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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
1,2
*, Laiss Bertola
1,2
, Rafaela Teixeira A
´vila
1,2
, Lafaiete Moreira
1,2
,
Gabriel Coutinho
3,4
, Edgar Nunes de Moraes
5
, Maria Aparecida Camargos Bicalho
5
, Rodrigo Nicolato
2,6
,
Breno Satler Diniz
2,6
, Leandro Fernandes Malloy-Diniz
1,2,6
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
´s-graduac¸a
˜oemCie
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
Abstract
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.
Conclusion:
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: jonasjardim@gmail.com
Introduction
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 | www.plosone.org 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
subjects.
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
Group
Comparison’s
MSDMSDMSDF g
2
Sidak’s
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
˜es
Neuropsicolo
´gicas (Naming Test of the Laboratory of Neuropsychological Investigations).
doi:10.1371/journal.pone.0073167.t001
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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
education.
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
Executive
Functions
Language/
Semantic Memory
Episodic
Memory
Visuospatial
Abilities
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.
doi:10.1371/journal.pone.0073167.t002
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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
[19].
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–
23].
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.
doi:10.1371/journal.pone.0073167.g001
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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
analysis.
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 –
Comprehension
0.84 (0.04)*** 14 86% 79% 0.73 (0.05)*** 15 69% 68% 0.68 (0.05)*** 14 56% 32%
Token Test –
Attention
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.
doi:10.1371/journal.pone.0073167.t003
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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-
collinearity.
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%.
Results
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
2
= 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.
doi:10.1371/journal.pone.0073167.g002
Neuropsy Assessment of Low Educated Older Adults
PLOS ONE | www.plosone.org 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,
x
2
= 221.43, p,0.001, R
2
= 78%). Six steps were performed by
the model starting with RAVLT-DR (x
2
= 114.43, p,0.001), then
adding, Mini-Mental State Examination (x
2
= 44.02, p,0.001),
Category Fluency Animals (x
2
= 30.76, p,0.001), RAVLT-Rec
(x
2
= 13.33, p ,0.001), TN-LIN-Nouns (x
2
= 12.05, p = 0.002) and
the Frontal Assessment Battery (x
2
= 6.83, p = 0.033). The
participant’s classification, considering chance, the final regression
model and error are shown in Figure 2.
Discussion
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.
Limitations
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
Neuropsy Assessment of Low Educated Older Adults
PLOS ONE | www.plosone.org 7 September 2013 | Volume 8 | Issue 9 | e73167
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.
Conclusion
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.
Acknowledgments
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
MACB RN BSD LFMD. Wrote the paper: JJP LB RTA LM GC ENM
MACB RN BSD LFMD.
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