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https://doi.org/10.1007/s11042-022-14203-1

Alzheimer disease diagnosis for magnetic resonance

brain images using deep learning neural networks

Heba M. Ahmed 1 & Zeinab F. Elsharkawy 2 & Ahmed S. Elkorany

3

Received: 20 April 2021 / Revised: 21 April 2022 / Accepted: 27 October 2022

# The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022

Abstract
In this work, a Deep Convolutional Neural Network (DCNN) framework for Alzheimer’s
Disease (AD) diagnosis based on brain Magnetic Resonance Imaging (MRI) scans is
presented. A multiclass DCNN classifier is used to discriminate between Normal Con-
trols (NC), Mild Cognitive Impairment (MCI), and AD. The Alzheimer’s Disease
Neuroimaging Initiative (ADNI) dataset was used to train and test the proposed DCNN.
Different train-test ratios have been examined. Average accuracies of 100% for AD/NC,
92.93% for NC/MCI, and 99.21% for AD/MCI were obtained. The proposed system
achieved an average accuracy of 93.86% for a three-way AD/MCI/NC classification. To
further examine the proposed system performance, Receiver Operation Characteristics
(ROC) analysis and Confusion Matrix (CM) were also used. For certain scenarios, the
Area Under ROC Curve (AUC) values of 1, 1, and 0.989 were obtained for AD, NC, and
MCI, respectively. The results show higher metrics compared to previously published
studies concerning AD diagnosis.

Keywords Deep CNN . ADNI . Alzheimer’s disease . MRI . ROC

* Zeinab F. Elsharkawy
[email protected]

Heba M. Ahmed
[email protected]

Ahmed S. Elkorany
[email protected]

1
Informatics Research Institute (IRI), City of Scientific Research and Technological Applications
(SRTA-City), Alexandria, Egypt
2
Engineering Department, Nuclear Research Center, Egyptian Atomic Energy Authority, Cairo, Egypt
3
Department of Electronics and Electrical Communication Engineering, Faculty of Electronic
Engineering, Menoufia University, Menouf 32952, Egypt
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1 Introduction

Alzheimer’s disease is a neurological brain disorder that results in the death of brain cells
responsible for memorizing and thinking skills. Its consequences increase slowly and
deteriorate over time making the patients unable to continue their ordinary daily activities.
As stated by the Alzheimer’s Association, AD is one of the top ten diseases in the United
States which causes death [4]. It is caused by many factors among which age is the most
significant. Elderly adults aged about 65 are at a high risk of suffering from this disease
[15]. The key to curing Alzheimer’s disease is early detection where appropriate treatment
can slow the disease’s progression. Therefore, the development of an early and accurate AD
diagnosis is essential.
Pattern recognition, classification, and Machine Learning (ML) have gained a great attrac-
tion recently in emerging an automated diagnosis system of brain diseases with neuro-images
such as MRI [2, 3], Diffusion Tensor Imaging (DTI) [9], functional MRI (fMRI) [26], Positron
Emission Tomography (PET) [20]. There is large number of researchers focused on advanced
ML models that utilize MRI data for AD diagnosis. These studies revealed that MRI scans are
the most proper imaging modality in clinical diagnosis [30] and can be used to track different
clinical AD phases [11].
Recently, advanced Deep Learning (DL) techniques especially Convolutional Neural
Networks (CNN), have gained great interest in solving problems in automated medical
imaging systems [5, 7]. The diagnosis of AD is a multi-tests assessment and requires a highly
discriminative feature representation for automated classification. DL methods are capable of
learning such representation from data. They can reveal latent or hidden features that can
improve disease detection and classification; hence it has been used in automated AD
diagnosis recently.
The current study aims to develop and validate a new DCNN framework capable of
identifying individual diagnoses of AD, MCI, and NC based on brain MRI scans. The
proposed classifier was trained and tested using the ADNI dataset. Specificity, Sen-
sitivity, Accuracy, and Balanced Accuracy are used to evaluate the new DCNN
classifier’s performance. The suggested 3-class classification algorithm’s performance
is also evaluated using ROC analysis and CM. The performance of the given method
was compared to previously published similar studies. The generated results outper-
form the published ones, demonstrating the robustness of the proposed DCNN
framework.
The rest of the paper is structured as follows. Section 2 introduces the materials and
methods that includes related AD diagnosis work and the proposed DCNN model. Section 3
states the experimental results. Finally, Section 4 reports the paper conclusion.

2 Materials and methods

2.1 Related work

Several studies have already been designed for early AD diagnosis. The majority of these AD
studies are based on artificial intelligence and the ADNI dataset. PET, Genetics, Cognitive
tests, MRI, Cerebrospinal fluid, and blood biomarkers are included in this dataset as predictors
of the disease. Except for the study in [13], which used only the Open Access Series of
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Imaging Studies (OASIS) dataset, the ADNI dataset was used in all of the studies in [1, 6, 8,
10, 12–14, 16–18, 21–25, 27–29, 31–36], and studies in [22–24] used both the ADNI and the
OASIS datasets.
First, we introduce the related studies for binary classification of AD. Raza et.al [23]
proposed a new ML-based screening and diagnosis of AD. The process of the AD diagnosis
was achieved by the DL analysis of MRI scans, followed by an activity screening using body-
worn inertial sensors. An accuracy of 95% was achieved to classify the patient’s daily
activities. Another classification approach for the detection of AD diagnosis, based on Mean
Diffusivity (MD) extracted from DTI and Structural MRI (sMRI) brain images, has been
introduced in [1]. An accuracy of 85.0%, 92.5%, and 80.0% respectively was accomplished
for AD/MCI, AD/NC, and MCI/NC.
The study in [28] utilized a parameter-based DL method to discriminate the MCI patients
who are susceptible to AD in 3 years and the MCI stable patients within the same period. The
obtained 10-fold cross-validated accuracy, the area under the curve (AUC), specificity, and
sensitivity are 86%, 0.925, 85%, and 87.5% respectively. A 3D DCNN architecture for brain
MRI classification has been presented in [16]. Classification of AD versus MCI and NC was
conducted on ADNI dataset. The study shows that similar performance can be obtained with
reduced steps (i.e., skipping feature extraction steps). Hon and Khan [13] presented a transfer
learning-based technique to identify AD using brain sMRI. Two DL techniques, i.e., Inception
V4 and VGG16 were examined. A better performance was reached compared with current DL
based approaches.
Automatic AD and MCI classifier that is based on brain MRI and deep neural networks was
designed by Basaia et.al [6]. The system performance was examined in identifying AD,
converters MCI (c-MCI) and Stable MCI (s-MCI). High accuracy levels were obtained in all
cases. In [24], DL technique was presented for AD diagnosis and monitoring of the AD
patient. The technique demonstrated the importance of high-accuracy AD diagnosis with
physical activities, as well as how these activities can be logged with high accuracy without
human intervention. Janghel et al. [14] applied the VGG 16 architecture of DCNN for features
extraction and SVM for the AD detection task. The CNN performance was improved by
performing some preprocessing on the image dataset before feature extraction. An average
accuracy of 99.95% and 73.46% was achieved respectively for the fMRI dataset and the PET
classification.
Xiao et al. [34] used Sparse logistic regression (SLR) for early AD diagnosis of 197
cases. To impose a sparsity constraint on logistic regression, SLR utilized L1/2 regulariza-
tion. When compared to other classical techniques, experimental results showed that the
SLR improved the AD/MCI classification performance. Several methods are also used for
AD diagnoses such as a multi-model DL framework in [18, 36]. In [18], a 3D Densely
Connected Convolutional Networks (3D DenseNet) was constructed to learn features of the
3D patches then these learned features were combined to classify disease status. To extract
the 3D patches features, a 3D Densely Connected Convolutional Network (3D DenseNet)
was built, and then these features were utilized for disease status classification. The
proposed multi-model procedure outscored single-model procedures as well as a number
of other competing methods. Two independent CNNs were used in [36] to obtain PET and
MRI image features. The results showed that the presented multi-modal auxiliary diagnosis
achieved a superb efficiency.
Concerning the three-way AD/MCI/NC classification, Gupta et al. [12] proposed an
approach for computerized AD diagnosis in which cross-domain features are used to
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represent MRI data. High classification performance was achieved using this approach.
Payan et al. [21] proposed a classification MRI-based technique that utilizes 3D CNNs and
sparse autoencoders to predict patient disease status. The results outperform the ordinary
3D CNNs algorithm in comparison to several other classifiers in the literature. Cárdenas-
peña et al. [10] presented a DL model based on central kernel alignment. They compared
the supervised pre-training method to two unsupervised initialization approaches. The
experiment showed that artificial neural network (ANN) pretraining outperforms the
contrasted algorithms and reduces the class biasing. Hence, better MCI discrimination is
obtained. Discrimination between AD, MCI, and NC individuals using 3D MRI and
neuropsychological measures (NM) was introduced in [27]. A fusion pipeline combines
data from multiple modalities including volumetric MRI and NM features. The results
show the effectiveness of the presented fusion pipeline compared to the 3D CNN architec-
tures. A robust automatic technique of High-level Layer Concatenation Autoencoder
(HiLCAE) and 3D-VGG16 are utilized to detect AD using MRI and PET images was
introduced by Vu et al. [32]. The experiment was conducted on an ADNI dataset and
classified into one of three classes: NC, MCI, and AD.
Wang et.al [33] proposed an ensemble of 3D-DenseNet for MCI and AD classification.
Many experiments were performed to analyze the performance of the system with different
architectures and hyper-parameters. The proposed model outperforms the other model using
the ADNI dataset. Xiao et al. [35] introduce a new classification framework to classify AD or
MCI from NC. Three different features (i.e., gray-level co-occurrence matrix (GLMC), Gabor
feature, and gray-matter volume) were used. The results show that the multi-feature fusion
improves system performance. Tong et al. [29] presented a new data fusion method from
multiple modalities for AD classification. The AUC of receiver-operator characteristic (ROC)
is 82.4% between MCI patients and NC, 98.1% between AD patients and NC, and 77.9% in a
3-way classification. Several techniques were also used for AD diagnoses such as DL
technology [8, 22], representation of regional abnormality via DL [17], universum SVM
[25], and hippocampal atrophy technique [31].
The related study with speech aspects was introduced in [19] where a new ML technique
used the spectrogram patient’s speech features for AD detection. The patients’ speech data
from NC and AD was collected and examined. The results presented that, among the used
models, the Logistic Regression CV model had accomplished the highest performance. As
mentioned before, deep learning methods are a new candidate in the medical imaging field.
Therefore, a CNN-based framework is examined in this paper for the MRI classification into
one of the three output groups.

2.2 Proposed work

The proposed network is a new DCNN that uses an MRI brain scan to automate AD
classification. For feature extraction, the proposed framework includes three convolutional
blocks. A convolutional layer, batch normalization layer, rectified linear unit (ReLU), and a
max-pooling (MAX P) layer make up each convolutional block (Conv). A stride of 2 and a
max-pooling of 2 × 2 was utilized in each layer. After the convolutional blocks, a fully
connected (FC) layer was applied for classification. The FC layer followed by Softmax
layer that has three different output categories results in the predicted probability distribu-
tion of three classes (NC, MCI and AD). Figure 1 shows the proposed 16 layers of CNN
architecture.
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(a) (b)
Fig. 1 a) The proposed CNN architecture b) The detailed convolution blocks

The fundamental block of DCNN is the convolution layer which contains kernels. These
kernels are convolved to detect patterns and features over input images. The kernel is a filter of
different windows (i.e., 3 × 3, 7 × 7, and 13 × 13) that are convolved over each input to
extract a feature map.
For example, if the convolutional layer is l, then the feature map of this layer is j and it can
be obtained as follows:

xlj ¼ blj þ ∑ xl−1 l

i *k i j ð1Þ
i∈N j

where

Nj the set of the input feature map.

xl−1
i the input feature map of the layer l (the output feature map of the previous layer).
k lij the partial input feature map convolutional kernel.
blj the bias offset of the feature map j after convolution.
∗ the convolutional calculation.
A nonlinear activation function called ReLU is applied after the convolution layer to obtain
nonlinear feature maps. ReLU select the maximum value between zero and the input Ix;
therefore, the nonlinear activation map f(x) is calculated as:
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f ðxÞ ¼ maxð0; I x Þ: ð2Þ

A DCNN gives translation-invariant feature maps via the use of the MAX P layer. Due to the
pooling layer, the feature representation is stable and more concise and reduces the next stage
computational burden. The max-pooling is computed as follows:
pool i; j ¼ max f ðxÞiþp; jþp ð3Þ
p

where the spatial positions are i and j, and p is the pooling window size.
In the end, the network normally has FC layers, where each feature map pixel is a neuron
and forward to every neuron in the FC layers. One FC layer is used in our architecture. The
softmax layer has three different output categories: AD, NC, and MCI. Depending on the
feature representation, any input image was classified into one of these three categories.
Furthermore, using the new proposed DCNN framework, the overall classification accuracy
is improved. A CNN has neurons with weights and biases, just like a traditional NN. During
the training task, the CNN learns these values and upgrades them with each new training task.
However, in the case of CNNs, all hidden neurons in a layer have the same weights and bias
values.

3 Experimental analysis

3.1 Dataset

The employed dataset used is the structural brain MRI scans which are provided by the ADNI
dataset (http://adni.loni.usc.edu/). A total number of 199 patients were reported, in which there
were 42 AD, 97 MCI, and 60 NC cases. Table 1 describes the demographic characteristics of
the used samples, including age, gender, and number. The employed dataset samples are
shown in Fig. 2.

3.2 Performance measurement

The performance examination was done using the following parameters i.e., Specificity,
Sensitivity, Accuracy, and Balanced Accuracy. This is done to evaluate the overall perfor-
mance of the proposed classification algorithm. True negative cases are referred to as
specificity, which is defined as the proportion of negative cases correctly classified as true
negative cases. True positive cases are referred to as sensitivity, which refers to the proportion
of actual true cases correctly classified. Accuracy is a term that describes how close a
measurement is to the actual value of a quantity. The average of each class’s proportion

Table 1 The dataset demographic information

Category AD NC MCI

Number 42 60 97
Female / Male 27/15 38/22 40/57
Age(Mean±SD) 74.21429 ±8.306729 75.23333 ±3.761386 74.47423 ±8.064961
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(a) (b) (c)

Fig. 2 Samples of the utilized dataset (a) AD (b) NC (c) MCI

corrects is used to calculate Balanced Accuracy. Table 2 illustrates these parameters. Where,
TN (True Negative), and TP (True Positive) are the accurately classified cases. Also, the FN (False
Negative), and FP (False Positive) are the inaccurately classified cases. The ROC analysis and CM
are also used to evaluate the performance of the proposed 3-class classification algorithm.

3.3 Experimental setup and evaluation

To evaluate the classifier performance initially, the database image set was divided into two
subsets i.e., testing set and training set. Different cases of dataset combinations are used (i.e.,
90% of the images for training and 10% for testing the network, 80% for training and 20% for
testing, and finally, 70% for training and 30% for testing).

Table 2 The classifier evaluation parameters

Parameters Mathematical equation

Sensitivity (SEN) TP
TPþFN
Specificity (SPE) TN
TNþFP
Accuracy (ACC) TPþTN
TPþTNþFPþFN
Balanced Accuracy (BAC) 0.5 ∗(Sensitivity+Specificity)

Table 3 Classification performance for (NC vs. AD)

ACC (%) SPE (%) SEN (%) BAC (%)

90% training-10%testing 100 100 100 100

80% training-20%testing 100 100 100 100
70% training-30%testing 100 100 100 100
Average 100 100 100 100
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Table 4 Classification performance for (NC vs. MCI)

ACC (%) SPE (%) SEN (%) BAC (%)

90% training-10%testing 93.75 90 100 95

80% training-20%testing 93.55 100 83.33 91.67
70% training-30%testing 91.49 93.10 88.89 90.996
Average 92.93 94.37 90.74 92.56

Table 5 Classification performance for (AD vs MCI)

ACC (%) SPE (%) SEN (%) BAC (%)

90% training-10%testing 100 100 100 100

80% training-20%testing 100 100 100 100
70% training-30%testing 97.62 100 92.31 96.154
Average 99.21 100 97.44 98.72

4 Result discussion

The DCNN Performance was validated with four classifications: Patients with NC vs. AD, NC
vs. MCI, MCI vs. AD, and finally three-class classification (NC, MCI, and AD).

4.1 NC vs. AD

In comparing the NC and AD, a 100% accuracy has been obtained. Table 3 shows the
Classification performance of (NC vs. AD). As can be seen in Table 3, the introduced method
is effective in classifying NC and AD, with the highest classification rate (100%), a sensitivity
of 100%, a specificity of 100%, and balanced accuracy of 100%.

4.2 NC vs. MCI

To further examine the system in terms of individual classes (NC vs. MCI), Table 4 reports the
Classification performance for (MCI vs NC). In distinguishing MCI from NC subjects, the
proposed method reached an accuracy of about 92.93%, a specificity of 94.37%, a sensitivity
of 90.74%, and balanced accuracy of 92.56%.

Table 6 Classification performance for three - class classification (AD, NC, and MCI)

ACC (%) SPE (%) SEN (%) BAC (%)

90% training-10%testing 95 97.62 96.67 97.15

80% training-20%testing 94.9 96.67 93.06 94.87
70% training-30%testing 91.67 95.47 92.13 93.80
Average 93.86 96.60 93.95 95.27
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98

97

96

95

94

93

92

91
70-30 80-20 90-10 Average

ACC SPE SEN BAC

Fig. 3 The proposed DCNN framework for 3-class classification

4.3 MCI vs AD

The experimental results of AD and MCI classification are reported in Table 5. As shown, the
highest accuracy and specificity (higher than 99%) are obtained. Moreover, sensitivity and
balanced accuracy obtained are about 97.44% and 98.72% respectively.

Fig. 4 The DCNN training behavior

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4.4 Three-class classification (classification of AD, NC, and MCI)

These are the results of the three-class classification. As reported in Table 6 and Fig. 3, the
proposed method reached an accuracy of about 93.86%, a sensitivity of 93.95%, a speci-
ficity of 96.60%, and balanced accuracy of 95.27%. According to the experimental results,
one can find that the proposed method is still effective and robust in the 3-class
classification.
Figure 4 shows the behavior of accuracy and loss during the training and evaluation
processes. The loss and accuracy values that obtained while training the proposed framework
revealed its efficiency on training and validation data. 70% of the data is used for training
while the rest is used for validating process. The findings show that as the loss value decreases,
the framework improves its accuracy.
The performance of the 3-class classification is depicted in the form of CMs in Fig. 5 and
ROC curves in Fig. 6 with different training-testing ratios (i.e., 70% - 30%, 80% - 20%, and
90% - 10%). In (90% - 10%) classification ratio, 20 images are tested including 4 AD, 6 NC
and 10 MCI. It is clear that only one image of MCI was misclassified and all AD and NC
images are correctly classified as described in Fig. 5c. The AUC values of 1, 1, and 0.989 were
obtained for AD, NC, and MCI, respectively. In the two other classification cases, 59 and 39
images are tested in (70% - 30%) and (80% - 20%), respectively and one image of AD and NC

(b)
(a)

(c)
Fig. 5 The Confusion matrices of the proposed 3-class classification model with different training-testing ratios
(a) 70% - 30% (b) 80% - 20% (c) 90% - 10%
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(a)
(b)

(c)
Fig. 6 ROC curves of the proposed 3-class classification model with different training-testing ratio (a) 70% -
30% (b) 80% - 20% (c) 90% - 10%

was misclassified as shown in Fig. 5b and c. The AUC values of the other classification cases
are clarified in Fig. 6b and c. The results declare that the (90% - 10%) classification case
obtained the best AD detection with a classification accuracy of 95%.
The method used to divide the database image set into subsets for training and testing has a
large impact on the results. The larger the images used in training the DCNN, the higher the
accuracy obtained. As a result, one of the most important reasons for improving the results is to
use a database with the largest images possible in the train phase, which increases the DCNN
classifier’s ability to discriminate between the different classes. The average accuracy for NC
versus MCI is relatively low, as can be seen from the results. As a result, the three classifi-
cations (AD, NC, and MCI) have a relatively low accuracy. This is due to the use of a small
number of dataset images and the MCI being a stage between NC and AD. MCI and NC have
a high similarity ratio.
The comparison of the average accuracy of the proposed method and the recently published
studies using the same ADNI datasets is shown in Table 7 and summarized in Fig. 7. From the
table and the figure, it is clear that the proposed classifier achieved the highest performance
compared to the literature. However, the CA of the proposed method for classification of (MCI
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Table 7 The comparison of the proposed classifier average accuracy with literature

Study Year Method Average Accuracy (%)

NC vs. AD MCI vs. NC AD vs. MCI NC vs. MCI vs. AD

[13] 2017Inception V4+VGG16 96.25 – – –

[24] 2019DL 98.74 – – –
[14] 2020VGG 16+SVM 99.95 – – –
[16] 20173D DCNN 80 58 – –
[34] 2020SLR 93.33 82.75 – –
[18] 20203D DenseNet 88.90% 76.25 – –
[8] 2020PCANet – 92.6 97.01 –
[27] 2018NM 76 75 76 –
[1] 2018DTI+MD 90.00 72.50 82.50 –
[6] 2019deep neural networks 99.2 76.1 85.9 –
[17] 2019Regional abnormality via DL 92.75 89.22 81.46 –
[36] 2019Two independent CNNs 98.47 85.74 88.20 –
[25] 2020Universum SVM 87.6 70.2 72.73 –
[22] 2020DL using transfer learning – – – 78.64
[29] 2017Data fusion method 98.3 98.3 – 72.9
[12] 2013Cross-domain features 93.80 83.30 86.30 78.20
[21] 20153D CNNs and sparse 95.39 92.11 86.84 89.47
autoencoders
[32] 2018 HiLCAE and 3D-VGG16 98.8 95 93 91.13
[35] 2017 multi-feature fusion 85.71 86.11 79.44 75.00
[31] 2020 hippocampal atrophy 94 95 82 82
Proposed DCNN framework 100 92.93 99.21 93.86

vs. NC) is less than of [31, 32], the proposed new DCNN achieved the highest CA of other
classification scenarios (i.e., NC vs. AD, MCI vs. AD, and AD vs. NC vs. MCI).

Fig. 7 Comparison of the proposed approach with literature

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5 Conclusion

In this study, a new efficient automated AD diagnosis DCNN based framework using brain
MRI scans was introduced and examined. DCNN performance was tested in distinguishing
NC, MCI, and AD. Experimental data are obtained using the ADNI dataset that includes 199
subjects. Four classification metrics were measured for four different situations of dataset
combinations i.e., NC vs. AD, NC vs. MCI, MCI vs. AD, and the most difficult scenario of 3-
class classification (NC, MCI, and AD). The experimental results are compared with the
published results. The proposed framework results outperform the literature in all four
classification situations in terms of Accuracy, Specificity, Sensitivity, and Balanced Accuracy.
In classifying NC and AD, the highest classification rate of 100% is obtained for Accuracy,
Sensitivity, Specificity, and Balanced accuracy. In distinguishing MCI from NC subjects, the
proposed method reached an accuracy of about 92.93%, a specificity of 94.37%, a sensitivity
of 90.74%, and balanced accuracy of 92.56%. In the case of AD and MCI classification the
highest accuracy and specificity (higher than 99%) are obtained. Moreover, sensitivity and
balanced accuracy obtained are about 97.44% and 98.72% respectively. Finally for the three-
class classification, the proposed method reached an accuracy of about 93.86%, a sensitivity of
93.95%, a specificity of 96.60%, and balanced accuracy of 95.27%. The small variations
between NC, MCI, and AD arises the need for more than 199 subjects to further improve the
framework performance. In the last situation, ROC and CM are also used. The AUC values of
1, 1, and 0.989 are achieved for AD, NC, and MCI, respectively.

6 Future work

The usage of another larger MRI dataset with pretrained CNN will be the upcoming challenge
to achieve better accuracy.

Declarations

Competing interests The authors report no declarations of interest.

References

1. Aderghal K, Khvostikov A, Krylov A, Benois-pineau J, Afdel K, Catheline G (2018) Classification of

Alzheimer disease on imaging modalities with deep cnns using cross-modal transfer learning. In IEEE
International Symposium on Computer-Based Medical Systems (IEEE), pp 345–350
2. Ahmed HM, Youssef BAB, Elkorany AS, Elsharkawy ZF, Saleeb AA, El-Samie FA (2019) Hybridized
classification approach for magnetic resonance brain images using gray wolf optimizer and support vector
machine. Multimed Tools Appl 78:27983–28002
3. Ahmed HM, Youssef BAB, Elkorany AS, Saleeb AA, Abd El-Samie F (2018) Hybrid gray wolf optimizer–
artificial neural network classification approach for magnetic resonance brain images. Appl Opt 57:B25–
B31
4. Alzheimer Association (2019) 2019 Alzheimer’s disease facts and figures. Alzheimers Dement 15:321–387
5. Backstrom K, Nazari M, Gu IYH, Jakola AS (2018) An efficient 3D deep convolutional network for
Alzheimer’s disease diagnosis using MR images. IEEE International Symposium on Biomedical Imaging
(IEEE), pp 149–153
6. Basaia S, Agosta F, Wagner L, Canu E, Magnani G (2019) Automated classification of Alzheimer ‘s disease
and mild cognitive impairment using a single MRI and deep neural networks. NeuroImage Clin 21
 Multimedia Tools and Applications

7. Basaia S, Agosta F, Wagner L, Canu E, Magnani G, Santangelo R, Filippi M (2019) Automated

classification of Alzheimer’s disease and mild cognitive impairment using a single MRI and deep neural
networks. NeuroImage: Clinical 21(2019):101645. https://doi.org/10.1016/j.nicl.2018.101645
8. Bi X, Li S, Xiao B, Li Y, Wang G, Ma X (2020) Computer aided Alzheimer’s disease diagnosis by an
unsupervised deep learning technology. Neurocomputing 392:296–304
9. Buono VL, Palmeri R, Corallo F, Allone C, Pria D, Bramanti P, Marino S (2020) Diffusion tensor imaging
of white matter degeneration in early stage of Alzheimer’s disease: a review. Int J Neurosci 130:243–250
10. Cárdenas-peña D, Collazos-huertas D, Castellanos-dominguez G (2016) Centered kernel alignment enhanc-
ing neural network Pretraining for MRI-based dementia diagnosis. Comput Math Methods Med 2016:1–10
11. Goryawala M, Zhou Q, Barker W, Loewenstein DA, Duara R, Adjouadi M (2015) Inclusion of neuropsy-
chological scores in atrophy models improves diagnostic classification of Alzheimer’s disease and mild
cognitive impairment. Comput Intell Neurosci 2015:1–14
12. Gupta A, Ayhan MS, Maida AS (2013) Natural image bases to represent neuroimaging data. In
International Conference on International Conference on Machine Learning, pp 987–994
13. Hon M, Khan NM (2017) Towards Alzheimer’s disease classification through transfer learning. In IEEE
International Conference on Bioinformatics and Biomedicine (IEEE), pp 1166–1169
14. Janghel RR, Rathore YK (2020) Deep convolution neural network based system for early diagnosis of
Alzheimer’s disease. IRBM. https://doi.org/10.1016/j.irbm.2020.06.006
15. Korolev IO (2014) Alzheimer ‘s disease: a clinical and basic science review. Med Student Res J 4:24–33
16. Korolev S, Safiullin A, Belyaev M, Dodonova Y (2017) Residual and plain convolutional neural networks for
3D brain MRI classification. In IEEE International Symposium on Biomedical Imaging (IEEE), pp 835–838
17. Lee E, Choi J-S, Kim M, Suk H-I (2019) Toward an interpretable Alzheimer’s disease diagnostic model
with regional abnormality representation via deep learning. NeuroImage 202:116113
18. Liu M, Li F, Yan H, Wang K, Ma Y, Shen L, Xu M, Initiative AsDN (2020) A multi-model deep
convolutional neural network for automatic hippocampus segmentation and classification in Alzheimer’s
disease. NeuroImage 208:116459
19. Liu L, Zhao S, Chen H, Wang A (2020) A new machine learning method for identifying Alzheimer’s
disease. Simul Model Pract Theory 99:102023
20. Nordberg A, Rinne JO, Kadir A, Lngström B (2010) The use of PET in Alzheimer disease. Nat Rev Neurol
6:78–87
21. Payan A, Montana G (2015) Predicting Alzheimer’s disease: a neuroimaging study with 3D convolutional
neural networks, computer, arXiv [Preprint]. Available at: https://arxiv.org/abs/1502.02506v1
22. Puente-Castro A, Fernandez-Blanco E, Pazos A, Munteanu CR (2020) Automatic assessment of
Alzheimer’s disease diagnosis based on deep learning technique. Comput Biol Med 120:103764
23. Raza M, Awais M, Ellahi W, Aslam N, Nguyen HX, Le-minh H (2019) Diagnosis and monitoring of
Alzheimer ‘s patients using classical and deep learning techniques. Expert Syst Appl 136:353–364
24. Raza M, Awais M, Ellahi W, Aslam N, Nguyen HX, Le-Minh H (2019) Diagnosis and monitoring of
Alzheimer’s patients using classical and deep learning techniques. Expert Syst Appl 136:353–364
25. Richhariya B, Tanveer M, Rashid AH (2020) Diagnosis of Alzheimer’s disease using universum support vector
machine based recursive feature elimination (USVM-RFE). Biomed Signal Process Control 59:101903
26. Sarraf S, Tofighi G Deep learning-based pipeline to recognize Alzheimer’s disease using fMRI data. In
2016 Future Technologies Conference (FTC, 2016), pp 816–820
27. Senanayake U, Dawes L, Sowmya A (2018) Deep fusion pipeline for mild cognitive impairment diagnosis.
In IEEE International Symposium on Biomedical Imaging (IEEE), pp 1394–1997
28. Spasov S, Passamonti L, Duggento A, Lio P, Toschi N (2019) A parameter-efficient deep learning approach
to predict conversion from mild cognitive impairment to Alzheimer ‘s disease. NeuroImage 189:276–287
29. Tong T, Gray K, Gao Q, Chen L, Rueckert D (2017) Multi-modal classification of Alzheimer’s disease
using nonlinear graph fusion. Pattern Recogn 63:171–181
30. Tong T, Wolz R, Gao Q, Guerrero R, Hajnal JV, Rueckert D (2014) Multiple instance learning for
classification of dementia in brain MRI. Med Image Anal 18:808–818
31. Uysal G, Ozturk M (2020) Hippocampal atrophy based Alzheimer’s disease diagnosis via machine learning
methods. J Neurosci Methods 337:108669
32. Vu T, Ho N, Yang H, Kim J, Song H (2018) Non-white matter tissue extraction and deep convolutional
neural network for Alzheimer ‘s disease detection. Soft Comput 22:6825–6833
33. Wang H, Shen Y, Wang S, Xiao T, Deng L, Wang X, Zhao X (2019) Ensemble of 3D densely connected
convolutional network for diagnosis of mild cognitive impairment and Alzheimer ‘s disease.
Neurocomputing 333:145–156
34. Xiao R, Cui X, Qiao H, Zheng X, Zhang Y (2020) Early diagnosis model of Alzheimer’s Disease based on
sparse logistic regression. Multimed Tools Appl. https://doi.org/10.1007/s11042-020-09738-0
Multimedia Tools and Applications

35. Xiao Z, Ding Y, Lan T, Zhang C, Luo C, Qin Z (2017) Brain MR image classification for Alzheimer ‘s
disease diagnosis based on multifeature fusion. Comput Math Methods Med 2017:1–13
36. Zhang F, Li Z, Zhang B, Du H, Wang B, Zhang X (2019) Multi-modal deep learning model for auxiliary
diagnosis of Alzheimer’s disease. Neurocomputing 361:185–195

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