Expert

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ELS EVI E R Expert Systems with Applications 14 (1998) 219-225

Using neural networks for differential diagnosis of Alzheimer

Disease and Vascular Dementia*
Elizabeth Garcla-P6rez
Subdireccidn General de Investigacidn, Instituto Nacional de Neurologfa y Neurocirugfa. Insurgentes Sur 3877, M~xico D.E, CP-14264, M~xico

Arturo Violante
Divisi6n de Servicios Cl[nicos, lnstituto Mexicano de Psiquiatr£a, Calzada M~xico Xochimilco lOl, M~xico D.E, CP-14370, M~xico

Francisco Cervantes-P~rez t
Departamento Acad~mico de Computacidn, lnstituto Tecnol6gico Autdnomo de Mdxico (ITAM), Av. Camino a Santa Teresa No. 930, Mdxico D.F.,
CP-10700, M~xico

Abstract

Differential diagnosis among different types of dementia, mainly between Alzheimer (AD) and Vascular Dementia (VD), offers
great difficulties due to the overlapping among the symptoms, and signs presented by patients suffering these illnesses. A differential
diagnosis of AD and VD can be obtained with a 100% of confidence through the analysis of brain tissue (i.e. a cerebral biopsy).
This gold test involves an invasive technique, and thus it is rarely applied. Besides these difficulties, to get an efficient differential
diagnosis of AD and VD is essential, because the therapeutic treatment needed by a patient differs depending on the illness he
suffers. In this paper, we explore the use of artificial neural networks technology to build an automaton to assist neurologists during
the differential diagnosis of AD and VD. First, different networks are analyzed in order to identify minimum sets of clinical tests,
from those normally applied, that still allows a differential diagnosis of AD and VD; and, second, an artificial neural network is
developed, using backpropagation and data based on these minimum sets, to assist physicians during the differential diagnosis of
AD and VD. Our results allow us to suggest that, by using our neural network, neurologists may improve their efficiency in getting
a correct differential diagnosis of AD and VD and, additionally, that some tests contribute little to the diagnosis, and that under some
combinations they make it rather more difficult. © 1998 Elsevier Science Ltd. All rights reserved

1. I N T R O D U C T I O N phenomenon has been observed with respect to brain

vascular disease, one of the main causes of Vascular
In the last years, because individuals' life expectations
Dementia (VD), which has become the third cause of
have increased all over the world, demential illnesses
death in people of that age (Cummings & Benson, 1992).
have become a main concern. Several studies have
Additionally, due to the incapacity these illnesses
shown that in people 65 years old or older, the presence
produce in people, their impact on public health is
of Alzheimcr Disease (AD) has increased from 1.3 to
considered as an issue of great importance.
6.2% (Ueda & Kawano, 1992; Gorelick & Roman, 1993;
Within the analysis of dementia, the diagnosis of AD
Joachin et al., 1988). In Mexico, the Mexican Society for
and VD is one of the main concerns, they represent
Alzheimer has reported that 6% of the people over 65
almost 90% of the illnesses presented by patients with
years of age have been diagnosed with Alzheimer
dementia (O'Brien, 1992; Boiler et al., 1989). A
(Cummings & Benson, 1992; Friedland, 1993). A similar
differential diagnosis between AD and VD presents great
difficulties due to the similarities found among their
* Due to circumstances beyond the publisher's control, this paper
symptoms characteristics, and in the clinical tests
appears in print without author corrections. required for their classification. These problems can be
Author for correspondence. overcome through the use of an invasive technique, i.e.

0957-4174/98/$19.00 Copyright © 1998 Elsevier Science Ltd. All rights reserved.

PH S0957-4174(97)00076-6
220 E. Garcfa-Pdrez et al./ Expert Systems with Applications 14 (1998) 219-225
cerebral biopsy (McKhann et al., 1984). Even though
this is a gold test (i.e. the only way to obtain the right
diagnosis), it must be taken into account that invasive
techniques present ethical problems, and that sometimes
they may give rise to other medical complications. Thus,
this technique is rarely used. Besides all of these
difficulties, a correct differential diagnosis of AD and
VD, as well as the identification of the right parameters
to validate it, must be reached efficiently; mainly,
because of the differences among the therapeutic treat-
ments associated with each of these illnesses, and their
possible natural development (e.g. VD can be associated
to modifiable risk factors like systemic arterial hyper-
tension). That is, the development of criteria for
differentially diagnose VD and AD is fundamental for
recognizing the underlying pathology, to start a proper
therapy, as well as to determine the frequency and the
prevalence of the disease.
The fact that the gold test to diagnose correctly AD
and VD involves an invasive technique, has meant that,
as an altemative way, neurologists analyze a huge
amount of data, obtained from a series of clinical studies
that should be practiced on the patient, before they may
produce a proper diagnosis. For example, in trying to
diagnose VD several techniques have been developed,
like the Hachinski scale (Hachinski & Lassan, 1974), a
set of observations generated from analyzing the
patient's history, and data from clinical tests that suggest
the presence of brain vascular disease, or enough damage
to be the cause of the corresponding dementia. It must be
pointed out that in some cases these studies are not
conclusive, because a patient having AD may, at the
same time, present a previous history of VD. In those
cases, a vascular etiology is defined, but without the
possibility of obtaining a correct differential diagnosis
(Villardita, 1993; Gorelick & Roman, 1993; von Reutern,
1991). The same occurs in patients with dementia, where
there are histological findings of AD and, at the same
time, changes that are compatible with a vascular origin
of the disease.
Additionally, Alzheimer is a progressive degenerative
disease, characterized by alterations in memory, orienta-
tion, and in a variety of cognitive functions. These
problems may appear at early stages, in people around 40
years old, but they are more frequently observed in
people over 60 (Cummings & Benson, 1992; Friedland,
1993), where neuropathological changes have been
recorded (Khachaturain, 1985; Selkoe, 1993; Mirsen et
al., 1991) together with the coexistence of vascular
factors in their etiology (O'Brien, 1992; Erkinjuntti et
al., 1987). All of this complicates even more the
differential diagnosis of AD and VD, and has required
the analysis of other type of data, and of brain images
(Boiler et al., 1989).
In the absence of specific indicators to diagnose AD or
VD, and trying to avoid the use of studies involving
invasive techniques, to find a clear differentiation
between both diseases becomes a very difficult task,
because of the overlapping among those symptoms
related to the cognitive impairment produced by AD and
VD, it has been imperative to search for alternative
methods, and technologies that allow us to establish
reliable differential diagnoses for defining, as soon as
possible, the proper treatment for the patient being
analyzed.
In this quest, computer aided diagnosis in medicine
has been done for quite some time now (Schwartz, 1970;
Schwartz et al., 1987; Shortliffe, 1976; Kulikowki, 1980;
Reggia & Tuhrim, 1985; Szolovitz et al., 1988), but it is
not until recently, with the integration of different
technologies (e.g. distributed artificial intelligence, neu-
ral networks, genetic algorithms and fuzzy logic), that
complex problems in medical diagnosis can be
approached. For example, pattern recognition in X-ray
images (Boone et al., 1990a,b; Gross et al., 1990;
Hallgren & Reynolds, 1992), biomedical signals analysis
(Gevins & Morgan, 1988; Mamelak et al., 1991; Alkon et
al., 1990; G~ibor & Seyal, 1992; Gfibor et al., 1993), and
prediction and diagnosis problems (Casselman & Maj,
1990; Poli et al., 1991; Moallemi, 1991; Baxt, 1991). In
general, this approach can be applied to situations where
problem solving with traditional techniques becomes
difficult, inefficient, or complicated.
Here, based on the dynamic properties displayed by
artificial neural networks, and their proven ability for
pattern recognition in complex situations (Widrow et al.,
1994), our aim is two-fold: first, to show how by using
artificial neural networks technology it is possible to
determine minimum sets of tests, from those normally
applied, that still allow a proper differential diagnosis of
AD and VD; and, second, to build a neural computing
automata, i.e. a distributed architecture of small neural
nets trained with the backpropagation algorithm (Rumel-
hart et al., 1986), to assist neurologist and non specialist
physicians to obtain differential diagnoses of AD and VD
with almost a 100% confidence.
2. DATA COLLECTION: TRAINING AND TEST
SETS
To carry out a differential diagnosis of AD and VD, it
must be taken into account that there are many possible
causes that alter cognitive functions in an individual.
Therefore, according to Eslinger and Damasio (1985),
and Bayles (1991), it is important to get a detailed
clinical history, including how the problem started (i.e.
sudden, or slow and progressive), to be able to establish
the nature of the initial dysfunction (e.g. loss of memory,
language alterations, problems to execute motor action,
and the incapacity for recognizing objects, colors or
situations). Information about changes in personality and
depressive symptoms must be also included (Bolla et al.,
1991; Fisher et al., 1990; Krall, 1983; Rovner et al.,
1989), as well as on the type of drugs or medication that
 E. Garcia-Pdrezet aL / ExpertSystems withApplications 14 (1998) 219-225
the patient had been taking, in older people it has been
observed that this fact may cause, or accelerate memory
failure (Spiegel et al., 1981).
In addition, without a unique methodology to carry out
the differential diagnosis of AD and VD, neurologists
must integrate those results mentioned in the previous
paragraph with findings generated by: (a) different tests
(e.g. physical and neurological exams, as well as blood
tests); (b) a psychological interview; (c) nutritional
information; and (d) an evaluation of the vascular
disease. Finally, to further increase this complexity, it
must be considered that there are different criteria to
produce a differential diagnosis of AD and VD. For
example, to diagnose AD (Kukull et al., 1983; Kukull &
Larson, 1990), two of the most frequently used criteria
are:
• That from The Diagnostic and Statistical Manual of
Mental disorders (DSMIII-R), which can be described
as follows: there must be a confirmed diagnosis of
dementia, with an insidious start, and it must be
possible to exclude other causes of dementia by using
data from the patient's clinic history, physical exams
and other lab studies.
• The clinic diagnosis of AD developed by a working
group of the NINCDS/ARDA, from the National
Institutes of Health in the USA (McKhann et al.,
1984). Their proposal may be resumed as:
Possible AD: Dementia diagnosed based on results of
clinic exams that show progressive dysfunction of
one, or more, cognitive processes, in the presence of
systemic, or cerebral alterations not considered as
the main cause of the dementia.
Probable AD: Early start of AD (subjects younger than
65 years old), diagnosed in the absence of systemic,
or cerebral alterations.
Definitive AD: Confirmed clinical criteria for AD,
based on data generated by invasive studies (i.e.
biopsy or autopsy), as well as on neurological and
psychiatric signs and symptoms.
Given the wide variety of possible causes, and the
complexity of the analysis of the symptoms and signs
presented by the patients, in their search to reach reliable
differential diagnoses of AD and VD, neurologists
depend on data obtained from a big set of exams and
studies, which can been grouped as follows:
(a) Demographic--This group includes information
related to the patient's age, sex, civil state, patient's
education, and occupation.
(b) Antecedents---Here, information from the patient's
clinical record is considered: smoke, alcoholism,
hereditary antecedents, hypertension, history of
depressive states, etc. These data are obtained by
asking the patient, or some reactive, and they are
221
used to find risk factors for artherioscleroses.
(c) Symptoms and signs~This group of data includes
information on the illness time evolution, if the
patient has orientation problems, changes in person-
ality, problems with numerical calculus, language
problems, or psychotic symptoms, etc.
(d) Neurological and neuropsychological scales--In
trying to verify a diagnosis of vascular dementia,
several methods have been designed, like Hachinski
scales (Hachinski & Lassan, 1974), that are a set of
observations from the patient's clinic history and a
clinical exam, from which it is possible to suggest
the presence of a brain-vascular illness, severe
enough to be the cause of a dementia. Loeb scale
represents another attempt for obtaining a differ-
ential diagnosis between VD and AD (Loeb, 1988;
Cummings, 1985). In both scales, it is evaluated
how the illness started (suddenly, or slowly), its
evolution, the presence of specific symptoms and
signs, and the history of arterial systemic hyper-
tension. The neuropsychological tests used in our
study are: (a) Mini Mental State Examination
(MMSE), designed to valorize cognitive functions
in a fast way (Folstein et al., 1975); (b) Geriatric
Depression Scale, designed to evaluate depression
in older people (Mattis, 1976; Diaz & Garcfa de la
Cadena, 1993); (c) Common Activities Scale, used
to evaluate social adaptive abilities in daily activ-
ities (Khachaturain, 1985; Diaz & Garcfa de la
Cadena, 1993).
(e) Electrophysiology--In this group we have electro-
encephalogram (EEG), and P300 studies. On the
one hand, EEG analysis results are normal at the
beginning of the illness, and the background
activity may become slower as the illness pro-
gresses. On the other hand, evoked potentials
studies, specifically P300, have been used to
corroborate some findings in the neuropsycho-
logical analysis, because the shifting of the latency
of the P300 component has been related to attention
and memory tests (Patterson et al., 1983).
(f) Neuroimaging analysis and other studies--Tomog-
raphy and Magnetic Resonance analyses are used to
valorize AD pathologies, such as: signs of brain
atrophy; increase in ventricle cavities, specially in
the third ventricle, etc. It has been shown that the
course of clinical deterioration in patients with
dementia is closely correlated to these changes
(DeLeon et al., 1980, 1983; Fox et al., 1975).
In order to build the corresponding neural net and taking
into consideration all these types of data, a database was
integrated with information from the clinical files of 58
well documented cases from the clinics for Brain
Vascular Disease and Cognition, at the National Institute
of Neurology and Neurosurgery Manuel Velasco Sudrez.
These cases were organized in three sets:
222 E. Garc(a-PFrez et al. / Expert Systems with Applications 14 (1998) 219-225
• Set/----19 subjects diagnosed with VD.
• Set II 16 subjects diagnosed with AD.
• Set 111--23 subjects with diagnosis of dementia (AD or
VD).
The first two sets were used as the training set, whereas
the third one was the test set.
3. N E T W O R K A R C H I T E C T U R E A N D TRAINING
PARAMETERS
Due to the complexity of the diagnosis, a nonlinear
mapping was expected. Therefore, a three layers feedfor-
ward neural net was selected (see Fig. 1), and trained
with the backpropagation learning algorithm, using the
commercial simulator Neuroshell2, version 1.5 for
windows. The number of characteristics for subject, to
define the number of neurons in the input layer, was 46;
while, the output layer was conformed by one neuron
because the differential diagnosis might only be AD or
VD. Based on an empirical formula, the simulator
defines the number of elements in the hidden layer,
which was 29. Different combinations of activation
functions were tried and finally, a linear activation
function was used for the elements in the input layer, a
logistic function for the hidden layer, and a hyperbolic
tangent function for the output neuron.
In the simulations, for the network parameters, we
used the following values:
• rate learning, r/=0.1;
• momentum, m = 0.1;
X1 X2 X3 X4 X46
Input
Layer
Hidden
Layer
Output
Layer
FIGURE 1. Neural network architecture. When using infor-
mation from all groups of data, a three-layer feedforward
network was trained with the Back,propagation learning
algorithm. The Input layer had 46 elements, whereas the
hidden layer had 29, and, because the diagnosis was AD or
VD, only one element comprised the output layer.
• initial weights value, o)=0.3; and
• error value to stop the training, E= 0.0000002.
4. RESULTS
Using all the data (Demographic, Antecedents, Symp-
toms, Scales, Electrophysiology, and Neuroimaging) of
each subject, included in the training set, a neural
network was trained during 65 hours in order to reach the
minimum average error of 0.0000002. Then, we pre-
sented the data corresponding to the 23 cases of the test
set, and only obtained the correct classification of 19
cases, that is an 82.6% efficacy.
Even though the results obtained with the trained
network were good, in terms of the number of cases
classified correctly (19 out of 23), our aim was to
improve it until an efficacy as close as possible to the
100%. The number of variables used to diagnose
between AD and VD is very large; apparently, neurolo-
gists have included new tests as new instrumentation has
become available. Thus, we built a series of neural
networks using different combinations of groups of data
as input vectors, in order to analyze the level of
importance associated to each data group during the
differential diagnosis of AD and VD. The number of
combinations of the six groups of data was 63; therefore,
63 neural nets were trained using the same architecture
and parameters as described above, included the one
trained with data from all groups, and the results
obtained are in Table 1.
The efficacy of all 63 nets was determined by using
data from the test set (Set III of 23 cases). From Table 1,
it can be observed that 11 networks produce better results
than the one trained with data from all six groups:
• Five networks classify correctly 21 of 23 test cases;
• Five other networks classify correctly 20 of 23 test
cases; and
• The network trained with data from demographic
records and scales studies, produces the best results, 22
of 23 test cases were classified correctly.
It must be pointed out that data from neurological and
neuropsychological scales appear in all these networks,
demographic information participates in six, electro-
physiological and antecedents studies in five, whereas
data from symptoms and neuroimaging only appear in
three of the networks. In addition, in some cases, the
combination of different groups of data improves the
classification of the test set: nets trained with only data
from antecedents and electrophysiological studies per-
form poorly (12 of 23 cases classified correctly), a
network trained with a combination of both groups of
data improves the classification a little bit (13 of 23),,but
when integrated with data from the scales group much
better results are obtained, 20 of the 23 test set cases are
classified correctly.
 E. Garc[a-Pdrez et al./ Expert Systems with Applications 14 (1998) 219-225 223

Another important aspect in our study is to define in
what cases the networks were wrong. This is shown in
Table 2. Cases 17 and 20 were the more difficult to
classify, four different networks misclassified them.
Then, cases 5, 12, 14 and 24 follow in complexity, they
were misclassified by three different networks; after-
wards, we have cases 16 and 18, which were classified
incorrectly by two networks; and, finally, only one
network failed to classify cases 4 and 22.
In order to get the correct classification of all elements
in the test set, an analysis of these 11 networks, and the
cases they misclassify was conducted. In every case,
there are more networks classifying them correctly than
the ones misclassifying them; thus, if an odd number of
these networks are run in parallel, and a neuron processor
is placed to integrate their outputs into a majority
function (see below), then all cases from the test set
could be classified correctly. Networks 8, 10, and 11 (see
Table 2), involve results from the analysis of neuroimag-
ing, a costly and slow exam, therefore, we studied the
situation where these networks were not considered for
the resulting parallel architecture. Because failure of
network 1 is included in the other three networks, its
participation is redundant, and could also be eliminated.
Thus, a set of seven neural networks (2, 3, 4, 5, 6, 7, and
9, in Table 2) was used to build the parallel architecture
shown in Fig. 2, where their outputs are processed by a
neuron-like element that carries out a majority function:
F(Y~,;0)= 1 if EY~->0 or 0 if ~EY~<0;, for i=2,3,4,5,6,7,8,9
where 0 is equal to 4.
By using this distributed parallel architecture, a
correct classification was obtained for all 23 cases in
the test set, that is, an efficacy of 100%. Additionally,
it should be noted that the required groups of data (i.e.
demographic, neurological and neuropsychological
scales, symptoms and signs, electrophysiological, and
antecedents) can be obtained during the first days of
medical consultation, and they represent no risk for the
patient. Thus, using the resulting network to assist a
neurologist, on a routine basis, in the differential
diagnosis of AD and VD would help to solve one of the
most pressing needs when seeing a patient for the first
time: to diagnose correctly the type of dementia he/she
has, and to be able to start immediately the proper
treatment, especially for cases of reversible dementias
where an etiological factor (thyroid, hormonal or phar-
macological disturbance is present) can be observed and
treated.
5. CONCLUSIONS
In medicine, there are many illnesses whose diagnosis is
a very difficult task, and people are still searching for
more efficient solutions. The sooner a patient starts the
proper treatment, the better chances of getting him
healthy again, or, as in the case of vascular dementia,
slowing down the illness evolution, or, as in the case of
AD, trying to make the rest of his life as comfortable as
possible.
The development of new tools to build computer
based machines to assist medical doctors in this quest has

Network l

YI
Network 2

WI

e F( Y; O)

e
Network 7
X7

FIGURE 2. A parallel distributed neural net was built by combining seven of the best 11 networks, the ones that classified
correctly 20 or more cases from the Test Set. Different sets of data (X,, X2, X~, X~, Xs, X~, XT) were used to train the
corresponding networks, and their outputs (Y, y=0,],...,7), were integrated by the output artificial neuron, which Implements
a majority function, with which an efficacy of 100% was obtained. That is, all 23 cases from the Test Set were classified
correctly.
224 E. Garcfa-Pdrez et al. / Expert Systems with Applications 14 (1998) 219-225
been a m a i n c o n c e m within the field of C y b e m e t i c s
(Weiner, 1948), and of Artificial Intelligence (Barr &
F e i g e n b a u m , 1982). In this paper, using tools based on
an e m e r g e n t technology (i.e. Neural Networks), we
described the design o f a n e w automata to aid physicians
in identifying c o m p l e x patterns in patients suffering
illnesses (i.e. A D and VD) which are difficult to
diagnose. This automata performs quite well: (a) it
presents a 100% efficacy, that is, it produces the correct
classification of all cases in the test set; (b) it helps
i m p r o v e the efficiency in the differential diagnosis of A D
and VD, because it uses data from tests that can be
carried out within the first few days after the patient
arrives at the clinic; and (c) it helps to reduce costs, our
analysis shows that differential diagnosis can be done
without considering n e u r o i m a g i n g data, the most costly
studies. In addition, our analysis allows us to suggest that
some specific data, or the c o m b i n a t i o n of information
from different groups of data, might not be participating
in the diagnosis, b u t rather they m a k e it more difficult.
However, it must be pointed out that the neural
networks were trained, and tested, with the only 58 well
d o c u m e n t e d cases available at the m o m e n t in the files of
the clinics for Brain Vascular Diseases, and for Cogni-
tion, at the National Institute for Neurology and
Neurosurgery M a n u e l Velasco Sudrez. Because A D and
V D might have different causes, it is highly probable that
future cases m a y have causes not considered in the
d e v e l o p m e n t o f our networks; therefore, w h e n e v e r these
n e w cases appear it will be necessary to retrain the
networks in order to include the n e w information.
Finally, based on our results, we m a y conclude that
this automata will aid neurologists, and general practitio-
ners not acquainted with the especiality, in the decision
m a k i n g process of d i a g n o s i n g whether a demential
patient presents AD, or multi-infarct VD. E v e n though
more testing of the n e t w o r k interacting with the neurolo-
gist is required to confirm its utility, it is clear that those
results discussed in this paper open a promising avenue
of research that will help i m p r o v e the task of diagnosing
patients with some type o f dementia. This limitation will
be explored in further studies.
REFERENCES
Alkon, D,, Blackwell, S., Barbour, S., Rigler, A., & Vogl, P. (1990).
Pattern-recognition by an artificial network derived from biologic
neuronal systems. Biological Cybernetics, 62, 363-376.
Barr, A., & Feigenbaum, E.A. (Eds.) (1982). Handbook of Artificial
Intelligence, Vol. 2. Stanford, CA: Heuristech Press.
Baxt, W. (1991). Use of an artificial neural network for the diagnosis of
myocardial infarction. Annals of Internal Medicine, 115, 843-848.
Bayles, K. (1991). Age at onset of Alzheimer's disease. Relation to
language dysfunction. Arch. Neurol., 48, 155-159.
Bolla, K. etal., (1991). Memory complaints in older adults. Fact or
fiction?. Arch. Neurol., 48, 61-64.
Boiler, E, L6pez, O. L., & Moossy, J. (1989). Diagnosis of dementia:
clinicopathologic correlations. Neurology, 38, 76-79.
Boone, J. M., Gross, G. W., & Greco-Hunt, V. (1990). Neural networks
in radiologic diagnosis. I. Introduction and illustration, lnves-
tigative Radiology, 25(9), 1012-1016.
Boone, J., Sigillito, V., & Shaber, G. (1990). Neural networks in
radiology: An introduction and evaluation in a signal detection task.
Medical Physics, 17(2), 234-241.
Casselman, E, & Maj, J. D. (1990). DASA/LARS: A large diagnostic
system using neural networks. Proceedings of lJCNN 90-Wash DC.
Washington, DC, pp. 11-539-542.
Cummings, J., & Benson, E (1992). Dementia: A Clinical Approach.
Stoneham, MA: Butterworth-Heinemann.
Cummings, J. L. (1985). Dementia. In Clinical Neuropsychiatry. Grune
& Stratton, pp. 75-95.
DeLeon, M. J. etal., (1980). Computed tomography in evaluations of
brain-behavior relationships in senile dementia of the Alzheimer's
type. Neurobiol. Aging, 1, 69-79.
DeLeon, M. J. etal., (1983). Positron emission tomographic studies of
aging and Alzheimer's disease. Am. J. Neuroradiol., 4, 568-571.
Dfaz, O. C., & Garcfa de la Cadena, R. C. (1993). Compendio de
Pruebas Neuropsicol6gicas para la Investigaci6n Clfnica en
Pacientes Neurol6gicos y Psiquidtricos. Laboratorio de Psicologfa
Experimental INNN MVS.
Erkinjuntti, T., Ketonen, L., & Sulkava, R. (1987). CT in the
differential diagnosis between Alzheimer's disease and vascular
dementia. Acta Neurol. Scand., 75, 262-270.
Eslinger, P., & Damasio, A. (1985). Neuropsychologic detection of
abnormal mental decline in older persons. JAMA, 253(5),
670-674.
Friedland, R. (1993). Alzheimer's disease: Clinical features and
differential diagnosis. Neurology, 43(Suppl 4), 545-551.
Fisher, P. etal., (1990). Depression in dementia of the Alzheimer type
and multi-infarct dementia. Am. J. Psychiatry, 147, 1484-1487.
Folstein, M. E, & Folstein, S. E. et al., (1975). Mini-mental state
examination. Journal of Psychiatric Research, 12, 189-198.
Fox, J. H. etal., (1975). The use of computerized tomography in the
diagnosis of senile dementia. J. Neurol. Neurosurg. Psychiatr., 38,
948-953.
G~bor, J., & Seyal, M. (1992). Automated interictal EEG spike
detection using artificial neural networks. Electroenceph. Clin.
Neurophysiol., 83, 271-280.
G,'lbor, J., Siegel, R., Horv~ith, Z., & Buzs~iki, G. (1993). Pattern
recognition of the electroencephalogram by artificial neural net-
works. Electroenceph. Clin. Neurophysiol., 86, 100-109.
Gevins, A., & Morgan, N. (1988). Applications of neural-network (NN)
signal processing in brain research. IEEE Transactions on Acous-
tics, Speech and Signal Processing, 36(7), 1152-1161.
Gorelick, Ph., & Roman, G. (1993). Vascular dementia: A time to seize
the moment. Neuroepidemiology, 12, 139-140.
Gross, G. W., Boone, J. M., Greco-Hunt, V., & Greenberg, B. (1990).
Neural networks in radiologic diagnosis. II. Interpretation of
neonatal chest radiographs. Inv. Radiology, 25(9), 1017-1023.
Hachinski, V. C., & Lassan, N. A. (1974). Multi-infarct dementia.
Lancet, 11, 201-210.
Hallgren, R., & Reynolds, H. (1992). Computer display of multi-
dimensional biomedical data. Journal of Clinical Engineering,
17(3), 235-243.
Joachin, C., Morris, J., & Selkoe, A. (1988). Clinically diagnosed
Alzheimer disease: Autopsy results in 150 cases. Ann. Neurol., 24,
50-56.
Khachaturain, Z. (1985). Diagnosis of Alzheimer's disease. Arch.
Neurol., 42, 1097-1104.
Krall, V. A. (1983). The relationship between senile dementia of the
Alzheimer type and depression. Canad. J. Psychiatr., 28, 304-306.
Kukull, W. A. etaL, (1983). Inter-ratter reliability for Alzheimer's
disease diagnosis. Neurology, 40, 257-260.
Kukull, W. A., & Larson, E. B. (1990). The validity of 3 clinical
diagnostic criteria for Alzheimer's disease. Neurology, 40,
1364-1369.
Kulikowki, C. A. (1980). Artificial intelligence. Methods and systems
for medical consultation. IEEE Trans Patt Anal Mach Intell, Sept.
 E. Garcfa-Pdrez et aL / Expert Systems with Applications 14 (1998) 219-225
Loeb, C. (1988). Clinical criteria for the diagnosis of vascular
dementia. Eur. Neurol., 28, 87-92.
Mamelak, A., Quattrochi, J., & Hobson, A. (1991). Automated staging
of sleep in cats using neural networks. Electroenceph. Clin.
NeurophysioL, 79, 52-61.
Mattis, S. (1976). Mental status examination for organic mental
syndrome in the elderly patient. In Bellack R. K. (Ed.), Geriatric
Psychiatry. Grune and Stratton, pp. 77-121.
McKhann, G., Drachman, D., & Folstein, M. (1984). Clinical diagnosis
of Alzheimer disease: Report of the N1NCDS-ADRDA work group
under the auspices of Department of the Health and Human
Services task force on Alzheimer Disease. Neurology, 34,
939-944.
Mirsen, T., Lee, D., &Wong, C. (1991). Clinical correlates of white-
matter changes on magnetic resonance imaging scans of the brain.
Arch. NeuroL, 48, 1015-1021.
Moallemi, C, (1991). Classifying cells for cancer diagnosis using
neural networks, IEEE Expert, 8-12.
O'Brien, M. D. (1992). Vascular dementia: Problems with definitions
nomenclature and classification. J. Stroke Cerebrovasc. Dis., 2,
217
Patterson, J. V. et al. (1983). Average Evoked Potentials in Dementia.
In B. Reisberg, (Ed.), Alzheimer's Disease. The Free press.
Poli, R., Cagnoni, S., Livi, R., Coppini, G., & Valli, G. (1991). A neural
network expert system for diagnosis and treating hypertension.
Computer, 1991, 64-71.
Reggia, J. A., & Tuhrim, S. (Eds.) (1985). Computer-Assisted Medical
Decision Making. Computers and Medicine, Vol. 2. New York:
Springer Verlag.
Rovner, B. W., Broadhead, J., Spencer, M,, Carson, K., & Folstein, M.
225
(1989). Depression and Alzheimer's disease. Am. J. Psychiatry,
146, 353-355.
Rumelhart, D., Hinton, G., & Williams, R. (1986). Learning representa-
tions by back-propagation errors. Nature, 323, 533-536.
Schwartz, W. B. (1970). Medicine and the computer. The promise and
problems of change. The New England Journal of Medicine,
283(23), 1257-1264.
Schwartz, W., Patil, R., & Szolovitz, P. (1987). Artificial intelligence in
medicine. Where do we stand?. The New England Journal of
Medicine, 316(11), 685~88.
Selkoe, D. J. (1993). Amyloid protein and Alzheimer's disease.
Reprinted from November 1991. Scientific American Medicine,
Special issue, 54-61.
Shortliffe, E. H. (1976). Computer-based Medical Consultations:
MYCIN. New York: Elsevier.
Spiegel, R. et al. (1981). Psychopharmacology an Introduction. John
Wiley.
Szolovitz, P., Patil, R., & Schwartz, W. (1988). Artificial intelligence in
medical diagnosis. Annals of Internal Medicine, 108, 80--87.
Ueda, K., & Kawano, H. (1992). Prevalence and etiology of dementia
in a Japanese community. Stroke, 23, 798-803.
Villardita, C. (1993). Alzheimer's Disease compared with cer-
ebrovascular dementia. Neuropsychological similarities and
differences. Acta Neurol. Scand., 87, 299-308.
von Reutern, A. (1991). Transcraneal doppler sonography examination
technique and normal reference values. Ultrasound Med. Biol.,
6(8), 746-761.
Widrow, B., Rumelhart, D., & Lehr, M. (1994). Neural networks:
applications in industry, business and science. Communications of
the ACM, 37(3), 93-105.