ITU-DESC: a missingness-aware machine-learning dementia risk score in the UK Biobank cohort

Abdullah Kavaklı; Faik Boray Tek

cs.LGOct 19, 2026

ITU-DESC: a missingness-aware machine-learning dementia risk score in the UK Biobank cohort

Authors: Abdullah Kavaklı, Faik Boray Tek

Organizations: Department of Artificial Intelligence and Data Engineering, Istanbul Technical University, Istanbul, Turkey.

Abstract

Background: Existing dementia risk scores rely on fixed, pre-selected features and linear models, or ignore bias from informative missingness in cohort data. Here we introduce the Istanbul Technical University Dementia Risk Score (ITU-DESC), an explainable machine-learning score for incident all-cause dementia that combines broad feature selection across roughly 8,000 candidate features with explicit control of missingness bias. Results: We studied approximately 500,000 UK Biobank participants with a median follow-up of 16.6 years. We withheld missingness patterns from the model using unconditional random hot-deck imputation. We stabilized feature selection by repeating BorutaSHAP-based feature selection with ten random-imputation seeds and selecting predictors chosen in at least eight of the ten seeds, which yielded 38 predictors. We trained a CatBoost gradient-boosted decision-tree model and evaluated it on a holdout test set of 50,041 participants. For all-cause incident dementia, ITU-DESC achieved an average precision of 0.138 (95% confidence interval 0.123-0.156) and an area under the receiver operating characteristic curve (ROC AUC) of 0.853 (0.844-0.863), significantly outperforming other risk scores, including the strongest comparator, the UK Biobank Dementia Risk Prediction model (0.118 and 0.841). We identified dementia risk predictors absent from established scores, including leukocyte telomere length and liver enzymes. Conclusions: ITU-DESC is the first dementia risk score to combine broad feature selection with explicit control of missingness bias.

Figures & tables

Panel of Figure 1 — Figure 1: Participant selection for the present study from the UK Biobank cohort. The upper boxes show the number of participants remaining after exclusions and the split of the eligible cohort into a 90% development set and a 10% holdout test set. The lower boxes report counts separately for the development (Dev.) and holdout test sides of the split. For each side, they give the number of participants without incident dementia during follow-up. They also report the numbers of incident dementia and Alzheimer’s disease cases within the 5-year, 10-year and full follow-up periods.

Panel of Figure 2 — Figure 2: Feature-selection pipeline. A stratified 90/10 split holds 10% of participants out as the test set. Within the 90% development set, the boxed two-stage pipeline consists of a five-fold SHAP screen that removes features with zero importance, followed by BorutaSHAP wrapper selection. The pipeline is repeated in full for each of the ten random-imputation seeds. Both stages therefore run ten times, and each seed carries its own screened feature set into its own wrapper run. Features selected in at least 8 of the 10 seeds form the ITU-DESC feature set. The model is then fitted on the development set and evaluated once on the holdout test set, which the selection stages never see.

Model	AP (95% CI)	$\Delta$ AP (95% CI)	$P$
ITU-DESC (our model)	0.138 (0.123, 0.156)	—	—
UKB-DRP You et al. (2022)	0.118 (0.105, 0.133)	0.021 (0.008, 0.033)	$<0.01$
UKBDRS Anatürk et al. (2023)	0.102 (0.092, 0.114)	0.036 (0.023, 0.050)	$<0.001$
UKBDRS (w/o APOE $\varepsilon$ 4)	0.084 (0.076, 0.093)	0.055 (0.041, 0.070)	$<0.001$
DRS Walters et al. (2016)	0.064 (0.058, 0.069)	0.075 (0.061, 0.090)	$<0.001$
CAIDE Kivipelto et al. (2006)	0.044 (0.040, 0.048)	0.094 (0.081, 0.110)	$<0.001$

Table 1: Discrimination of ITU-DESC and established dementia risk scores for all-incident dementia 0 0 footnotetext: All models were evaluated on the same holdout test set (

n=50{,}041

;

1{,}138

incident dementia cases), under identical outcome definitions, using isotonic-calibrated predictions. The upper panel reports average precision and the lower panel reports ROC AUC for the same models. Differences are ITU-DESC minus the comparator and were calculated from unrounded estimates. ROC AUC estimates, confidence intervals, differences and two-sided

P

values were derived using DeLong’s method. AP confidence intervals were obtained by paired subject-level bootstrap resampling (10,000 resamples; percentile method), whereas AP

P

values were obtained using two-sided paired permutation tests (2,000 permutations). AP, average precision; CI, confidence interval; ROC AUC, area under the receiver operating characteristic curve.

Figure 3: Comparison of ITU-DESC with established dementia risk scores. All models were evaluated on the holdout test set using calibrated predictions. a , Receiver operating characteristic curves for all-incident all-cause dementia (

1{,}138

incident cases). b , Precision–recall curves for all-incident all-cause dementia. c , Receiver operating characteristic curves for all-incident Alzheimer’s disease (

513

incident cases). d , Precision–recall curves for all-incident Alzheimer’s disease. The dotted line marks chance discrimination in a and c , and the outcome prevalence in b and d , which equals the average precision of a non-informative model. Discrimination estimates and pairwise comparisons are reported in Table 1 for dementia and Additional file 1: Table S12 for Alzheimer’s disease.

Figure 4: Discrimination of ITU-DESC across the 5-year, 10-year and all-incident horizons. A single fitted model underlies all three horizons, evaluated on the holdout test set using calibrated predictions. a , Receiver operating characteristic curves for all-cause dementia. b , Precision–recall curves for all-cause dementia. c , Receiver operating characteristic curves for Alzheimer’s disease. d , Precision–recall curves for Alzheimer’s disease. The dotted line marks chance discrimination in a and c . Discrimination values are reported in Additional file 1: Table S13, and the case counts underlying each horizon in Fig. 1 .

Figure 5: Flexible calibration of ITU-DESC for the all-incident outcomes. Both panels use the holdout test set. a , All-cause dementia. b , Alzheimer’s disease. Observed risk, estimated by locally estimated scatterplot smoothing (LOESS), is plotted against predicted risk with pointwise 95% confidence bands, calculated as the smoothed estimate plus or minus 1.96 standard errors of the local observed proportion. Histograms along the bottom of each panel show the distribution of predicted risks. Calibration slope, mean predicted risk against observed incidence and Brier score are given in Additional file 1: Table S23.

Figure 6: SHAP summary plot for ITU-DESC for all-incident dementia. Each point represents one participant and is plotted according to the feature’s SHAP value, corresponding to its signed contribution to the model output on the log-odds scale. Points are colored by feature value. Features are ordered from top to bottom by mean absolute SHAP value. SHAP values were computed on the holdout test set ( $n=50{,}041$ ), using the model refit on the full development set.

Figure 7: Cumulative discrimination of ITU-DESC as predictors are added in SHAP-rank order for all-incident dementia. The x-axis lists the top-

k

features ranked by mean absolute SHAP value computed on the 90% development set. a , Development-set SHAP importance of each feature. b , ROC AUC when the model is refit on the development set using the top-

k

features and evaluated on the holdout test set (

n=50{,}041

). c , Precision–recall AUC (average precision) for the same refits. Each point is a single holdout-test evaluation.

Appendix figures & tables6 assets

Supplementary material from the paper’s appendix.

Appendix

	Development ( $n=450{,}369$ )		Holdout test ( $n=50{,}041$ )
Outcome	Cases	%	Cases	%
Dementia, 5-year	681	0.151	75	0.150
Dementia, 10-year	3,802	0.844	421	0.841
Dementia, all-incident	10,242	2.274	1,138	2.274
Alzheimer’s disease, 5-year	231	0.051	26	0.052
Alzheimer’s disease, 10-year	1,506	0.334	167	0.334

Appendix

Table S1: Outcome counts and prevalences in the development and holdout test sets.

	Development		Holdout test
Variable	$n$	%	$n$	%	Diff.
Sex (stratified on)
Female	245,018	54.404	27,225	54.405	0.002
Male	205,351	45.596	22,816	45.595	0.002
Age at recruitment (acceptance criterion)
Mean, years	450,369	56.541	50,041	56.495	0.0057

Appendix

Table S2: Balance of the 90% development and 10% holdout test sets. Percentages are column percentages within each set; Diff. is the absolute difference in percentage points. For age at recruitment, a continuous variable, the % cells give the mean age in years and Diff. gives the standardized mean difference (SMD). For predictor availability,

n

and % are the participants with a recorded value. Assessment centers are given as UK Biobank Field 54 codes. Ethnicity categories derive from UK Biobank Field 21000. The split was stratified on the six outcomes (Table S1 ) and sex. Age, ethnicity and assessment center were prespecified acceptance criteria checked after the split, not stratification variables. Predictor availability was reported but neither stratified on nor subject to a threshold.

Stage	Operation	Columns
Raw extract	—	32,612
Compression	Baseline instance only; per-field collapse and typing	11,926
Outcome removal	Dementia- and outcome-linked fields ( $-586$ )	11,340
Expansion	148 multiple-choice fields replaced by 26,501 indicators	37,693
Preprocessing	A priori exclusions ( $-28{,}057$ )	9,636
Final selection	Remaining a priori exclusions and derived features	7,978

Appendix

Table S3: Column count at each stage of construction and exclusion. Counts are columns, including the participant identifier.

Group	Entries	Representative fields
Outcome or temporal leakage	2,692	42018, 42020, 130000–132605, 41272
Diet: single-day 24-hour recall	8	20077, 26068, 105010
Study administration and timing	243	21711–21771, 20751, 32365–32368
COVID-19	201	27981–28174, 29156–29161
Employment history	81	22601, 22602, 22603
Assay and genotyping quality control	72	22000–22030, 32050–32065, 3061

Appendix

Table S4: A priori feature exclusions by group. Counts are distinct excluded entries, deduplicated across pipeline stages, and are a lower bound on the number of columns removed.

Origin	Columns	Parent fields
UK Biobank field, one column each	6,854	3,726
Multiple-choice one-hot indicators	1,119	112
Derived for this work	4	—
Total	7,977	3,838

Appendix

Table S5: Composition of the 7,977-column candidate feature set that remained after the a priori exclusions and entered feature selection.

Library	Parameter	Value	Source
CatBoost	Evaluation metric	PRAUC	set
	Task type	CPU	set
	Threads	all available	set
	Verbosity	silent, no on-disk logs	set
	Random seed	fixed	set
	Loss function	Logloss	supplied

Appendix

Table S6: Training configuration of the gradient-boosting models. Set marks a value we passed to the constructor; supplied marks one the library chose, and those follow from the versions listed above. Random seeds were held fixed across runs. MVS, minimal variance sampling.

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