neuropsychological testes for patients with
similar characteristics. In this sense, the study is clinically relevant,
with different cutoffs for several neuropsychological tests for three
different comparisons, and could be used along with other
methods to the diagnosis of AD and MCI, as well for the
differentiation of these two conditions. However the cutoffs must
be used cautiously, since the accuracy of each test independently is
usually moderate, especially on the MCI x AD differentiation.
The present results should be viewed in light of study
limitations. This is a cross-sectional study and the MCI patients
were not followed-up to assess the progression to dementia.
Previous studies suggest that there are significant baseline
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differences in cognitive performance between MCI converters and
non-converters what may significantly influence the definition of
cut-off scores to differentiate MCI from normal aging and
dementia subjects [40,41,42]. The participants were recruited
from a geriatric outpatient clinic and the present results may not
be generalized to the general population. Additional studies with
independent and community-based samples are necessary to
evaluate and validate the psychometric properties and the
proposed cut-off scores for the neuropsychological protocol.
The present study shows strong evidence of the validity of a
neuropsychological protocol designed for the cognitive assessment
of older adults with low educational level. The measures are valid
for the assessment of executive functions, language, memory and
visuospatial abilities. It has good accuracy for the diagnosis of AD
and MCI patients. Future studies are necessary to replicate these
finding, to verify its applicability under other clinical conditions
and to develop population-based norms for this protocol.
We would like to thank the geriatricians, gerontologists and neuropsychol-
ogists from the Instituto Jenny Faria de Atenc¸a˜o a` Sau´de do Idoso for the
patient’s assessment and Care Planning.
Author Contributions
Conceived and designed the experiments: JJP LB RTA LM GC ENM
MACB RN BSD LFMD. Performed the experiments: JJP LB RTA LM
GC ENM MACB RN BSD LFMD. Analyzed the data: JJP LFMD.
Contributed reagents/materials/analysis tools: JJP LB RTA LM GC ENM
1. Salmon DP, Bondi MW (2009) Neuropsychological Assessment of Dementia.
Annu Rev Psychol 60: 257–282.
2. Diniz BS, Yassuda MS, Pereira FS, Flaks MK, Viola LF, et al. (2008) Mild
cognitive impairment: cognitive screening or neuropsychological assessment?
Rev Bras Psiquiatr 30(4): 316–321.
3. Schmand B, Eikelenboom P, van Gool WA, Alzheimer’s Disease Neuroimaging
Initiative (2011) Value of neuropsychological tests, neuroimaging, and
biomarkers for diagnosing Alzheimer’s disease in younger and older age cohorts.
J Am Geriatr Soc 59(9): 1705–1710.
4. Brucki SM, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto IH (2003)
Sugesto˜es para o Uso do Mini-Exame do Estado Mental no Brasil. Arq
Neuropsiquiatr 61(3B): 777–781.
5. Brucki SMD, Malheiros SMF, Okamoto IH, Bertolucci PHF (1997) Dados
normativos para o teste de flueˆncia verbal categoria animais em nosso meio. Arq
Neuropsiquiatr 55(1): 56–61.
6. Porto CS, Fichman GC, Caramelli P, Bahia VS, Nitrini R (2003) Brazilian
version of the Mattis Dementia Rating Scale: Diagnosis of mild dementia in
Alzheimer’s disease. Arq Neuropsiquiatr 61(2B): 339–345.
7. Nitrini R, Caramelli P, Herrera E Jr, Porto CS, Charchat-Fichman H, et al.
(2004) Performance of illiterate and literate nondemented elderly subjects in two
tests of long term memory. J Int Neuropsychol Soc 10:634–638.
8. Apraha mian I, Diniz BS, Izbicki R, Radanovic M, Nunes PV, et al. (2011)
Optimizing the CAMCOG test in the screening for mild cognitive impairment
and incipient dementia: saving time with relevant domains. Int J Geriatr
Psychiatry 26(4): 403–408.
9. Malloy-Diniz LF, Lasmar VAP, Gazinelli LSR, Fuentes D, Salgado JV (2007a)
The Rey Auditory-Verbal Learning Test: applicability for the Brazilian elderly
population. Rev Bras Psiquiatr 29(4): 324–329.
10. de Paula JJ, Bertola L, Nicolato R, Moraes EN, Malloy-Diniz LF (2012a)
Evaluating Language Comprehension in Alzheimer’s disease: the use of the
Token Test. Arq Neuropsiquiatr 70(6): 435–440.
11. de Pau la JJ, Cunha LMP, Nicolato R, Moraes EN, Bicalho MA, et al. (2012b)
Reliability and construct validity of the Rey-Auditory Verbal Learning Test in
Brazilian elders. Rev Psiquiatr Clı
´n 39(1): 19–23.
12. de Paula JJ, Schlottfeldt CG, Moreira L, Cotta M, Bicalho MA, et al. (2010)
Psychometric properties a brief neuropsychological protocol for use in geriatric
populations. Rev Psiquiatr Clı
´n 37(6): 251–255.
13. Morei ra L, Schlottfeldt CG, de Paula JJ, Daniel MT, Paiva A, et al. (2011)
Normative study of the Token Test (short version): preliminary data for a sample
of Brazilian seniors. Rev Psiquiatr Clı
´n 38(3): 97–101.
14. Minis te´rio do Planejamento, Orc¸amento e Gesta˜ o. (Instituto Brasileiro de
Geografia e Estatı
´stica IBGE). Contagem Populacional. Available: Http://www. Accessed: 20 Jun 2013.
15. Morri s JC (1993) The Clinical Dementia Rating (CDR): current version and
scoring rules. Neurology 43(11): 2412–2414.
16. Sheik J, Yesavage J (1986) Geriatric Depression Scale (GDS): recent evidence
and development of a shorter version. Clin Gerontol 5:165–172.
17. McKhann G, Drachman D, Folstein M, Katzman R, Price D, et al. (1984)
Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work
group under the auspices of department of health and human services task force
on Alzheimer’s disease. Neurology 34(7): 939–944.
18. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, et al. (2001) Current
concepts in mild cognitive impairment. Arch Neurol 58(12): 1985–1992.
19. Cotta MF, Malloy-Diniz LF, Nicolato R, Moraes EN, Rocha FL, et al. (2012)
The Rey Auditory-Verbal Learning Test (RAVLT) on the differential diagnosis
of normal and pathological aging. Contextos Clı
´nicos 5(1): 10–25.
20. Duboi s B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: A frontal assessment
battery at bedside. Neurology 55: 1621–1626.
21. de Paula JJ, Moura SM, Bocardi MB, Moraes EN, Malloy-Diniz LF, et al. (2013)
Screening for executive dysfunction with the Frontal Assessment Battery:
psychometric properties analysis and representative normative data for Brazilian
older adults. Psicologia em Pesquisa 7(1):89–98.
22. de Paula JJ, Malloy-Diniz LF (2013) Executive functions as predictors of
functional performance in mild Alzheimer’s dementia and mild cognitive
impairment elderly. Estud psicol 18(1):117–124.
23. de Paula JJ, Moreira L, Nicolato R, de Marco LA, Correa H, et al. (2012c) The
Tower of London Test: Different Scoring Criteria for Diagnosing Alzheimer’s
disease and Mild Cognitive Impairment. Psychol Rep 110(2): 477–488.
24. Fontanari J (1989) O Token Test: elegaˆ ncia e concisa˜o na avaliac¸a˜o da
compreensa˜o do afa´sico. Validac¸a˜o da versa˜o de De Renzi para o Portugueˆs.
Neurobiologia 52(3): 167–176.
25. Senhorini MC, Amaro Ju´nior E, de Mello Ayres A, de Simone A, Busatto GF
(2006) Phonemic fluency in Portuguese-speaking subjects in Brazil: ranking of
letters. J Clin Exp Neuropsychol 28(7):1191–1200.
26. Kessels RPC, van den Berg E, Ruis C, Brands AMA (2008) The Backward Span
of the Corsi Block-Tapping Task and Its Association with the WAIS-III Digit
Span. Assessment 15(4): 426–434.
27. Huntley JD, Howard RJ (2010) Working memory in early Alzheimer’s disease: a
neuropsychological review. Int J Geriatr Psychiatry 25(2): 121–132.
28. Shulman KI (2000) Clock-drawing: Is it the ideal cognitive screening test?
Int J Geriatr Psychiatry, 15(6), 548–561.
29. Tuokko H, Hadjistavropo ulos T, Rae S, O’Rourke N (2000) A comparison of
alternative approaches to the scoring of clock drawing. Arch Clin Neuropsychol
15: 137–148.
30. Baiyewu O, Unverzagt FW, Lane KA, Gureje O, Ogunniyi A, et al. (2005) The
Stick Design test: A new measure of visuoconstructional ability. J Int
Neuropsychol Soc 11(5): 598–605.
31. Unverzagt FW, Morgan OS, Thesiger CH, Eldemire DA, Luseko J, et al. (1999)
Clinical utility of CERAD neuropsychological battery in elderly Jamaicans. J Int
Neuropsychol Soc 5: 255–259.
32. de Paula JJ, Costa MV, Bocardi MB, Cortezzi MC, Moraes EN, et al. (2013)
The Stick Design Test on the Assessment of older adults with low formal
Education: evidences of construct, criterion-related and ecological validity. Int
Psychogeriatr epub ahead of print.
33. Malloy-Diniz LF, Bentes RC, Figueiredo PM, Branda˜o-Bretas D, Costa-
Abranches S, et al. (2007) Normalizacio´n de una baterı
´a de tests para evaluar las
habilidades de comprensio´n del lenguaje, fluidez verbal y denominacio´n en
nin˜os brasilen˜os de 7 a 10an˜os: resultados preliminares. Rev Neur ol 44(5): 275–
34. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW (1963) Studies of
illness in the aged. The index of ADL: a standardized measure of biological and
psychosocial function. JAMA, 185(12): 914–919.
35. Lawton MP, Brody EM (1969) Assessment of older people: Self-Maintaining and
Instrumental Activities of Daily Living. Gerontologist 9:179–185
36. Salthouse TA (2003) Localizing age-related individual differences in a
hierarchical structure. Intelligence 32: 541–561.
37. IBM Corp Released 2010. IBM SPSS Statistics for Windows, Version 19.0.
Armonk, NY: IBM Corp.
38. Farley KL, Higginson CI, Sherman MF, MacDougall E (2011) The ecological
validity of clinical tests of visuospatial function in community-dwelling older
adults. Arch Clin Neuropsychol 26(8): 728–738.
39. Davies SR, Field AR, Andersen T, Pestell C (2011) The ecological validity of the
Rey-Osterrieth Complex Figure: predicting everyday problems in children with
neuropsychological disorders. J Clin Exp Neuropsychol 33(7): 820–31.
40. Forlenza OV, Diniz BS, Talib LL, Radanovic M, Yassuda MS, et al. (2010)
Clinical and biological predictors of Alzheimer’s disease in patients with
amnestic mild cognitive impairment. Rev Bras Psiquiatr. 32(3): 216–22.
Neuropsy Assessment of Low Educated Older Adults
PLOS ONE | 8 September 2013 | Volume 8 | Issue 9 | e73167
41. Cui Y, Liu B, Zhen X, Fan M, Liu T, et al. (2011) Identification of Conversion
from Mild Cognitive Impairment to Alzheimer’s Disease Using Multivariate
Predictors. PLoS One 6(7): e21896.
42. Zhang D, Shen D, the Alzheimer’s Disease Neuroimaging Initiative (2011)
Predicting future clinical changes in MCI patients using longitudinal and
multimodal biomarkers. PLoS One 7(3): e33182.
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... One of the first symptoms of Alzheimer's disease is a subjective worsening of memory functioning, followed by objective impairment in standardized neuropsychological tests (McKhann et al., 2011). In the neuropsychological assessment, different aspects of memory are investigated, including the ability to store, retain, and recall new information (de Paula et al., 2013). The Rey Auditory-Verbal Learning Test (RAVLT) is a test for episodic memory assessment, with components related to recent memory, verbal learning, immediate and delayed recall, and recognition memory (de Paula & Malloy-Diniz, 2018). ...
... It is considered a quick, easy-toadminister, and efficient test to measure cognitive abilities and detect episodic memory losses (Cotta et al., 2012). The test can differentiate normal aging, MCI and, AD with relatively high accuracy (de Paula et al., 2013). ...
... The former refers to the immediate recall from a word list evoked after applying a distraction task and, the latter, a delayed recall evoked after 30 min of exposition (Malloy-Diniz et al., 2007). These two measures, along with the sum of words remembered during learning trials, are usually the most precise in identifying memory deficits in MCI and AD (de Paula et al., 2013) and can be used for differential diagnosis, between other conditions (Barulli et al., 2019;Bussè et al., 2017;Hessen, 2011). A common clinical interpretation of A6 and A7 scores is that a reduction in the number of words recalled in A7 relative to A6 suggests a storage deficit, which is expected in MCI and AD (Lezak et al., 2004). ...
... The neuropsychological assessment was carried out face to face by a single trained neuropsychologist for all included patients. It consisted of a neurocognitive battery for the evaluation of attention (five digits test), psychomotor speed (nine-hole test), memory (Rey Auditory-Verbal Learning Test (RAVLT)), executive function (EF) (Frontal Assessment Battery (FAB)), visual-spatial processing (Rey Figure Test), language (TN_LIN) [13,14] and reasoning/problem solving (IQ (Vienna Matrices)) [15]. Patients were considered to have CD if the score of each test was 2.0 or more standard deviations below the normative score corrected for age, education, sex, and ethnic group, when necessary. ...
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Background Cognitive dysfunction (CD) is a widespread manifestation in adult systemic lupus erythematosus (SLE) patients, but this subject is rarely examined in patients with childhood-onset SLE (cSLE). This study aimed to assess the frequency of CD, its associations with lupus clinical manifestations and its impact on the health-related quality of life (HRQL) in young adult cSLE patients. Methods We evaluated 39 cSLE patients older than 18 years. They underwent a rheumatologic evaluation and extensive neuropsychological assessment, encompassing all cognitive domains described by the American College of Rheumatology. HRQL was assessed with the WHOOQOL-BREEF, General Activities of Daily Living Scale (GADL) and Systemic Lupus Erythematosus-specific quality-of-life instrument (SLEQOL). The activity of SLE was evaluated with the modified sle disease activity index (sledai-2k). Results Impairment in at least one cognitive domain was found in 35 (87.2%) patients. The most compromised domains were attention (64.1%), memory (46.2%), and executive functions (38.5%). Patients with cognitive impairment were older, had more accumulated damage and had worse socioeconomic status. Regarding the association between cognitive dysfunction and HRQL, memory impairment was correlated with worse environmental perception and a worse relationship with the treatment. Conclusion In this study, the frequency of CD in cSLE patients was as high as that in the adult SLE population. CD can significantly impact the response of cSLE patients to treatment, justifying preventive measures in the care of this population.
... Participants were excluded if neuropsychological evaluation suggested dementia (scores lower than two standard deviation in two or more cognitive domain). The neuropsychological battery was comprised by the following tests: Mattis Dementia Rating Scale (26) , Digit Span Forward and Backward (27) , Five Digits (28) , Rey Auditory-Verbal Learning Test (RAVLT) (29) , Verbal Phonemic Fluency (30) , Frontal Assessment Battery (FAB) (31) , Taylor's Complex Figure Simplified (32) , Corsi's Cubes (33) , Clock Drawing Test (34) , Stick Design Test (35) , Laboratory of Neuropsychological Investigations Naming Test (36) and Pfeffer's Functionality Scale (37) . Participants were also excluded if they presented mood disorders due to general medical conditions, other psychiatric conditions (except nicotine dependence), infectious or active autoimmune diseases or if they were using illicit drugs or presented alcohol abuse. ...
... However, a more comprehensive assessment may be necessary to design and evaluate the effects of interventions as well as for monitoring the progression of language symptoms in adults with aphasia and PPA (34,35). The Token Test (36) is often employed and has been translated and adapted into several languages, including Brazilian Portuguese (37,38). It evaluates comprehension at the sentence level by asking the participants to execute commands. ...
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Sentence-comprehension deficits have been described in patients with primary progressive aphasia (PPA). However, most instruments to address this domain in more detail and in a clinical context have not been adapted and translated into several languages, posing limitations to clinical practice and cross-language research. Objectives The study aimed to (1) test the applicability of the Brazilian version of the Test for Reception of Grammar (TROG2-Br) to detect morphosyntactic deficits in patients with PPA; (2) investigate the association between performance in the test and sociodemographic and clinical variables (age, years of formal education, and disease duration); (3) characterize the performance of individuals presenting with the three more common variants of PPA (non-fluent, semantic, and logopenic) and mixed PPA (PPA-Mx) and analyze whether TROG-2 may assist in the distinction of these clinical profiles. Methods A total of 74 cognitively healthy participants and 34 individuals diagnosed with PPA were assessed with TROG2-Br. Overall scores (correct items, passed blocks), types, and categories of errors were analyzed. Results In controls, block scores were significantly correlated with years of formal education (Spearman's r = 0.33, p = 004) but not with age. In PPA, age, education, and disease duration were not significantly associated with performance in the test. Controls presented a significantly higher performance on TROG2-Br compared to PPA individuals and their errors pattern pointed to mild general cognitive processing difficulties (attention, working memory). PPA error types pointed to processing and morphosyntactic deficits in nonfluent or agrammatic PPA, (PPA-NF/A), logopenic PPA (PPA-L), and PPA-Mx. The semantic PPA (PPA-S) subgroup was qualitatively more similar to controls (processing difficulties and lower percentage of morphosyntactic errors). TROG2-Br presented good internal consistency and concurrent validity. Discussion Our results corroborate findings with TROG-2 in other populations. The performance of typical older adults with heterogeneous levels of education is discussed along with recommendations for clinical use of the test and future directions of research.
... Tests (Single or Combined) Showing Higher Accuracy for the Detection of Suspected Cognitive Decline in low literacy Groups Pérez-Leguizamón et al. (2017) Modified Community screening instrument for Dementia (CSID) Fuh et al. (1995), Phung et al. (2015) Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) Nielsen et al. (2016) IQCODE combined with RUDAS De Paula et al. (2017) IQCODE combined with MMSE Brito-Marques and Cabral-Filho (2005) Modified MMSE (3MS) Sales et al. (2011) Severe MMSE (SMMSE) Paddick et al. (2017) Alzheimer's disease assessment scale-cognitive (ADAS-Cog) Maillet et al. (2017) Test of associative memory ( Appollonio et al. (2005) Bedford Alzheimer Nursing Severity Scale (BANS-S) and the modified test for severe impairment (mTSI) Takada et al., 2006) Delayed recall in the brief cognitive screening Battery (DR-BCSB) Chan et al. (2006) C-Executive interview (EXIT)-25 Iavarone et al. (2007) Activities of daily life (ADL) Iavarone et al. (2007) Instrumental activities of daily life (IADL) Caldas et al. (2012) Leganés cognitive test Calero et al. (2002) Boston naming test in its reduced version of 15 items (BNT-15) Phung et al. (2014) 10/66 Dementia research group (DRG) De Paula et al. (2013) Combined battery that includes Rey auditory verbal learning test, frontal evaluation, phonemic and semantic fluency, Stick design test, Clock drawing test, Digits test, Token test, Naming and activities of daily living instrumental activities of daily life), in which the information is obtained through an informant, effectively avoid the educational bias. Use of informants is envisaged as a possible solution to the problem of estimating cognitive decline, as informants have knowledge of both the subject's current and premorbid behavior, and may inform based on observations of performance in everyday life rather than on artificial cognitive tasks (Jorm & Jacomb, 1989) On the other end, instruments like the AMT and AD8, with a "ceiling effect" and thus little sensitivity for populations with higher educational level (i.e., six or more years of education), may be suitable for subjects with lower education level. ...
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This study presents a systematic review on existing cognitive screening tools for mild cognitive impairment and dementia in populations with low education and literacy levels. Cochrane Library, PubMed and LILACS databases were examined for studies including adults aged 50 years old or older with low educational level. 61 articles were included. Despite its frequent use, studies on Mini-Mental State Examination (MMSE) revealed that educational level biased the score obtained, regardless of other factors. Separately, the Informant Questionnaire on Cognitive Decline in the Elderly, the Fototest, or the Eurotest, appear to minimize the effect of education and literacy. MMSE is unreliable for individuals with low literacy. Tasks involving reading, writing, arithmetics, drawing, praxis, visuospatial, and visuoconstructive skills have a greater educational bias than naming, orientation, or memory. An adequate determination of educational level and validation of instruments in populations with heterogeneous levels of literacy requires further research.
... Individuals with cognitive impairment also underwent a neuropsychological assessment and have been followed at the same Center for two or more years. The neuropsychological battery used was previously validated for assessment of older adults with low educational level and with heterogeneous cognitive background (29). All tests were validated for use with Brazilian elderly and cut-off points were considered according to their education level. ...
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Background: Alzheimer's disease (AD) biomarkers are of great relevance in clinical research, especially after the AT(N) framework. They enable early diagnosis, disease staging and research with new promising drugs, monitoring therapeutic response. However, the high cost and low availability of the most well-known methods limits their use in low and medium-income countries. In this context, Millipore xMap ® Luminex may be a cost-effective alternative. In our study, using INNOTEST ® as reference, we assess the diagnostic accuracy of Millipore xMap ® and propose a cutoff point for AD. Methods: We performed lumbar puncture of seven older individuals with clinically defined AD, 17 with amnestic mild cognitive impairment (aMCI) and 11 without objective cognitive impairment-control group (CG). Cerebrospinal fluid (CSF) biomarkers concentrations for aB42, p-Tau, and t-Tau were measured by INNOTEST ® and Millipore xMap ® , and then the techniques were compared to assess the diagnostic accuracy of the new test and to define a cutoff. Results: INNOTEST ® and Millipore xMap ® measurements showed all correlations >0.8 for the same biomarker, except for t-Tau that was 0.66. Millipore xMap ® measurements showed a robust accuracy for all biomarkers, with AUC higher than 0.808 (t-Tau), and the best for Aβ42 (AUC = 0.952). The most accurate cutoffs were found at 1012.98 pg/ml (Aβ42), 64.54 pg/ml (p-tau), 3251.81 pg/ml (t-tau), 3.370 (t-Tau/Aβ42), and 0.059 (p-Tau/Aβ42). Conclusion: Given its good accuracy and cost-effectiveness, Milliplex xMap ® tests seems a reliable and promising tool, especially for low and middle-income countries.
... CDT sensitivity and specificity are not very high, namely, 76% and 81%, respectively; nevertheless, these features could be improved depending on the way the clock-drawing test is implied. CDT provides both significant quantitative and qualitative information; therefore, it is embedded in others' test (Yoo and Lee 2016;Kim et al. 2016;de Paula et al. 2013). It is considered to be extremely sensitive of early dementia screening and identification (Beber et al. 2016;Vyhnálek et al. 2016;Ricci et al. 2016). ...
Alzheimer's disease (AD) precipitation in the elderly population increases the need for sensitive biomarkers that can be applied to large population screening. Buccal cells can be obtained easily, noninvasively, and contain many proteins related to cerebral processes. Hence, they offer an ideal candidate for AD biomarker discovery. The purpose of this study is to provide an overview of the current research landscape covering both clinical and methodological issues. A brief summary is given on related laboratory techniques to ascertain protein concentration changes due to AD. At the end, we describe a protocol designed in our laboratory for disease early diagnosis.
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Background The influence of hippocampal connectivity on memory performance is well established in individuals with high educational attainment. However, the role of hippocampal connectivity in illiterate populations remains poorly understood. Methods Thirty-five illiterate adults were administered a literacy assessment (Test of Functional Health Literacy in Adults - TOFHLA), structural and resting state functional MRI and an episodic memory test (Free and Cued Selective Reminding Test). Illiteracy was defined as a TOFHLA score below 53. We evaluated the correlation between hippocampal connectivity at rest and both free recall and literacy scores. Results Participants were mostly female (57.1%) and Black (84.8%), with a median age of 50 years. The median TOFHLA literacy score was 28.0 [21.0;42.5] out of 100 points and the median free recall score was 30.0 [26.2;35] out of 48 points. The median gray matter volume of both the left and right hippocampi was 2.3 [2.1; 2.4] cm³. We observed a significant connectivity between both hippocampi and the precuneus and the ventral medial prefrontal cortex. Interestingly, the right hippocampal connectivity positively correlated with the literacy scores (β = 0.58, p = 0.008). There was no significant association between episodic memory and hippocampal connectivity. Neither memory nor literacy scores correlated with hippocampal gray matter volume. Conclusions Low literacy levels correlate with hippocampal connectivity in illiterate adults. The lack of association with memory scores might be associated with low brain reserve in illiterate adults.
Objective: As the third largest immigrant population in Houston, Texas, Brazilians represent a large bloc of the community in need of culturally and linguistically informed healthcare. In particular, the number of older adults within this population is rapidly growing, emphasizing the increased need to develop socially responsible neuropsychological assessment practices that can meet the needs of this demographic. Additionally, early symptoms of cognitive decline in Brazilian older adults can be culturally perceived as normal aging and may be masked by cultural and lifestyle practices (i.e., scaffolding by family members) that result in lack of appreciation for cognitive and functional decrements. With increased knowledge and awareness of Brazilian culture and customs, we can better understand and assess brain-behavior relationships, provide tailored assessment services, and determine the clinical implications for this population. Methods: Test instruments in Portuguese were identified through systematic literature searches, and in consultation with clinicians serving the Portuguese community in the United States, and cultural brokers involved in Brazilian-based neuropsychology. Results: A multidomain neuropsychological battery with accompanying normative data for use with adults from this community is presented. A case illustration is utilized to highlight limitations and strengths of the proposed battery, which includes core and supplemental measures. Conclusion: Neuropsychologists are encouraged to familiarize themselves with the proposed protocol, understand the psychometric limitations of the available tools, and make an earnest attempt toward providing socially responsible neuropsychological care via the appropriate use of culturally and linguistically tailored instruments and clinical practices.
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This study aimed to map and categorize the psychosocial assessment instruments, with available psychometric evidence, for elderly Brazilians. Through a scoping review, 5.258 studies were identified and after applying the eligibility criteria, 237 studies were included for analytical synthesis. Part of the extracted data was presented in four blocks: Review identifiers (information about the studies); Population (information about the participants); Psychosocial Instruments (organized by categories); Psychometric properties (type of evidence). 192 instruments were highlighted, which were organized into five subcategories, being “Anxiety, Depression and Stress”, “Physical Activity, Ability to Work and Mobility”, “Intelligence and Cognition”, “Health, Well-Being and Quality of Life” and “Geriatric’s Syndromes and Violence”. This study does not exhaust the alternatives of instruments available to elderly Brazilians, but allows a broader view, gathering in a single source, evidence that can generate reflection and add to the research and practice of all those interested in the theme.
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OBJECTIVE: Evaluate the performance on verbal fluency (VF) in our population in a Brazilian sample checking the influence of age and literacy. METHODS: 336 people without neurological or psychiatric complaints evaluated through Mini-Mental State Examination and VF (animals). For comparison, and to determine cut-off points, 65 people with cognitive loss followed at our clinic were also evaluated. RESULTS: We found a mean of 13.8 animals in 1 minute, with the following distribution: illiterates, 11.9; up 4 years of education, 12.8; 4 to 7 years, 13.4; 8 years or more, 15.8 (p= 0.0001). In relation to age the means were: up to 64 years, 13.7; 65 years or more, 13.9. There was no difference between the two groups. The cut-off points were 9 for people under 8 years of education with a sensitivity of 75% for illiterates, 100% for low educational level (up 4 years),and 87% for middle level (4 to 7 years). The specificity was respectively 79%, 84%, and 88%. For the high educational level the mean was 13 with a sensitivity of 86% and specificity of 67%. CONCLUSIONS: In the VF (animals) there is a significant influence of schooling and different cut-off points should be used.
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Introduction: The Frontal Assessment Battery (FAB) is a for the assessment of executive functions. We investigated its validity and reliability and proposed normative data in a representative sample of older adults. Method: 391 healthy elderly subjects and 93 Alzheimer’s disease (AD) patients performed the FAB. Internal consistency, convergent correlations, ROC curve and logistic regression were used to assess its psychometric properties. Results: We found good internal consistency, significant correlations with other tests and moderate accuracy (64%) for AD diagnosis. The use of specific subtests increased diagnostic potential (75%). Normative data stratified by age and education were proposed. Conclusion: The FAB showed adequate psychometric properties. The normative values stratified by age and education can improve its clinical use for neuropsychological assessment.
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Background: The assessment of visuospatial abilities is usually performed by drawing tasks. In patients with very low formal education, the use of these tasks might be biased by their cultural background. The Stick Design Test was developed for the assessment of this population. We aim to expand the test psychometric properties by assessing its construct, criterion-related and ecological validity in older adults with low formal education. Method: Healthy older adults (n = 63) and Alzheimer's disease patients (n = 92) performed the Stick Design Test, Mini-Mental State Examination, Digit Span Forward and the Clock Drawing Test. Their caregivers answered Personal Care and Instrumental Activities of Daily Living). Construct validity was assessed by factor analysis, convergent correlations (with the Clock Drawing Test), and divergent correlations (with Digit Span Forward); criterion-related validity by receiver operating characteristic curve analysis and binary logistic regression; and Ecological validity by correlations with ADL. Results: The test factor structure was composed by one component (R 2 = 64%). Significant correlations with the Clock Drawing Test and Digit Span Forward were found, and the relationship was stronger with the first measure. The test was less associated with formal education than the Clock Drawing Test. It classified about 76% of the participants correctly and had and additive effect with the Mini-Mental State Examination (84% of correct classification). The test also correlated significantly with measures of ADL, suggesting ecological validity. Conclusions: The Stick Design Test shows evidence of construct, criterion-related and ecological validity. It is an interesting alternative to drawing tasks for the assessment of visuospatial abilities.