Development and external validation of a novel dementia risk prediction score in the UK Biobank cohort
Alzheimer's & Dementia, 2021•Wiley Online Library
Background Globally, up to 40% of dementia cases may be prevented if several key risk
factors, such as low education and obesity, are targeted. This has motivated interest into the
development of risk scores that aim to quantify an individual's risk of developing dementia
within a given time frame. However, translation to a clinical setting has been hampered by
either a lack of external validation, poor out‐of‐sample performance, or the integration of
measures (eg, MRI, cognitive testing) that are costly or time intensive to administer. This …
factors, such as low education and obesity, are targeted. This has motivated interest into the
development of risk scores that aim to quantify an individual's risk of developing dementia
within a given time frame. However, translation to a clinical setting has been hampered by
either a lack of external validation, poor out‐of‐sample performance, or the integration of
measures (eg, MRI, cognitive testing) that are costly or time intensive to administer. This …
Background
Globally, up to 40% of dementia cases may be prevented if several key risk factors, such as low education and obesity, are targeted. This has motivated interest into the development of risk scores that aim to quantify an individual’s risk of developing dementia within a given time frame. However, translation to a clinical setting has been hampered by either a lack of external validation, poor out‐of‐sample performance, or the integration of measures (e.g., MRI, cognitive testing) that are costly or time intensive to administer.
This study aimed to develop a novel dementia risk score suitable for a primary care setting and compare its discrimination accuracy with other risk scores.
Method
208,108 UK Biobank (UKB) participants were examined, with cases of incident dementia (mean time to diagnosis ± SD = 5.91 years ± 2.02) identified through self‐report, hospital inpatient records and death certificates (n = 1,270, 0.6%). The dataset was randomly split into a training (80%) and test set (20%). Potential predictors (n = 30) included Apolipoprotein E4 (APOE4) status and cardiovascular, medical and lifestyle factors collected at baseline. Logistic LASSO regression was employed for variable selection and logistic regression was then used to derive beta coefficients for each predictor included in the UKB dementia risk score (UKB‐DRS). The area under the curve (i.e., AUC) was used to compare the discriminative ability of the UKB‐DRS to the CAIDE, ANU‐ADRI, Dementia Risk Score (i.e., DRS) and Framingham risk score, in both the test set and the Whitehall II study (WHIII, n = 2,974), which served as an external dataset.
Result
The UKB‐DRS consisted of age, sex, education, APOE4 status, a medical history of diabetes, stroke and depression and a family history of dementia. The UKB‐DRS demonstrated good discrimination accuracy in both the test set (AUC [95% ] = 0.79 [0.77, 0.82]) and external dataset (AUC [95% CI] = 0.83 [0.79,0.87]). Additionally, the UKB‐DRS outperformed all other risk scores (the DRS had the next best AUC [95% CI]: UKB = 0.77 [0.74, 0.8]; WHII = 0.77 [0.73, 0.81]).
Conclusion
This study contributes a novel dementia risk score that may be used to guide primary prevention strategies.
Wiley Online Library
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