Exploring Handwriting-Based Biomarkers for Alzheimer’s Disease: Identifying Discriminative Features and Tasks to Enhance Diagnostic Accuracy
Abstract
1. Introduction
- A baseline set of 18 handwriting features is expanded by incorporating 30 additional features previously used in various handwriting recognition tasks, and their relevance for AD detection is systematically analyzed.
- Feature selection techniques are applied to identify the most informative features for distinguishing patients, with the aim of supporting the clinical interpretation of handwriting impairments associated with AD.
- On the basis of the selected features, the number of handwriting tasks is reduced from 25 to 14, with the goal of simplifying the assessment protocol and reducing the cognitive and physical burden on patients.
- Overall, the proposed approach emphasizes interpretability and clinical applicability while building upon established methodologies in the literature.
2. Related Work
3. Materials and Methods
3.1. Dataset
3.2. Feature Extraction and Normalization
3.3. Feature Selection
3.3.1. RF_Importance
3.3.2. XGBoost Feature Importance
3.3.3. L1 Regularization
3.3.4. RFE
3.4. Classification
3.4.1. SVM
3.4.2. RF
3.4.3. LR
3.4.4. MLP
3.4.5. XGBoost
3.5. Task Selection
3.6. Ensemble Learning
3.6.1. Soft Voting
3.6.2. Hard Voting
3.7. Use of Generative Artificial Intelligence Tools
4. Experimental Results and Discussion
4.1. Experimental Settings
4.2. Task Reduction Strategy
4.3. Evaluation of Discriminative Features for AD Diagnosis
4.3.1. Feature Selection Analyses for the 25-Task Feature Set
4.3.2. Feature Selection Analyses for the 14-Task Feature Set
4.3.3. Clinical Interpretation of Discriminative Handwriting Features
4.4. Performance Evaluation of Feature Sets with Classification Algorithms
4.4.1. Classification Performance Using the 25-Task Feature Set
4.4.2. Classification Performance Using the 14-Task Feature Set
4.5. Comparative Analysis of Classification Performance Between the 25-Task and 14-Task Datasets
4.6. Comparison with Previous Studies Using the DARWIN Dataset
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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| No | Feature Name | Subject of the Relevant Study | No | Feature Name | Subject of the Relevant Study |
|---|---|---|---|---|---|
| 1 | Total Time | AD [7] | 25 | Mean Stroke Width | PD [29] |
| 2 | Air Time | AD [7] | 26 | Mean Centroid Distance | CD [30,31] |
| 3 | Paper Time | AD [7] | 27 | Mean Min. Dist. between Strokes | CD [30,31] |
| 4 | Mean Speed on paper | AD [7] | 28 | Mean Stroke Endpoint Distance | CD [30,31] |
| 5 | Mean Speed in air | AD [7] | 29 | Mean Vertical Alignment | CD [30,31] |
| 6 | Mean Acceleration on paper | AD [7] | 30 | Mean Horizontal Alignment | CD [30,31] |
| 7 | Mean Acceleration in air | AD [7] | 31 | Horizontal Shannon Entropy | PD [29,32,33] |
| 8 | Mean Jerk on paper | AD [7] | 32 | Vertical Shannon Entropy | PD [29,32,33] |
| 9 | Mean Jerk in air | AD [7] | 33 | Horizontal Rényi Entropy (2) | PD [29,32,33] |
| 10 | Pressure Mean | AD [7] | 34 | Horizontal Rényi Entropy (3) | PD [29,32,33] |
| 11 | Pressure Variation | AD [7] | 35 | Vertical Rényi Entropy (2) | PD [29,32,33] |
| 12 | GMRT on paper | AD [7] | 36 | Vertical Rényi Entropy (3) | PD [29,32,33] |
| 13 | GMRT in air | AD [7] | 37 | X-axis Total Energy | PD [32,33] |
| 14 | Mean GMRT | AD [7] | 38 | Y-axis Total Energy | PD [32,33] |
| 15 | Pendowns Number | AD [7] | 39 | X-axis Teager–Kaiser Energy | PD [32,33] |
| 16 | Max X Extension | AD [7] | 40 | Y-axis Teager–Kaiser Energy | PD [32,33] |
| 17 | Max Y Extension | AD [7] | 41 | X-axis CE Signal-to-Noise Ratio | PD [32,33] |
| 18 | Dispersion Index | AD [7] | 42 | Y-axis CE Signal-to-Noise Ratio | PD [32,33] |
| 19 | Mean Azimuth | CD [34], MCI [35], ESR [36], SR [37] | 43 | X-axis TKE Signal-to-Noise Ratio | PD [32,33] |
| 20 | Mean Slope | SR [38] | 44 | Y-axis TKE Signal-to-Noise Ratio | PD [32,33] |
| 21 | Total Displacement | PD [29] | 45 | Speed Std Dev | PD [39] |
| 22 | Horizontal Displacement | PD [29] | 46 | Pressure Std Dev | HDA [40] |
| 23 | Vertical Displacement | PD [29] | 47 | Altitude | MCI [35], ESR [36], SR [37], PD [29] |
| 24 | Mean Stroke Height | PD [29] | 48 | Horizontal Intrinsic Shannon Entropy | PD [29] |
| ID | Feature Name | [7] | [41] | [8] | This Study | ID | Feature Name | [7] | [41] | [8] | This Study |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | TT | + | - | + | + | 25 | MSW | - | - | - | + |
| 2 | AT | + | - | - | + | 26 | MCD | - | - | - | + |
| 3 | PT | + | - | - | + | 27 | MMDS | - | - | - | + |
| 4 | MSP | + | - | - | + | 28 | MSED | - | - | - | + |
| 5 | MSA | + | - | - | + | 29 | MVA | - | - | - | + |
| 6 | MAP | + | - | - | + | 30 | MHA | - | - | - | + |
| 7 | MAA | + | - | - | + | 31 | HSE | - | - | - | + |
| 8 | MJP | + | - | - | + | 32 | VSE | - | - | - | + |
| 9 | MJA | + | - | - | + | 33 | HRE2 | - | - | - | + |
| 10 | PM | + | + | + | + | 34 | HRE3 | - | - | - | + |
| 11 | PV | + | - | - | + | 35 | VRE2 | - | - | - | + |
| 12 | GMRTP | + | - | - | + | 36 | VRE3 | - | - | - | + |
| 13 | GMRTA | + | - | - | + | 37 | CEX | - | - | - | + |
| 14 | GMRT | + | - | - | + | 38 | CEY | - | - | - | + |
| 15 | PWN | + | + | + | + | 39 | TKEX | - | - | - | + |
| 16 | XE | + | + | + | + | 40 | TKEY | - | - | - | + |
| 17 | YE | + | + | + | + | 41 | SNRCEX | - | - | - | + |
| 18 | DI | + | - | - | + | 42 | SNRCEY | - | - | - | + |
| 19 | MA | - | + | + | + | 43 | SNRTKEX | - | - | - | + |
| 20 | MS | - | + | + | + | 44 | SNRTKEY | - | - | - | + |
| 21 | TD | - | + | + | + | 45 | SSD | - | - | - | + |
| 22 | HD | - | - | - | + | 46 | PSD | - | - | - | + |
| 23 | VD | - | - | - | + | 47 | Altitude | - | - | - | + |
| 24 | MSH | - | - | - | + | 48 | HIMF1 | - | - | - | + |
| Task Number | Total Empty Files | Healthy Empty | Patient Empty | Task Number | Total Empty Files | Healthy Empty | Patient Empty |
|---|---|---|---|---|---|---|---|
| 19 | 28 | 6 | 22 | 16 | 4 | 2 | 2 |
| 21 | 13 | 3 | 10 | 17 | 4 | 2 | 2 |
| 25 | 12 | 2 | 10 | 18 | 4 | 2 | 2 |
| 20 | 10 | 2 | 8 | 8 | 4 | 4 | 0 |
| 22 | 10 | 2 | 8 | 2 | 3 | 3 | 0 |
| 24 | 10 | 2 | 8 | 6 | 3 | 2 | 1 |
| 23 | 9 | 2 | 7 | 9 | 3 | 2 | 1 |
| 13 | 6 | 2 | 4 | 3 | 2 | 1 | 1 |
| 14 | 6 | 2 | 4 | 7 | 2 | 2 | 0 |
| 12 | 5 | 3 | 2 | 4 | 1 | 1 | 0 |
| 15 | 5 | 2 | 3 | 5 | 1 | 1 | 0 |
| 10 | 4 | 2 | 2 | 1 | 0 | 0 | 0 |
| 11 | 4 | 2 | 2 |
| Task No | Unnormalized | Z-Score | Min–Max | Task No | Unnormalized | Z-Score | Min–Max |
|---|---|---|---|---|---|---|---|
| 9 | 97 | 109 | 97 | 20 | 13 | 13 | 13 |
| 7 | 33 | 23 | 33 | 3 | 13 | 13 | 13 |
| 8 | 31 | 30 | 31 | 5 | 13 | 13 | 13 |
| 10 | 20 | 19 | 20 | 24 | 12 | 13 | 12 |
| 13 | 19 | 19 | 19 | 1 | 11 | 11 | 11 |
| 14 | 19 | 19 | 19 | 21 | 11 | 11 | 11 |
| 23 | 17 | 16 | 17 | 25 | 11 | 11 | 11 |
| 4 | 16 | 16 | 16 | 18 | 10 | 10 | 10 |
| 12 | 16 | 16 | 16 | 17 | 9 | 9 | 9 |
| 16 | 16 | 16 | 16 | 19 | 7 | 7 | 7 |
| 11 | 15 | 15 | 15 | 22 | 4 | 4 | 4 |
| 2 | 14 | 14 | 14 | 15 | 0 | 0 | 0 |
| 6 | 13 | 13 | 13 |
| Feature | Unnormalized | Z-Score | Min–Max | Overall Average | Feature | Unnormalized | Z-Score | Min–Max | Overall Average |
|---|---|---|---|---|---|---|---|---|---|
| SNRCEX | 6.75 | 6.75 | 6.80 | 6.77 | GMRTP | 2.00 | 2.00 | 2.40 | 2.13 |
| MA | 5.25 | 5.25 | 5.40 | 5.30 | VSE | 2.00 | 2.25 | 2.00 | 2.08 |
| MS | 4.50 | 4.50 | 4.60 | 4.53 | MCD | 2.00 | 1.75 | 2.40 | 2.05 |
| MVA | 4.25 | 4.50 | 4.60 | 4.45 | HIMF1 | 1.75 | 1.75 | 2.00 | 1.83 |
| Altitude | 4.25 | 4.00 | 4.60 | 4.28 | PT | 1.75 | 2.00 | 1.60 | 1.78 |
| MJA | 4.00 | 4.00 | 4.20 | 4.07 | MSED | 1.75 | 1.75 | 1.80 | 1.77 |
| TKEX | 4.00 | 3.75 | 4.00 | 3.92 | HRE2 | 1.50 | 1.75 | 2.00 | 1.75 |
| YE | 3.50 | 3.50 | 4.00 | 3.67 | VRE3 | 1.50 | 1.75 | 1.80 | 1.68 |
| MSW | 3.50 | 3.50 | 3.80 | 3.60 | SNRCEY | 1.50 | 1.50 | 2.00 | 1.67 |
| GMRTA | 3.50 | 3.25 | 4.00 | 3.58 | VD | 1.50 | 1.25 | 1.60 | 1.45 |
| HSE | 3.25 | 3.50 | 3.40 | 3.38 | CEY | 1.50 | 1.25 | 1.60 | 1.45 |
| SNRTKEY | 3.25 | 3.00 | 3.20 | 3.15 | PWN | 1.25 | 1.00 | 2.00 | 1.42 |
| MJP | 3.00 | 3.00 | 3.20 | 3.07 | MAA | 1.25 | 1.50 | 1.20 | 1.32 |
| PSD | 3.00 | 3.00 | 3.00 | 3.00 | DI | 1.00 | 1.00 | 1.40 | 1.13 |
| MMDS | 2.75 | 2.75 | 3.20 | 2.90 | VRE2 | 1.00 | 1.25 | 1.00 | 1.08 |
| PV | 3.00 | 2.50 | 3.20 | 2.90 | MSP | 1.00 | 1.25 | 1.00 | 1.08 |
| MHA | 2.75 | 2.75 | 2.80 | 2.77 | CEX | 1.00 | 1.00 | 1.20 | 1.07 |
| MSH | 2.50 | 2.50 | 3.00 | 2.67 | TKEY | 1.00 | 1.00 | 1.20 | 1.07 |
| AT | 2.50 | 2.75 | 2.60 | 2.62 | MAP | 0.75 | 1.00 | 0.80 | 0.85 |
| MSA | 2.25 | 2.50 | 2.20 | 2.32 | TT | 0.75 | 0.75 | 0.80 | 0.77 |
| XE | 2.25 | 2.00 | 2.40 | 2.22 | HD | 0.75 | 0.75 | 0.80 | 0.77 |
| HRE3 | 2.00 | 2.25 | 2.20 | 2.15 | SSD | 0.75 | 0.50 | 0.60 | 0.62 |
| GMRT | 2.00 | 2.00 | 2.40 | 2.13 | PM | 0.50 | 0.25 | 0.80 | 0.52 |
| SNRTKEX | 2.00 | 2.00 | 2.40 | 2.13 | TD | 0.25 | 0.25 | 0.80 | 0.43 |
| Feature | Unnormalized | Z-Score | Min–Max | Overall Average | Feature | Unnormalized | Z-Score | Min–Max | Overall Average |
|---|---|---|---|---|---|---|---|---|---|
| SNRCEX | 6.75 | 6.75 | 6.75 | 6.75 | GMRTP | 2.00 | 2.00 | 2.00 | 2.00 |
| MA | 5.25 | 5.25 | 5.25 | 5.25 | SNRTKEX | 2.00 | 2.00 | 2.00 | 2.00 |
| MS | 4.50 | 4.50 | 4.50 | 4.50 | MCD | 2.00 | 1.75 | 2.00 | 1.92 |
| MVA | 4.25 | 4.50 | 4.25 | 4.33 | PT | 1.75 | 2.00 | 1.75 | 1.83 |
| Altitude | 4.25 | 4.00 | 4.25 | 4.17 | MSED | 1.75 | 1.75 | 1.75 | 1.75 |
| MJA | 4.00 | 4.00 | 4.00 | 4.00 | HIMF1 | 1.75 | 1.75 | 1.75 | 1.75 |
| TKEX | 4.00 | 3.75 | 4.00 | 3.92 | VRE3 | 1.50 | 1.75 | 1.50 | 1.58 |
| MSW | 3.50 | 3.50 | 3.50 | 3.50 | HRE2 | 1.50 | 1.75 | 1.50 | 1.58 |
| YE | 3.50 | 3.50 | 3.50 | 3.50 | SNRCEY | 1.50 | 1.50 | 1.50 | 1.50 |
| GMRTA | 3.50 | 3.25 | 3.50 | 3.42 | VD | 1.50 | 1.25 | 1.50 | 1.42 |
| HSE | 3.25 | 3.50 | 3.25 | 3.33 | CEY | 1.50 | 1.25 | 1.50 | 1.42 |
| SNRTKEY | 3.25 | 3.00 | 3.25 | 3.17 | MAA | 1.25 | 1.50 | 1.25 | 1.33 |
| PSD | 3.00 | 3.00 | 3.00 | 3.00 | PWN | 1.25 | 1.00 | 1.25 | 1.17 |
| MJP | 3.00 | 3.00 | 3.00 | 3.00 | MSP | 1.00 | 1.25 | 1.00 | 1.08 |
| PV | 3.00 | 2.50 | 3.00 | 2.83 | VRE2 | 1.00 | 1.25 | 1.00 | 1.08 |
| MHA | 2.75 | 2.75 | 2.75 | 2.75 | DI | 1.00 | 1.00 | 1.00 | 1.00 |
| MMDS | 2.75 | 2.75 | 2.75 | 2.75 | TKEY | 1.00 | 1.00 | 1.00 | 1.00 |
| AT | 2.50 | 2.75 | 2.50 | 2.58 | CEX | 1.00 | 1.00 | 1.00 | 1.00 |
| MSH | 2.50 | 2.50 | 2.50 | 2.50 | MAP | 0.75 | 1.00 | 0.75 | 0.83 |
| MSA | 2.25 | 2.50 | 2.25 | 2.33 | HD | 0.75 | 0.75 | 0.75 | 0.75 |
| XE | 2.25 | 2.00 | 2.25 | 2.17 | TT | 0.75 | 0.75 | 0.75 | 0.75 |
| HRE3 | 2.00 | 2.25 | 2.00 | 2.08 | SSD | 0.75 | 0.50 | 0.75 | 0.67 |
| VSE | 2.00 | 2.25 | 2.00 | 2.08 | PM | 0.50 | 0.25 | 0.50 | 0.42 |
| GMRT | 2.00 | 2.00 | 2.00 | 2.00 | TD | 0.25 | 0.25 | 0.25 | 0.25 |
| Classifier | Feature Selection | k | Accuracy (%) | F1 Score (%) | Sensitivity (%) | Specificity (%) | Std Accuracy |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | L1 Regularization | 110 | 94.20 | 94.19 | 94.10 | 94.44 | 4.81 |
| Hard Ensemble | L1 Regularization | 120 | 91.96 | 91.91 | 97.78 | 86.67 | 3.11 |
| Hard Ensemble | L1 Regularization | 125 | 91.89 | 91.84 | 95.00 | 88.89 | 6.63 |
| Hard Ensemble | L1 Regularization | 145 | 91.42 | 91.41 | 94.10 | 88.89 | 7.22 |
| Hard Ensemble | L1 Regularization | 115 | 90.65 | 90.65 | 90.28 | 91.11 | 6.75 |
| Hard Ensemble | RF Importance | 150 | 89.33 | 89.26 | 91.90 | 87.04 | 4.57 |
| Hard Ensemble | L1 Regularization | 105 | 88.56 | 88.44 | 90.97 | 86.11 | 4.55 |
| Hard Ensemble | L1 Regularization | 100 | 88.50 | 88.31 | 97.78 | 80.00 | 5.73 |
| Hard Ensemble | RF Importance | 130 | 88.43 | 88.35 | 90.56 | 86.67 | 4.28 |
| Hard Ensemble | RFE Random Forest | 110 | 88.43 | 88.41 | 90.56 | 86.67 | 4.28 |
| Hard Ensemble | L1 Regularization | 140 | 88.43 | 88.30 | 87.78 | 88.89 | 7.28 |
| Hard Ensemble | L1 Regularization | 130 | 88.40 | 88.32 | 93.75 | 83.33 | 8.99 |
| Hard Ensemble | RFE Random Forest | 145 | 88.32 | 88.27 | 94.10 | 83.33 | 4.94 |
| Hard Ensemble | L1 Regularization | 135 | 87.47 | 87.34 | 89.81 | 85.19 | 5.71 |
| Hard Ensemble | RFE Random Forest | 115 | 87.32 | 87.29 | 88.33 | 86.67 | 4.82 |
| Classifier | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | 87.13 | 2.27 | 94.20 | 83.79 | 87.07 | 90.36 | 84.33 |
| XGBoost | 80.77 | 1.92 | 84.54 | 76.96 | 80.57 | 81.26 | 80.15 |
| RandomForest | 80.38 | 1.17 | 83.40 | 78.20 | 80.18 | 81.51 | 79.18 |
| Soft Ensemble | 79.00 | 1.33 | 81.11 | 76.47 | 78.67 | 82.77 | 75.35 |
| 76.84 | 1.92 | 81.01 | 72.97 | 76.42 | 81.65 | 72.19 | |
| SVM | 76.70 | 2.49 | 80.42 | 72.39 | 76.29 | 80.80 | 72.79 |
| MLPClassifier | 75.79 | 2.18 | 81.08 | 71.34 | 75.24 | 81.61 | 70.19 |
| Feature Selection | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| L1 Regularization | 80.90 | 4.24 | 94.20 | 73.69 | 80.62 | 84.22 | 77.66 |
| RF Importance | 80.28 | 3.72 | 89.32 | 71.34 | 80.00 | 83.01 | 77.70 |
| RFE RandomForest | 78.52 | 4.12 | 88.43 | 72.39 | 78.17 | 82.20 | 75.03 |
| XGB Importance | 78.36 | 3.62 | 86.85 | 73.04 | 78.03 | 81.97 | 74.86 |
| Classifier | Feature Selection | k | Accuracy (%) | F1 Score (%) | Sensitivity (%) | Specificity (%) | Std Accuracy |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | L1 Regularization | 120 | 93.07 | 93.05 | 97.78 | 88.89 | 2.71 |
| Hard Ensemble | L1 Regularization | 100 | 92.89 | 92.77 | 100.00 | 86.11 | 6.95 |
| Hard Ensemble | L1 Regularization | 110 | 92.81 | 92.80 | 94.10 | 91.67 | 3.05 |
| Hard Ensemble | L1 Regularization | 135 | 90.72 | 90.65 | 95.00 | 86.67 | 6.66 |
| Hard Ensemble | RFE Random Forest | 150 | 90.31 | 90.30 | 92.13 | 88.89 | 6.89 |
| Hard Ensemble | L1 Regularization | 150 | 89.71 | 89.67 | 87.50 | 91.67 | 7.40 |
| Hard Ensemble | L1 Regularization | 125 | 89.67 | 89.55 | 92.78 | 86.67 | 6.25 |
| Hard Ensemble | RF Importance | 150 | 89.54 | 89.46 | 92.78 | 86.67 | 5.08 |
| Hard Ensemble | L1 Regularization | 105 | 88.56 | 88.44 | 90.97 | 86.11 | 4.55 |
| Hard Ensemble | L1 Regularization | 115 | 88.43 | 88.40 | 90.28 | 86.67 | 4.28 |
| Hard Ensemble | RF Importance | 115 | 88.43 | 88.35 | 93.06 | 84.44 | 5.97 |
| Hard Ensemble | RFE Random Forest | 110 | 88.43 | 88.41 | 90.56 | 86.67 | 4.28 |
| Hard Ensemble | RF Importance | 130 | 88.43 | 88.35 | 90.56 | 86.67 | 4.28 |
| Hard Ensemble | L1 Regularization | 145 | 88.40 | 88.29 | 91.90 | 85.19 | 5.34 |
| Hard Ensemble | XGB Importance | 145 | 88.34 | 88.31 | 92.13 | 85.19 | 6.05 |
| Classifier | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | 87.25 | 2.48 | 93.07 | 82.74 | 87.19 | 90.44 | 84.48 |
| XGBoost | 80.61 | 1.62 | 83.99 | 77.61 | 80.44 | 81.58 | 79.53 |
| RandomForest | 80.18 | 1.11 | 83.40 | 77.65 | 79.99 | 81.68 | 78.65 |
| Soft Ensemble | 78.82 | 1.34 | 81.63 | 75.92 | 78.51 | 82.38 | 75.38 |
| - | 76.86 | 1.94 | 81.01 | 72.97 | 76.43 | 81.70 | 72.16 |
| SVM | 76.67 | 2.46 | 80.42 | 72.39 | 76.26 | 80.78 | 72.77 |
| MLPClassifier | 75.74 | 2.07 | 81.08 | 71.34 | 75.18 | 81.53 | 70.16 |
| Feature Selection | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| L1 Regularization | 80.90 | 4.22 | 93.07 | 73.69 | 80.61 | 84.47 | 77.40 |
| RF Importance | 80.00 | 3.60 | 89.54 | 71.34 | 79.72 | 82.90 | 77.26 |
| RFE RandomForest | 78.61 | 4.36 | 90.30 | 72.39 | 78.28 | 82.38 | 75.05 |
| XGB Importance | 78.27 | 3.62 | 88.34 | 73.04 | 77.96 | 81.73 | 74.93 |
| Classifier | Feature Selection | k | Accuracy (%) | F1 Score (%) | Sensitivity (%) | Specificity (%) | Std Accuracy |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | L1 Regularization | 110 | 92.81 | 92.80 | 94.10 | 91.67 | 3.05 |
| Hard Ensemble | L1 Regularization | 120 | 91.96 | 91.91 | 97.78 | 86.67 | 3.11 |
| Hard Ensemble | L1 Regularization | 100 | 91.42 | 91.28 | 100.00 | 83.33 | 7.22 |
| Hard Ensemble | L1 Regularization | 135 | 90.72 | 90.65 | 95.00 | 86.67 | 6.66 |
| Hard Ensemble | L1 Regularization | 115 | 90.65 | 90.65 | 90.28 | 91.11 | 6.75 |
| Hard Ensemble | RFE Random Forest | 150 | 90.31 | 90.30 | 92.13 | 88.89 | 6.89 |
| Hard Ensemble | L1 Regularization | 150 | 89.71 | 89.67 | 87.50 | 91.67 | 7.40 |
| Hard Ensemble | RF Importance | 150 | 89.54 | 89.46 | 92.78 | 86.67 | 5.08 |
| Hard Ensemble | L1 Regularization | 105 | 88.56 | 88.44 | 90.97 | 86.11 | 4.55 |
| Hard Ensemble | L1 Regularization | 125 | 88.50 | 88.37 | 90.28 | 86.67 | 5.73 |
| Hard Ensemble | RFE Random Forest | 110 | 88.43 | 88.41 | 90.56 | 86.67 | 4.28 |
| Hard Ensemble | RF Importance | 130 | 88.43 | 88.35 | 90.56 | 86.67 | 4.28 |
| Hard Ensemble | RF Importance | 115 | 88.43 | 88.35 | 93.06 | 84.44 | 5.97 |
| Hard Ensemble | L1 Regularization | 130 | 88.40 | 88.37 | 91.90 | 85.19 | 7.50 |
| Hard Ensemble | RFE Random Forest | 125 | 88.32 | 88.27 | 94.10 | 83.33 | 4.94 |
| Classifier | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | 87.14 | 2.41 | 92.81 | 82.48 | 87.08 | 90.27 | 84.43 |
| XGBoost | 80.61 | 1.61 | 83.99 | 77.61 | 80.45 | 81.58 | 79.53 |
| Random Forest | 80.36 | 1.25 | 83.40 | 77.61 | 80.17 | 81.54 | 79.12 |
| Soft Ensemble | 78.81 | 1.34 | 81.11 | 76.44 | 78.50 | 82.38 | 75.35 |
| LogisticRegression | 76.73 | 1.95 | 81.01 | 72.29 | 76.30 | 81.52 | 72.09 |
| SVM | 76.71 | 2.51 | 80.42 | 72.39 | 76.30 | 80.83 | 72.79 |
| MLPClassifier | 75.78 | 2.11 | 81.08 | 71.34 | 75.22 | 81.61 | 70.16 |
| Feature Selection | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| L1 Regularization | 80.90 | 4.15 | 92.81 | 73.69 | 80.63 | 84.35 | 77.53 |
| RF Importance | 80.09 | 3.65 | 89.54 | 71.34 | 79.80 | 82.95 | 77.37 |
| RFE Random Forest | 78.60 | 4.36 | 90.30 | 72.29 | 78.26 | 82.41 | 74.99 |
| XGB Importance | 78.20 | 3.55 | 86.85 | 73.04 | 77.89 | 81.56 | 74.94 |
| Normalization | Best Acc (%) | Best F1 | k Features | Sensitivity (%) | Specificity (%) | Sens-Spec Balance | Most Stable Std | Mean Acc |
|---|---|---|---|---|---|---|---|---|
| Unnormalized | 94.20 | 94.19 | 110 | 94.10 | 94.44 | 0.35 | 3.11 | 79.52 |
| Min–Max | 93.07 | 93.05 | 120 | 97.78 | 88.89 | 8.89 | 2.71 | 79.45 |
| Z-Score | 92.81 | 92.80 | 110 | 94.10 | 91.67 | 2.43 | 3.05 | 79.45 |
| Classifier | Feature Selection | k | Accuracy (%) | F1 Score (%) | Sensitivity (%) | Specificity (%) | Std Accuracy |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | RFE Random Forest | 150 | 91.42 | 91.38 | 88.54 | 94.44 | 3.31 |
| Hard Ensemble | RF Importance | 125 | 91.26 | 91.23 | 96.88 | 86.11 | 3.49 |
| Hard Ensemble | L1 Regularization | 145 | 91.23 | 91.10 | 87.73 | 94.44 | 6.20 |
| Hard Ensemble | RF Importance | 130 | 90.36 | 90.32 | 96.06 | 85.19 | 5.83 |
| Hard Ensemble | RFE Random Forest | 125 | 89.48 | 89.46 | 92.78 | 86.67 | 5.00 |
| Hard Ensemble | RFE Random Forest | 120 | 89.38 | 89.36 | 92.13 | 87.04 | 4.48 |
| Hard Ensemble | L1 Regularization | 140 | 89.26 | 89.16 | 89.68 | 88.89 | 7.13 |
| Hard Ensemble | L1 Regularization | 100 | 88.45 | 88.42 | 90.05 | 87.04 | 6.34 |
| Hard Ensemble | RF Importance | 150 | 88.40 | 88.38 | 91.90 | 85.19 | 6.28 |
| Hard Ensemble | RFE Random Forest | 100 | 88.40 | 88.40 | 90.05 | 87.04 | 5.34 |
| Hard Ensemble | L1 Regularization | 115 | 88.38 | 88.22 | 85.91 | 90.48 | 4.88 |
| Hard Ensemble | L1 Regularization | 135 | 88.34 | 88.23 | 85.65 | 90.74 | 7.54 |
| Hard Ensemble | RF Importance | 140 | 87.81 | 87.76 | 90.28 | 85.71 | 7.36 |
| Hard Ensemble | L1 Regularization | 145 | 88.40 | 88.29 | 91.90 | 85.19 | 5.34 |
| Hard Ensemble | XGB Importance | 145 | 88.34 | 88.31 | 92.13 | 85.19 | 6.05 |
| Classifier | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | 87.55 | 1.54 | 91.42 | 84.31 | 87.48 | 89.22 | 96.88 |
| XGBoost | 82.05 | 1.41 | 85.13 | 79.38 | 81.77 | 82.78 | 87.08 |
| Soft Ensemble | 81.50 | 1.74 | 84.51 | 78.20 | 81.21 | 84.02 | 88.47 |
| Random Forest | 81.27 | 1.12 | 84.02 | 79.35 | 81.10 | 81.02 | 84.86 |
| SVM | 79.62 | 1.71 | 82.71 | 76.44 | 79.33 | 82.49 | 88.33 |
| MLPClassifier | 76.62 | 2.03 | 82.16 | 72.35 | 76.05 | 82.02 | 89.31 |
| LogisticRegression | 78.59 | 2.01 | 81.60 | 74.84 | 78.28 | 82.75 | 90.56 |
| Feature Selection | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| RFE RandomForest | 80.40 | 3.75 | 91.42 | 72.35 | 80.17 | 82.43 | 78.46 |
| RF Importance | 81.49 | 3.60 | 91.26 | 74.77 | 81.15 | 85.77 | 77.36 |
| L1 Regularization | 82.27 | 3.08 | 91.23 | 75.36 | 82.03 | 83.32 | 81.17 |
| XGB Importance | 79.95 | 3.54 | 87.49 | 72.45 | 79.64 | 82.36 | 77.49 |
| Classifier | Feature Selection | k | Accuracy (%) | F1 Score (%) | Sensitivity (%) | Specificity (%) | Std Accuracy |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | L1 Regularization | 120 | 92.16 | 92.03 | 91.67 | 92.59 | 8.04 |
| Hard Ensemble | RFE Random Forest | 150 | 91.42 | 91.38 | 88.54 | 94.44 | 3.31 |
| Hard Ensemble | RF Importance | 130 | 90.36 | 90.32 | 96.06 | 85.19 | 5.83 |
| Hard Ensemble | RFE Random Forest | 120 | 90.31 | 90.29 | 93.98 | 87.04 | 6.04 |
| Hard Ensemble | RF Importance | 125 | 89.79 | 89.76 | 93.75 | 86.11 | 3.10 |
| Hard Ensemble | RF Importance | 120 | 89.41 | 89.35 | 92.50 | 86.67 | 6.44 |
| Hard Ensemble | L1 Regularization | 125 | 89.38 | 89.36 | 90.05 | 88.89 | 5.82 |
| Hard Ensemble | L1 Regularization | 140 | 89.26 | 89.16 | 89.68 | 88.89 | 7.13 |
| Hard Ensemble | L1 Regularization | 145 | 89.08 | 88.94 | 89.29 | 88.89 | 9.26 |
| Hard Ensemble | L1 Regularization | 105 | 88.45 | 88.42 | 90.05 | 87.04 | 6.34 |
| Hard Ensemble | XGB Importance | 145 | 88.43 | 88.38 | 90.56 | 86.67 | 4.28 |
| Hard Ensemble | XGB Importance | 140 | 88.43 | 88.42 | 88.06 | 88.89 | 7.01 |
| Hard Ensemble | RF Importance | 150 | 88.40 | 88.38 | 91.90 | 85.19 | 6.28 |
| Hard Ensemble | L1 Regularization | 115 | 88.38 | 88.22 | 85.91 | 90.48 | 4.88 |
| Hard Ensemble | L1 Regularization | 110 | 88.38 | 88.31 | 85.91 | 90.48 | 5.73 |
| Classifier | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | 87.63 | 1.69 | 92.16 | 84.71 | 87.57 | 88.96 | 86.47 |
| XGBoost | 81.96 | 1.67 | 85.16 | 78.72 | 81.68 | 83.15 | 80.71 |
| Soft Ensemble | 81.44 | 1.72 | 84.51 | 78.20 | 81.14 | 83.93 | 78.91 |
| RandomForest | 81.52 | 1.16 | 83.43 | 79.35 | 81.36 | 81.53 | 81.50 |
| SVM | 79.62 | 1.71 | 82.71 | 76.44 | 79.33 | 82.49 | 76.72 |
| MLPClassifier | 76.62 | 2.03 | 82.16 | 72.35 | 76.05 | 82.02 | 71.37 |
| LogisticRegression | 78.59 | 2.01 | 81.60 | 74.84 | 78.28 | 82.75 | 74.46 |
| Feature Selection | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| L1 Regularization | 82.49 | 3.18 | 92.16 | 75.36 | 82.25 | 83.81 | 81.11 |
| RFE RandomForest | 80.43 | 3.78 | 91.42 | 72.35 | 80.20 | 82.30 | 78.62 |
| RF Importance | 81.37 | 3.56 | 90.36 | 74.77 | 81.04 | 85.62 | 77.26 |
| XGB Importance | 79.93 | 3.58 | 88.43 | 72.45 | 79.62 | 82.45 | 77.38 |
| Classifier | Feature Selection | k | Accuracy (%) | F1 Score (%) | Sensitivity (%) | Specificity (%) | Std Accuracy |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | RF Importance | 125 | 91.26 | 91.23 | 96.88 | 86.11 | 3.49 |
| Hard Ensemble | L1 Regularization | 145 | 91.23 | 91.10 | 87.73 | 94.44 | 6.20 |
| Hard Ensemble | RF Importance | 130 | 90.36 | 90.32 | 96.06 | 85.19 | 5.83 |
| Hard Ensemble | RFE Random Forest | 150 | 89.95 | 89.91 | 88.54 | 91.67 | 5.67 |
| Hard Ensemble | RFE Random Forest | 125 | 89.48 | 89.46 | 92.78 | 86.67 | 5.00 |
| Hard Ensemble | L1 Regularization | 110 | 89.22 | 89.17 | 87.70 | 90.48 | 5.09 |
| Hard Ensemble | L1 Regularization | 140 | 88.47 | 88.32 | 88.09 | 88.89 | 7.48 |
| Hard Ensemble | L1 Regularization | 115 | 88.44 | 88.29 | 84.90 | 91.67 | 4.52 |
| Hard Ensemble | L1 Regularization | 125 | 88.40 | 88.35 | 85.88 | 90.74 | 3.83 |
| Hard Ensemble | RF Importance | 150 | 88.40 | 88.38 | 91.90 | 85.19 | 6.28 |
| Hard Ensemble | RFE Random Forest | 120 | 88.40 | 88.40 | 90.05 | 87.04 | 5.34 |
| Hard Ensemble | L1 Regularization | 135 | 88.34 | 88.23 | 85.65 | 90.74 | 7.54 |
| Hard Ensemble | XGB Importance | 100 | 88.23 | 88.04 | 84.38 | 91.67 | 8.32 |
| Hard Ensemble | RF Importance | 140 | 87.81 | 87.76 | 90.28 | 85.71 | 7.36 |
| Hard Ensemble | RF Importance | 135 | 87.72 | 87.58 | 88.29 | 87.30 | 7.52 |
| Classifier | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| Hard Ensemble | 87.41 | 1.55 | 91.26 | 84.22 | 87.33 | 89.00 | 86.01 |
| XGBoost | 82.08 | 1.51 | 86.34 | 79.38 | 81.80 | 82.80 | 81.26 |
| RandomForest | 81.34 | 1.35 | 84.58 | 78.27 | 81.19 | 81.14 | 81.53 |
| Soft Ensemble | 81.47 | 1.77 | 84.54 | 77.61 | 81.18 | 84.04 | 78.86 |
| SVM | 79.58 | 1.66 | 82.71 | 76.44 | 79.29 | 82.46 | 76.67 |
| MLP Classifier | 76.59 | 2.03 | 81.60 | 72.35 | 76.01 | 82.17 | 71.17 |
| LogisticRegression | 78.64 | 2.07 | 81.60 | 74.84 | 78.33 | 82.78 | 74.54 |
| Feature Selection | Mean Acc (%) | Std Acc | Max Acc (%) | Min Acc (%) | Mean F1 (%) | Mean Sens (%) | Mean Spec (%) |
|---|---|---|---|---|---|---|---|
| RF Importance | 81.40 | 3.57 | 91.26 | 74.77 | 81.06 | 85.78 | 77.16 |
| L1 Regularization | 82.35 | 3.07 | 91.23 | 75.36 | 82.10 | 83.44 | 81.20 |
| RFE RandomForest | 80.28 | 3.65 | 89.95 | 72.35 | 80.05 | 82.32 | 78.32 |
| XGB Importance | 80.04 | 3.62 | 88.24 | 72.45 | 79.73 | 82.40 | 77.63 |
| Normalization | Best Acc (%) | Best F1 | k Features | Sensitivity (%) | Specificity (%) | Sens-Spec Balance | Most Stable Std | Mean Acc |
|---|---|---|---|---|---|---|---|---|
| Unnormalized | 91.42 | 91.38 | 150 | 88.54 | 94.44 | 5.90 | 2.90 | 81.03 |
| Min–Max | 92.16 | 92.03 | 120 | 91.67 | 92.59 | 0.93 | 2.90 | 81.05 |
| Z-Score | 91.26 | 91.23 | 125 | 96.88 | 86.11 | 10.76 | 2.90 | 81.02 |
| Dataset | Normalization | Mean Accuracy (%) | Best Accuracy (%) | Best Model | k |
|---|---|---|---|---|---|
| 25-Task | Unnormalized | 79.52 ± 4.07 | 94.20 | Hard Ensemble + L1 | 110 |
| 25-Task | Min–Max | 79.45 ± 4.09 | 93.07 | Hard Ensemble + L1 | 120 |
| 25-Task | Z-Score | 79.45 ± 4.07 | 92.81 | Hard Ensemble + L1 | 110 |
| 14-Task | Unnormalized | 81.03 ± 3.60 | 91.42 | Hard Ensemble + RFE | 150 |
| 14-Task | Min–Max | 81.05 ± 3.65 | 92.16 | Hard Ensemble + L1 | 120 |
| 14-Task | Z-Score | 81.02 ± 3.59 | 91.26 | Hard Ensemble + RF | 125 |
| Metric | 25-Task Dataset | 14-Task Dataset | Change (%) |
|---|---|---|---|
| Total Number of Features | 1200 | 672 | −44.00% |
| Average Number of Selected Features | 125 | 125 | 0 |
| Mean Accuracy | 79.47% | 81.03% | +1.56% |
| Maximum Accuracy | 94.20% | 91.61% | −1.75% |
| Mean F1-Score | 79.16% | 80.75% | +1.59% |
| Standard Deviation | 4.08% | 3.61% | −11.52% |
| Training Time (Relative) | 100% | ~60% | −40% |
| Memory Usage (Relative) | 100% | ~65% | −35% |
| Dataset | Normalization | Best Accuracy (%) | Best Model | k |
|---|---|---|---|---|
| 18-Feature–25-Task | Unnormalized, Min–Max | 89.87 | Hard Ensemble + RF_Importance | 125 |
| 48-Feature–25-Task | Unnormalized | 94.20 | Hard Ensemble + L1 | 110 |
| 48-Feature–14-Task | Min–Max | 92.16 | Hard Ensemble + L1 | 120 |
| Study | Model | # of Features/Task | # of Tasks | Accuracy (%) |
|---|---|---|---|---|
| Singh & Chaturvedi [25] | Stacking Ensemble | 18 | 25 | 88.57 |
| Saha et al. [57] | Stacking Ensemble (RF + LR/XGB/LightGBM/CatBoost (CB)) | 18 | 25 | 99.3 |
| Mitra & Rehman [58] | Stacking Ensemble with Feature Selection | 18 | 25 | 97.14 |
| Öcal [59] | LightGBM + AdaBoost + CatBoost (Hard Voting) | 18 | 25 | 97.14 |
| Demircioğlu [56] | SHAP + SVM | 18 | 25 | 96.23 |
| Cilia et al. [7] | RF | 18 | 25 | 88.29 |
| Nardone et al. [8] | CatBoost | 31 + 4 (demographic) | 34 | 80.81 |
| Cilia et al. [41] | Decision Tree (DT) | 22 + 4 (demographic) | 6 | 89.00 |
| This study | Hard Ensemble + RF Importance | 18 | 25 | 89.87 |
| This study | Hard Ensemble + L1 | 48 | 25 | 94.20 |
| This study | Hard Ensemble + L1 | 48 | 14 | 92.16 |
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Akyürek Anacur, C.; Günay Yılmaz, A.; Dizdaroğlu, B. Exploring Handwriting-Based Biomarkers for Alzheimer’s Disease: Identifying Discriminative Features and Tasks to Enhance Diagnostic Accuracy. Diagnostics 2026, 16, 697. https://doi.org/10.3390/diagnostics16050697
Akyürek Anacur C, Günay Yılmaz A, Dizdaroğlu B. Exploring Handwriting-Based Biomarkers for Alzheimer’s Disease: Identifying Discriminative Features and Tasks to Enhance Diagnostic Accuracy. Diagnostics. 2026; 16(5):697. https://doi.org/10.3390/diagnostics16050697
Chicago/Turabian StyleAkyürek Anacur, Cansu, Asuman Günay Yılmaz, and Bekir Dizdaroğlu. 2026. "Exploring Handwriting-Based Biomarkers for Alzheimer’s Disease: Identifying Discriminative Features and Tasks to Enhance Diagnostic Accuracy" Diagnostics 16, no. 5: 697. https://doi.org/10.3390/diagnostics16050697
APA StyleAkyürek Anacur, C., Günay Yılmaz, A., & Dizdaroğlu, B. (2026). Exploring Handwriting-Based Biomarkers for Alzheimer’s Disease: Identifying Discriminative Features and Tasks to Enhance Diagnostic Accuracy. Diagnostics, 16(5), 697. https://doi.org/10.3390/diagnostics16050697

